EP4096646A1 - Methoden zur behandlung von krebs mit einem antitigit-antagonistischen antikörper - Google Patents

Methoden zur behandlung von krebs mit einem antitigit-antagonistischen antikörper

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Publication number
EP4096646A1
EP4096646A1 EP21705841.1A EP21705841A EP4096646A1 EP 4096646 A1 EP4096646 A1 EP 4096646A1 EP 21705841 A EP21705841 A EP 21705841A EP 4096646 A1 EP4096646 A1 EP 4096646A1
Authority
EP
European Patent Office
Prior art keywords
subject
dose
weeks
subjects
cancer
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
EP21705841.1A
Other languages
English (en)
French (fr)
Inventor
Catherine LAI
Janet LAU
Anthony Jongha LEE
Shi Li
Yvonne Gail LIN-LIU
Christina Jeanne MATHENY
Diana Mendus
Raymond D. Meng
Anh NGUYEN DUC
Jilpa Bhupendra PATEL
Thinh Quang Pham
Isabelle Anne ROONEY
Heather Blythe STEVENS
Sarah Marie TROUTMAN
Lijia Wang
Yulei Wang
Patrick Georges Robert WILLIAMS
Benjamin Wu
Yibing Yan
Aijing ZHANG
Xiaosong Zhang
Marcus Dale BALLINGER
Hila BARAK
Elizabeth Alexandra BENNETT
Marcela Lucia CASTRO
Edward Namserk CHA
Hui Min Phyllis CHAN
Stephen CHUI
Christopher Roland COTTER
Viraj Vinay DEGAONKAR
Barbara Jennifer Gitlitz
Tien HOANG
Kimberly Mayumi KOMATSUBARA
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
F Hoffmann La Roche AG
Genentech Inc
Original Assignee
F Hoffmann La Roche AG
Genentech Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from PCT/US2020/024526 external-priority patent/WO2021194481A1/en
Priority claimed from PCT/US2020/049415 external-priority patent/WO2022050954A1/en
Application filed by F Hoffmann La Roche AG, Genentech Inc filed Critical F Hoffmann La Roche AG
Publication of EP4096646A1 publication Critical patent/EP4096646A1/de
Pending legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/337—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/555—Heterocyclic compounds containing heavy metals, e.g. hemin, hematin, melarsoprol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
    • A61K31/7068—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/243—Platinum; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • C07K16/2827—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against B7 molecules, e.g. CD80, CD86
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • A61K2039/507—Comprising a combination of two or more separate antibodies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/54—Medicinal preparations containing antigens or antibodies characterised by the route of administration
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/545—Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin

Definitions

  • the present invention relates to methods, uses, and compositions for the treatment of cancer. More specifically, the invention concerns the treatment of patients having cancer with an anti-TIG IT antagonist antibody (e.g., treatment with an anti-TIG IT antagonist antibody as a monotherapy or a combination therapy).
  • an anti-TIG IT antagonist antibody e.g., treatment with an anti-TIG IT antagonist antibody as a monotherapy or a combination therapy.
  • Cancers are characterized by the uncontrolled growth of cell subpopulations. Cancers are the leading cause of death in the developed world and the second leading cause of death in developing countries, with over 14 million new cancer cases diagnosed and over eight million cancer deaths occurring each year. Cancer care thus represents a significant and ever-increasing societal burden.
  • the invention provides a method of treating a subject having a cancer, the method comprising administering to the subject a dosing regimen comprising one or more dosing cycles of an anti-TIG IT antagonist antibody at a dose of about 500 mg to about 700 mg every three weeks, a PD-1 axis binding antagonist at a dose of about 900 mg to about 1500 mg every three weeks, a platinum-based chemotherapeutic agent every three weeks, and a non-platinum-based chemotherapeutic agent every three weeks.
  • the invention provides a method of treating a subject having a cancer, the method comprising administering to the subject a dosing regimen comprising one or more dosing cycles of an anti-TIGIT antagonist antibody at a dose of about 700 mg to about 1000 mg every four weeks and a PD-1 axis binding antagonist at a dose of about 1400 mg to 2000 mg every four weeks.
  • the invention provides a method of treating a subject having a cancer, the method comprising administering to the subject a dosing regimen comprising one or more dosing cycles of an anti-TIGIT antagonist antibody at a dose of about 300 mg to about 600 mg every two weeks and a PD-1 axis binding antagonist at a dose of about 600 mg to about 1200 mg every two weeks.
  • the invention provides a kit comprising an anti-TIGIT antagonist antibody for use in combination with a PD-1 axis binding antagonist for treating a subject having a cancer according to the methods provided herein.
  • the invention provides an anti-TIGIT antagonist antibody and a PD-1 axis binding antagonist for use in a method of treating a subject having a cancer, wherein the method is according to the methods provided herein.
  • the invention provides use of an anti-TIGIT antagonist antibody in the manufacture of a medicament for treating a subject having a cancer in combination with a PD-1 axis binding antagonist, wherein the treatment is according to the methods provided herein.
  • the invention provides a method of treating a subject having a cancer, the method comprising administering to the subject a dosing regimen comprising one or more dosing cycles of an anti-TIGIT antagonist antibody at a dose of about 700 mg to about 1000 mg every four weeks and a PD-1 axis binding antagonist at a dose of about 1400 mg to 2000 mg every four weeks.
  • the invention provides a method of treating a subject having a cancer, the method comprising administering to the subject a dosing regimen comprising one or more dosing cycles of an anti-TIGIT antagonist antibody at a dose of about 300 mg to about 600 mg every two weeks and a PD-1 axis binding antagonist at a dose of about 600 mg to about 1200 mg every two weeks.
  • the invention provides a method of treating a subject having a cancer, the method comprising administering to the subject a dosing regimen comprising one or more dosing cycles of an anti-TIGIT antagonist antibody at a dose of about 500 mg to about 700 mg every three weeks, a PD-1 axis binding antagonist at a dose of about 900 mg to about 1500 mg every three weeks, a platinum- based chemotherapeutic agent every three weeks, and a non-platinum-based chemotherapeutic agent every three weeks.
  • the invention provides a method of treating a subject having a cancer, the method comprising administering to the subject a dosing regimen comprising one or more dosing cycles of an anti-TIGIT antagonist antibody at a dose of about 500 mg to about 700 mg every three weeks and an anti-PD-1 antagonist antibody at a dose of about 100 mg to about 300 mg every three weeks, wherein the anti-PD-1 antagonist antibody is pembrolizumab.
  • the invention provides a method of treating a subject having a cancer, the method comprising administering to the subject a dosing regimen comprising one or more dosing cycles of tiragolumab and pembrolizumab, wherein the pembrolizumab is administered at a dose of between about 300 mg to about 500 mg every six weeks.
  • the invention provides a method for treating a subject having a cancer, the method comprising administering to the subject a dosing regimen comprising one or more dosing cycles of an anti-TIGIT antagonist antibody at a dose of between about 500 mg to about 700 mg every three weeks, a PD-1 axis binding antagonist at a dose of between about 900 mg to about 1500 mg every three weeks, and an antimetabolite at a dose of between about 10 mg/m 2 to about 10000 mg/m 2 twice a day orally every three weeks for 2-weeks on/1 -week off.
  • the invention provides a method of treating a subject having a cancer, the method comprising administering to the subject a dosing regimen comprising one or more dosing cycles of an anti-TIGIT antagonist antibody at a dose of about 500 mg to about 700 mg every three weeks, a PD-1 axis binding antagonist at a dose of about 900 mg to about 1500 mg every three weeks, gemcitabine, and nab-paclitaxel.
  • the invention provides a method for treating a subject having a cancer, the method comprising administering to the subject a dosing regimen comprising one or more dosing cycles of an anti-TIGIT antagonist antibody at a dose of between about 500 mg to about 700 mg every three weeks, a PD-1 axis binding antagonist at a dose of between about 900 mg to about 1500 mg every three weeks, and a VEGF antagonist at a dose of between about 1 mg/kg to about 35 mg/kg every three weeks.
  • the invention provides a method of treating a subject having a cancer, the method comprising administering to the subject a dosing regimen comprising an induction phase and a maintenance phase, wherein (a) the induction phase comprises one or more dosing cycles of an anti- TIGIT antagonist antibody at a dose of about 500 mg to about 700 mg every three weeks, a PD-1 axis binding antagonist at a dose of about 900 mg to about 1500 mg every three weeks, a platinum-based chemotherapeutic agent every three weeks, and a non-platinum-based chemotherapeutic agent every three weeks; and (b) the maintenance phase comprises one or more additional dosing cycles of the anti- TIGIT antagonist antibody every three weeks, the PD-1 axis binding antagonist every three weeks, and the non-platinum-based chemotherapeutic agent every three weeks, and wherein the maintenance phase does not comprise administration of the platinum-based chemotherapeutic agent.
  • the induction phase comprises one or more dosing cycles of an anti- TIGIT antagonist antibody at
  • the invention provides a method of treating a subject having a cancer, the method comprising administering to the subject a dosing regimen comprising an induction phase and a maintenance phase, wherein (a) the induction phase comprises one or more dosing cycles of an anti- TIGIT antagonist antibody at a dose of about 500 mg to about 700 mg every three weeks, a PD-1 axis binding antagonist at a dose of about 900 mg to about 1500 mg every three weeks, a platinum-based chemotherapeutic agent every three weeks, and a non-platinum-based chemotherapeutic agent every three weeks; and (b) the maintenance phase comprises one or more additional dosing cycles of the anti- TIGIT antagonist antibody at a dose of about 700 mg to about 1000 mg every four weeks and the PD-1 axis binding antagonist at a dose of about 1400 mg to 2000 mg every four weeks, wherein the maintenance phase does not comprise administration of the platinum-based chemotherapeutic agent or non-platinum-based chemotherapeutic agent.
  • the induction phase
  • the invention provides a method of treating a subject or population of subjects having a lung cancer, the method comprising administering to the subject or population of subjects a dosing regimen comprising one or more dosing cycles of an effective amount of an anti-TIGIT antagonist antibody, a PD-1 axis binding antagonist, a platinum-based chemotherapeutic agent, and a topoisomerase II inhibitor, wherein the treatment extends progression-free survival (PFS) of the subject as compared to treatment with the PD-1 axis binding antagonist, the platinum-based chemotherapeutic agent, and the topoisomerase II inhibitor without the anti-TIGIT antagonist antibody.
  • a dosing regimen comprising one or more dosing cycles of an effective amount of an anti-TIGIT antagonist antibody, a PD-1 axis binding antagonist, a platinum-based chemotherapeutic agent, and a topoisomerase II inhibitor, wherein the treatment extends progression-free survival (PFS) of the subject as compared to treatment with the PD-1 axi
  • the invention provides a method of treating a population of subjects having a lung cancer, the method comprising administering to the population of subjects a dosing regimen comprising one or more dosing cycles of an effective amount of an anti-TIGIT antagonist antibody, a PD- 1 axis binding antagonist, a platinum-based chemotherapeutic agent, and a topoisomerase II inhibitor, wherein the treatment results in a median PFS of the population of subjects of about 8.2 months to about 9.2 months.
  • the invention provides a method of treating a subject or population of subjects having a lung cancer, the method comprising administering to the subject or population of subjects a dosing regimen comprising one or more dosing cycles of an effective amount of an anti-TIGIT antagonist antibody, a PD-1 axis binding antagonist, a platinum-based chemotherapeutic agent, and a topoisomerase II inhibitor, wherein the treatment extends OS of the subject as compared to treatment with the PD-1 axis binding antagonist, the platinum-based chemotherapeutic agent, and the topoisomerase II inhibitor without the anti-TIGIT antagonist antibody.
  • the invention provides a method of treating a population of subjects having a lung cancer, the method comprising administering to the population of subjects a dosing regimen comprising one or more dosing cycles of an effective amount of an anti-TIGIT antagonist antibody, a PD- 1 axis binding antagonist, a platinum-based chemotherapeutic agent, and a topoisomerase II inhibitor, wherein the treatment results in a median OS of the population of subjects of about 15.3 months to about 17.6 months.
  • the invention provides a method of treating a subject or population of subjects having a lung cancer, the method comprising administering to the subject or population of subjects a dosing regimen comprising one or more dosing cycles of an anti-TIG IT antagonist antibody, a PD-1 axis binding antagonist, a first chemotherapeutic agent which is a platinum-based chemotherapeutic agent, and a second chemotherapeutic agent which is a non-platinum-based chemotherapeutic agent.
  • a dosing regimen comprising four 21 -day dosing cycles of tiragolumab,
  • the invention provides a method for treating a subject having a resectable lung cancer, the method comprising administering to the subject one or more dosing cycles of an anti- TIGIT antagonist antibody at a dose of between about 500 mg to about 700 mg every three weeks and a PD-1 axis binding antagonist at a dose of between about 900 mg to about 1500 mg every three weeks.
  • the invention provides a method for treating a subject having a lung cancer, the method comprising administering to the subject one or more dosing cycles of an anti-TIG IT antagonist antibody and a PD-1 axis binding antagonist, wherein at least one of the dosing cycles comprises administering to the subject the anti-TIG IT antagonist antibody at a dose of between about 500 mg to about 700 mg every three weeks and the PD-1 axis binding antagonist at a dose of between about 900 mg to about 1500 mg every three weeks as a neoadjuvant treatment.
  • the invention provides a method for treating a subject having a resectable lung cancer, the method comprising administering to the subject one or more dosing cycles of tiragolumab at a dose of about 600 mg every three weeks, atezolizumab at a dose of about 1200 mg every three weeks, and (a) (i) carboplatin at a dose targeted to achieve an AUC of 5 mg/mL/min or an AUC of 6 mg/mL/min every three weeks; or (ii) cisplatin at a dose of about 75 mg/m 2 every three weeks; and (b) (i) pemetrexed at a dose of about 500 mg/m 2 every three weeks or gemcitabine at a dose of about 1000 mg/m 2 or about 1250 mg/m 2 on Days 1 and 8 of each dosing cycle; or (ii) paclitaxel at a dose of about 175 mg/m 2 or about 200 mg/m 2 every three weeks.
  • the invention provides a method for treating a subject having a lung cancer, the method comprising administering to the subject one or more dosing cycles of tiragolumab and atezolizumab, wherein (I) at least one of the dosing cycles is a neoadjuvant treatment and comprises administering to the subject (a) tiragolumab at a dose of about 1200 mg every three weeks; (b) atezolizumab at a dose of about 1200 mg every three weeks as a neoadjuvant treatment; and (c) (i) carboplatin at a dose targeted to achieve an AUC of 5 mg/mL/min every three weeks and gemcitabine at a dose of about 1000 mg/m 2 on Days 1 and 8 of each dosing cycle; (ii) carboplatin at a dose targeted to achieve an AUC of 6 mg/mL/min every three weeks and paclitaxel at a dose of about 175 mg/m 2 or about 200 mg/m 2 every
  • the invention provides a method for treating a subject or population of subjects having a cervical cancer with a detectable expression level of PD-L1 , the method comprising administering to the subject or population of subjects one or more dosing cycles of an anti-TIGIT antagonist antibody at a dose of between about 500 mg to about 700 mg every three weeks and a PD-1 axis binding antagonist at a dose of between about 900 mg to about 1500 mg every three weeks.
  • the invention provides a method of selecting a therapy for a subject having a cervical cancer, the method comprising (a) detecting the protein expression level of PD-L1 on tumor cells from a tumor sample from the subject by an IHC assay using an anti-PD-L1 antibody suitable for staining; and (b) selecting for the subject having a detectable expression level of PD-L1 a therapy comprising one or more dosing cycles of an anti-TIGIT antagonist antibody administered at a dose of between about 500 mg to about 700 mg every three weeks and a PD-1 axis binding antagonist administered at a dose of between about 900 mg to about 1500 mg every three weeks based on PD-L1 expression on tumor cells having been detected.
  • the invention provides a method for treating a subject having a cervical cancer with a detectable expression level of PD-L1 , the method comprising administering to the subject one or more dosing cycles of tiragolumab at a dose of about 600 mg every three weeks and atezolizumab at a dose of about 1200 mg every three weeks.
  • the invention provides a method of treating a subject or population of subjects having a breast cancer, the method comprising administering to the subject or population of subjects a dosing regimen comprising one or more dosing cycles of tiragolumab at a dose of about 840 mg every four weeks, atezolizumab at a dose of about 1680 mg every four weeks, and nab-paclitaxel at a dose of about 100 mg/m 2 for 3-weeks on/1 -week off.
  • a dosing regimen comprising one or more dosing cycles of tiragolumab at a dose of about 840 mg every four weeks, atezolizumab at a dose of about 1680 mg every four weeks, and nab-paclitaxel at a dose of about 100 mg/m 2 for 3-weeks on/1 -week off.
  • the invention provides a method of treating a subject having an early triple negative breast cancer (eTNBC), the method comprising administering to the subject a dosing regimen comprising one or more dosing cycles of an anti-TIG IT antagonist antibody at a dose of about 300 mg to about 600 mg every two weeks and a PD-1 axis binding antagonist at a dose of about 600 mg to about 1200 mg every two weeks.
  • eTNBC early triple negative breast cancer
  • the invention provides a method of treating a subject having an eTNBC, the method comprising administering to the subject a dosing regimen comprising tiragolumab at a dose of about 420 mg every two weeks, atezolizumab at a dose of about 840 mg every two weeks, and (a) (i) nab-paclitaxel at a dose of about 125 mg/m 2 every week and carboplatin at a dose targeted to achieve an AUC of 5 mg/mL/min every three weeks for the first 12 weeks of the dosing regimen; and (ii) doxorubicin at a dose of about 60 mg/m 2 every two weeks, cyclophosphamide at a dose of about 600 mg/m 2 every two weeks, and G-CSF or GM-CSF every two weeks for weeks 13-19 of the dosing regimen; or (b) (i) nab-paclitaxel at a dose of about 125 mg/m 2 every week for the first 12 weeks of
  • the invention provides a method for treating a subject or population of subjects having an SCCHN with a detectable expression level of PD-L1 , the method comprising administering to the subject or population of subjects one or more dosing cycles of an anti-TIGIT antagonist antibody at a dose of between about 500 mg to about 700 mg every three weeks and a PD-1 axis binding antagonist at a dose of between about 900 mg to about 1500 mg every three weeks.
  • the invention provides a method of selecting a therapy for a subject or population of subjects having an SCCHN, the method comprising: (a) detecting a protein expression level of PD-L1 in a tumor sample from the subject or population of subjects by an IHC assay using an anti-PD- L1 antibody suitable for staining; and (b) selecting for the subject or population of subjects having a detectable expression level of PD-L1 a therapy comprising one or more dosing cycles of a PD-1 axis binding antagonist at a dose of between about 900 mg to about 1500 mg every three weeks and an anti- TIGIT antagonist antibody at a dose of between about 500 mg to about 700 mg every three weeks based on PD-L1 expression having been detected.
  • the invention provides a method for treating a subject having an SCCHN with a detectable expression level of PD-L1 , the method comprising administering to the subject one or more dosing cycles of tiragolumab at a dose of about 600 mg every three weeks and atezolizumab at a dose of about 1200 mg every three weeks.
  • the invention provides a method of treating a subject or population of subjects having a hepatocellular carcinoma (HCC), the method comprising administering to the subject or population of subjects one or more dosing cycles of an anti-TIG IT antagonist antibody and a PD-1 axis binding antagonist, wherein the subject or population of subjects have received no prior systemic treatment for HCC.
  • HCC hepatocellular carcinoma
  • the invention provides a method of treating a subject or population of subjects having an HCC, the method comprising administering to the subject or population of subjects one or more dosing cycles of an anti-TIGIT antagonist antibody, a PD-1 axis binding antagonist, and a VEGF antagonist.
  • the invention provides a method of treating a subject or population of subjects having an HCC, the method comprising administering to the subject one or more dosing cycles of tiragolumab at a dose of about 600 mg every three weeks, atezolizumab at a dose of about 1200 mg every three weeks, and bevacizumab at a dose of about 15 mg/kg every three weeks.
  • the invention provides a method for treating a subject or population of subjects having an MIBC, the method comprising administering to the subject one or more dosing cycles of an anti-TIGIT antagonist antibody at a dose of between about 500 mg to about 700 mg every three weeks and a PD-1 axis binding antagonist at a dose of between about 900 mg to about 1500 mg every three weeks, wherein the subject is ineligible for treatment with a platinum-based chemotherapeutic agent.
  • the invention provides a method for treating a subject or population of subjects having an MIBC, the method comprising administering to the subject one or more dosing cycles of an anti-TIGIT antagonist antibody at a dose of between about 500 mg to about 700 mg every three weeks and a PD-1 axis binding antagonist at a dose of between about 900 mg to about 1500 mg every three weeks, wherein the treatment is a perioperative treatment.
  • the invention provides a method for treating a subject or population of subjects having an MIBC, the method comprising administering to the subject or population of subjects one or more dosing cycles of tiragolumab at a dose of about 600 mg every three weeks and atezolizumab at a dose of about 1200 mg every three weeks, wherein the subject or subjects are cisplatin ineligible.
  • the invention provides a method for treating a subject or population of subjects having an MIBC, the method comprising administering to the subject or population of subjects one or more dosing cycles of tiragolumab at a dose of about 600 mg every three weeks and atezolizumab at a dose of about 1200 mg every three weeks, wherein the treatment is a perioperative treatment.
  • the invention provides a method for treating a subject or population of subjects having an mUC, the method comprising administering to the subject or population of subjects a dosing regimen comprising one or more dosing cycles of an anti-TIGIT antagonist antibody at a dose of between about 500 mg to about 700 mg every three weeks and a PD-1 axis binding antagonist at a dose of between about 900 mg to about 1500 mg every three weeks.
  • the invention provides a method for treating a subject or population of subjects having an mUC, the method comprising administering to the subject or population of subjects one or more dosing cycles of tiragolumab at a dose of about 600 mg every three weeks and atezolizumab at a dose of about 1200 mg every three weeks.
  • the invention provides a method for treating a subject or population of subjects having an mUC, the method comprising administering to the subject or population of subjects a first dosing regimen followed by a second dosing regimen, wherein (a) the first dosing regimen comprises one or more dosing cycles of tiragolumab at a dose of about 600 mg every three weeks and atezolizumab at a dose of about 1200 mg every three weeks; and (b) the second dosing regimen comprises one or more dosing cycles of atezolizumab at a dose of about 1200 mg every three weeks and (i) enfortumab vedotin is administered at a dose of 1 .25 mg/kg every week for 2-weeks on/1 week off or (ii) sacituzumab govitecan is administered at a dose of 10 mg/kg every week for 2-weeks on/1 week off, wherein the second dosing regimen is administered to the subject or population of subjects after the subject or population of subjects have experienced disease progression
  • the invention provides a method of treating a subject or population of subjects having a pancreatic cancer, the method comprising administering to the subject or population of subjects a dosing regimen comprising one or more 28-day dosing cycles of tiragolumab at a dose of about 420 mg on Days 1 and 15 of each 28-day dosing cycle, atezolizumab at a dose of about 840 mg on Days 1 and 15 of each 28-day dosing cycle, gemcitabine at a dose of about 1000 mg/m 2 on Days 1 , 8, and 15 of each 28-day dosing cycle, and nab-paclitaxel at a dose of about 125 mg/m 2 on Days 1 , 8, and 15 of each 28- day dosing cycle.
  • a dosing regimen comprising one or more 28-day dosing cycles of tiragolumab at a dose of about 420 mg on Days 1 and 15 of each 28-day dosing cycle, atezolizumab at a dose of about 840 mg on
  • the invention provides a method for treating a subject or population of subjects having an advanced or metastatic esophageal cancer, the method comprising administering to the subject or population of subjects a dosing regimen comprising one or more 21 -day dosing cycles of an anti-TIG IT antagonist antibody at a dose of between about 500 mg to about 700 mg on Day 1 of each dosing cycle and a PD-1 axis binding antagonist at a dose of between about 900 mg to about 1500 mg on Day 1 of each dosing cycle.
  • the invention provides a method for treating a subject or population of subjects having an esophageal cancer, the method comprising administering to the subject or population of subjects a dosing regimen comprising one or more 21 -day dosing cycles of an anti-TIG IT antagonist antibody at a dose of between about 500 mg to about 700 mg on Day 1 of each dosing cycle and a PD-1 axis binding antagonist at a dose of between about 900 mg to about 1500 mg on Day 1 of each dosing cycle, wherein the subject or subjects have been previously treated with a platinum-based chemotherapeutic agent and a non-platinum-based chemotherapeutic agent.
  • the invention provides a method for treating a subject or population of subjects having an advanced or metastatic esophageal cancer, the method comprising administering to the subject or population of subjects a dosing regimen comprising one or more 21 -day dosing cycles of tiragolumab at a dose of about 600 mg on Day 1 of each dosing cycle, atezolizumab at a dose of about 1200 mg on Day 1 of each dosing cycle, cisplatin at a dose of about 80 mg/m 2 on Day 1 of each dosing cycle, and 5-fluorouracil at a dose of 800 mg/m 2 /24 hours on Days 1 -5 of each 21 -day cycle, wherein cisplatin is omitted from the dosing regimen after six doses.
  • a dosing regimen comprising one or more 21 -day dosing cycles of tiragolumab at a dose of about 600 mg on Day 1 of each dosing cycle, atezolizumab at a dose of about 1200 mg
  • the invention provides a method for treating a subject or population of subjects having an advanced or metastatic esophageal cancer, the method comprising administering to the subject or population of subjects a first dosing regimen and a second dosing regimen, wherein (a) the first dosing regimen comprises one or more 21 -day dosing cycles of cisplatin at a dose of about 80 mg/m 2 on Day 1 of each dosing cycle and 5-fluorouracil at a dose of 800 mg/m 2 /24 hours on Days 1 -5 of each 21 - day cycle, wherein cisplatin is omitted from the dosing regimen after six doses; and (b) the second dosing regimen comprises one or more 21 -day dosing cycles of tiragolumab at a dose of about 600 mg on Day 1 of each dosing cycle and atezolizumab at a dose of about 1200 mg on Day 1 of each dosing cycle.
  • the invention provides a kit comprising a PD-1 axis binding antagonist and/or an anti-TIG IT antagonist antibody for treating a subject having a cancer according to the methods provided herein.
  • the invention provides a kit comprising a PD-1 axis binding antagonist for use in combination with an anti-TIGIT antagonist antibody for treating a subject having a cancer according to the methods provided herein.
  • the invention provides a kit comprising an anti-TIGIT antagonist antibody for use in combination with a PD-1 axis binding antagonist for treating a subject having a cancer according to the methods provided herein.
  • the invention provides an anti-TIGIT antagonist antibody and a PD-1 axis binding antagonist for use in a method of treating a subject or population of subjects having a cancer, wherein the method is according to the methods provided herein.
  • the invention provides use of an anti-TIGIT antagonist antibody in the manufacture of a medicament for treating a subject or population of subjects having a cancer in combination with a PD-1 axis binding antagonist, wherein the treatment is according to the methods provided herein.
  • FIG. 1 is a flow chart showing the Phase lb chemotherapy expansion and Phase lb Q4W dosing expansion).
  • FIG. 2 is a flow chart of a phase lb trial schema.
  • EOCG Eastern Cooperative Oncology Group
  • IHC immunohistochemistry
  • PD-L1 + programmed death-ligand 1 positive
  • Q4W every 4 weeks
  • RECIST v1 .1 Response Criteria in Solid Tumors, Version 1 .1
  • TFI treatment-free interval
  • TNBC triple-negative breast cancer.
  • FIG. 3 is a flow chart of a phase la study design.
  • CRC colorectal cancer
  • DLT dose-limiting toxicity
  • GC gastric cancer
  • HNSCC head and neck squamous cell carcinoma
  • IV intravenous
  • MAD maximum administered dose
  • MSI microsatellite instability
  • MSS microsatellite-stable
  • MTD maximum tolerated dose
  • NSCLC non-small cell lung cancer
  • OC ovarian cancer
  • PD progression of disease
  • PK pharmacokinetic
  • RCC renal cell carcinoma
  • TNBC triple-negative breast cancer
  • UBC urothelial bladder cancer.
  • FIG. 4 is a flow chart of the phase lb tiragolumab and atezolizumab expansion cohorts, serial biopsy cohort, and Q4W dosing expansion cohort study design.
  • CIT cancer immunotherapy
  • DLT dose-limiting toxicity
  • HNSCC head and neck squamous cell carcinoma
  • IV intravenous
  • MAD maximum administered dose
  • MSI microsatellite instability
  • MSS microsatellite-stable
  • MTD maximum tolerated dose
  • NSCLC non-small cell lung cancer
  • PD progression of disease
  • PD 1 programmed death-1
  • PD-L1 programmed death ligand 1
  • PK pharmacokinetic
  • TIGIT T-cell Immunoreceptor with Ig and ITIM domains.
  • FIG. 5 is a flow chart of the phase lb chemotherapy expansion cohorts study design.
  • FIG. 6 is a flow chart of the phase lb non-chemotherapy expansion cohorts study design.
  • FIG. 7 is a flow chart showing the conditions for continuing study treatment beyond progression.
  • ECOG Eastern Cooperative Oncology Group
  • RECIST Response Evaluation Criteria in Solid Tumors.
  • FIG. 8 is a flow chart showing crossover from phase la to phase lb.
  • AE adverse event
  • DLT dose-limiting toxicity
  • PD progression of disease.
  • FIG. 9 is a graph showing the pharmacokinetics of tiragolumab.
  • FIG. 10 is a series of graphs showing the pharmacodynamics of tiragolumab.
  • FIG. 13 is a graph showing tumor size reduction in phase la tiragolumab dose-escalation study.
  • FIG. 14 is a graph showing tumor size reduction in phase lb tiragolumab and atezolizumab dose- escalation study.
  • FIG. 15 is a graph showing CIT-naive PD-L1 -positive NSCLC tumor size reduction in phase lb tiragolumab and atezolizumab dose-escalation study.
  • FIG. 16 is a graph showing CIT-naive PD-L1 -positive NSCLC tumor size reduction over time in phase lb tiragolumab and atezolizumab dose-escalation study.
  • FIG. 17 is a flow chart of a phase III trial schema.
  • L first-line
  • CE carboplatin and etoposide
  • ECOG PS Eastern Cooperative Oncology Group performance status
  • ES-SCLC extensive-stage small cell lung cancer
  • LDH lactase dehydrogenase
  • RECIST Response Evaluation Criteria in Solid Tumors
  • ITT intent-to-treat
  • PP primary population.
  • FIG. 18 is a schematic diagram of the study design showing the parameters for the selection of subjects, stratification criteria, randomization into treatment arms, and treatment endpoints.
  • FIG. 19 is a schematic diagram showing the design of the GO42501 Phase II clinical trial.
  • Cohort A consists of PD-L1 high patients. Patients in Cohort A are treated with atezolizumab (Atezo) and tiragolumab (Tira) every three weeks (Q3W) for 4 cycles.
  • Cohort B consists of patients having any PD-L1 status.
  • Patients in Cohort B are treated with Atezo, Tira, and platinum-based doublet chemotherapy (Chemo) Q3W for 4 cycles. Chest computed tomography (CT) is performed after Cycle 2 and Cycle 4. Surgery is performed for patients in both cohorts, and major pathological response (MPR) and pathological complete response (pCR) are assessed. Following surgery, patients in Cohort A are treated with Atezo and Tira Q3W for 16 cycles or Chemo Q3W for 4 cycles. Patients in Cohort B are treated with Atezo and Tira Q3W for 16 cycles. Postoperative radiotherapy (PORT) is optional for R1/R2 resections and/or ypN2 prior to adjuvant administration. Survival follow-up is performed.
  • CT computed tomography
  • MPR major pathological response
  • pCR pathological complete response
  • PORT Postoperative radiotherapy
  • PORT is optional for R1/R2 resections and/or ypN2 prior to adjuvant administration. Survival follow-up is performed.
  • FIG. 20 is a flow chart showing patient enrollment in the GO42501 Phase II clinical trial.
  • Cohort A PD-L1 high patients; PD-L1 tumor proportion score (TPS) > 50%
  • TPS tumor proportion score
  • a safety lead-in is performed using 6 patients. If surgical safety criteria are not met, enrollment of Cohort A is halted. If surgical safety criteria are met, enrollment of Cohort A is continued.
  • Cohort B patients with any PD-L1 status
  • a safety lead-in is performed using 6 patients with PD-L1 TPS ⁇ 50%. If surgical safety criteria are not met, enrollment of Cohort B is halted.
  • FIG. 21 is a flow chart of a phase II trial schema.
  • IRC independent review committee
  • PD-L1 programmed death-ligand 1
  • Q3W every 3 weeks
  • R randomization
  • s/p status-post
  • IV intravenous.
  • FIG. 22 is a flow chart of a Phase lb trial schema.
  • TNBC triple-negative breast cancer
  • G-CSF granulocyte colony-stimulating factor
  • GM-CSF granulocyte-macrophage colony-stimulating factor
  • Rand. randomization
  • pCR pathologic complete response
  • QW once a week
  • Q2W every two weeks
  • Q3W every three weeks.
  • FIG. 23 is a flow chart of a Phase II trial schema.
  • HPV Human papillomavirus
  • IHC immunohistochemistry
  • IV intravenous
  • Q3W every 3 weeks
  • PD-L1 low TIC 10%-49%
  • PD-L1 high TIC > 50%
  • SCCHN squamous cell carcinoma of head and neck
  • RECIST Response Evaluation Criteria in Solid Tumors.
  • FIG. 24 is a schematic diagram showing the design of the muscle-invasive bladder cancer (MIBC) cohorts of the W039613 Phase Ib/ll clinical trial.
  • MIBC muscle-invasive bladder cancer
  • FIG. 25 is a schematic diagram showing the design of the metastatic urothelial carcinoma (mUC) cohorts of the W039613 Phase Ib/ll clinical trial.
  • mUC metastatic urothelial carcinoma
  • Atezolizumab (Atezo; control); atezolizumab and enfortumab vedotin (EV); atezolizumab and niraparib (Nira); atezolizumab and Hu5F9-G4; atezolizumab and tiragolumab (Tira); atezolizumab and sacituzumab govitecan (SG); atezolizumab and tocilizumab (TCZ); atezolizumab and R07122290 (FAP- 4-1 BBL); or R07121661 (PD1 /TIM-3) during Stage 1 .
  • Stage 1 patients who experience loss of clinical benefit, as determined by the investigator, or unacceptable toxicity may be eligible to receive a different treatment combination during Stage 2, provided they meet the eligibility criteria.
  • the Atezo+Nira arm has 40 patients.
  • Patients who received enfortumab vedotin in Stage 1 do not receive enfortumab vedotin in Stage 2, and patients who received sacituzumab govitecan in Stage 1 do not receive sacituzumab govitecan in Stage 2; other patients who are eligible for more than one treatment arm are assigned a treatment arm by the investigator.
  • the Atezo+R07122290 (FAP-4-1 BBL) arm is only opened in ex-U.S. countries.
  • FIG. 26 is a diagram showing the objective response rate (ORR) (complete response/partial response (CR/PR); stable disease/progressive disease (SD/PD); or not evaluable (NE)) in patients from the CITYSCAPE trial having low or high PD-L1 TPS as assessed by the pharmDx 22C3 IHC assay (high TPS >50%; low TPS 1-49%) or low or high PD-L1 tumor content (TC) as assessed by the CE-IVD VENTANA SP263 IHC assay (high TC >50%; low TC 1-49%).
  • ORR objective response rate
  • CR/PR complete response/partial response
  • SD/PD stable disease/progressive disease
  • NE not evaluable
  • FIG. 27A is a bar graph showing the response rate (95% confidence interval (Cl)) for patients from the CITYSCAPE trial having a TPS >1% as measured using the 22C3 IHC assay.
  • FIG. 27B is a bar graph showing the response rate (95% Cl) for patients from the CITYSCAPE trial having a TC >1% as measured using the SP263 IHC assay (and TPS >1% as measured using the 22C3 IHC assay).
  • FIG. 28A is a graph showing progression-free survival (percent) for patients from the CITYSCAPE trial who were treated with tiragolumab and atezolizumab (tira + atezo) or placebo + atezo and had a TPS >1% as measured using the 22C3 IHC assay.
  • the inset table shows median PFS in months (mo) and hazard ratio (HR).
  • FIG. 28B is a graph showing progression-free survival (percent) for patients from the CITYSCAPE trial who were treated with tiragolumab and atezolizumab (tira + atezo) or placebo + atezo and had a TC >1% as measured using the SP263 IHC assay (and TPS >1% as measured using the 22C3 IHC assay).
  • the inset table shows median PFS in months and HR.
  • FIG. 29A is a bar graph showing the response rate (95% confidence interval (Cl)) for patients from the CITYSCAPE trial having a TPS >50% as measured using the 22C3 IHC assay.
  • FIG. 29B is a bar graph showing the response rate (95% Cl) for patients from the CITYSCAPE trial having a TC >50% as measured using the SP263 IHC assay.
  • FIG. 30A is a graph showing progression-free survival (percent) for patients from the CITYSCAPE trial who were treated with tiragolumab and atezolizumab (tira + atezo) or placebo + atezo and had a TPS >50% as measured using the 22C3 IHC assay.
  • the inset table shows median PFS in months and HR.
  • FIG. 30B is a graph showing progression-free survival (percent) for patients from the CITYSCAPE trial who were treated with tiragolumab and atezolizumab (tira + atezo) or placebo + atezo and had a TC >50% as measured using the SP263 IHC assay.
  • the inset table shows median PFS in months and HR.
  • the present invention provides therapeutic methods and compositions for treatment of cancer (e.g., a lung cancer (e.g., an early stage lung cancer (e.g., a resectable lung cancer), a SCLC (e.g., an ES-SCLC), a NSCLC (e.g., a squamous NSCLC or a non-squamous NSCLC, a locally advanced unresectable NSCLC, a Stage NIB NSCLC, a recurrent or metastatic NSCLC (e.g., a locally advanced unresectable or metastatic non-squamous NSCLC (e.g., Stage IV non-squamous NSCLC)), or a Stage IV NSCLC (e.g., wherein the subject has not been previously treated for Stage IV NSCLC))); a cervical cancer (e.g., a Stage IVB, metastatic, recurrent, or persistent cervical cancer, e.g., a metastatic and/or recurrent
  • the invention is based, at least in part, on the discovery that immunotherapies including an anti-TIGIT antibody (e.g., an anti-TIGIT antagonist antibody, such as tiragolumab) in combination with a PD-1 axis binding antagonist, a VEGF antagonist, and/or a chemotherapeutic agent can be useful in the treatment of cancer.
  • an anti-TIGIT antibody e.g., an anti-TIGIT antagonist antibody, such as tiragolumab
  • a PD-1 axis binding antagonist e.g., an anti-TIGIT antagonist antibody, such as tiragolumab
  • a VEGF antagonist e.g., vascular endothelial growth factor
  • chemotherapeutic agent e.g., chemotherapeutic agent
  • level of expression or “expression level” in general are used interchangeably and generally refer to the amount of a biomarker in a biological sample. “Expression” generally refers to the process by which information (e.g., gene-encoded and/or epigenetic information) is converted into the structures present and operating in the cell. Therefore, as used herein, “expression” may refer to transcription into a polynucleotide, translation into a polypeptide, or even polynucleotide and/or polypeptide modifications (e.g., posttranslational modification of a polypeptide).
  • Fragments of the transcribed polynucleotide, the translated polypeptide, or polynucleotide and/or polypeptide modifications shall also be regarded as expressed whether they originate from a transcript generated by alternative splicing or a degraded transcript, or from a post translational processing of the polypeptide, e.g., by proteolysis.
  • “Expressed genes” include those that are transcribed into a polynucleotide as mRNA and then translated into a polypeptide, and also those that are transcribed into RNA but not translated into a polypeptide (for example, transfer and ribosomal RNAs).
  • an “amount” or “level” (e.g., expression level) of a biomarker can be measured by methods known to one skilled in the art and also disclosed herein.
  • the amount or level of a biomarker associated with an increased clinical benefit to an individual can, for example, be a detectable level in a biological sample.
  • the expression level or amount of a biomarker can be used to identify/characterize a subject having a cancer who may be likely to respond to, or benefit from, a particular therapy (e.g., a therapy comprising one or more dosing cycles of a PD-1 axis binding antagonist and an anti-TIG IT antagonist antibody or a therapy comprising one or more dosing cycles of an anti-TIG IT antagonist antibody).
  • “Increased expression,” “increased expression level,” “increased levels,” “elevated expression,” “elevated expression levels,” or “elevated levels” refers to an increased expression or increased levels of a biomarker in an individual relative to a control, such as an individual or individuals who are not suffering from the disease or disorder (e.g., cancer) or an internal control (e.g., a housekeeping biomarker).
  • a control such as an individual or individuals who are not suffering from the disease or disorder (e.g., cancer) or an internal control (e.g., a housekeeping biomarker).
  • “Decreased expression,” “decreased expression level,” “decreased levels,” “reduced expression,” “reduced expression levels,” or “reduced levels” refers to a decrease expression or decreased levels of a biomarker in an individual relative to a control, such as an individual or individuals who are not suffering from the disease or disorder (e.g., cancer) or an internal control (e.g., a housekeeping biomarker). In some aspects, reduced expression is little or no expression.
  • the presence and/or expression level/amount of various biomarkers described herein in a sample can be analyzed by a number of methodologies, many of which are known in the art and understood by the skilled artisan, including, but not limited to, immunohistochemistry (“IHC”), Western blot analysis, immunoprecipitation, molecular binding assays, ELISA, ELIFA, flow cytometry, fluorescence activated cell sorting (“FACS”), MassARRAY, proteomics, quantitative blood based assays (e.g., Serum ELISA), biochemical enzymatic activity assays, in situ hybridization (ISH), fluorescence in situ hybridization (FISH), Southern analysis, Northern analysis, whole genome sequencing, massively parallel DNA sequencing (e.g., next-generation sequencing), NANOSTRING ® , polymerase chain reaction (PCR) including quantitative real time PCR (qRT-PCR) and other amplification type detection methods, such as, for example, branched DNA, SISBA, TMA and the like, RNA-
  • Typical protocols for evaluating the status of genes and gene products are found, for example in Ausubel et al. , eds., 1995, Current Protocols In Molecular Biology, Units 2 (Northern Blotting), 4 (Southern Blotting), 15 (Immunoblotting) and 18 (PCR Analysis). Multiplexed immunoassays such as those available from Rules Based Medicine or Meso Scale Discovery (“MSD”) may also be used.
  • MSD Meso Scale Discovery
  • correlate or “correlating” is meant comparing, in any way, the performance and/or results of a first analysis or protocol with the performance and/or results of a second analysis or protocol. For example, one may use the results of a first analysis or protocol in carrying out a second protocol and/or one may use the results of a first analysis or protocol to determine whether a second analysis or protocol should be performed. With respect to the aspect of polypeptide analysis or protocol, one may use the results of the polypeptide expression analysis or protocol to determine whether a specific therapeutic regimen should be performed. With respect to the aspect of polynucleotide analysis or protocol, one may use the results of the polynucleotide expression analysis or protocol to determine whether a specific therapeutic regimen should be performed.
  • substantially reduced denotes a sufficiently high degree of difference between two numeric values (generally one associated with a molecule and the other associated with a reference/comparator molecule) such that one of skill in the art would consider the difference between the two values to be of statistical significance within the context of the biological characteristic measured by said values (e.g ., KD values).
  • the difference between said two values is, for example, greater than about 10%, greater than about 20%, greater than about 30%, greater than about 40%, and/or greater than about 50% as a function of the value for the reference/comparator molecule.
  • substantially similar denotes a sufficiently high degree of similarity between two numeric values (for example, one associated with an antibody of the invention and the other associated with a reference/comparator antibody), such that one of skill in the art would consider the difference between the two values to be of little or no biological and/or statistical significance within the context of the biological characteristic measured by said values (e.g., KD values).
  • the difference between said two values is, for example, less than about 50%, less than about 40%, less than about 30%, less than about 20%, and/or less than about 10% as a function of the reference/comparator value.
  • the phrase “based on” when used herein means that the information about one or more biomarkers is used to inform a treatment decision, information provided on a package insert, or marketing/promotional guidance, and the like.
  • TIGIT or “T -cell immunoreceptor with Ig and ITIM domains” as used herein refers to any native TIGIT from any vertebrate source, including mammals such as primates (e.g., humans) and rodents (e.g., mice and rats), unless otherwise indicated.
  • TIGIT is also known in the art as DKFZp667A205, FLJ39873, V-set and immunoglobulin domain-containing protein 9, V-set and transmembrane domain-containing protein 3, VSIG9, VSTM3, and WUCAM.
  • the term encompasses “full-length,” unprocessed TIGIT (e.g., full-length human TIGIT having the amino acid sequence of SEQ ID NO: 30), as well as any form of TIGIT that results from processing in the cell (e.g., processed human TIGIT without a signal sequence, having the amino acid sequence of SEQ ID NO: 31 ).
  • the term also encompasses naturally occurring variants of TIGIT, e.g., splice variants or allelic variants.
  • the amino acid sequence of an exemplary human TIGIT may be found under UniProt Accession Number Q495A1 .
  • programmed death ligand 1 and “PD-L1” refer herein to native sequence human PD- L1 polypeptide.
  • Native sequence PD-L1 polypeptides are provided under Uniprot Accession No.
  • the native sequence PD-L1 may have the amino acid sequence as set forth in Uniprot Accession No. Q9NZQ7-1 (isoform 1).
  • the native sequence PD-L1 may have the amino acid sequence as set forth in Uniprot Accession No. Q9NZQ7-2 (isoform 2).
  • the native sequence PD-L1 may have the amino acid sequence as set forth in Uniprot Accession No. Q9NZQ7-3 (isoform 3).
  • the term also encompasses naturally occurring variants of PD-L1 , e.g., splice variants, or allelic variants.
  • PD-L1 is also referred to in the art as “programmed cell death 1 ligand 1 ,” “PDCD1 LG1 ,” “CD274,” “B7-H,” and “PDL1
  • PD-1 or “Programmed Cell Death protein 1 ” refers herein to any native PD-1 from any vertebrate source, including mammals such as primates (e.g., humans) and rodents (e.g., mice and rats), unless otherwise indicated.
  • PD-1 is also known in the art as CD279, PDCD1 , and programmed cell death 1.
  • the term also encompasses naturally occurring variants of PD-1 , e.g., splice variants, or allelic variants.
  • the amino acid sequence of an exemplary human PD-1 may be found under UniProt Accession Number Q15116.
  • PD-L2 or “Programmed Cell Death 1 Ligand 2” refers herein to any native PD-L2 from any vertebrate source, including mammals such as primates (e.g., humans) and rodents (e.g., mice and rats), unless otherwise indicated.
  • PD-L2 is also known in the art as CD273 molecule, B7DC, and PDCD1 L2.
  • the term also encompasses naturally occurring variants of PD-L2, e.g., splice variants, or allelic variants.
  • the amino acid sequence of an exemplary human PD-L2 may be found under UniProt Accession Number Q9BQ51 .
  • antagonist is used in the broadest sense, and includes any molecule that partially or fully blocks, inhibits, or neutralizes a biological activity of a native polypeptide disclosed herein.
  • Suitable antagonist molecules specifically include antagonist antibodies or antibody fragments (e.g., antigen binding fragments), fragments or amino acid sequence variants of native polypeptides, peptides, antisense oligonucleotides, small organic molecules, etc.
  • Methods for identifying antagonists of a polypeptide may comprise contacting a polypeptide with a candidate antagonist molecule and measuring a detectable change in one or more biological activities normally associated with the polypeptide.
  • PD-1 axis binding antagonist refers to a molecule that inhibits the interaction of a PD-1 axis binding partner with either one or more of its binding partners, so as to remove T-cell dysfunction resulting from signaling on the PD-1 signaling axis, with a result being to restore or enhance T-cell function (e.g., proliferation, cytokine production, and/or target cell killing).
  • a PD-1 axis binding antagonist includes a PD-L1 binding antagonist, a PD-1 binding antagonist, and a PD-L2 binding antagonist.
  • the PD-1 axis binding antagonist includes a PD-L1 binding antagonist or a PD-1 binding antagonist.
  • the PD-1 axis binding antagonist is a PD-L1 binding antagonist.
  • the PD-1 axis binding antagonist is a PD-1 binding antagonist. In another aspect, the PD-1 axis binding antagonist is a PD-L2 binding antagonist.
  • PD-1 binding antagonist refers to a molecule that decreases, blocks, inhibits, abrogates or interferes with signal transduction resulting from the interaction of PD-1 with one or more of its binding partners, such as PD-L1 and/or PD-L2.
  • PD-1 (programmed death 1) is also referred to in the art as “programmed cell death 1 ,” “PDCD1 ,” “CD279,” and “SLEB2.”
  • An exemplary human PD-1 is shown in UniProtKB/Swiss-Prot Accession No. Q15116.
  • the PD-1 binding antagonist is a molecule that inhibits the binding of PD-1 to one or more of its binding partners.
  • the PD-1 binding antagonist inhibits the binding of PD-1 to PD-L1 and/or PD-L2.
  • PD-1 binding antagonists include anti-PD-1 antibodies, antigen-binding fragments thereof, immunoadhesins, fusion proteins, oligopeptides, and other molecules that decrease, block, inhibit, abrogate or interfere with signal transduction resulting from the interaction of PD-1 with PD-L1 and/or PD-L2.
  • a PD-1 binding antagonist reduces the negative co-stimulatory signal mediated by or through cell surface proteins expressed on T lymphocytes mediated signaling through PD-1 so as render a dysfunctional T- cell less dysfunctional (e.g., enhancing effector responses to antigen recognition).
  • the PD-1 binding antagonist binds to PD-1 .
  • the PD-1 binding antagonist is an anti-PD-1 antibody (e.g., an anti-PD-1 antagonist antibody).
  • anti-PD-1 antagonist antibodies include nivolumab, pembrolizumab, MEDI-0680 (AMP 514), PDR001 (spartalizumab), REGN2810 (cemiplimab), BGB-108, prolgolimab, camrelizumab, sintilimab, tislelizumab, toripalimab, dostarlimab, retifanlimab, sasanlimab, penpulimab, CS1003, HLX10, SCT-I10A, zimberelimab, balstilimab, genolimzumab, Bl 754091 , cetrelimab, YBL-006, BAT1306, HX008, budigalimab, AMG 404, CX-188, JTX-4014, 609A, Sym021 , LZM009, F520, SG001 , AM0001 , ENUM 244C8, ENUM 388
  • a PD-1 binding antagonist is MDX-1106 (nivolumab). In another specific aspect, a PD-1 binding antagonist is MK-3475 (pembrolizumab, previously known as lambrolizumab). In another specific aspect, a PD-1 binding antagonist is a PD-L2 Fc fusion protein, e.g., AMP-224. In another specific aspect, a PD-1 binding antagonist is MEDI-0680. In another specific aspect, a PD-1 binding antagonist is PDR001 (spartalizumab). In another specific aspect, a PD-1 binding antagonist is REGN2810 (cemiplimab). In another specific aspect, a PD-1 binding antagonist is BGB-108.
  • a PD-1 binding antagonist is prolgolimab. In another specific aspect, a PD-1 binding antagonist is camrelizumab. In another specific aspect, a PD-1 binding antagonist is sintilimab. In another specific aspect, a PD-1 binding antagonist is tislelizumab. In another specific aspect, a PD-1 binding antagonist is toripalimab.
  • Other additional exemplary PD-1 binding antagonists include BION- 004, CB201 , AUNP-012, ADG104, and LBL-006.
  • anti-PD-1 antagonist antibody refers to an antibody or an antigen-binding fragment or variant thereof that is capable of binding PD-1 with sufficient affinity such that it substantially or completely inhibits the biological activity of PD-1 .
  • an anti-PD-1 antagonist antibody may decrease, block, inhibit, abrogate or interfere with signal transduction resulting from the interaction of PD- 1 with either one or more of its binding partners, such as PD-L1 and/or PD-L2. It will be understood by one of ordinary skill in the art that in some instances, an anti-PD-1 antagonist antibody may antagonize one PD-1 activity without affecting another PD-1 activity.
  • an anti-PD-1 antagonist antibody for use in certain of the methods or uses described herein is an anti-PD-1 antagonist antibody that antagonizes PD-1 activity in response to one of its binding partners (e.g., PD-L1 or PD-L2) without affecting or minimally affecting any of the other PD-1 interactions.
  • the extent of binding of an anti-PD-1 antagonist antibody to an unrelated, non-PD-1 protein is less than about 10% of the binding of the antibody to PD-1 as measured, e.g., by a radioimmunoassay (RIA).
  • an anti-PD- 1 antagonist antibody that binds to PD-1 has a dissociation constant (KD) of ⁇ 1 mM, ⁇ 100 nM, ⁇ 10 nM,
  • an anti-PD-1 antagonist antibody binds to an epitope of PD-1 that is conserved among PD-1 from different species or an epitope on PD-1 that allows for cross-species reactivity.
  • the anti-PD-1 antagonist antibody is pembrolizumab (previously known as lambrolizumab).
  • the anti-PD-1 antagonist antibody is nivolumab.
  • PD-L1 binding antagonist refers to a molecule that decreases, blocks, inhibits, abrogates, or interferes with signal transduction resulting from the interaction of PD-L1 with either one or more of its binding partners, such as PD-1 and/or B7-1 .
  • a PD-L1 binding antagonist is a molecule that inhibits the binding of PD-L1 to its binding partners.
  • the PD-L1 binding antagonist inhibits binding of PD-L1 to PD-1 and/or B7-1 .
  • the PD-L1 binding antagonists include anti-PD-L1 antibodies, antigen-binding fragments thereof, immunoadhesins, fusion proteins, oligopeptides and other molecules that decrease, block, inhibit, abrogate or interfere with signal transduction resulting from the interaction of PD-L1 with one or more of its binding partners, such as PD-1 and/or B7-1 .
  • a PD-L1 binding antagonist reduces the negative co-stimulatory signal mediated by or through cell surface proteins expressed on T lymphocytes mediated signaling through PD- L1 so as to render a dysfunctional T-cell less dysfunctional (e.g., enhancing effector responses to antigen recognition).
  • the PD-L1 binding antagonist binds to PD-L1 .
  • a PD- L1 binding antagonist is an anti-PD-L1 antibody (e.g., an anti-PD-L1 antagonist antibody).
  • anti-PD-L1 antagonist antibodies include atezolizumab, MDX-1105, MEDI4736 (durvalumab),
  • MSB0010718C (avelumab), SHR-1316, CS1001 , envafolimab, TQB2450, ZKAB001 , LP-002, CX-072, IMC-001 , KL-A167, APL-502, cosibelimab, lodapolimab, FAZ053, TG-1501 , BGB-A333, BCD-135, AK- 106, LDP, GR1405, HLX20, MSB2311 , RC98, PDL-GEX, KD036, KY1003, YBL-007, and HS-636.
  • the anti-PD-L1 antibody is atezolizumab, MDX-1105, MEDI4736 (durvalumab), or MSB0010718C (avelumab).
  • the PD-L1 binding antagonist is MDX-1105.
  • the PD-L1 binding antagonist is MEDI4736 (durvalumab).
  • the PD-L1 binding antagonist is MSB0010718C (avelumab).
  • the PD-L1 binding antagonist may be a small molecule, e.g., GS-4224, INCB086550, MAX-10181 , INCB090244, CA-170, or ABSK041 , which in some instances may be administered orally.
  • Other exemplary PD-L1 binding antagonists include AVA-004, MT-6035, VXM10, LYN192, GB7003, and JS-003.
  • the PD-L1 binding antagonist is atezolizumab, marketed as TECENTRIQTM. Atezolizumab is described in WHO Drug Information (International Nonproprietary Names for Pharmaceutical Substances), Proposed INN: List 112, Vol. 28, No. 4, published January 16, 2015 (see page 485).
  • an anti PD-L1 antibody is MSB0015718C.
  • anti-PD-L1 antagonist antibody refers to an antibody or an antigen-binding fragment or variant thereof that is capable of binding PD-L1 with sufficient affinity such that it substantially or completely inhibits the biological activity of PD-L1 .
  • an anti-PD-L1 antagonist antibody may decrease, block, inhibit, abrogate or interfere with signal transduction resulting from the interaction of PD- L1 with either one or more of its binding partners, such as PD-1 and/or B7-1 .
  • an anti-PD-L1 antagonist antibody may antagonize one PD-L1 activity without affecting another PD-L1 activity.
  • an anti-PD-L1 antagonist antibody for use in certain of the methods or uses described herein is an anti-PD-L1 antagonist antibody that antagonizes PD-L1 activity in response to one of its binding partners (e.g., PD-1 or B7-1 ) without affecting or minimally affecting any of the other PD-L1 interactions.
  • the extent of binding of an anti- PD-L1 antagonist antibody to an unrelated, non-PD-L1 protein is less than about 10% of the binding of the antibody to PD-L1 as measured, e.g., by a radioimmunoassay (RIA).
  • an anti-PD- L1 antagonist antibody that binds to PD-L1 has a dissociation constant (KD) of ⁇ 1 mM, ⁇ 100 nM, ⁇ 10 nM, ⁇ 1 nM, ⁇ 0.1 nM, ⁇ 0.01 nM, or ⁇ 0.001 nM (e.g., 10 -8 M or less, e.g., from 10 -8 M to 10 -13 M, e.g., from 10 _ 9 M to 10 13 M).
  • KD dissociation constant
  • an anti-PD-L1 antagonist antibody binds to an epitope of PD-L1 that is conserved among PD-L1 from different species or an epitope on PD-L1 that allows for cross-species reactivity.
  • the anti-PD-L1 antagonist antibody is atezolizumab.
  • PD-L2 binding antagonist refers to a molecule that decreases, blocks, inhibits, abrogates or interferes with signal transduction resulting from the interaction of PD-L2 with either one or more of its binding partners, such as PD-1 .
  • PD-L2 (programmed death ligand 2) is also referred to in the art as “programmed cell death 1 ligand 2,” “PDCD1 LG2,” “CD273,” “B7-DC,” “Btdc,” and “PDL2.”
  • An exemplary human PD-L2 is shown in UniProtKB/Swiss-Prot Accession No. Q9BQ51 .
  • a PD-L2 binding antagonist is a molecule that inhibits the binding of PD-L2 to one or more of its binding partners. In a specific aspect, the PD-L2 binding antagonist inhibits binding of PD-L2 to PD-1 .
  • Exemplary PD-L2 antagonists include anti-PD-L2 antibodies, antigen binding fragments thereof, immunoadhesins, fusion proteins, oligopeptides and other molecules that decrease, block, inhibit, abrogate or interfere with signal transduction resulting from the interaction of PD-L2 with either one or more of its binding partners, such as PD-1 .
  • a PD-L2 binding antagonist reduces the negative co-stimulatory signal mediated by or through cell surface proteins expressed on T lymphocytes mediated signaling through PD-L2 so as render a dysfunctional T-cell less dysfunctional (e.g., enhancing effector responses to antigen recognition).
  • the PD-L2 binding antagonist binds to PD- L2.
  • a PD-L2 binding antagonist is an immunoadhesin.
  • PD-1 axis binding antagonists include cemiplimab, prolgolimab, camrelizumab, sintilimab, tislelizumab, toripalimab, dostarlimab, retifanlimab, spartalizumab, sasanlimab, penpulimab, CS1003, HLX10, SCT-I10A, SHR-1316, CS1001 , envafolimab, TQB2450, ZKAB001 , LP- 002, zimberelimab, balstilimab, genolimzumab, Bl 754091 , cetrelimab, YBL-006, BAT1306, HX008, CX- 072, IMC-001 , KL-A167, budigalimab, AMG 404, CX-188, JTX-4014, 609A, Sym021 , LZM009, F520,
  • atezolizumab is an Fc-engineered, humanized, non-glycosylated lgG1 kappa immunoglobulin that binds PD-L1 and comprises the heavy chain sequence of SEQ ID NO: 28 and the light chain sequence of SEQ ID NO: 29.
  • Atezolizumab comprises a single amino acid substitution (asparagine to alanine) at position 297 on the heavy chain (N297A) using EU numbering of Fc region amino acid residues, which results in a non-glycosylated antibody that has minimal binding to Fc receptors.
  • Atezolizumab is also described in WHO Drug Information (International Nonproprietary Names for Pharmaceutical Substances), Proposed INN: List 112, Vol. 28, No. 4, published January 16, 2015 (see page 485).
  • pembrolizumab is a recombinant humanized monoclonal lgG4 antibody directed against human cell surface receptor PD-1 . Pembrolizumab is also described in WHO Drug Information (International Nonproprietary Names for Pharmaceutical Substances), Proposed INN: List 72, Vol. 28, No. 3, published 2014 (see page 407).
  • tiragolumab is a fully human lgG1 /kappa MAb-derived in Open Monoclonal Technology (OMT) rats that binds TIGIT and comprises the heavy chain sequence of SEQ ID NO: 33 and the light chain sequence of SEQ ID NO: 34.
  • Tiragolumab comprises two N-linked glycosylation sites (N306) in the Fc domain. Tiragolumab is also described in WHO Drug Information (International Nonproprietary Names for Pharmaceutical Substances), Proposed INN: List 117, Vol. 31 , No. 2, published July 7, 2017 (see page 343).
  • Bevacizumab is a recombinant humanized monoclonal antibody that recognizes all isoforms of VEGF, which is described in WHO Drug Information (International Nonproprietary Names for Pharmaceutical Substances), Proposed INN: List 83, Vol. 14, No. 2, published 2000 (see page 107). Bevacizumab comprises the heavy chain variable region sequence of SEQ ID NO: X and the light chain variable region sequence of SEQ ID NO: X.
  • anti-TIGIT antagonist antibody refers to an antibody or an antigen-binding fragment or variant thereof that is capable of binding TIGIT with sufficient affinity such that it substantially or completely inhibits the biological activity of TIGIT.
  • an anti-TIGIT antagonist antibody may block signaling through PVR, PVRL2, and/or PVRL3 so as to restore a functional response by T-cells (e.g., proliferation, cytokine production, target cell killing) from a dysfunctional state to antigen stimulation.
  • an anti-TIGIT antagonist antibody may block signaling through PVR without impacting PVR- CD226 interaction.
  • an anti- TIGIT antagonist antibody may antagonize one TIGIT activity without affecting another TIGIT activity.
  • an anti-TIGIT antagonist antibody for use in certain of the methods or uses described herein is an anti-TIGIT antagonist antibody that antagonizes TIGIT activity in response to one of PVR interaction, PVRL3 interaction, or PVRL2 interaction, e.g., without affecting or minimally affecting any of the other TIGIT interactions.
  • the extent of binding of an anti-TIGIT antagonist antibody to an unrelated, non-TIGIT protein is less than about 10% of the binding of the antibody to TIGIT as measured, e.g., by a radioimmunoassay (RIA).
  • RIA radioimmunoassay
  • an anti-TIGIT antagonist antibody that binds to TIGIT has a dissociation constant (KD) of ⁇ 1 mM, ⁇ 100 nM, ⁇ 10 nM, ⁇ 1 nM, ⁇ 0.1 nM, ⁇ 0.01 nM, or ⁇ 0.001 nM (e.g., 1 O -8 M or less, e.g., from 1 O -8 M to 10 -13 M, e.g., from 10 -9 M to 10 -13 M).
  • KD dissociation constant
  • an anti-TIGIT antagonist antibody binds to an epitope of TIGIT that is conserved among TIGIT from different species or an epitope on TIGIT that allows for cross-species reactivity.
  • the anti-TIGIT binding antibody has intact Fc-mediated effector function (e.g., tiragolumab, vibostolimab, etigilimab, EOS084448, or TJ-T6). In some aspects, the anti-TIGIT binding antibody has enhanced Fc- mediated effector function (e.g., SGN-TGT). In other aspects, the anti-TIGIT binding antibody lacks Fc- mediated effector function (e.g., domvanalimab, BMS-986207, ASP8374, or COM902).
  • the anti-TIGIT binding antibody is an lgG1 class antibody (e.g., tiragolumab, vibostolimab, domvanalimab, BMS-986207, etigilimab, BGB-A1217, SGN-TGT, EOS084448 (EOS-448), TJ-T6, or AB308).
  • the anti-TIGIT binding antibody is an lgG4 class antibody (e.g., ASP8374 or COM902).
  • the anti-TIGIT antagonist antibody is tiragolumab.
  • administering is meant a method of giving a dosage of a compound (e.g., an anti-TIGIT antagonist antibody, a PD-1 axis binding antagonist (e.g., an anti-PD-L1 antibody), a VEGF antagonist, or a chemotherapeutic agent (e.g., a platinum-based chemotherapeutic agent (e.g., carboplatin or cisplatin) and/or one or more non-platinum-based chemotherapeutic agents (e.g., an alkylating agent (e.g., cyclophosphamide), a taxane (e.g., paclitaxel, e.g., nab-paclitaxel), and/or a topoisomerase II inhibitor (e.g., doxorubicin))) or a composition (e.g., a pharmaceutical composition, e.g., a pharmaceutical composition including an anti-TIGIT antagonist antibody
  • the compounds and/or compositions utilized in the methods described herein can be administered, for example, intravenously (e.g., by intravenous infusion), subcutaneously, intramuscularly, intradermally, percutaneously, intraarterially, intraperitoneally, intralesionally, intracranially, intraarticularly, intraprostatically, intrapleurally, intratracheally, intranasally, intravitreally, intravaginally, intrarectally, topically, intratumorally, peritoneally, subconjunctivally, intravesicularlly, mucosally, intrapericardially, intraumbilically, intraocularly, orally, topically, locally, by inhalation, by injection, by infusion, by continuous infusion, by localized perfusion bathing target cells directly, by catheter, by lavage, in cremes, or in lipid compositions.
  • the method of administration can vary depending on various factors (e.g., the compound or composition being administered and the severity of the condition, disease, or disorder being treated).
  • a “fixed” or “flat” dose of a therapeutic agent refers to a dose that is administered to a patient without regard for the weight or body surface area (BSA) of the patient.
  • a therapeutic agent e.g., an anti-TIGIT antagonist antibody, a PD-1 axis binding antagonist (e.g., an anti-PD-L1 antibody), a VEGF antagonist, a chemotherapeutic agent (e.g., a platinum-based chemotherapeutic agent or non-platinum-based chemotherapeutic agent), an ADC (e.g., enfortumab vedotin or sacituzumab govitecan), or a CSF (e.g., pegfilgrastim, filgrastim, or sargramostim)) refers to a dose that is administered to a patient without regard for the weight or body surface area (BSA) of the patient.
  • the fixed or flat dose is therefore not provided as a mg/kg dose or a
  • treatment refers to clinical intervention designed to alter the natural course of the individual or cell being treated during the course of clinical pathology. Desirable effects of treatment include delaying or decreasing the rate of disease progression, ameliorating or palliating the disease state, and remission or improved prognosis.
  • an individual is successfully “treated” if one or more symptoms associated with cancer are mitigated or eliminated, including, but are not limited to, reducing the proliferation of (or destroying) cancerous cells, decreasing symptoms resulting from the disease, increasing the quality of life of those suffering from the disease, decreasing the dose of other medications required to treat the disease, delaying the progression of the disease, and/or prolonging survival of individuals.
  • treating comprises effective cancer treatment with an effective amount of a therapeutic agent (e.g., an anti-TIGIT antagonist antibody, a PD-1 axis binding antagonist, a VEGF antagonist, a chemotherapeutic agent (e.g., a platinum-based chemotherapeutic agent or non-platinum-based chemotherapeutic agent), an ADC (e.g., enfortumab vedotin or sacituzumab govitecan), and/or a CSF (e.g., pegfilgrastim, filgrastim, or sargramostim)) or combination of therapeutic agents.
  • a therapeutic agent e.g., an anti-TIGIT antagonist antibody, a PD-1 axis binding antagonist, a VEGF antagonist, a chemotherapeutic agent (e.g., a platinum-based chemotherapeutic agent or non-platinum-based chemotherapeutic agent), an ADC (e.g., enfortum
  • Treating herein includes, inter alia, adjuvant therapy, neoadjuvant therapy, non-metastatic cancer therapy (e.g., locally advanced cancer therapy), and metastatic cancer therapy.
  • the treatment may be first-line treatment (e.g., the patient may be previously untreated or not have received prior systemic therapy), or second line or later treatment.
  • a treatment regimen that includes administration of a PD-1 axis binding antagonist (e.g., atezolizumab), a VEGF antagonist, a chemotherapeutic agent (e.g., a platinum-based chemotherapeutic agent or non-platinum-based chemotherapeutic agent), an ADC (e.g., enfortumab vedotin or sacituzumab govitecan), and/or a CSF (e.g., pegfilgrastim, filgrastim, or sargramostim) and an anti-TIGIT antagonist antibody (e.g., an anti-TIG IT antagonist antibody as disclosed herein, e.g., tiragolumab).
  • a PD-1 axis binding antagonist e.g., atezolizumab
  • a VEGF antagonist e.g., a VEGF antagonist
  • a chemotherapeutic agent e.g., a platinum-based chemo
  • a drug that is administered “concurrently” with one or more other drugs is administered during the same treatment cycle, on the same day of treatment, as the one or more other drugs, and, optionally, at the same time as the one or more other drugs.
  • the concurrently administered drugs are each administered on day 1 of a 3-week cycle.
  • perioperative treatment refers to a treatment that is administered before and after a surgery.
  • a perioperative treatment may include administration of a neoadjuvant therapy prior to a surgery (e.g., a cystectomy) and a therapy (e.g., an adjuvant therapy) following the surgery.
  • a perioperative treatment may include a neoadjuvant therapy (e.g., an anti-TIGIT antagonist antibody and a PD-1 axis binding antagonist neoadjuvant therapy) that is administered after diagnosis and before (e.g., about 1 , 2, 3, 4, 5, 6, 7, 8, 9, 12, 13, 14, 15 weeks or more before) a surgery (e.g., a cystectomy) and a therapy (e.g., an adjuvant therapy (e.g., an anti-TIGIT antagonist antibody and a PD-1 axis binding antagonist adjuvant therapy)) following the surgery (e.g., about 1 , 2, 3, 4, 5, 6, 7, 8, 9, 12, 13, 14, 15 weeks or more following the surgery).
  • a neoadjuvant therapy e.g., an anti-TIGIT antagonist antibody and a PD-1 axis binding antagonist neoadjuvant therapy
  • a surgery e.g., a cystectomy
  • a therapy e.g., an
  • a “disorder” or “disease” is any condition that would benefit from treatment including, but not limited to, disorders that are associated with some degree of abnormal cell proliferation, e.g., cancer.
  • disfunction in the context of immune dysfunction, refers to a state of reduced immune responsiveness to antigenic stimulation.
  • disfunctional also includes refractory or unresponsive to antigen recognition, specifically, impaired capacity to translate antigen recognition into downstream T-cell effector functions, such as proliferation, cytokine production (e.g., gamma interferon) and/or target cell killing.
  • cancer and “cancerous” refer to or describe the physiological condition in mammals that is typically characterized by unregulated cell growth.
  • Cancers include solid tumor cancers and non solid tumor cancers and locally advanced or metastatic cancers (e.g., locally advanced or metastatic tumors). Examples of cancer include but are not limited to, carcinoma, lymphoma, blastoma, sarcoma, and leukemia or lymphoid malignancies.
  • UC urothelial carcinoma
  • bladder cancer e.g., muscle invasive bladder cancer (MIBC) and non-muscle invasive bladder cancer (NMIBC), e.g., BCG-refractory NMIBC), MIBC urothelial bladder cancer (UBC); kidney or renal cancer (e.g., renal cell carcinoma (RCC)); cancer of the urinary tract; lung cancer, such as small cell lung cancer (SCLC), which includes extensive stage SCLC (ES-SCLC); non-small cell lung cancer (NSCLC), which includes squamous NSCLC or non-squamous NSCLC, including locally advanced unresectable NSCLC (e.g., Stage NIB NSCLC), or recurrent or metastatic NSCLC (e.g., Stage IV NSCLC), adenocarcinoma of the lung, or squamous cell cancer (e.g., epithelial s
  • mUC locally advanced and metastatic UC
  • MIBC muscle invasive bladder cancer
  • the term “persistent cervical cancer” as used herein refers to a cervical cancer that has not been rendered undetectable or benign after previous therapy.
  • Stage IVB cervical cancer refers to a cervical cancer that is classified as such using a cervical cancer staging system (e.g., International Federation of Gynecology and Obstetrics (FIGO) staging system).
  • a cervical cancer is classified as Stage IVB if it has metastasized to distant organs (including the parenchyma of the spleen or liver) or to the inguinal and extra-abdominal lymph nodes.
  • recurrent cervical cancer refers to a cervical cancer that has been detected or has returned following an initial treatment with surgery, radiation therapy, and/or chemotherapy.
  • TNBC refers to breast cancer that lacks expression of ER, PR, and HER2.
  • eTNBC refers to T2-4d TNBC (e.g., cT2-cT4, cN0-cN3, and cMO).
  • Head and neck cancers include cancers that begin in the mucosal surfaces of the upper aerodigestive tract and affect the oral cavity, oropharynx, larynx, hypopharynx, and nasopharynx.
  • urothelial carcinoma and “UC” refer to a type of cancer that typically occurs in the urinary system, and includes muscle-invasive bladder cancer (MIBC) and muscle-invasive urinary tract urothelial cancer (UTUC). UC is also referred to in the art as transitional cell carcinoma (TCC).
  • MIBC muscle-invasive bladder cancer
  • UTUC muscle-invasive urinary tract urothelial cancer
  • TCC transitional cell carcinoma
  • tumor refers to all neoplastic cell growth and proliferation, whether malignant or benign, and all pre
  • tumor cell refers to any tumor cell present in a tumor or a sample thereof. Tumor cells may be distinguished from other cells that may be present in a tumor sample, for example, stromal cells and tumor-infiltrating immune cells, using methods known in the art and/or described herein.
  • Tumor immunity refers to the process in which tumors evade immune recognition and clearance. Thus, as a therapeutic concept, tumor immunity is “treated” when such evasion is attenuated, and the tumors are recognized and attacked by the immune system. Examples of tumor recognition include tumor binding, tumor shrinkage, and tumor clearance.
  • Metastasis is meant the spread of cancer from its primary site to other places in the body. Cancer cells can break away from a primary tumor, penetrate into lymphatic and blood vessels, circulate through the bloodstream, and grow in a distant focus (metastasize) in normal tissues elsewhere in the body. Metastasis can be local or distant. Metastasis is a sequential process, contingent on tumor cells breaking off from the primary tumor, traveling through the bloodstream, and stopping at a distant site. At the new site, the cells establish a blood supply and can grow to form a life-threatening mass.
  • Cytotoxic agent refers to any agent that is detrimental to cells (e.g., causes cell death or destruction, inhibits proliferation, or otherwise inhibits or prevents a cellular function).
  • Cytotoxic agents include, but are not limited to, radioactive isotopes (e.g., At 211 , I 131 , I 125 , Y 90 , Re 186 , Re 188 , Sm 153 , Bi 212 , P 32 , Pb 212 and radioactive isotopes of Lu); chemotherapeutic agents or drugs (e.g., methotrexate, adriamicin, vinca alkaloids (vincristine, vinblastine, etoposide), doxorubicin, melphalan, mitomycin C, chlorambucil, daunorubicin or other intercalating agents); growth inhibitory agents; enzymes and fragments thereof such as nucleolytic enzymes; antibiotics; and toxins such as small molecule toxins or
  • Exemplary cytotoxic agents can be selected from anti-microtubule agents, platinum coordination complexes, alkylating agents, topoisomerase II inhibitors, antimetabolites, topoisomerase I inhibitors, hormones and hormonal analogues, signal transduction pathway inhibitors, non-receptor tyrosine kinase angiogenesis inhibitors, immunotherapeutic agents, proapoptotic agents, inhibitors of LDH-A, inhibitors of fatty acid biosynthesis, cell cycle signaling inhibitors, HDAC inhibitors, proteasome inhibitors, and inhibitors of cancer metabolism.
  • the cytotoxic agent is a platinum-based chemotherapeutic agent (e.g., carboplatin or cisplatin).
  • the cytotoxic agent is an antagonist of EGFR, e.g., N-(3- ethynylphenyl)-6,7-bis(2-methoxyethoxy)quinazolin-4-amine (e.g., erlotinib).
  • the cytotoxic agent is a RAF inhibitor, e.g., a BRAF and/or CRAF inhibitor.
  • the RAF inhibitor is vemurafenib.
  • the cytotoxic agent is a PI3K inhibitor.
  • “Chemotherapeutic agent” includes chemical compounds useful in the treatment of cancer.
  • chemotherapeutic agents include erlotinib (TARCEVA ® , Genentech/OSI Pharm.), bortezomib (VELCADE ® , Millennium Pharm.), disulfiram, epigallocatechin gallate, salinosporamide A, carfilzomib, 17-AAG (geldanamycin), radicicol, lactate dehydrogenase A (LDH-A), fulvestrant (FASLODEX ® , AstraZeneca), sunitinib (SUTENT ® , Pfizer/Sugen), letrozole (FEMARA ® , Novartis), imatinib mesylate (GLEEVEC ® , Novartis), finasunate (VATALANIB ® , Novartis), oxaliplatin (ELOXATIN ® , Sanofi), 5-FU (5-fluor
  • dynemicin including dynemicin A; bisphosphonates, such as clodronate; an esperamicin; as well as neocarzinostatin chromophore and related chromoprotein enediyne antibiotic chromophores), aclacinomysins, actinomycin, authramycin, azaserine, bleomycins, cactinomycin, carabicin, caminomycin, carzinophilin, chromomycinis, dactinomycin, daunorubicin, detorubicin, 6-diazo-5-oxo-L-norleucine, ADRIAMYCIN ® (doxorubicin), morpholino-doxorubicin, cyanomorpholino-doxorubicin, 2-pyrrolino-doxorubicin and deoxydoxorubicin), epirubicin, e
  • Chemotherapeutic agents also include (i) anti-hormonal agents that act to regulate or inhibit hormone action on tumors such as anti-estrogens and selective estrogen receptor modulators (SERMs), including, for example, tamoxifen (including NOLVADEX ® ; tamoxifen citrate), raloxifene, droloxifene, iodoxyfene, 4-hydroxytamoxifen, trioxifene, keoxifene, LY117018, onapristone, and FARESTON ® (toremifine citrate); (ii) aromatase inhibitors that inhibit the enzyme aromatase, which regulates estrogen production in the adrenal glands, such as, for example, 4(5)-imidazoles, aminoglutethimide, MEGASE ® (megestrol acetate), AROMASIN ® (exemestane; Pfizer), formestanie, fadrozole, RIVISOR ® (vorozole),
  • Chemotherapeutic agents also include “platinum-based” chemotherapeutic agents, also referred to herein as “platinum agents,” which comprise an organic compound which contains platinum as an integral part of the molecule. Typically, platinum-based chemotherapeutic agents are coordination complexes of platinum. Platinum-based chemotherapeutic agents are sometimes called “platins” in the art. Examples of platinum-based chemotherapeutic agents include, but are not limited to, cisplatin, carboplatin, oxaliplatin, nedaplatin, triplatin tetranitrate, phenanthriplatin, picoplatin, lipoplatin, and satraplatin.
  • Platinum-based chemotherapeutic agents may be administered in combination with one or more additional chemotherapeutic agents, e.g., a nucleoside analog (e.g., gemcitabine), an antimetabolite (e.g., pemetrexed or gemcitabine), or a taxane (e.g., paclitaxel or nab- paclitaxel).
  • a nucleoside analog e.g., gemcitabine
  • an antimetabolite e.g., pemetrexed or gemcitabine
  • a taxane e.g., paclitaxel or nab- paclitaxel
  • eligible for treatment with a platinum-based chemotherapy means that the subject is eligible for treatment with a platinum-based chemotherapy, either in the attending clinician’s judgment or according to standardized criteria for eligibility for platinum-based chemotherapy that are known in the art.
  • Chemotherapeutic agents also include “non-platinum-based chemotherapeutic agents,” which, as used herein, refer to chemotherapeutic agents that are not “platinum-based.” As used herein, the terms “non-platinum-based chemotherapeutic agents” and “non-platinum agents” are used interchangeably.
  • non-platinum-based chemotherapeutic agents include antimetabolites (e.g., pemetrexed and gemcitabine), topoisomerase II inhibitors (e.g., etoposide, teniposide, doxorubicin, daunorubicin, mitoxantrone, amsacrine, an ellipticine, aurintricarboxylic acid, or HU-331), taxanes (e.g., paclitaxel (e.g., albumin-engineered paclitaxel, also referred to as nanoparticle-albumin-bound paclitaxel (nab-paclitaxel)), docetaxel, larotaxel, cabazitaxel, milataxel, tesetaxel, and/or orataxel).
  • exemplary non-platinum-based chemotherapeutic agents also include alkylating agents (e.g., cyclophosphamide).
  • nucleoside analog refers to a nucleoside that includes a nucleic acid analog and a sugar. Nucleoside analogs may function as antimetabolites. Exemplary nucleoside analogues include but are not limited to gemcitabine, cytarabine, fludarabine, and cladribine.
  • Taxanes as used herein is a diterpene which may bind to tubulin, promoting microtubule assembly and stabilization and/or prevent microtubule depolymerization.
  • Taxanes included herein include taxoid 10-deacetylbaccatin III and/or derivatives thereof.
  • Exemplary taxanes include, but are not limited to, paclitaxel (i.e., TAXOL ® , CAS # 33069-62-4), docetaxel (i.e., TAXOTERE ® , CAS # 114977-28- 5), larotaxel, cabazitaxel, milataxel, tesetaxel, and/or orataxel.
  • the taxane is an albumin-coated nanoparticle (e.g., nab-paclitaxel, i.e., ABRAXANE ® and/or nab-docetaxel, ABI-008).
  • the taxane is nab-paclitaxel (ABRAXANE ® ).
  • the taxane is formulated in CREMAPHOR ® (e.g., TAXOL ® ) and/or in Tween such as polysorbate 80 (e.g., TAXOTERE ® ).
  • the taxane is liposome-encapsulated taxane.
  • the taxane is a prodrug form and/or conjugated form of taxane (e.g., DHA covalently conjugated to paclitaxel, paclitaxel poliglumex, and/or linoleyl carbonate-paclitaxel).
  • the paclitaxel is formulated with substantially no surfactant (e.g., in the absence of CREMAPHOR and/or Tween-such as TOCOSOL ® paclitaxel).
  • an “antimetabolite” as used herein is a chemotherapeutic agent that interferes with and inhibits (wholly or partially) an endogenous (normal) metabolic process within a cell (e.g., a cancer cell).
  • Antimetabolites include gemcitabine, pemetrexed, capecitabine, hydroxyurea, methotrexate, fluorouracil, cladribine, mercaptopurine, and pralatrexate.
  • Chemotherapeutic agents also include dexamethasone, interferons, colchicine, metoprine, cyclosporine, amphotericin, metronidazole, alemtuzumab, alitretinoin, allopurinol, amifostine, arsenic trioxide, asparaginase, BCG live, bevacizumab, bexarotene, cladribine, clofarabine, darbepoetin alfa, denileukin, dexrazoxane, epoetin alfa, elotinib, filgrastim, histrelin acetate, ibritumomab, interferon alfa- 2a, interferon alfa-2b, lenalidomide, levamisole, mesna, methoxsalen, nandrolone, nelarabine, nofetumomab, oprelvekin
  • Chemotherapeutic agents also include hydrocortisone, hydrocortisone acetate, cortisone acetate, tixocortol pivalate, triamcinolone acetonide, triamcinolone alcohol, mometasone, amcinonide, budesonide, desonide, fluocinonide, fluocinolone acetonide, betamethasone, betamethasone sodium phosphate, dexamethasone, dexamethasone sodium phosphate, fluocortolone, hydrocortisone-17- butyrate, hydrocortisone-17-valerate, aclometasone dipropionate, betamethasone valerate, betamethasone dipropionate, prednicarbate, clobetasone-17-butyrate, clobetasol-17-propionate, fluocortolone caproate, fluocortolone pivalate and fluprednidene acetate; immune selective
  • MARINOL® beta-lapachone; lapachol; colchicines; betulinic acid; acetylcamptothecin, scopolectin, and 9-aminocamptothecin); podophyllotoxin; tegafur (UFTORAL®); bexarotene (TARGRETIN®); bisphosphonates such as clodronate (for example, BONEFOS® or OSTAC®), etidronate (DIDROCAL®), NE-58095, zoledronic acid/zoledronate (ZOMETA®), alendronate (FOSAMAX®), pamidronate (AREDIA®), tiludronate (SKELID®), or risedronate (ACTONEL®); and epidermal growth factor receptor (EGF-R); vaccines such as THERATOPE® vaccine; perifosine, COX-2 inhibitor (e.g., celecoxib or etoricoxib), proteosome inhibitor (e.g., PS341)
  • Chemotherapeutic agents also include non-steroidal anti-inflammatory drugs with analgesic, antipyretic and anti-inflammatory effects.
  • NSAIDs include non-selective inhibitors of the enzyme cyclooxygenase.
  • Specific examples of NSAIDs include aspirin, propionic acid derivatives such as ibuprofen, fenoprofen, ketoprofen, flurbiprofen, oxaprozin and naproxen, acetic acid derivatives such as indomethacin, sulindac, etodolac, diclofenac, enolic acid derivatives such as piroxicam, meloxicam, tenoxicam, droxicam, lornoxicam and isoxicam, fenamic acid derivatives such as mefenamic acid, meclofenamic acid, flufenamic acid, tolfenamic acid, and COX-2 inhibitors such as celecoxib, etoricoxib, lumirac
  • NSAIDs can be indicated for the symptomatic relief of conditions such as rheumatoid arthritis, osteoarthritis, inflammatory arthropathies, ankylosing spondylitis, psoriatic arthritis, Reiter’s syndrome, acute gout, dysmenorrhoea, metastatic bone pain, headache and migraine, postoperative pain, mild-to-moderate pain due to inflammation and tissue injury, pyrexia, ileus, and renal colic.
  • conditions such as rheumatoid arthritis, osteoarthritis, inflammatory arthropathies, ankylosing spondylitis, psoriatic arthritis, Reiter’s syndrome, acute gout, dysmenorrhoea, metastatic bone pain, headache and migraine, postoperative pain, mild-to-moderate pain due to inflammation and tissue injury, pyrexia, ileus, and renal colic.
  • Chemotherapeutic agents also include “EGFR inhibitors,” which refers to compounds that bind to or otherwise interact directly with EGFR and prevent or reduce its signaling activity, and is alternatively referred to as an “EGFR antagonist.” Examples of such agents include small molecules that bind to EGFR.
  • EGFR antagonists include small molecules such as compounds described in US Patent Nos: 5,616,582, 5,457,105, 5,475,001 , 5,654,307, 5,679,683, 6,084,095, 6,265,410, 6,455,534, 6,521 ,620, 6,596,726, 6,713,484, 5,770,599, 6,140,332, 5,866,572, 6,399,602, 6,344,459, 6,602,863, 6,391 ,874, 6,344,455, 5,760,041 , 6,002,008, and 5,747,498, as well as the following PCT publications: W098/14451 , W098/50038, W099/09016, and WO99/24037.
  • EGFR antagonists include OSI-774 (CP-358774, erlotinib, TARCEVA® Genentech/OSI Pharmaceuticals); PD 183805 (Cl 1033, 2- propenamide, N-[4-[(3-chloro-4-fluorophenyl)amino]-7-[3-(4-morpholinyl)propoxy]-6-quinazolinyl]-, dihydrochloride, Pfizer Inc.); ZD1839, gefitinib (IRESSA ® ) 4-(3’-Chloro-4’-fluoroanilino)-7-methoxy-6-(3- morpholinopropoxy)quinazoline, AstraZeneca); ZM 105180 ((6-amino-4-(3-methylphenyl-amino)- quinazoline, Zeneca); BIBX-1382 (N8-(3-chloro-4-fluoro-phenyl)-N2-(1-
  • Chemotherapeutic agents also include “tyrosine kinase inhibitors” including the EGFR-targeted drugs noted in the preceding paragraph; inhibitors of insulin receptor tyrosine kinases, including anaplastic lymphoma kinase (Aik) inhibitors, such as AF-802 (also known as CH-5424802 or alectinib), ASP3026, X396, LDK378, AP26113, crizotinib (XALKORI ® ), and ceritinib (ZYKADIA ® ); small molecule HER2 tyrosine kinase inhibitor such as TAK165 available from Takeda; CP-724,714, an oral selective inhibitor of the ErbB2 receptor tyrosine kinase (Pfizer and OSI); dual-HER inhibitors such as EKB-569 (available from Wyeth) which preferentially binds EGFR but inhibits both HER2 and EGFR- overexpressing cells;
  • anthracycline relates to a chemotherapeutic agent, an anticancer agent for inducing apoptosis, preferably by inhibiting the rebinding of DNA in topoisomerase II.
  • examples include doxorubicin (adriamycin), daunorubicin (daunomycin), epirubicin, idarubicin, rhodomycin, pyrarubicin, valrubicin, N-trifluoro-acetyl doxorubicin-14-valerate, aclacinomycin, morpholinodoxorubicin (morpholino- DOX), cyanomorpholino-doxorubicin (cyanomorpholino-DOX), 2-pyrrolino-doxorubicin (2-PDOX), 5- iminodaunomycin, mitoxantrone and aclacinomycin A (aclarubicin).
  • the anthracycline is administered in combination with an alkyl
  • alkylating agent as used herein is a chemotherapeutic agent which causes DNA damage by attaching an alkyl group to DNA.
  • Alkylating agents include cyclophosphamide and N,N',N"- triethylenethiophosphoramide.
  • an “effective amount” of a compound for example, an anti-TIG IT antagonist antibody, a PD-1 axis binding antagonist (e.g., anti-PD-L1 antibody), a VEGF antagonist, a chemotherapeutic agent (e.g., a platinum-based chemotherapeutic agent or non-platinum-based chemotherapeutic agent), an ADC (e.g., enfortumab vedotin or sacituzumab govitecan), or a CSF (e.g., pegfilgrastim, filgrastim, or sargramostim), is at least the minimum amount required to achieve the desired therapeutic result, such as a measurable increase in overall survival or progression-free survival of a particular disease or disorder (e.g., a cancer).
  • a chemotherapeutic agent e.g., a platinum-based chemotherapeutic agent or non-platinum-based chemotherapeutic agent
  • an ADC e.g.
  • an effective amount herein may vary according to factors such as the disease state, age, sex, and weight of the patient, and the ability of the antibody to elicit a desired response in the subject.
  • An effective amount is also one in which any toxic or detrimental effects of the treatment are outweighed by the therapeutically beneficial effects.
  • beneficial or desired results include results such as eliminating or reducing the risk, lessening the severity, or delaying the onset of the disease, including biochemical, histological and/or behavioral symptoms of the disease, its complications, and intermediate pathological phenotypes presenting during development of the disease.
  • beneficial or desired results include clinical results such as decreasing one or more symptoms resulting from the disease (e.g., reduction or delay in cancer-related pain, symptomatic skeletal-related events (SSE), reduction in symptoms per the European Organization for Research and Treatment of Cancer Quality-of- Life Questionnaire (EORTC QLQ-C30, e.g., fatigue, nausea, vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, or general level of physical emotional, cognitive, or social functioning), reduction in pain as measured by, e.g., the 10-point pain severity (measured at its worst) numerical rating scale (NRS), increasing the quality of life of those suffering from the disease, decreasing the dose of other medications required to treat the disease, enhancing effect of another medication such as via targeting, delaying the progression of the disease (e.g., progression-free survival or radiographic progression-free survival (rPFS); delay of unequivocal clinical progression (e.g., cancer-related pain progression, symptomatic skeletal-related event, deterioration in
  • an effective amount of the drug may have the effect in reducing the number of cancer cells; reducing the tumor size; inhibiting (i.e., slow to some extent or desirably stop) cancer cell infiltration into peripheral organs; inhibit (i.e., slow to some extent and desirably stop) tumor metastasis; inhibiting to some extent tumor growth; and/or relieving to some extent one or more of the symptoms associated with the disorder.
  • An effective amount can be administered in one or more administrations.
  • an effective amount of drug, compound, or pharmaceutical composition is an amount sufficient to accomplish prophylactic or therapeutic treatment either directly or indirectly.
  • an effective amount of a drug, compound, or pharmaceutical composition may or may not be achieved in conjunction with another drug, compound, or pharmaceutical composition.
  • an “effective amount” may be considered in the context of administering one or more therapeutic agents, and a single agent may be considered to be given in an effective amount if, in conjunction with one or more other agents, a desirable result may be or is achieved.
  • beneficial or desired results are reduction in symptoms associated with lung cancer per the health-related quality of life (HRQoL) questionnaire as assessed by symptoms in lung cancer (SILC) scale (e.g., time to deterioration (TTD) in cough dyspnea and chest pain) and/or delaying time to lung-specific antigen progression).
  • Immunogenicity refers to the ability of a particular substance to provoke an immune response. Tumors are immunogenic and enhancing tumor immunogenicity aids in the clearance of the tumor cells by the immune response. Examples of enhancing tumor immunogenicity include but are not limited to treatment with a TIGIT and/or PD-L1 antagonist (e.g., anti-TIGIT antagonist antibodies and/or anti-PD-L1 antibodies).
  • a TIGIT and/or PD-L1 antagonist e.g., anti-TIGIT antagonist antibodies and/or anti-PD-L1 antibodies.
  • “Individual response” or “response” can be assessed using any endpoint indicating a benefit to the subject, including, without limitation, (1 ) inhibition, to some extent, of disease progression (e.g., progression of cancer, e.g., a lung cancer (e.g., small cell lung cancer (SCLC), which includes extensive stage SCLC (ES-SCLC); non-small cell lung cancer (NSCLC), which includes squamous NSCLC or non- squamous NSCLC, including locally advanced unresectable NSCLC (e.g., Stage NIB NSCLC), or recurrent or metastatic NSCLC (e.g., Stage IV NSCLC), adenocarcinoma of the lung), a UC, e.g., a bladder cancer (e.g., an MIBC), a urothelial bladder cancer (UBC), a pancreatic cancer (e.g., a pancreatic ductal adenocarcinoma (P
  • pathological complete response is defined as the proportion of patients with an absence of residual invasive cancer of the complete resected specimen.
  • pathological complete response or “pCR” refers to eradication of tumor from both breast and lymph nodes (ypTO/is ypNO).
  • pathological downstaging rate is defined as the proportion of patients that reach ⁇ pT1pN0 at the time of cystectomy.
  • partial response refers to at least a 30% decrease in the sum of the longest diameters (SLD) of target lesions, taking as reference the baseline SLD.
  • ORR objective response rate
  • DOR duration of objective response
  • sustained response refers to the sustained effect on reducing tumor growth after cessation of a treatment.
  • the tumor size may remain to be the same or smaller as compared to the size at the beginning of the administration phase.
  • the sustained response has a duration at least the same as the treatment duration, at least 1 .5x, 2. Ox, 2.5x, or 3. Ox length of the treatment duration.
  • an “effective response” of a subject or a subject’s “responsiveness” to treatment with a medicament and similar wording refers to the clinical or therapeutic benefit imparted to a subject as risk for, or suffering from, a disease or disorder, such as cancer.
  • a disease or disorder such as cancer.
  • such benefit includes any one or more of: extending survival (including overall survival and progression free survival); resulting in an objective response (including a CR or a PR); or improving signs or symptoms of cancer.
  • a subject who “does not have an effective response” to treatment refers to a subject who does not have any one of extending survival (including overall survival and progression free survival); resulting in an objective response (including a CR or a PR); or improving signs or symptoms of cancer.
  • survival refers to the patient remaining alive, and includes overall survival as well as progression-free survival.
  • overall survival and “OS” refer to the length of time from either the date of diagnosis or the start of treatment for a disease (e.g., cancer) that the patient is still alive.
  • OS may be defined as the time from randomization to death from any cause.
  • all survival rate refers to the percentage of subjects in a group who are alive after a particular duration of time, e.g., six months, 1 year, or 5 years from the time of diagnosis or treatment.
  • recurrence-free survival is defined as the time from Day 1 in the first cycle after surgery to the first documented recurrence of disease or death from any cause.
  • ETS event-free survival
  • progression-free survival refers to the length of time during and after treatment during which the disease being treated (e.g., cancer) does not get worse. Progression-free survival may include the amount of time patients have experienced a CR or a PR, as well as the amount of time patients have experienced stable disease.
  • stable disease or “SD” refers to neither sufficient shrinkage of target lesions to qualify for CR or PR, nor sufficient increase to qualify for PD, taking as reference the smallest SLD since the treatment started.
  • progressive disease or “PD” refers to at least a 20% increase in the sum of the longest diameters (SLD) of target lesions, taking as reference the smallest SLD recorded since the treatment started or the presence of one or more new lesions.
  • SLD longest diameters
  • MPR major pathological response
  • “delaying progression” of a disorder or disease means to defer, hinder, slow, retard, stabilize, and/or postpone development of the disease or disorder (e.g., cancer). This delay can be of varying lengths of time, depending on the history of the disease and/or subject being treated. As is evident to one skilled in the art, a sufficient or significant delay can, in effect, encompass prevention, in that the subject does not develop the disease. For example, in a late stage cancer, development of central nervous system (CNS) metastasis, may be delayed.
  • CNS central nervous system
  • reducing or inhibiting cancer relapse means to reduce or inhibit tumor or cancer relapse, or tumor or cancer progression.
  • reduced or inhibit is meant the ability to cause an overall decrease of 20%, 30%, 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, or greater.
  • Reduce or inhibit can refer to the symptoms of the disorder being treated (e.g., cancer), the presence or size of metastases, or the size of the primary tumor.
  • extending survival is meant increasing overall or progression free survival in a treated patient relative to an untreated patient (e.g., relative to a patient not treated with the medicament), or relative to a patient who does not express a biomarker at the designated level, and/or relative to a patient treated with an approved anti-tumor agent.
  • An objective response refers to a measurable response, including CR or PR.
  • detecting and “detection” are used herein in the broadest sense to include both qualitative and quantitative measurements of a target molecule. Detecting includes identifying the mere presence of the target molecule in a sample as well as determining whether the target molecule is present in the sample at detectable levels. Detecting may be direct or indirect.
  • a “PD-L1 -positive tumor cell fraction” is the percentage of viable tumor cells showing partial or complete membrane staining (exclusive of cytoplasmic staining) at any intensity relative to all viable tumor cells present in a sample, following staining of the sample in the context of an immunohistochemical (IHC) assay, e.g., an IHC assay staining for PD-L1 using the antibody SP142, SP263, 22C3, or 28-8.
  • IHC immunohistochemical
  • non-tumor cells e.g., tumor-infiltrating immune cells, normal cells, necrotic cells, and debris
  • any given diagnostic PD-L1 antibody may correspond with a particular IHC assay protocol and/or scoring terminology that can be used to derive a PD-L1 -positive tumor cell fraction.
  • a PD- L1 -positive tumor cell fraction can be derived from a tumor cell sample stained with SP263, 22C3, SP142, or 28-8 using OPTIVIEW® detection on Benchmark ULTRA, EnVision Flex on AutostainerLink 48, OPTIVIEW® detection and amplification on Benchmark ULTRA, or EnVision Flex on AutostainerLink 48, respectively.
  • a PD-L1 -positive tumor cell fraction may be calculated using the PD-L1 IHC 22C3 pharmDx assay (Dako) according to the formula above.
  • Dako PD-L1 IHC 22C3 pharmDx assay
  • the sensitivities can vary between different PD-L1 antibodies used in IHC assays. For example, only about 64% of samples that meet a 1% TC or 25% TC threshold, as defined respectively by staining with 28-8 or 22C3 and SP263, meet the threshold when stained using SP142.
  • the terms PD-L1 -positive tumor cell fraction and “tumor proportion score” (TPS) are used interchangeably.
  • Ventana SP142 IHC assay is conducted according to the Ventana PD-L1 (SP142) Assay package insert (Tucson, AZ: Ventana Medical Systems, Inc.), which is incorporated herein by reference in its entirety.
  • the “Ventana SP263 IHC assay” is conducted according to the Ventana PD-L1 (SP263) Assay package insert (Tucson, AZ: Ventana Medical Systems, Inc.), which is incorporated herein by reference in its entirety.
  • the “pharmDx 22C3 IHC assay” is conducted according to the PD-L1 IHC 22C3 pharmDx package insert (Carpinteria, CA: Dako, Agilent Pathology Solutions), which is incorporated herein by reference in its entirety.
  • the “pharmDx 28-8 IHC assay” is conducted according to the PD-L1 IHC 28-8 pharmDx package insert (Carpinteria, CA: Dako, Agilent Pathology Solutions), which is incorporated herein by reference in its entirety.
  • Tumor-infiltrating immune cell refers to any immune cell present in a tumor or a sample thereof.
  • Tumor-infiltrating immune cells include, but are not limited to, intratumoral immune cells, peritumoral immune cells, other tumor stroma cells (e.g., fibroblasts), or any combination thereof.
  • Such tumor-infiltrating immune cells can be, for example, T lymphocytes (such as CD8+ T lymphocytes and/or CD4+ T lymphocytes), B lymphocytes, or other bone marrow-lineage cells, including granulocytes (e.g., neutrophils, eosinophils, and basophils), monocytes, macrophages, dendritic cells (e.g., interdigitating dendritic cells), histiocytes, and natural killer cells.
  • T lymphocytes such as CD8+ T lymphocytes and/or CD4+ T lymphocytes
  • B lymphocytes or other bone marrow-lineage cells, including granulocytes (e.g., neutrophils, eosinophils, and basophils), monocytes, macrophages, dendritic cells (e.g., interdigitating dendritic cells), histiocytes, and natural killer cells.
  • granulocytes e.g., neutrophils,
  • biomarker refers to an indicator, e.g., predictive, diagnostic, and/or prognostic, which can be detected in a sample, for example, PD-L1 , ctDNA, or cytokines (e.g., cytokines associated with T-cell activation and/or lymphocyte subpopulations).
  • the biomarker may serve as an indicator of a particular subtype of a disease or disorder (e.g., cancer) characterized by certain, molecular, pathological, histological, and/or clinical features.
  • a biomarker is a gene.
  • Biomarkers include, but are not limited to, polypeptides, polynucleotides (e.g., DNA (e.g., ctDNA), and/or RNA), polynucleotide copy number alterations (e.g., DNA copy numbers), polypeptide and polynucleotide modifications (e.g., posttranslational modifications), carbohydrates, and/or glycolipid-based molecular markers.
  • the biomarker is PD-L1 .
  • the biomarker is ctDNA.
  • the biomarker is one or more cytokines (e.g., one or more cytokines associated with T-cell activation and/or lymphocyte subpopulations).
  • the biomarker is a cell (e.g., an immune cell, e.g., a T cell, e.g., a T cell subset, e.g., an activated T cell).
  • the biomarker is a direct or indirect indicator of human papillomavirus (HPV) status.
  • the biomarker is p16.
  • the biomarker is an HPV protein or nucleic acid.
  • housekeeping biomarker refers to a biomarker or group of biomarkers (e.g., polynucleotides and/or polypeptides) which are typically similarly present in all cell types.
  • the housekeeping biomarker is a “housekeeping gene.”
  • a “housekeeping gene” refers herein to a gene or group of genes which encode proteins whose activities are essential for the maintenance of cell function and which are typically similarly present in all cell types.
  • circulating tumor DNA and “ctDNA” refer to tumor-derived DNA in the circulatory system that is not associated with cells.
  • ctDNA is a type of cell-free DNA (cfDNA) that may originate from tumor cells or from circulating tumor cells (CTCs).
  • ctDNA may be found, e.g., in the bloodstream of a patient, or in a biological sample (e.g., blood, serum, plasma, or urine) obtained from a patient.
  • ctDNA may include aberrant mutations (e.g., patient-specific variants) and/or methylation patterns.
  • antibody includes monoclonal antibodies (including full-length antibodies which have an immunoglobulin Fc region), polyclonal antibodies, antibody compositions with polyepitopic specificity, multispecific antibodies (e.g., bispecific antibodies), diabodies, and single-chain molecules, as well as antibody fragments, including antigen-binding fragments, such as Fab, F(ab’)2, and Fv, so long as they exhibit the desired biological activity.
  • immunoglobulin Ig
  • the antibody is a full-length monoclonal antibody.
  • IgG immunoglobulins defined by the chemical and antigenic characteristics of their constant regions.
  • antibodies can be assigned to different classes.
  • immunoglobulins There are five major classes of immunoglobulins: IgA, IgD, IgE, IgG, and IgM, and several of these may be further divided into subclasses (isotypes), e.g., lgG1 , lgG2, lgG3, lgG4, lgA1 , and lgA2.
  • the heavy chain constant domains that correspond to the different classes of immunoglobulins are called a, g, e, y, and m, respectively.
  • An antibody may be part of a larger fusion molecule, formed by covalent or non- covalent association of the antibody with one or more other proteins or peptides.
  • the basic 4-chain antibody unit is a heterotetrameric glycoprotein composed of two identical light (L) chains and two identical heavy (H) chains.
  • An IgM antibody consists of 5 of the basic heterotetramer units along with an additional polypeptide called a J chain, and contains 10 antigen binding sites, while IgA antibodies comprise from 2-5 of the basic 4-chain units which can polymerize to form polyvalent assemblages in combination with the J chain.
  • the 4-chain unit is generally about 150,000 Daltons.
  • Each L chain is linked to an H chain by one covalent disulfide bond, while the two H chains are linked to each other by one or more disulfide bonds depending on the H chain isotype.
  • Each H and L chain also has regularly spaced intrachain disulfide bridges.
  • Each H chain has at the N- terminus, a variable domain (VH) followed by three constant domains (CH) for each of the a and y chains and four CH domains for m and e isotypes.
  • Each L chain has at the N-terminus, a variable domain (VL) followed by a constant domain at its other end.
  • the VL is aligned with the VH and the CL is aligned with the first constant domain of the heavy chain (CH1 ).
  • Particular amino acid residues are believed to form an interface between the light chain and heavy chain variable domains.
  • the pairing of a VH and VL together forms a single antigen-binding site.
  • immunoglobulins can be assigned to different classes or isotypes. There are five classes of immunoglobulins: IgA, IgD, IgE, IgG and IgM, having heavy chains designated a, d, e, y, and m, respectively.
  • HVR hypervariable region
  • antibodies comprise six CDRs: three in the VH (CDR-H1 , CDR-H2, CDR-H3), and three in the VL (CDR-L1 , CDR-L2, CDR-L3).
  • Exemplary CDRs herein include:
  • CDRs are determined according to Kabat et al., supra.
  • CDR designations can also be determined according to Chothia, supra, McCallum, supra, or any other scientifically accepted nomenclature system.
  • “Framework” or “FR” refers to variable domain residues other than complementary determining regions (CDRs).
  • the FR of a variable domain generally consists of four FR domains: FR1 , FR2, FR3, and FR4. Accordingly, the CDR and FR sequences generally appear in the following sequence in VH (or VL): FR1 -CDR-H1 (CDR-L1 )-FR2- CDR-H2(CDR-L2)-FR3- CDR-H3(CDR-L3)-FR4.
  • variable-domain residue-numbering as in Kabat or “amino-acid-position numbering as in Kabat,” and variations thereof, refers to the numbering system used for heavy-chain variable domains or light-chain variable domains of the compilation of antibodies in Kabat et al., supra. Using this numbering system, the actual linear amino acid sequence may contain fewer or additional amino acids corresponding to a shortening of, or insertion into, a FR or HVR of the variable domain.
  • a heavy-chain variable domain may include a single amino acid insert (e.g., residue 52a according to Kabat) after residue 52 of H2 and inserted residues (e.g., residues 82a, 82b, and 82c, etc. according to Kabat) after heavy-chain FR residue 82.
  • the Kabat numbering of residues may be determined for a given antibody by alignment at regions of homology of the sequence of the antibody with a “standard” Kabat numbered sequence.
  • the Kabat numbering system is generally used when referring to a residue in the variable domain (approximately residues 1 -107 of the light chain and residues 1 -113 of the heavy chain) (e.g., Kabat et al., Sequences of Immunological Interest. 5th Ed. Public Health Service, National Institutes of Health, Bethesda, Md. (1991 )).
  • the “EU numbering system” or “EU index” is generally used when referring to a residue in an immunoglobulin heavy chain constant region (e.g., the EU index reported in Kabat et al., supra).
  • the “EU index as in Kabat” refers to the residue numbering of the human lgG1 EU antibody.
  • variable refers to the fact that certain segments of the variable domains differ extensively in sequence among antibodies.
  • the V domain mediates antigen binding and defines the specificity of a particular antibody for its particular antigen.
  • variability is not evenly distributed across the entire span of the variable domains. Instead, it is concentrated in three segments called hypervariable regions (HVRs) both in the light-chain and the heavy chain variable domains.
  • HVRs hypervariable regions
  • the more highly conserved portions of variable domains are called the framework regions (FR).
  • the variable domains of native heavy and light chains each comprise four FR regions, largely adopting a beta-sheet configuration, connected by three HVRs, which form loops connecting, and in some cases forming part of, the beta-sheet structure.
  • the HVRs in each chain are held together in close proximity by the FR regions and, with the HVRs from the other chain, contribute to the formation of the antigen binding site of antibodies (see Kabat etal., Sequences of Immunological Interest, Fifth Edition, National Institute of Health, Bethesda, MD (1991)).
  • the constant domains are not involved directly in the binding of antibody to an antigen, but exhibit various effector functions, such as participation of the antibody in antibody- dependent cellular toxicity.
  • variable region refers to the amino-terminal domains of the heavy or light chain of the antibody.
  • variable domains of the heavy chain and light chain may be referred to as “VH” and “VL”, respectively. These domains are generally the most variable parts of the antibody (relative to other antibodies of the same class) and contain the antigen binding sites.
  • “Framework” or “FR” refers to variable domain residues other than hypervariable region (HVR) residues.
  • the FR of a variable domain generally consists of four FR domains: FR1 , FR2, FR3, and FR4. Accordingly, the HVR and FR sequences generally appear in the following sequence in VH (or VL): FR1 - H1 (L1 )-FR2-H2(L2)-FR3-H3(L3)-FR4.
  • full-length antibody “intact antibody,” and “whole antibody” are used interchangeably to refer to an antibody in its substantially intact form, as opposed to an antibody fragment.
  • whole antibodies include those with heavy and light chains including an Fc region.
  • the constant domains may be native sequence constant domains (e.g., human native sequence constant domains) or amino acid sequence variants thereof.
  • the intact antibody may have one or more effector functions.
  • naked antibody refers to an antibody that is not conjugated to a heterologous moiety (e.g., a cytotoxic moiety) or radiolabel.
  • the naked antibody may be present in a pharmaceutical composition.
  • an “antibody fragment” comprises a portion of an intact antibody, preferably the antigen-binding and/or the variable region of the intact antibody.
  • antibody fragments include Fab, Fab’, F(ab’)2 and Fv fragments; diabodies; linear antibodies (see U.S. Patent 5,641 ,870, Example 2; Zapata et ah, Protein Eng. 8(10): 1057-1062 [1995]); single-chain antibody molecules and multispecific antibodies formed from antibody fragments. Papain digestion of antibodies produced two identical antigen-binding fragments, called “Fab” fragments, and a residual “Fc” fragment, a designation reflecting the ability to crystallize readily.
  • the Fab fragment consists of an entire L chain along with the variable region domain of the H chain (VH), and the first constant domain of one heavy chain (CH1 ).
  • Each Fab fragment is monovalent with respect to antigen binding, i.e., it has a single antigen-binding site.
  • Pepsin treatment of an antibody yields a single large F(ab’)2 fragment which roughly corresponds to two disulfide linked Fab fragments having different antigen-binding activity and is still capable of cross-linking antigen.
  • Fab’ fragments differ from Fab fragments by having a few additional residues at the carboxy terminus of the CH1 domain including one or more cysteines from the antibody hinge region.
  • Fab’-SH is the designation herein for Fab’ in which the cysteine residue(s) of the constant domains bear a free thiol group.
  • F(ab’)2 antibody fragments originally were produced as pairs of Fab’ fragments which have hinge cysteines between them. Other chemical couplings of antibody fragments are also known.
  • the Fc fragment comprises the carboxy-terminal portions of both FI chains held together by disulfides.
  • the effector functions of antibodies are determined by sequences in the Fc region, the region which is also recognized by Fc receptors (FcR) found on certain types of cells.
  • “Functional fragments” of the antibodies of the invention comprise a portion of an intact antibody, generally including the antigen binding or variable region of the intact antibody or the Fc region of an antibody which retains or has modified FcR binding capability.
  • antibody fragments include linear antibody, single-chain antibody molecules and multispecific antibodies formed from antibody fragments.
  • “Fv” is the minimum antibody fragment which contains a complete antigen-recognition and - binding site. This fragment consists of a dimer of one heavy- and one light-chain variable region domain in tight, non-covalent association. From the folding of these two domains emanate six hypervariable loops (3 loops each from the H and L chain) that contribute the amino acid residues for antigen binding and confer antigen binding specificity to the antibody. However, even a single variable domain (or half of an Fv comprising only three HVRs specific for an antigen) has the ability to recognize and bind antigen, although at a lower affinity than the entire binding site.
  • Single-chain Fv also abbreviated as “sFv” or “scFv” are antibody fragments that comprise the VH and VL antibody domains connected into a single polypeptide chain.
  • the sFv polypeptide further comprises a polypeptide linker between the VH and VL domains which enables the sFv to form the desired structure for antigen binding.
  • Fc region herein is used to define a C-terminal region of an immunoglobulin heavy chain that contains at least a portion of the constant region.
  • the term includes native sequence Fc regions and variant Fc regions.
  • a human IgG heavy chain Fc region extends from Cys226, or from Pro230, to the carboxyl-terminus of the heavy chain.
  • antibodies produced by host cells may undergo post-translational cleavage of one or more, particularly one or two, amino acids from the C- terminus of the heavy chain.
  • an antibody produced by a host cell by expression of a specific nucleic acid molecule encoding a full-length heavy chain may include the full-length heavy chain, or it may include a cleaved variant of the full-length heavy chain. This may be the case where the final two C- terminal amino acids of the heavy chain are glycine (G446) and lysine (K447). Therefore, the C-terminal lysine (Lys447), or the C-terminal glycine (Gly446) and lysine (Lys447), of the Fc region may or may not be present.
  • a heavy chain including an Fc region as specified herein, comprised in an antibody disclosed herein comprises an additional C-terminal glycine-lysine dipeptide (G446 and K447).
  • a heavy chain including an Fc region as specified herein, comprised in an antibody disclosed herein comprises an additional C-terminal glycine residue (G446).
  • a heavy chain including an Fc region as specified herein, comprised in an antibody disclosed herein comprises an additional C-terminal lysine residue (K447).
  • the Fc region contains a single amino acid substitution N297A of the heavy chain.
  • numbering of amino acid residues in the Fc region or constant region is according to the EU numbering system, also called the EU index, as described in Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD, 1991 .
  • Fc receptor or “FcR” describes a receptor that binds to the Fc region of an antibody.
  • the preferred FcR is a native sequence human FcR.
  • a preferred FcR is one which binds an IgG antibody (a gamma receptor) and includes receptors of the FcyRI, FcyRII, and FcyRIII subclasses, including allelic variants and alternatively spliced forms of these receptors, FcyRII receptors include FcyRIIA (an “activating receptor”) and FcyRIIB (an “inhibiting receptor”), which have similar amino acid sequences that differ primarily in the cytoplasmic domains thereof.
  • Activating receptor FcyRIIA contains an immunoreceptor tyrosine-based activation motif (ITAM) in its cytoplasmic domain.
  • Inhibiting receptor FcyRIIB contains an immunoreceptor tyrosine-based inhibition motif (ITIM) in its cytoplasmic domain (see M. Daeron, Annu. Rev. Immunol. 15:203-234 (1997). FcRs are reviewed in Ravetch and Kinet, Annu. Rev. Immunol. 9: 457-92 (1991); Capel et al., Immunomethods 4: 25-34 (1994); and de Haas et al., J.
  • diabodies refers to small antibody fragments prepared by constructing sFv fragments (see preceding paragraph) with short linkers (about 5-10) residues) between the VH and VL domains such that inter-chain but not intra-chain pairing of the V domains is achieved, thereby resulting in a bivalent fragment, i.e., a fragment having two antigen-binding sites.
  • Bispecific diabodies are heterodimers of two “crossover” sFv fragments in which the VH and VL domains of the two antibodies are present on different polypeptide chains.
  • Diabodies are described in greater detail in, for example, EP 404,097; WO 93/11161 ; Hollinger etai, Proc. Natl. Acad. Sci. USA 90: 6444-6448 (1993).
  • the monoclonal antibodies herein specifically include “chimeric” antibodies (immunoglobulins) in which a portion of the heavy and/or light chain is identical with or homologous to corresponding sequences in antibodies derived from a particular species or belonging to a particular antibody class or subclass, while the remainder of the chain(s) is (are) identical with or homologous to corresponding sequences in antibodies derived from another species or belonging to another antibody class or subclass, as well as fragments of such antibodies, so long as they exhibit the desired biological activity (U.S. Patent No. 4,816,567; Morrison et al., Proc. Natl. Acad. Sci. USA, 81:6851-6855 (1984)).
  • Chimeric antibodies of interest herein include PRIMATIZED ® antibodies wherein the antigen-binding region of the antibody is derived from an antibody produced by, e.g., immunizing macaque monkeys with an antigen of interest.
  • humanized antibody is used a subset of “chimeric antibodies.”
  • the “class” of an antibody refers to the type of constant domain or constant region possessed by its heavy chain.
  • the heavy chain constant domains that correspond to the different classes of immunoglobulins are called a, d, e, g, and m, respectively.
  • Binding affinity refers to the strength of the sum total of non-covalent interactions between a single binding site of a molecule (e.g., an antibody) and its binding partner (e.g., an antigen, e.g., TIGIT, PD-L1 , or VEGF).
  • binding affinity refers to intrinsic binding affinity which reflects a 1 :1 interaction between members of a binding pair (e.g., antibody and antigen).
  • the affinity of a molecule X for its partner Y can generally be represented by the dissociation constant (KD). Affinity can be measured by common methods known in the art, including those described herein.
  • a “human antibody” is an antibody that possesses an amino-acid sequence corresponding to that of an antibody produced by a human and/or has been made using any of the techniques for making human antibodies as disclosed herein. This definition of a human antibody specifically excludes a humanized antibody comprising non-human antigen-binding residues.
  • Human antibodies can be produced using various techniques known in the art, including phage-display libraries. Hoogenboom and Winter, J. Mol. Biol., 227:381 (1991); Marks eta ⁇ ., J. Mol. Biol., 222:581 (1991). Also available for the preparation of human monoclonal antibodies are methods described in Cole etal., Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, p.
  • Human antibodies can be prepared by administering the antigen to a transgenic animal that has been modified to produce such antibodies in response to antigenic challenge, but whose endogenous loci have been disabled, e.g., immunized xenomice (see, e.g., U.S. Pat. Nos. 6,075,181 and 6,150,584 regarding XENOMOUSETM technology). See also, for example, Li et ah, Proc. Natl. Acad. Sci. USA, 103:3557-3562 (2006) regarding human antibodies generated via a human B-cell hybridoma technology.
  • “Humanized” forms of non-human (e.g., murine) antibodies are chimeric antibodies that contain minimal sequence derived from non-human immunoglobulin.
  • a humanized antibody is a human immunoglobulin (recipient antibody) in which residues from an HVR (hereinafter defined) of the recipient are replaced by residues from an HVR of a non-human species (donor antibody) such as mouse, rat, rabbit or non-human primate having the desired specificity, affinity, and/or capacity.
  • donor antibody such as mouse, rat, rabbit or non-human primate having the desired specificity, affinity, and/or capacity.
  • framework (“FR”) residues of the human immunoglobulin are replaced by corresponding non human residues.
  • humanized antibodies may comprise residues that are not found in the recipient antibody or in the donor antibody.
  • a humanized antibody will comprise substantially all of at least one, and typically two, variable domains, in which all or substantially all of the hypervariable loops correspond to those of a non-human immunoglobulin sequence, and all or substantially all of the FR regions are those of a human immunoglobulin sequence, although the FR regions may include one or more individual FR residue substitutions that improve antibody performance, such as binding affinity, isomerization, immunogenicity, etc.
  • the number of these amino acid substitutions in the FR are typically no more than 6 in the H chain, and in the L chain, no more than 3.
  • the humanized antibody optionally will also comprise at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin.
  • Fc immunoglobulin constant region
  • an “isolated antibody” when used to describe the various antibodies disclosed herein means an antibody that has been identified and separated and/or recovered from a cell or cell culture from which it was expressed. Contaminant components of its natural environment are materials that would typically interfere with diagnostic or therapeutic uses for the polypeptide, and can include enzymes, hormones, and other proteinaceous or non-proteinaceous solutes.
  • an antibody is purified to greater than 95% or 99% purity as determined by, for example, electrophoretic (e.g., SDS- PAGE, isoelectric focusing (IEF), capillary electrophoresis) or chromatographic (e.g., ion exchange or reverse phase HPLC).
  • electrophoretic e.g., SDS- PAGE, isoelectric focusing (IEF), capillary electrophoresis
  • chromatographic e.g., ion exchange or reverse phase HPLC.
  • the antibody will be purified (1 ) to a degree sufficient to obtain at least 15 residues of N-terminal or internal amino acid sequence by use of a spinning cup sequenator, or (2) to homogeneity by SDS-PAGE under non-reducing or reducing conditions using Coomassie blue or, preferably, silver stain.
  • Isolated antibody includes antibodies in situ within recombinant cells, because at least one component of the polypeptide natural environment will not be present. Ordinarily, however, isolated polypeptide will be prepared by at least one purification step.
  • the term “monoclonal antibody” as used herein refers to an antibody obtained from a population of substantially homogeneous antibodies, i.e. , the individual antibodies comprising the population are identical and/or bind the same epitope, except for possible variant antibodies, e.g., containing naturally occurring mutations or arising during production of a monoclonal antibody preparation, such variants generally being present in minor amounts.
  • polyclonal antibody preparations typically include different antibodies directed against different determinants (epitopes)
  • each monoclonal antibody of a monoclonal antibody preparation is directed against a single determinant on an antigen.
  • the modifier “monoclonal” indicates the character of the antibody as being obtained from a substantially homogeneous population of antibodies, and is not to be construed as requiring production of the antibody by any particular method.
  • the monoclonal antibodies in accordance with the present invention may be made by a variety of techniques, including but not limited to the hybridoma method, recombinant DNA methods, phage-display methods, and methods utilizing transgenic animals containing all or part of the human immunoglobulin loci.
  • the term “binds,” “specifically binds to,” or is “specific for” refers to measurable and reproducible interactions such as binding between a target and an antibody, which is determinative of the presence of the target in the presence of a heterogeneous population of molecules including biological molecules.
  • an antibody that specifically binds to a target (which can be an epitope) is an antibody that binds this target with greater affinity, avidity, more readily, and/or with greater duration than it binds to other targets.
  • the extent of binding of an antibody to an unrelated target is less than about 10% of the binding of the antibody to the target as measured, for example, by a radioimmunoassay (RIA).
  • an antibody that specifically binds to a target has a dissociation constant (KD) of ⁇ 1 mM, ⁇ 100 nM, ⁇ 10 nM, ⁇ 1 nM, or ⁇ 0.1 nM.
  • KD dissociation constant
  • an antibody specifically binds to an epitope on a protein that is conserved among the protein from different species.
  • specific binding can include, but does not require exclusive binding.
  • the term as used herein can be exhibited, for example, by a molecule having a KD for the target of 10 -4 M or lower, alternatively 10 _5 M or lower, alternatively 10 -6 M or lower, alternatively 10 -7 M or lower, alternatively 10 -8 M or lower, alternatively 10 -9 M or lower, alternatively 10 _1 ° M or lower, alternatively 10 -11 M or lower, alternatively 10 -12 M or lower or a KD in the range of 10 -4 M to 10 -6 M or 10 -6 M to 10 _1 ° M or 10 -7 M to 10 9 M.
  • affinity and KD values are inversely related. A high affinity for an antigen is measured by a low KD value.
  • the term “specific binding” refers to binding where a molecule binds to a particular polypeptide or epitope on a particular polypeptide without substantially binding to any other polypeptide or polypeptide epitope.
  • Percent (%) amino acid sequence identity with respect to a reference polypeptide sequence is defined as the percentage of amino acid residues in a candidate sequence that are identical with the amino acid residues in the reference polypeptide sequence, after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent sequence identity, and not considering any conservative substitutions as part of the sequence identity. Alignment for purposes of determining percent amino acid sequence identity can be achieved in various ways that are within the skill in the art, for instance, using publicly available computer software such as BLAST, BLAST-2, ALIGN or Megalign (DNASTAR) software. Those skilled in the art can determine appropriate parameters for aligning sequences, including any algorithms needed to achieve maximal alignment over the full length of the sequences being compared.
  • % amino acid sequence identity values are generated using the sequence comparison computer program ALIGN-2.
  • the ALIGN-2 sequence comparison computer program was authored by Genentech, Inc., and the source code has been filed with user documentation in the U.S. Copyright Office, Washington D.C., 20559, where it is registered under U.S. Copyright Registration No. TXU510087.
  • the ALIGN-2 program is publicly available from Genentech, Inc., South San Francisco, California, or may be compiled from the source code.
  • the ALIGN-2 program should be compiled for use on a UNIX operating system, including digital UNIX V4.0D. All sequence comparison parameters are set by the ALIGN-2 program and do not vary.
  • % amino acid sequence identity of a given amino acid sequence A to, with, or against a given amino acid sequence B is calculated as follows:
  • subject or “individual” is meant a mammal, including, but not limited to, a human or non-human mammal, such as a bovine, equine, canine, ovine, or feline. In some aspects, the subject is a human. Patients are also subjects herein.
  • the term “patient” refers to a human patient.
  • the patient may be an adult.
  • diagnosis is used herein to refer to the identification or classification of a molecular or pathological state, disease or condition (e.g., cancer).
  • diagnosis may refer to identification of a particular type of cancer.
  • Diagnosis may also refer to the classification of a particular subtype of cancer, for instance, by histopathological criteria, or by molecular features (e.g., a subtype characterized by expression of one or a combination of biomarkers (e.g., particular genes or proteins encoded by said genes)).
  • sample refers to a composition that is obtained or derived from a subject and/or individual of interest that contains a cellular and/or other molecular entity that is to be characterized and/or identified, for example, based on physical, biochemical, chemical, and/or physiological characteristics.
  • tumor sample refers to any sample obtained from a subject of interest that would be expected or is known to contain the cellular and/or molecular entity that is to be characterized.
  • Samples include, but are not limited to, tissue samples, primary or cultured cells or cell lines, cell supernatants, cell lysates, platelets, serum, plasma, vitreous fluid, lymph fluid, synovial fluid, follicular fluid, seminal fluid, amniotic fluid, milk, whole blood, blood-derived cells, urine, cerebro-spinal fluid, saliva, sputum, tears, perspiration, mucus, stool, tumor lysates, and tissue culture medium, tissue extracts such as homogenized tissue, tumor tissue, cellular extracts, and combinations thereof.
  • tissue sample or “cell sample” is meant a collection of similar cells obtained from a tissue of a subject or individual.
  • the source of the tissue or cell sample may be solid tissue as from a fresh, frozen and/or preserved organ, tissue sample, biopsy, and/or aspirate; blood or any blood constituents such as plasma; bodily fluids such as cerebral spinal fluid, amniotic fluid, peritoneal fluid, or interstitial fluid; cells from any time in gestation or development of the subject.
  • the tissue sample may also be primary or cultured cells or cell lines.
  • the tissue or cell sample is obtained from a disease tissue/organ.
  • a “tumor sample” is a tissue sample obtained from a tumor or other cancerous tissue.
  • the tissue sample may contain a mixed population of cell types (e.g., tumor cells and non-tumor cells, cancerous cells and non-cancerous cells).
  • the tissue sample may contain compounds which are not naturally intermixed with the tissue in nature such as preservatives, anticoagulants, buffers, fixatives, wax, nutrients, antibiotics, or the like.
  • the sample is a tumor tissue sample.
  • the tumor tissue sample is a UC tumor tissue sample (e.g., a bladder cancer tumor tissue sample (e.g., an MIBC tumor tissue sample)).
  • the sample is a transurethral resection of bladder tumor (TURBT) sample.
  • the sample is a cystectomy or nephroureterectomy sample.
  • the tumor tissue sample is a lung cancer tumor tissue sample (e.g., an early stage lung cancer tissue sample (e.g., an NSCLC tumor tissue sample (e.g., a stage II, MIA, or NIB NSCLC tumor tissue sample), e.g., squamous or non-squamous NSCLC tumor tissue sample, e.g., a resectable NSCLC tumor tissue sample)).
  • an early stage lung cancer tissue sample e.g., an NSCLC tumor tissue sample (e.g., a stage II, MIA, or NIB NSCLC tumor tissue sample), e.g., squamous or non-squamous NSCLC tumor tissue sample, e.g., a resectable NSCLC tumor tissue sample)
  • an early stage lung cancer tissue sample e.g., an NSCLC tumor tissue sample (e.g., a stage II, MIA, or NIB NSCLC tumor tissue sample)
  • the sample is a locally advanced unresectable NSCLC tumor tissue sample (e.g., Stage NIB NSCLC tumor tissue sample), or recurrent or metastatic NSCLC tumor tissue sample (e.g., Stage IV NSCLC tumor tissue sample)), a pancreatic cancer tumor tissue sample (e.g., a PDAC tumor tissue sample), e.g., a metastatic PDAC tumor tissue sample)), or a breast cancer tumor tissue sample (e.g., a HER2+ breast cancer tumor tissue sample or a TNBC tumor tissue sample).
  • a locally advanced unresectable NSCLC tumor tissue sample e.g., Stage NIB NSCLC tumor tissue sample
  • recurrent or metastatic NSCLC tumor tissue sample e.g., Stage IV NSCLC tumor tissue sample
  • a pancreatic cancer tumor tissue sample e.g., a PDAC tumor tissue sample
  • a metastatic PDAC tumor tissue sample e.g., a metastatic PDAC tumor tissue sample
  • breast cancer tumor tissue sample
  • a “section” of a tissue sample is meant a single part or piece of a tissue sample, for example, a thin slice of tissue or cells cut from a tissue sample (e.g., a tumor sample). It is to be understood that multiple sections of tissue samples may be taken and subjected to analysis, provided that it is understood that the same section of tissue sample may be analyzed at both morphological and molecular levels, or analyzed with respect to polypeptides (e.g., by immunohistochemistry) and/or polynucleotides (e.g., by in situ hybridization).
  • polypeptides e.g., by immunohistochemistry
  • polynucleotides e.g., by in situ hybridization
  • a “reference sample,” “reference cell,” “reference tissue,” “control sample,” “control cell,” or “control tissue,” as used herein, refers to a sample, cell, tissue, standard, or level that is used for comparison purposes.
  • a reference sample, reference cell, reference tissue, control sample, control cell, or control tissue is obtained from a healthy and/or non-diseased part of the body (e.g., tissue or cells) of the same subject or individual.
  • the reference sample, reference cell, reference tissue, control sample, control cell, or control tissue may be healthy and/or non-diseased cells or tissue adjacent to the diseased cells or tissue (e.g., cells or tissue adjacent to a tumor).
  • a reference sample is obtained from an untreated tissue and/or cell of the body of the same subject or individual.
  • a reference sample, reference cell, reference tissue, control sample, control cell, or control tissue is obtained from a healthy and/or non-diseased part of the body (e.g., tissues or cells) of an individual who is not the subject or individual.
  • a reference sample, reference cell, reference tissue, control sample, control cell, or control tissue is obtained from an untreated tissue and/or cell of the body of an individual who is not the subject or individual.
  • protein refers to any native protein from any vertebrate source, including mammals such as primates (e.g., humans) and rodents (e.g., mice and rats), unless otherwise indicated.
  • the term encompasses “full-length,” unprocessed protein as well as any form of the protein that results from processing in the cell.
  • the term also encompasses naturally occurring variants of the protein, e.g., splice variants or allelic variants.
  • Polynucleotide or “nucleic acid,” as used interchangeably herein, refers to polymers of nucleotides of any length, and include DNA and RNA.
  • the nucleotides can be deoxyribonucleotides, ribonucleotides, modified nucleotides or bases, and/or their analogs, or any substrate that can be incorporated into a polymer by DNA or RNA polymerase, or by a synthetic reaction.
  • polynucleotides as defined herein include, without limitation, single- and double-stranded DNA, DNA including single- and double-stranded regions, single- and double-stranded RNA, and RNA including single- and double-stranded regions, hybrid molecules comprising DNA and RNA that may be single- stranded or, more typically, double-stranded or include single- and double-stranded regions.
  • polynucleotide refers to triple-stranded regions comprising RNA or DNA or both RNA and DNA. The strands in such regions may be from the same molecule or from different molecules.
  • the regions may include all of one or more of the molecules, but more typically involve only a region of some of the molecules.
  • One of the molecules of a triple-helical region often is an oligonucleotide.
  • polynucleotide and nucleic acid specifically includes mRNA and cDNAs.
  • a polynucleotide may comprise modified nucleotides, such as methylated nucleotides and their analogs. If present, modification to the nucleotide structure may be imparted before or after assembly of the polymer. The sequence of nucleotides may be interrupted by non-nucleotide components. A polynucleotide may be further modified after synthesis, such as by conjugation with a label.
  • modifications include, for example, “caps,” substitution of one or more of the naturally-occurring nucleotides with an analog, internucleotide modifications such as, for example, those with uncharged linkages (e.g., methyl phosphonates, phosphotriesters, phosphoamidates, carbamates, and the like) and with charged linkages (e.g., phosphorothioates, phosphorodithioates, and the like), those containing pendant moieties, such as, for example, proteins (e.g., nucleases, toxins, antibodies, signal peptides, poly-L-lysine, and the like), those with intercalators (e.g., acridine, psoralen, and the like), those containing chelators (e.g., metals, radioactive metals, boron, oxidative metals, and the like), those containing alkylators, those with modified linkages (e.g., alpha anomeric nucleic acids
  • any of the hydroxyl groups ordinarily present in the sugars may be replaced, for example, by phosphonate groups, phosphate groups, protected by standard protecting groups, or activated to prepare additional linkages to additional nucleotides, or may be conjugated to solid or semi-solid supports.
  • the 5’ and 3’ terminal OH can be phosphorylated or substituted with amines or organic capping group moieties of from 1 to 20 carbon atoms.
  • Other hydroxyls may also be derivatized to standard protecting groups.
  • Polynucleotides can also contain analogous forms of ribose or deoxyribose sugars that are generally known in the art, including, for example, 2’-0- methyl-, 2’-0-allyl-, 2’-fluoro-, or 2’-azido-ribose, carbocyclic sugar analogs, a-anomeric sugars, epimeric sugars such as arabinose, xyloses or lyxoses, pyranose sugars, furanose sugars, sedoheptuloses, acyclic analogs, and abasic nucleoside analogs such as methyl riboside.
  • One or more phosphodiester linkages may be replaced by alternative linking groups.
  • linking groups include, but are not limited to, aspects wherein phosphate is replaced by P(0)S (“thioate”), P(S)S (“dithioate”), “(0)NR2 (“amidate”), P(0)R, P(0)OR’, CO or CH2 (“formacetal”), in which each R or R’ is independently H or substituted or unsubstituted alkyl (1-20 C) optionally containing an ether (-0-) linkage, aryl, alkenyl, cycloalkyl, cycloalkenyl or araldyl. Not all linkages in a polynucleotide need be identical. The preceding description applies to all polynucleotides referred to herein, including RNA and DNA.
  • Carriers as used herein include pharmaceutically acceptable carriers, excipients, or stabilizers that are nontoxic to the cell or mammal being exposed thereto at the dosages and concentrations employed. Often the physiologically acceptable carrier is an aqueous pH buffered solution.
  • physiologically acceptable carriers include buffers such as phosphate, citrate, and other organic acids; antioxidants including ascorbic acid; low molecular weight (less than about 10 residues) polypeptide; proteins, such as serum albumin, gelatin, or immunoglobulins; hydrophilic polymers such as polyvinylpyrrolidone; amino acids such as glycine, glutamine, asparagine, arginine or lysine; monosaccharides, disaccharides, and other carbohydrates including glucose, mannose, or dextrins; chelating agents such as EDTA; sugar alcohols such as mannitol or sorbitol; salt-forming counterions such as sodium; and/or nonionic surfactants such as TWEENTM, polyethylene glycol (PEG), and PLURONICSTM.
  • buffers such as phosphate, citrate, and other organic acids
  • antioxidants including ascorbic acid
  • proteins such as serum albumin,
  • phrases “pharmaceutically acceptable” indicates that the substance or composition must be compatible chemically and/or toxicologically, with the other ingredients comprising a formulation, and/or the mammal being treated therewith.
  • pharmaceutical formulation or “pharmaceutical composition” refers to a preparation which is in such form as to permit the biological activity of an active ingredient contained therein to be effective, and which contains no additional components which are unacceptably toxic to a subject to which the formulation would be administered.
  • package insert is used to refer to instructions customarily included in commercial packages of therapeutic products or medicaments that contain information about the indications, usage, dosage, administration, combination therapy, other medicaments to be combined with the packaged product, and/or contraindications and/or warnings concerning the use of such therapeutic products or medicaments.
  • the term “induction phase” refers to a series of one or more dosing cycles (e.g., about 4-6 cycles) of one or more therapeutic agents (e.g., an anti-TIGIT antagonist antibody, a PD-1 axis binding antagonist, and/or a chemotherapeutic agent) administered to a subject, wherein the one or more dosing cycles are optionally followed by a maintenance phase.
  • one or more therapeutic agents e.g., an anti-TIGIT antagonist antibody, a PD-1 axis binding antagonist, and/or a chemotherapeutic agent
  • maintenance phase refers to a series of one or more dosing cycles of one or more therapeutic agents (e.g., an anti-TIGIT antagonist antibody, a PD-1 axis binding antagonist, and/or a chemotherapeutic agent) that are administered to a subject subsequent to an induction phase.
  • therapeutic agents e.g., an anti-TIGIT antagonist antibody, a PD-1 axis binding antagonist, and/or a chemotherapeutic agent
  • the maintenance phase is initiated only if the subject did not experience disease progression or unacceptable toxicity during the induction phase.
  • the induction phase and maintenance phase may or may not comprise use of the same therapeutic agents.
  • the induction phase includes use of an anti-TIGIT antagonist antibody, a PD-1 axis binding antagonist, a platinum-based chemotherapeutic agent, and a non-platinum-based chemotherapeutic agent
  • the maintenance phase includes use of an anti-TIGIT antagonist antibody and a PD-1 axis binding antagonist.
  • the term “ineligible for treatment with a platinum-based chemotherapy” or “unfit for treatment with a platinum-based chemotherapy” means that the subject is ineligible or unfit for treatment with a platinum-based chemotherapy, either in the attending clinician’s judgment or according to standardized criteria for eligibility for platinum-based chemotherapy that are known in the art.
  • the criteria set forth in Gaisky et al. Lancet Oncol. 12(3) :211-4, 2011 may be used to determine whether a subject is eligible for cisplatin-based chemotherapy.
  • mUC metastatic UC
  • WHO World Health Association
  • ECG Eastern Cooperative Oncology Group
  • NCI National Cancer Institute
  • CTCAE Common Terminology Criteria for Adverse Events
  • CTCAE CTCAE v.4.0 Grade > 2 peripheral neuropathy
  • NYHA New York Heart Association
  • a patient is considered unfit for cisplatin-based chemotherapy if they have one or more of the following: impaired renal function (e.g., glomerular filtration rate (GFR) >30 but ⁇ 60 mL/min); GFR may be assessed by direct measurement (i.e.
  • impaired renal function e.g., glomerular filtration rate (GFR) >30 but ⁇ 60 mL/min
  • GFR may be assessed by direct measurement (i.e.
  • a subject having one of the following may be eligible for carboplatin-based chemotherapy: impaired renal function (e.g., GFR >30 but ⁇ 60 mL/min); GFR may be assessed by direct measurement (i.e., creatinine clearance or ethyldediaminetetra-acetate) or, if not available, by calculation from serum/plasma creatinine (Cockcroft-Gault formula)); hearing loss (e.g., CTCAE v4.0 Grade > 2 audiometric hearing loss of 25 decibels at two contiguous frequencies); peripheral neuropathy (e.g., NCI CTCAE v4.0 Grade > 2 peripheral neuropathy (i.e., sensory alteration or paresthesia, including tingling)); and/or ECOG performance status assessment (e.g., an ECOG performance status of 2).
  • impaired renal function e.g., GFR >30 but ⁇ 60 mL/min
  • GFR may be assessed by direct measurement (i.e., creatinine clearance or ethyld
  • cisplatin ineligibility may be defined by any one of the following criteria: (i) impaired renal function (GFR ⁇ 60 mL/min); GFR may be assessed by direct measurement (i.e., creatinine clearance or ethyldediaminetetra-acetate) or, if not available, by calculation from serum/plasma creatinine (Cockcroft Gault formula); (ii) a hearing loss (measured by audiometry) of 25 dB at two contiguous frequencies; (iii) Grade 2 or greater peripheral neuropathy (i.e., sensory alteration or parasthesis including tingling); and (iv) ECOG Performance Status of 2.
  • GFR impaired renal function
  • GFR may be assessed by direct measurement (i.e., creatinine clearance or ethyldediaminetetra-acetate) or, if not available, by calculation from serum/plasma creatinine (Cockcroft Gault formula)
  • a hearing loss measured by audiometry
  • Grade 2 or greater peripheral neuropathy
  • cancer e.g., a solid tumor and/or a locally advanced or metastatic cancer, e.g., a lung cancer (e.g., an early stage lung cancer (e.g., a resectable lung cancer), a small cell lung cancer (SCLC) (e.g., an extensive stage (ES)-SCLC), a non-small cell lung cancer (NSCLC) (e.g., a squamous NSCLC or a non-squamous NSCLC, a locally advanced unresectable NSCLC, a Stage NIB NSCLC, a recurrent or metastatic NSCLC (e.g., a locally advanced unresectable or metastatic non-squamous NSCLC (e.g., Stage IV non-squamous NSCLC)), or a Stage IV NSCLC (e.g., wherein the subject has not been previously treated for Stage IV NSCLC))); a cervical cancer (e.g., an early stage lung cancer (e
  • the present invention includes methods and uses involving administration of an effective amount of an anti-TIGIT antagonist antibody (e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab) and a PD-1 axis binding antagonist (e.g., an anti-PD-L1 antagonist antibody, such as atezolizumab, or an anti-PD-1 antagonist antibody, such as e.g., pembrolizumab) to a subject in need thereof every four weeks (e.g., on Day 1 of each 28-day dosing cycle).
  • an anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • a PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody, such as atezolizumab, or an anti-PD-1 antagonist antibody, such as e.g., pembrolizumab
  • administering results in a complete response (CR) or a partial response (PR).
  • a complete response CR
  • PR partial response
  • administering results in an increase in progression-free survival (PFS) or duration of objective response (DOR).
  • PFS progression-free survival
  • DOR duration of objective response
  • administering results in an increase in overall survival (OS).
  • OS overall survival
  • administering results in an increase in PFS of the subject, e.g., as compared to treatment with the PD-1 axis binding antagonist without the anti-TIGIT antagonist antibody or as compared to treatment with the anti-TIGIT antagonist antibody without the PD-1 axis binding antagonist.
  • the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody, such as atezolizumab
  • the effective amount of the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody, such as atezolizumab
  • OS of the subject e.g., as compared to treatment with the PD-1 axis binding antagonist without the anti-TIGIT antagonist antibody or as compared to treatment with the anti-TIGIT antagonist antibody without the PD-1 axis binding antagonist.
  • the present invention includes methods and uses involving administration of an effective amount of an anti-TIGIT antagonist antibody (e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab) to a subject in need thereof every four weeks (e.g., on Day 1 of each 28-day dosing cycle).
  • an anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody, e.g., atezolizumab, or an anti-PD-1 antagonist antibody, such as e.g., pembrolizumab
  • the PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody, e.g., atezolizumab, or an anti-PD-1 antagonist antibody, such as e.g., pembrolizumab
  • is administered every two weeks e.g., on Days 1 and 15 of each 28-day dosing cycle
  • every three weeks e.g., on Day 1 of each 21 -day dosing cycle
  • every four weeks e.g., on Day 1 of each 28-day dosing cycle.
  • administration of the effective amount of the anti-TIGIT antagonist antibody results in a CR or a PR.
  • administration of the effective amount of the anti-TIG IT antagonist antibody results in an increase in PFS of the subject compared to a reference.
  • administration of the effective amount of the anti-TIGIT antagonist antibody results in an increase in DOR.
  • administration of the effective amount of the anti-TIGIT antagonist antibody extends OS of the subject.
  • the present invention includes methods and uses involving administration of an effective amount of an anti-TIGIT antagonist antibody (e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab) to a subject in need thereof every two weeks (e.g., on Days 1 and 15 of each 28-day dosing cycle).
  • an anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody, e.g., atezolizumab, or an anti-PD-1 antagonist antibody, such as e.g., pembrolizumab
  • the PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody, e.g., atezolizumab, or an anti-PD-1 antagonist antibody, such as e.g., pembrolizumab
  • is administered every two weeks e.g., on Days 1 and 15 of each 28-day dosing cycle
  • every three weeks e.g., on Day 1 of each 21 -day dosing cycle
  • every four weeks e.g., on Day 1 of each 28-day dosing cycle.
  • the present invention includes methods and uses involving administration of an effective amount of an anti- TIGIT antagonist antibody (e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab) and a PD-1 axis binding antagonist (e.g., an anti-PD-L1 antagonist antibody, such as atezolizumab, or an anti-PD-1 antagonist antibody, such as e.g., pembrolizumab) to a subject in need thereof every two weeks (e.g., on Days 1 and 15 of each 28-day dosing cycle).
  • an anti- TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • a PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody, such as atezolizumab, or an anti-PD-1 antagonist antibody, such as e.g., pembrolizumab
  • administering results in a CR or a PR.
  • the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody, such as atezolizumab
  • administering results in an increase in PFS of the subject, e.g., as compared to treatment with the PD-1 axis binding antagonist without the anti-TIGIT antagonist antibody or as compared to treatment with the anti-TIGIT antagonist antibody without the PD-1 axis binding antagonist.
  • the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody, such as atezolizumab
  • administering extends OS of the subject, e.g., as compared to treatment with the PD-1 axis binding antagonist without the anti-TIGIT antagonist antibody or as compared to treatment with the anti-TIGIT antagonist antibody without the PD-1 axis binding antagonist.
  • the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody, such as atezolizumab
  • the present invention includes methods and uses involving administration of an effective amount of an anti-TIGIT antagonist antibody (e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab) to a subject in need thereof every three weeks (e.g., on Day 1 of each 21 -day dosing cycle).
  • an anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody, e.g., atezolizumab, or an anti-PD-1 antagonist antibody, such as e.g., pembrolizumab
  • the PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody, e.g., atezolizumab, or an anti-PD-1 antagonist antibody, such as e.g., pembrolizumab
  • is administered every two weeks e.g., on Days 1 and 15 of each 28-day dosing cycle
  • every three weeks e.g., on Day 1 of each 21 -day dosing cycle
  • every four weeks e.g., on Day 1 of each 28-day dosing cycle.
  • the present invention includes methods and uses involving administration of an effective amount of an anti-TIG IT antagonist antibody (e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab) to a subject in need thereof every three weeks (e.g., on Day 1 of each 21 -day dosing cycle).
  • administration of the effective amount of the anti-TIGIT antagonist antibody results in a CR or a PR.
  • administration of the effective amount of the anti-TIGIT antagonist antibody results in an increase in PFS of the subject compared to a reference.
  • administration of the effective amount of the anti- TIGIT antagonist antibody extends OS of the subject.
  • the present invention includes a method of treating a subject having a cancer, the method comprising administering to the subject a dosing regimen comprising one or more dosing cycles of an anti-TIGIT antagonist antibody at a dose of about 500 mg to about 700 mg every three weeks, a PD-1 axis binding antagonist at a dose of about 900 mg to about 1500 mg every three weeks, a platinum-based chemotherapeutic agent every three weeks, and a non-platinum-based chemotherapeutic agent every three weeks.
  • the method comprises administering to the subject a dosing regimen comprising one or more dosing cycles of an anti-TIGIT antagonist antibody at a dose of 500 mg to 700 mg every three weeks, a PD-1 axis binding antagonist at a dose of 900 mg to 1500 mg every three weeks, a platinum-based chemotherapeutic agent every three weeks, and a non- platinum-based chemotherapeutic agent every three weeks.
  • the PD-1 axis binding antagonist and the anti-TIGIT antagonist antibody are administered without a chemotherapeutic agent (e.g., without any chemotherapeutic agent, e.g., the entire dosing regimen is devoid of administration of a chemotherapeutic agent to the subject).
  • the subject has not been previously treated with a therapy (e.g., a cancer immunotherapy and/or a chemotherapeutic agent) for the cancer.
  • a therapy e.g., a cancer immunotherapy and/or a chemotherapeutic agent
  • the subject has received prior treatment with a therapy (e.g., a cancer immunotherapy and/or a chemotherapeutic agent) for the cancer.
  • the subject has not received prior systemic therapy (e.g., e.g., prior systemic therapy with curative intent, e.g., chemotherapy) within at least the month prior to the administration with the PD-1 axis binding antagonist and the anti-TIGIT antagonist antibody (e.g., within the two months prior, three months prior, four months prior, six months prior, one year prior, two years prior, three years prior, four years prior, five years prior, or ten years prior to the administration with the PD-1 axis binding antagonist and the anti-TIGIT antagonist antibody).
  • the subject is chemotherapy naive.
  • the PD-1 axis binding antagonist and the anti-TIGIT antagonist antibody are administered in conjunction with a chemotherapy.
  • a once-every-two-weeks (Q2W), once-every-three-weeks (Q3W), or once-every-four-weeks (Q4W) dosing regimen of the PD-1 axis binding antagonist and/or the anti-TIGIT antagonist antibody can be administered in conjunction with one or more chemotherapeutic agents.
  • the one or more chemotherapeutic agents can be administered at the same frequency as the frequency of administration of the PD-1 axis binding antagonist and the anti-TIG IT antagonist antibody (Q2W, Q3W, or Q4W) or at a different frequency (e.g., 3-weeks on/1 -week off schedule (e.g., Days 1 , 8, and 15 of every 28-day cycle)).
  • the PD-1 axis binding antagonist and the anti-TIGIT antagonist antibody are administered every two weeks and the one or more chemotherapeutic agents is administered every week, 3-weeks on/1 -week off, every two weeks, every three weeks, or every four weeks.
  • the PD-1 axis binding antagonist and the anti-TIGIT antagonist antibody are administered every three weeks and the one or more chemotherapeutic agents is administered every week, two weeks, every three weeks, or every four weeks.
  • the PD-1 axis binding antagonist and the anti-TIGIT antagonist antibody are administered every four weeks and the one or more chemotherapeutic agents is administered every week, 3-weeks on/1 -week off, every two weeks, every three weeks, or every four weeks.
  • a chemotherapeutic agent is administered multiple times per week (e.g., 2, 3, 4, 5, 6 or 7 times per week (e.g., at Days 1 , 2, and 3 of a dosing cycle).
  • the dose of a chemotherapeutic agent is reduced after one or more initial doses (e.g., after one, two, three, four, or more initial doses).
  • a subsequent dose of the chemotherapeutic agent e.g., a platinum-based chemotherapeutic agent (e.g., carboplatin or cisplatin) and/or one or more non-platinum-based chemotherapeutic agents (e.g., an alkylating agent (e.g., cyclophosphamide), a taxane (e.g., paclitaxel, e.g., nab-paclitaxel), and/or a topoisomerase II inhibitor (e.g., doxorubicin))
  • a topoisomerase II inhibitor e.g., doxorubicin
  • an initial dose of nab-paclitaxel of 125 mg/m 2 can be reduced for a subsequent dose, e.g., to 100 mg/m 2 or 75 mg/m 2 ; an initial dose of nab-paclitaxel of 100 mg/m 2 can be reduced for a subsequent dose, e.g., to 75 mg/m 2 ; an initial dose of paclitaxel of about 175 mg/m 2 can be reduced for a subsequent dose, e.g., to 150 mg/m 2 , 125 mg/m 2 , 100 mg/m 2 , or 75 mg/m 2 ; an initial dose of paclitaxel of about 200 mg/m 2 can be reduced for a subsequent dose, e.g., to 175 mg/m 2 , 150 mg/m 2 , 125 mg/m 2 , 100 mg/m 2 , or 75 mg/m 2 ; an initial dose of gemcitabine of about 1000 mg/m 2 can be reduced for a subsequent dose, e.g., to
  • an initial dose of nab-paclitaxel of 125 mg/m 2 can be reduced for a subsequent dose, e.g., to 100 mg/m 2 or 75 mg/m 2 ; an initial dose of nab-paclitaxel of 100 mg/m 2 can be reduced for a subsequent dose, e.g., to 75 mg/m 2 ; an initial dose of paclitaxel of 175 mg/m 2 can be reduced for a subsequent dose, e.g., to 150 mg/m 2 , 125 mg/m 2 , 100 mg/m 2 , or 75 mg/m 2 ; an initial dose of paclitaxel of 200 mg/m 2 can be reduced for a subsequent dose, e.g., to 175 mg/m 2 , 150 mg/m 2 , 125 mg/m 2 , 100 mg/m 2 , or 75 mg/m 2 ; an initial dose of paclitaxel of 200 mg/m 2 can be reduced for a subsequent dose, e.g., to 1
  • the present invention includes methods and uses involving administration of an effective amount of an anti-TIGIT antagonist antibody (e.g., an anti-TIG IT antagonist antibody as disclosed herein, e.g., tiragolumab), a PD-1 axis binding antagonist (e.g., an anti-PD-L1 antagonist antibody, such as atezolizumab, or an anti-PD-1 antagonist antibody such as pembrolizumab), and a chemotherapy combination to a subject in need thereof.
  • an anti-TIGIT antagonist antibody e.g., an anti-TIG IT antagonist antibody as disclosed herein, e.g., tiragolumab
  • a PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody, such as atezolizumab, or an anti-PD-1 antagonist antibody such as pembrolizumab
  • the anti-TIGIT antagonist antibody e.g., anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody, e.g., atezolizumab
  • the anti-TIGIT antagonist antibody are administered every two weeks (e.g., on Days 1 and 15 of each 28-day dosing cycle), every three weeks (e.g., on Day 1 of each 21 -day dosing cycle), or every four weeks (e.g., on Day 1 of each 28-day dosing cycle).
  • the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody, e.g., atezolizumab
  • the PD-1 axis binding antagonist is administered every two weeks (e.g., on Days 1 and 15 of each 28-day dosing cycle), every three weeks (e.g., on Day 1 of each 21 -day dosing cycle), or every four weeks (e.g., on Day 1 of each 28-day dosing cycle).
  • the chemotherapy combination includes an effective amount of a first non-platinum-based chemotherapeutic agent and an effective amount of a second non-platinum-based chemotherapeutic agent.
  • the first non-platinum-based chemotherapeutic agent is an antimetabolite and the second non-platinum-based chemotherapeutic agent is a taxane.
  • the chemotherapy combination e.g., the antimetabolite (e.g., gemcitabine, pemetrexed, or capecitabine) and the taxane (e.g., nab-paclitaxel and paclitaxel)
  • the chemotherapy combination is administered weekly, biweekly, or three times every four weeks (e.g., on Days 1 , 8, and 15 of each 28-day dosing cycle).
  • the method involves administration of an effective amount of an anti- TIGIT antagonist antibody (e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab), a PD-1 axis binding antagonist (e.g., an anti-PD-L1 antagonist antibody, e.g., atezolizumab), gemcitabine, and paclitaxel to a subject in need thereof, wherein the anti-TIGIT antagonist antibody (e.g., anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab) and the PD-1 axis binding antagonist (e.g., an anti-PD-L1 antagonist antibody, e.g., atezolizumab) are administered every two weeks (e.g., on Days 1 and 15 of each 28-day dosing cycle) and the chemotherapy combination (e.g., the antimetabolite and the taxane (e.g., gemcitabine and paclitaxel)) is administered every two weeks
  • administering results in a CR or a PR.
  • the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody, such as atezolizumab
  • the antimetabolite e.g., gemcitabine
  • the taxane e.g., paclitaxel
  • administering results in an increase in PFS of the subject.
  • the anti-TIG IT antagonist antibody e.g., an anti-TIG IT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody, such as atezolizumab
  • the antimetabolite e.g., gemcitabine
  • the taxane e.g., paclitaxel
  • administering extends OS of the subject.
  • the anti-TIGIT antagonist antibody e.g., an anti-TIG IT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody, such as atezolizumab
  • the antimetabolite e.g., gemcitabine
  • the taxane e.g., paclitaxel
  • the present invention includes methods and uses involving administration of an effective amount of an anti-TIGIT antagonist antibody (e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab), a PD-1 axis binding antagonist (e.g., an anti-PD-L1 antagonist antibody, such as atezolizumab, or an anti-PD-1 antagonist antibody such as pembrolizumab), and a chemotherapy combination to a subject in need thereof, wherein the chemotherapy combination includes an effective amount of a platinum-based chemotherapeutic agent and an effective amount of a non-platinum-based chemotherapeutic agent.
  • an anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • a PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody, such as atezolizumab, or an anti-PD-1 antagonist antibody such as pembrolizum
  • the anti-TIGIT antagonist antibody e.g., anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody, e.g., atezolizumab
  • the anti-TIGIT antagonist antibody are administered every two weeks (e.g., on Days 1 and 15 of each 28-day dosing cycle), every three weeks (e.g., on Day 1 of each 21 -day dosing cycle), or every four weeks (e.g., on Day 1 of each 28-day dosing cycle).
  • the platinum-based chemotherapeutic agent is carboplatin or cisplatin and the non-platinum-based chemotherapeutic agent is an antimetabolite (e.g., pemetrexed).
  • the chemotherapy combination e.g., the platinum-based chemotherapeutic agent and the antimetabolite (e.g., pemetrexed)
  • the method involves administration of an effective amount of an anti- TIGIT antagonist antibody (e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab), a PD-1 axis binding antagonist (e.g., an anti-PD-L1 antagonist antibody, e.g., atezolizumab), a platinum- based chemotherapeutic agent (e.g., carboplatin or cisplatin), and an antimetabolite (e.g., pemetrexed) to a subject in need thereof, wherein the anti-TIGIT antagonist antibody (e.g., anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab) and the PD-1 axis binding antagonist (e.g., an anti-PD-L1 antagonist antibody, e.g., atezolizumab) are administered every three weeks (e.g., on Day 1 of each 21 - day dosing cycle) and the
  • the dosing continues for four-to-six induction dosing cycles (e.g., four induction dosing cycles, five induction dosing cycles, or six induction dosing cycles).
  • maintenance therapy can be administered in one or more subsequent (maintenance) dosing cycles.
  • the one or more maintenance dosing cycles does not include the platinum-based chemotherapeutic agent.
  • administering results in a CR or a PR.
  • the anti-TIG IT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody, such as atezolizumab
  • the platinum-based chemotherapeutic agent e.g., carboplatin or cisplatin
  • the antimetabolite e.g., pemetrexed
  • administering results in an increase in PFS of the subject.
  • the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody, such as atezolizumab
  • the platinum-based chemotherapeutic agent e.g., carboplatin or cisplatin
  • the antimetabolite e.g., pemetrexed
  • administering extends OS of the subject.
  • the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody, such as atezolizumab
  • the platinum-based chemotherapeutic agent e.g., carboplatin or cisplatin
  • the antimetabolite e.g., pemetrexed
  • the subject receiving the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., anti- PD-L1 antagonist antibody, such as atezolizumab
  • the platinum-based chemotherapeutic agent e.g., carboplatin or cisplatin
  • the antimetabolite e.g., pemetrexed
  • the cancer may be a lung cancer (e.g., an early stage lung cancer (e.g., a resectable lung cancer), a SCLC (e.g., an ES-SCLC), a NSCLC (e.g., a squamous NSCLC or a non-squamous NSCLC, a locally advanced unresectable NSCLC, a Stage NIB NSCLC, a recurrent or metastatic NSCLC (e.g., a locally advanced unresectable or metastatic non- squamous NSCLC (e.g., Stage IV non-squamous NSCLC)), or a Stage IV NSCLC (e.g., wherein the subject has not been previously treated for Stage IV NSCLC))); a cervical cancer (e.g., a Stage IVB, metastatic, recurrent, or persistent cervical cancer, e.g., a metastatic and/or recurrent PD-L1 -positive cervical carcinoma
  • the present invention also includes methods and uses involving administration of an effective amount of an anti-TIGIT antagonist antibody (e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab), a PD-1 axis binding antagonist (e.g., an anti-PD-L1 antagonist antibody, such as atezolizumab, or an anti-PD-1 antagonist antibody such as pembrolizumab), and a chemotherapy (e.g., a taxane (e.g., paclitaxel or nab-paclitaxel)) to a subject in need thereof.
  • an anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • a PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody, such as atezolizumab, or an anti-PD-1 antagonist antibody such as pembrolizumab
  • a chemotherapy
  • the anti-TIGIT antagonist antibody e.g., anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody, e.g., atezolizumab
  • the anti-TIGIT antagonist antibody are administered every two weeks (e.g., on Days 1 and 15 of each 28-day dosing cycle), every three weeks (e.g., on Day 1 of each 21 -day dosing cycle), or every four weeks (e.g., on Day 1 of each 28-day dosing cycle).
  • the anti-TIG IT antagonist antibody e.g., anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody, e.g., atezolizumab
  • the chemotherapy is administered weekly, every two weeks, every four weeks, or three times every four weeks (e.g., on Days 1 , 8, and 15 of each 28-day dosing cycle).
  • the chemotherapy is administered weekly.
  • an anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • a PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody, such as atezolizumab, or an anti-PD-1 antagonist antibody such as pembrolizumab
  • a chemotherapy e.g., a taxane (e.g., paclitaxel or nab-paclitaxel) results in a CR or a PR.
  • an anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • a PD- 1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody, such as atezolizumab, or an anti-PD-1 antagonist antibody such as pembrolizumab
  • a chemotherapy e.g., a taxane (e.g., paclitaxel or nab- paclitaxel) results in an increase in PFS of the subject compared to a reference.
  • an anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • a PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody, such as atezolizumab, or an anti-PD-1 antagonist antibody such as pembrolizumab
  • a chemotherapy e.g., a taxane (e.g., paclitaxel or nab-paclitaxel) results in an increase in DOR.
  • an anti-TIGIT antagonist antibody e.g., an anti- TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • a PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody, such as atezolizumab, or an anti-PD-1 antagonist antibody such as pembrolizumab
  • a chemotherapy e.g., a taxane (e.g., paclitaxel or nab-paclitaxel)
  • a taxane e.g., paclitaxel or nab-paclitaxel
  • the present invention also includes methods and uses involving administration of an effective amount of an anti-TIGIT antagonist antibody (e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab), a PD-1 axis binding antagonist (e.g., an anti-PD-L1 antagonist antibody, such as atezolizumab, or an anti-PD-1 antagonist antibody such as pembrolizumab), and a chemotherapy combination to a subject in need thereof, wherein the chemotherapy combination includes an effective amount of a platinum-based chemotherapeutic agent and an effective amount of a non-platinum-based chemotherapeutic agent, wherein the non-platinum-based chemotherapeutic agent is a taxane (e.g., paclitaxel or nab-paclitaxel).
  • an anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the anti-TIGIT antagonist antibody e.g., anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody, e.g., atezolizumab
  • the anti-TIGIT antagonist antibody are administered every two weeks (e.g., on Days 1 and 15 of each 28-day dosing cycle), every three weeks (e.g., on Day 1 of each 21 -day dosing cycle), or every four weeks (e.g., on Day 1 of each 28-day dosing cycle).
  • the chemotherapy combination e.g., the platinum-based chemotherapeutic agent and the taxane (e.g., paclitaxel or nab- paclitaxel)
  • the chemotherapy combination are administered weekly, every two weeks, every four weeks, or three times every four weeks (e.g., on Days 1 , 8, and 15 of each 28-day dosing cycle).
  • the method involves administration of an effective amount of an anti- TIGIT antagonist antibody (e.g., an anti-TIG IT antagonist antibody as disclosed herein, e.g., tiragolumab), a PD-1 axis binding antagonist (e.g., an anti-PD-L1 antagonist antibody, e.g., atezolizumab), a platinum- based chemotherapeutic agent (e.g., carboplatin or cisplatin), and a taxane (e.g., paclitaxel or nab- paclitaxel) to a subject in need thereof, wherein the anti-TIGIT antagonist antibody (e.g., anti-TIG IT antagonist antibody as disclosed herein, e.g., tiragolumab) and the PD-1 axis binding antagonist (e.g., an anti-PD-L1 antagonist antibody, e.g., atezolizumab) are administered every three weeks (e.g., on Day 1 of each
  • the dosing continues for four-to-six induction dosing cycles (e.g., four induction dosing cycles, five induction dosing cycles, or six induction dosing cycles).
  • maintenance therapy can be administered in one or more subsequent (maintenance) dosing cycles.
  • the one or more maintenance dosing cycles does not include the platinum-based chemotherapeutic agent.
  • administering results in a CR or a PR.
  • the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody, such as atezolizumab
  • the platinum-based chemotherapeutic agent e.g., carboplatin or cisplatin
  • the taxane e.g., paclitaxel or nab-paclitaxel
  • administering results in an increase in PFS of the subject.
  • the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody, such as atezolizumab
  • the platinum- based chemotherapeutic agent e.g., carboplatin or cisplatin
  • the taxane e.g., paclitaxel or nab- paclitaxel
  • administering extends OS of the subject.
  • the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody, such as atezolizumab
  • the platinum-based chemotherapeutic agent e.g., carboplatin or cisplatin
  • the taxane e.g., paclitaxel or nab-paclitaxel
  • the subject receiving the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., anti- PD-L1 antagonist antibody, such as atezolizumab
  • the platinum-based chemotherapeutic agent e.g., carboplatin or cisplatin
  • the taxane e.g., paclitaxel or nab-paclitaxel
  • the cancer may be a lung cancer (e.g., an early stage lung cancer (e.g., a resectable lung cancer), a SCLC (e.g., an ES-SCLC), a NSCLC (e.g., a squamous NSCLC or a non-squamous NSCLC, a locally advanced unresectable NSCLC, a Stage NIB NSCLC, a recurrent or metastatic NSCLC (e.g., a locally advanced unresectable or metastatic non-squamous NSCLC (e.g., Stage IV non-squamous NSCLC)), or a Stage IV NSCLC (e.g., wherein the subject has not been previously treated for Stage IV NSCLC))); a cervical cancer (e.g., a Stage IVB, metastatic, recurrent, or persistent cervical cancer, e.g., a metastatic and/or recurrent PD-L1- positive cervical carcinoma);
  • an anti-TIG IT antagonist antibody e.g., an anti-TIG IT antagonist antibody as disclosed herein, e.g., tiragolumab
  • a PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody, such as atezolizumab, or an anti-PD-1 antagonist antibody such as pembrolizumab
  • the chemotherapy combination includes an effective amount of a platinum-based chemotherapeutic agent and an effective amount of a non-platinum-based chemotherapeutic agent, wherein the non-platinum-based chemotherapeutic agent is a topoisomerase II inhibitor (e.g., etoposide).
  • the anti-TIGIT antagonist antibody e.g., anti-TIG IT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody, e.g., atezolizumab
  • the anti-TIGIT antagonist antibody are administered every two weeks (e.g., on Days 1 and 15 of each 28-day dosing cycle), every three weeks (e.g., on Day 1 of each 21 -day dosing cycle), or every four weeks (e.g., on Day 1 of each 28-day dosing cycle).
  • the chemotherapy combination e.g., the platinum-based chemotherapeutic agent and the topoisomerase II inhibitor (e.g., etoposide)
  • the chemotherapy combination are administered weekly, every two weeks, every four weeks, or three times every four weeks (e.g., on Days 1 , 8, and 15 of each 28-day dosing cycle).
  • the topoisomerase II inhibitor e.g., etoposide
  • the platinum-based chemotherapeutic agent e.g., three times per week, e.g., on Days 1 , 2, and 3 of each dosing cycle.
  • the method involves administration of an effective amount of an anti- TIGIT antagonist antibody (e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab), a PD-1 axis binding antagonist (e.g., an anti-PD-L1 antagonist antibody, e.g., atezolizumab), a platinum- based chemotherapeutic agent (e.g., carboplatin or cisplatin), and a topoisomerase II inhibitor (e.g., etoposide) to a subject in need thereof, wherein the anti-TIGIT antagonist antibody (e.g., anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab) and the PD-1 axis binding antagonist (e.g., an anti-PD-L1 antagonist antibody, e.g., atezolizumab) are administered every three weeks (e.g., on Day 1 of each 21 -day dosing
  • the dosing continues for four-to-six induction dosing cycles (e.g., four induction dosing cycles, five induction dosing cycles, or six induction dosing cycles).
  • maintenance therapy can be administered in one or more subsequent (maintenance) dosing cycles.
  • the one or more maintenance dosing cycles does not include the platinum-based chemotherapeutic agent or the topoisomerase II inhibitor (e.g., etoposide).
  • the effective amount of the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., anti- PD-L1 antagonist antibody, such as atezolizumab
  • the platinum-based chemotherapeutic agent e.g., carboplatin or cisplatin
  • the topoisomerase II inhibitor e.g., etoposide results in (a) a CR or a PR.
  • the effective amount of the anti-TIGIT antagonist antibody e.g., an anti-TIG IT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., anti- PD-L1 antagonist antibody, such as atezolizumab
  • the platinum-based chemotherapeutic agent e.g., carboplatin or cisplatin
  • the topoisomerase II inhibitor e.g., etoposide
  • the effective amount of the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody, such as atezolizumab
  • the platinum-based chemotherapeutic agent e.g., carboplatin or cisplatin
  • the topoisomerase II inhibitor e.g., etoposide
  • the subject receiving the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., anti- PD-L1 antagonist antibody, such as atezolizumab
  • the platinum-based chemotherapeutic agent e.g., carboplatin or cisplatin
  • the topoisomerase II inhibitor e.g., etoposide
  • the cancer may be a lung cancer (e.g., an early stage lung cancer (e.g., a resectable lung cancer), a SCLC (e.g., an ES-SCLC), a NSCLC (e.g., a squamous NSCLC or a non-squamous NSCLC, a locally advanced unresectable NSCLC, a Stage NIB NSCLC, a recurrent or metastatic NSCLC (e.g., a locally advanced unresectable or metastatic non-squamous NSCLC (e.g., Stage IV non-squamous NSCLC)), or a Stage IV NSCLC (e.g., wherein the subject has not been previously treated for Stage IV NSCLC))); a cervical cancer (e.g., a Stage IVB, metastatic, recurrent, or persistent cervical cancer, e.g., a metastatic and/or recurrent PD-L1- positive cervical carcinoma);
  • an anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • a PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody, such as atezolizumab, or an anti-PD-1 antagonist antibody such as pembrolizumab
  • a VEGF antagonist e.g., an anti-VEGF antibody (e.g., bevacizumab)) to a subject in need thereof.
  • the anti-TIGIT antagonist antibody e.g., anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody, e.g., atezolizumab
  • the VEGF antagonist e.g., an anti-VEGF antibody (e.g., bevacizumab)
  • the anti-TIGIT antagonist antibody e.g., anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody, e.g., atezolizumab
  • the VEGF antagonist e.g., an anti-VEGF antibody (e.g., bevacizumab)
  • are administered every three weeks e.g., on Day 1 of each 21 -day dosing cycle).
  • the method involves administration of an effective amount of an anti- TIGIT antagonist antibody (e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab), a PD-1 axis binding antagonist (e.g., an anti-PD-L1 antagonist antibody, e.g., atezolizumab), and the VEGF antagonist (e.g., an anti-VEGF antibody (e.g., bevacizumab)) to a subject in need thereof, wherein the anti-TIGIT antagonist antibody (e.g., anti-TIG IT antagonist antibody as disclosed herein, e.g., tiragolumab), the PD-1 axis binding antagonist (e.g., an anti-PD-L1 antagonist antibody, e.g., atezolizumab), and the VEGF antagonist (e.g., an anti-VEGF antibody (e.g., bevacizumab)) are administered every three weeks (e.g.,
  • the effective amount of the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody, such as atezolizumab
  • the VEGF antagonist e.g., an anti-VEGF antibody (e.g., bevacizumab)
  • the effective amount of the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody, such as atezolizumab
  • the VEGF antagonist e.g., an anti-VEGF antibody (e.g., bevacizumab) results in an increase in PFS of the subject.
  • the subject receiving the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., anti- PD-L1 antagonist antibody, such as atezolizumab
  • the VEGF antagonist e.g., an anti-VEGF antibody (e.g., bevacizumab)
  • a solid tumor or a locally advanced or metastatic cancer e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., anti- PD-L1 antagonist antibody, such as atezolizumab
  • the VEGF antagonist e.g., an anti-VEGF antibody (e.g., bevacizumab)
  • a solid tumor or a locally advanced or metastatic cancer e.g., bevacizumab
  • the cancer may be a lung cancer (e.g., an early stage lung cancer (e.g., a resectable lung cancer), a SCLC (e.g., an ES-SCLC), a NSCLC (e.g., a squamous NSCLC or a non-squamous NSCLC, a locally advanced unresectable NSCLC, a Stage NIB NSCLC, a recurrent or metastatic NSCLC (e.g., a locally advanced unresectable or metastatic non-squamous NSCLC (e.g., Stage IV non-squamous NSCLC)), or a Stage IV NSCLC (e.g., wherein the subject has not been previously treated for Stage IV NSCLC))); a cervical cancer (e.g., a Stage IVB, metastatic, recurrent, or persistent cervical cancer, e.g., a metastatic and/or recurrent PD-L1 -positive cervical carcinoma);
  • the present invention includes a method of treating cancer in a cancer patient comprising administering to the patient a combination of atezolizumab, bevacizumab, and tiragolumab in an amount effective to treat the cancer.
  • an anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • an anti-PD-1 antagonist antibody e.g., an anti-PD-1 antagonist antibody
  • a VEGF antagonist e.g., an anti-VEGF antibody (e.g., bevacizumab)
  • the anti-PD-1 antagonist antibody is pembrolizumab.
  • the anti-TIGIT antagonist antibody e.g., anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • an anti-PD-1 antagonist antibody e.g., an anti-PD-1 antagonist antibody
  • a VEGF antagonist e.g., an anti-VEGF antibody (e.g., bevacizumab)
  • the anti-PD-1 antagonist antibody is pembrolizumab.
  • the method involves administration of an effective amount of an anti- TIGIT antagonist antibody (e.g., an anti-TIG IT antagonist antibody as disclosed herein, e.g., tiragolumab), an anti-PD-1 antagonist antibody, and a VEGF antagonist (e.g., an anti-VEGF antibody (e.g., bevacizumab)) to a subject in need thereof, wherein the anti-TIG IT antagonist antibody (e.g., anti-TIG IT antagonist antibody as disclosed herein, e.g., tiragolumab), the anti-PD-1 antagonist antibody, and the VEGF antagonist (e.g., an anti-VEGF antibody (e.g., bevacizumab)) are administered every three weeks (e.g., on Day 1 of each 21 -day dosing cycle), wherein the anti-PD-1 antagonist antibody is pembrolizumab.
  • an anti- TIGIT antagonist antibody e.g., an anti-TIG IT antagonist antibody as disclosed herein, e.g
  • the effective amount of the anti-TIGIT antagonist antibody e.g., an anti-TIG IT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the anti-PD-1 antagonist antibody e.g., tiragolumab
  • the VEGF antagonist e.g., an anti-VEGF antibody (e.g., bevacizumab)
  • the effective amount of the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the anti-PD-1 antagonist antibody e.g., tiragolumab
  • the VEGF antagonist e.g., an anti-VEGF antibody (e.g., bevacizumab)
  • the subject receiving the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the anti-PD-1 antagonist antibody e.g., tiragolumab
  • the VEGF antagonist e.g., an anti-VEGF antibody (e.g., bevacizumab)
  • the anti-PD-1 antagonist antibody is pembrolizumab.
  • the cancer may be a lung cancer (e.g., an early stage lung cancer (e.g., a resectable lung cancer), a SCLC (e.g., an ES-SCLC), a NSCLC (e.g., a squamous NSCLC or a non- squamous NSCLC, a locally advanced unresectable NSCLC, a Stage NIB NSCLC, a recurrent or metastatic NSCLC (e.g., a locally advanced unresectable or metastatic non-squamous NSCLC (e.g., Stage IV non-squamous NSCLC)), or a Stage IV NSCLC (e.g., wherein the subject has not been previously treated for Stage IV NSCLC))); a cervical cancer (e.g., a Stage IVB, metastatic, recurrent, or persistent cervical cancer, e.g., a metastatic and/or recurrent PD-L1 -positive cervical carcinoma
  • tiragolumab is administered every three weeks (e.g., on Day 1 and Day 22 of each 42-day dosing cycle) and pembrolizumab is administered every six weeks (e.g., on Day 1 of each 42-day dosing cycle).
  • the method involves administration of an effective amount of tiragolumab and pembrolizumab to a subject in need thereof, wherein tiragolumab is administered every three weeks (e.g., on Day 1 and Day 22 of each 42-day dosing cycle) and pembrolizumab is administered every six weeks (e.g., on Day 1 of each 42-day dosing cycle).
  • the effective amount of tiragolumab and pembrolizumab results in an increase in OS of the subject, wherein the anti-PD-1 antagonist antibody is pembrolizumab.
  • the effective amount of tiragolumab and pembrolizumab results in an increase in PFS of the subject, wherein the anti-PD-1 antagonist antibody is pembrolizumab.
  • the subject receiving tiragolumab and pembrolizumab is being treated for a solid tumor or a locally advanced or metastatic cancer, wherein the anti-PD-1 antagonist antibody is pembrolizumab.
  • the cancer may be a lung cancer (e.g., an early stage lung cancer (e.g., a resectable lung cancer), a SCLC (e.g., an ES-SCLC), a NSCLC (e.g., a squamous NSCLC or a non-squamous NSCLC, a locally advanced unresectable NSCLC, a Stage NIB NSCLC, a recurrent or metastatic NSCLC (e.g., a locally advanced unresectable or metastatic non-squamous NSCLC (e.g., Stage IV non-squamous NSCLC)), or a Stage IV NSCLC (e.g., wherein the subject has not been previously treated for Stage IV NSCLC)));
  • a lung cancer
  • Also provided herein are methods of treating a subject having a cancer the methods comprising administering to the subject a dosing regimen comprising one or more dosing cycles of an anti-TIG IT antagonist antibody at a dose of about 500 mg to about 700 mg every three weeks, a PD-1 axis binding antagonist at a dose of about 900 mg to about 1500 mg every three weeks, a platinum-based chemotherapeutic agent every three weeks, and a non-platinum-based chemotherapeutic agent every three weeks.
  • the method comprises an induction phase and a maintenance phase.
  • the induction phase and maintenance phase each comprise one or more dosing cycles.
  • the maintenance phase does not comprise administration of the platinum- based chemotherapeutic agent.
  • the maintenance phase does not comprise administration of the non-platinum-based chemotherapeutic agent.
  • the maintenance phase comprises one or more dosing cycles of an anti-TIGIT antagonist antibody at a dose of about 700 mg to about 1000 mg every four weeks and a PD-1 axis binding antagonist at a dose of about 1400 mg to 2000 mg every four weeks.
  • Also provided herein are methods of treating a subject having a cancer the methods comprising administering to the subject a dosing regimen comprising one or more dosing cycles of an anti-TIGIT antagonist antibody at a dose of about 500 mg to about 700 mg every three weeks and an anti-PD-1 antagonist antibody at a dose of about 100 mg to about 300 mg every three weeks, wherein the anti-PD-1 antagonist antibody is pembrolizumab.
  • an anti-TIGIT antagonist antibody and a PD-1 axis binding antagonist for use in a method of treating a subject or population of subjects having a cancer, wherein the method is according to a method provided herein.
  • an anti-TIGIT antagonist antibody in the manufacture of a medicament for treating a subject or population of subjects having a cancer in combination with a PD-1 axis binding antagonist, wherein the treatment is according to a method provided herein.
  • the PD-1 axis binding antagonist are provided in separate formulations.
  • the anti-TIGIT antagonist antibody and the PD-1 axis binding antagonist are provided in a single formulation.
  • tiragolumab and atezolizumab are combined in an IV bag prior to administration.
  • the cancer may be solid tumor or a locally advanced or metastatic cancer.
  • the cancer is a lung cancer (e.g., an early stage lung cancer (e.g., a resectable lung cancer), a SCLC (e.g., an ES-SCLC), a NSCLC (e.g., a squamous NSCLC or a non-squamous NSCLC, a locally advanced unresectable NSCLC, a Stage NIB NSCLC, a recurrent or metastatic NSCLC (e.g., a locally advanced unresectable or metastatic non- squamous NSCLC (e.g., Stage IV non-squamous NSCLC)), or a Stage IV NSCLC (e.g., wherein the subject has not been previously treated for Stage IV NSCLC))); a cervical cancer (e.g., a Stage IVB, metastatic, recurrent,
  • a cervical cancer e.g., a Stage IVB,
  • the subject has no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumor aberrations.
  • EGFR epidermal growth factor receptor
  • ALK anaplastic lymphoma kinase
  • the subject does not have a sensitizing EGFR gene mutation or ALK gene rearrangement.
  • the subject has an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1 .
  • Methods for detecting the mutational status EGFR and ALK are well known in the art, and include, but are not limited to, sequencing DNA from clinical samples (e.g., tumor biopsies or blood samples (e.g., circulating tumor DNA in blood)) using a next-generation sequencing method, such as the targeted gene pulldown and sequencing method described in Frampton et al. ( Nature Biotechnology. 31 (11): 1023-1033, 2013), which is incorporated by reference herein in its entirety.
  • Such a next- generation sequencing method can be used with any of the methods disclosed herein to detect various mutations (e.g., insertions, deletions, base substitutions, focal gene amplifications, and/or homozygous gene deletions), while enabling the use of small samples (e.g., from small-core needle biopsies, fine- needle aspirations, and/or cell blocks) or fixed samples (e.g., formalin-fixed and paraffin-embedded (FFPE) samples).
  • Other methods for the detection of the mutational status of EGFR and ALK include fluorescence in situ hybridization (FISH) and immunohistochemical (IHC) methods. Exemplary methods for the detection of the mutational status of ALK are disclosed in U.S. Patent No: 9,651 ,555, which is herein incorporated by reference in its entirety.
  • the VENTANA ® anti -ALK (D5F3) IHC assay is used to determine the mutational status of the ALK gene.
  • the mutation is a sensitizing EGFR mutation.
  • Sensitizing EGFR mutations are well known in the art and include those described in U.S. Publication No: US 2018/0235968 and in Juan et al. (Therapeutic Advances in Medical Oncology. 9(3): 201-216, 2017), which are incorporated by reference herein in their entireties.
  • the sensitizing EGFR mutation is a mutation in any one of exons 18-21 (e.g., a mutation in exon 18, exon 19, exon 20, and/or exon 21 ).
  • the sensitizing EGFR mutation is a deletion of exon 19 (dell 9).
  • sensitizing EGFR mutation is a L858R point mutation in exon 21 .
  • the sensitizing EGFR mutation is a G719X point mutation in exon 18, wherein “X” is most commonly C, A, or S.
  • the sensitizing EGFR mutation is a G719S point mutation in exon 18.
  • the sensitizing EGFR mutation is a G719A point mutation in exon 18.
  • the sensitizing EGFR mutation is a S720F point mutation in exon 18.
  • the sensitizing EGFR mutation is a L861 Q point mutation in exon 21 .
  • the sensitizing EGFR mutation is a L861 R point mutation in exon 21 . In other instances, the sensitizing EGFR mutation is a T790M point mutation. In some instances, the sensitizing EGFR mutation is an E709X point mutation, where “X” is most commonly K, A, or H. In some instances, the sensitizing EGFR mutation is a S768I point mutation.
  • the mutation is an ALK gene rearrangement.
  • ALK gene rearrangements are well known in the art and include those described in U.S. Patent No: 9,651 ,555 and in Du et al. ( Thoracic Cancer. 9: 423-430, 2018), which are incorporated herein by reference in their entireties.
  • the ALK gene rearrangement results in the creation of an oncogenic ALK tyrosine kinase that activates downstream signaling pathways resulting in increased cell proliferation and survival.
  • the ALK " gene rearrangement is an ALK " rearrangement with a gene selected from the group consisting of EML4, KIF5B, KLC1, TFG, TPR, HIP1, STRN, DCTN1, SQSTM1, NPM1, BCL11A, BIRC6, RANBP2, ATIC, CLTC, TMP4, and MSN resulting in the formation of a fusion oncogene.
  • the ALK " gene rearrangement is an EML4 rearrangement with ALK resulting in the formation of the fusion oncogene EML4-ALK.
  • the subject does not have a pulmonary lymphoepithelioma-like carcinoma subtype of NSCLC.
  • Methods for detecting the subtype of NSCLC are well known in the art, and include, but are not limited to, methods of determination by histopathological criteria, or by molecular features (e.g., a subtype characterized by expression of one or a combination of biomarkers (e.g., particular genes or proteins encoded by said genes)).
  • the sample is selected from the group consisting of a tissue sample, a whole blood sample, a serum sample, and a plasma sample.
  • the tissue sample is a tumor sample.
  • the subject does not have an active Epstein-Barr virus (EBV) infection or a known or suspected chronic active EBV infection.
  • Indicators of active or chronic active EBV infections for use in the methods described herein can include, but are not limited to, EBV IgM, EBV IgG, Epstein-Barr nuclear antigen (EBNA), and Epstein-Barr viral particles detected in a sample from the subject (e.g., a blood or serum sample).
  • EBV IgM EBV IgG
  • Epstein-Barr nuclear antigen (EBNA) Epstein-Barr viral particles
  • EBNA Epstein-Barr nuclear antigen
  • Epstein-Barr viral particles in a sample from a subject are well known in the art, and include, but are not limited to, methods involving serological diagnosis (e.g., the detection of EBV DNA (e.g., by PCR analysis of a blood sample for the detection of EBV viral particles) or EBV antigens or anti-EBV antibodies (e.g., detection of EBNA, EBV IgM, or EBV IgG using heterophilic antibodies).
  • the sample is selected from the group consisting of a whole blood sample, a serum sample, and a plasma sample.
  • the subject is negative for EBV IgM and/or negative by EBV PCR.
  • the subject is negative for EBV IgM and/or negative by EBV PCR and is positive for EBV IgG and/or positive for Epstein-Barr nuclear antigen (EBNA).
  • EBNA Epstein-Barr nuclear antigen
  • the subject is negative for EBV IgG and/or negative for EBNA.
  • the subject has a PD-L1 selected tumor (e.g., a tumor PD-L1 expression with a minimum PD-L1 -positive tumor cell fraction or TPS > 30% (e.g., > 50%) as determined by an IHC with the SP263 or 22C3 antibody or a proportion of tumor area occupied by PD-L1 expressing tumor-infiltrating immune cells (ICs) is greater than or equal to 1% in the tumor sample as determined by an IHC with the SP142 antibody).
  • a PD-L1 selected tumor e.g., a tumor PD-L1 expression with a minimum PD-L1 -positive tumor cell fraction or TPS > 30% (e.g., > 50%) as determined by an IHC with the SP263 or 22C3 antibody or a proportion of tumor area occupied by PD-L1 expressing tumor-infiltrating immune cells (ICs) is greater than or equal to 1% in the tumor sample as determined by an IHC with the SP142 antibody).
  • ICs
  • the PD-L1 selected tumor is a tumor that has been determined to have a PD-L1 -positive tumor cell fraction or PD-L1 TPS of greater than, or equal to, 30% (e.g., greater than, or equal to, 50%) by an immunohistochemical (IHC) assay.
  • the PD-L1 selected tumor is a tumor that has been determined to have a proportion of tumor area occupied by PD-L1 -expressing immune cells (ICs) greater than or equal to 1% by an immunohistochemical (IHC) assay.
  • the IHC assay uses the anti-PD-L1 antibody SP263, 22C3, SP142, or 28-8.
  • the IHC assay uses anti- PD-L1 antibody SP263. In some instances, the IHC assay uses anti-PD-L1 antibody SP142. In some instances, the IHC assay uses anti-PD-L1 antibody 22C3. In some instances, the tumor sample has been determined to have a TPS of greater than, or equal to, 50%.
  • the PD-L1 -positive tumor cell fraction is greater than, or equal to, 50% (e.g., as determined by positive staining with the anti- PD-L1 antibody SP263 (e.g., using the Ventana assay), as determined by positive staining with the anti- PD-L1 antibody 22C3 (e.g., using the pharmDx assay), or as determined by positive staining with the anti- PD-L1 antibody 28-8). In some embodiments, the PD-L1 -positive tumor cell fraction is greater than, or equal to, 30%, as determined by positive staining with the anti-PD-L1 antibody SP142.
  • the ICs has been determined to be greater than, or equal to, 1% (e.g., as determined using the Ventana (SP142) PD-L1 IHC assay). In some instances, the ICs has been determined to be greater than, or equal to, 5% (e.g., as determined using the Ventana (SP142) PD-L1 IHC assay). In some instances, the ICs has been determined to be greater than, or equal to, 10% (e.g., as determined using the Ventana (SP142) PD-L1 IHC assay).
  • the ICs has been determined to be greater than, or equal to, 1% and less than 50% (e.g., as determined using the Ventana (SP142) PD-L1 IHC assay). In some instances, the ICs has been determined to be greater than, or equal to, 1% and less than 30% (e.g., as determined using the Ventana (SP142) PD-L1 IHC assay).
  • a tumor sample obtained from the individual has a detectable protein expression level of PD-L1 .
  • the detectable protein expression level of PD-L1 has been determined by an IHC assay.
  • the IHC assay uses anti-PD-L1 antibody SP142.
  • the tumor sample has been determined to have a detectable expression level of PD-L1 in greater than, or equal to, 1% of the tumor cells in the tumor sample.
  • the tumor sample has been determined to have a detectable expression level of PD-L1 in greater than, or equal to, 1% and less than 5% of the tumor cells in the tumor sample.
  • the tumor sample has been determined to have a detectable expression level of PD-L1 in greater than, or equal to, 5% and less than 50% of the tumor cells in the tumor sample. In some instances, the tumor sample has been determined to have a detectable expression level of PD-L1 in greater than, or equal to, 50% of the tumor cells in the tumor sample. In some instances, the tumor sample has been determined to have a detectable expression level of PD-L1 in tumor-infiltrating immune cells that comprise greater than, or equal to, 1% of the tumor sample. In some instances, the tumor sample has been determined to have a detectable expression level of PD-L1 in tumor-infiltrating immune cells that comprise greater than, or equal to, 1% and less than 5% of the tumor sample.
  • the tumor sample has been determined to have a detectable expression level of PD-L1 in tumor-infiltrating immune cells that comprise greater than, or equal to, 5% and less than 10% of the tumor sample. In some instances, the tumor sample has been determined to have a detectable expression level of PD-L1 in tumor-infiltrating immune cells that comprise greater than, or equal to, 10% of the tumor sample.
  • a tumor sample obtained from the individual has a detectable nucleic acid expression level of PD-L1 .
  • the detectable nucleic acid expression level of PD-L1 has been determined by RNA-seq, RT-qPCR, qPCR, multiplex qPCR or RT-qPCR, microarray analysis, SAGE, MassARRAY technique, ISH, or a combination thereof.
  • the sample is selected from the group consisting of a tissue sample, a whole blood sample, a serum sample, and a plasma sample.
  • the tissue sample is a tumor sample.
  • the tumor sample comprises tumor-infiltrating immune cells, tumor cells, stromal cells, and any combinations thereof.
  • a subject’s response to the therapy can be characterized by one or more measures.
  • the treatment results in a CR or a PR.
  • the treatment results in an increase in PFS or DOR.
  • the treatment results in an increase in PFS of the subject, e.g., as compared to treatment with the PD-1 axis binding antagonist without the anti-TIG IT antagonist antibody or as compared to treatment with the anti-TIGIT antagonist antibody without the PD-1 axis binding antagonist.
  • the treatment may result in an increase in PFS of the subject, e.g., as compared to treatment with the PD-1 axis binding antagonist without the anti-TIGIT antagonist antibody or as compared to treatment with the anti-TIGIT antagonist antibody without the PD-1 axis binding antagonist.
  • an anti- TIGIT antagonist antibody e.g., tiragolumab
  • a PD-1 axis binding antagonist e.g., atezolizumab
  • an anti-TIGIT antagonist antibody e.g., tiragolumab
  • a PD-1 axis binding antagonist e.g., atezolizumab
  • one or more chemotherapeutic agents e.g., a platinum-based chemotherapeutic agent (e.g., carboplatin or cisplatin) and/or one or more non-platinum-based chemotherapeutic agents (e.g., an alkylating agent (e.g., cyclophosphamide), a taxane (e.g., paclitaxel, e.g., nab-paclitaxel), and/or a topoisomerase II inhibitor (e.g., doxorubicin))
  • the treatment may result in an increase in PFS of the subject, e.g., as compared to (i) treatment with the PD-1 axis binding antagonist and the one or more chemotherapeutic agents without the
  • the treatment extends OS of the subject, e.g., as compared to treatment with the PD-1 axis binding antagonist without the anti-TIGIT antagonist antibody or as compared to treatment with the anti-TIGIT antagonist antibody without the PD-1 axis binding antagonist.
  • the treatment may result in an increase in OS of the subject, e.g., as compared to treatment with the PD-1 axis binding antagonist without the anti-TIGIT antagonist antibody or as compared to treatment with the anti-TIGIT antagonist antibody without the PD-1 axis binding antagonist.
  • an anti-TIGIT antagonist antibody e.g., tiragolumab
  • a PD-1 axis binding antagonist e.g., atezolizumab
  • an anti-TIGIT antagonist antibody e.g., tiragolumab
  • a PD-1 axis binding antagonist e.g., atezolizumab
  • one or more chemotherapeutic agents e.g., a platinum-based chemotherapeutic agent (e.g., carboplatin or cisplatin) and/or one or more non-platinum-based chemotherapeutic agents (e.g., an antimetabolite (e.g., pemetrexed, gemcitabine, or capecitabine), a taxane (e.g., paclitaxel, e.g., nab-paclitaxel), and/or a topoisomerase II inhibitor (e.g., etoposide))
  • the treatment may result in an increase in OS of the subject, e.g., as compared to (i) treatment with the PD-1 axis binding antagonist and the one or more chemotherapeutic agents
  • Progression-free survival of the subject can be measured according to RECIST v1 .1 criteria, as described in Eisenhauer et al. , Eur. J. Cancer. 2009, 45:228-47.
  • PFS is measured as the period of time from the start of treatment to the first occurrence of disease progression as determined by RECIST v1 .1 criteria.
  • PFS is measured as the time from the start of treatment to the time of death.
  • a treatment described herein extends the PFS of the subject by at least about 2.4 months (e.g., by 2.4-120 months, by 2.5-100 months, by 3.0-80 months, by 4.0-60 months, by 5.0-48 months, by 6.0-36 months, by 8.0-24 months, or by 10-12 months, e.g., by at least about 2.4 months, 2.5 months, 2.6 months, 2.7 months, 2.8 months, 2.9 months, 3.0 months, 3.1 months, 3.2 months, 3.3 months, 3.4 months, 3.5 months, 3.6 months, 3.7 months, 3.8 months, 3.9 months, 4.0 months, 4.1 months, 4.2 months, 4.3 months, 4.4 months, 4.5 months, 4.6 months, 4.7 months, 4.8 months, 4.9 months, 5.0 months, 5.1 months, 5.2 months, 5.3 months, 5.4 months, 5.5 months, 5.6 months, 5.7 months, 5.8 months, 5.9 months, 6.0 months, 6.5 months, 7.0 months, 7.5 months, 8.0 months, or 10-12
  • the treatment extends the PFS of the subject by at least about 4 months (e.g., by 4-120 months, by 5-100 months, by 6-80 months, by 7-60 months, by 8-48 months, by 9-36 months, or by 10-24 months, e.g., by at least about 4.0 months, 4.1 months, 4.2 months, 4.3 months, 4.4 months, 4.5 months, 4.6 months, 4.7 months, 4.8 months, 4.9 months, 5.0 months, 5.1 months, 5.2 months, 5.3 months, 5.4 months, 5.5 months, 5.6 months, 5.7 months, 5.8 months, 5.9 months, 6.0 months, 6.5 months, 7.0 months, 7.5 months, 8.0 months, 8.5 months, 9.0 months, 9.5 months, 10 months, 10.5 months, 11 months, 11 .5 months, 12 months, 13 months, 14 months, 15 months, 16 months, 17 months, 18 months, 19 months, 20 months, 21 months, 22 months, 23 months, 24 months, 25 months, 26 months, 27 months, 28 months, 29
  • the treatment extends the PFS of the subject by at least about 2 months (e.g., by 2-120 months, by 3-100 months, by 4-80 months, by 6-60 months, by 8-48 months, by 9-36 months, or by 10-24 months, e.g., by at least about 2.0 months, 2.1 months, 2.2 months, 2.3 months, 2.4 months, 2.5 months, 2.6 months, 2.7 months, 2.8 months, 2.9 months, 3.0 months, 3.1 months, 3.2 months, 3.3 months, 3.4 months, 3.5 months, 3.6 months, 3.7 months, 3.8 months, 3.9 months, 4.0 months, 4.1 months, 4.2 months, 4.3 months, 4.4 months, 4.5 months, 4.6 months, 4.7 months, 4.8 months, 4.9 months, 5.0 months, 5.1 months, 5.2 months, 5.3 months, 5.4 months, 5.5 months, 5.6 months, 5.7 months, 5.8 months, 5.9 months, 6.0 months, 6.5 months, 7.0 months, 7.5 months, 8.0 months, 8.5
  • a treatment described herein extends the DOR of the subject by at least about 2.4 months (e.g., by 2.4-120 months, by 2.5-100 months, by 3.0-80 months, by 4.0-60 months, by 5.0-48 months, by 6.0-36 months, by 8.0-24 months, or by 10-12 months, e.g., by at least about 2.4 months, 2.5 months, 2.6 months, 2.7 months, 2.8 months, 2.9 months, 3.0 months, 3.1 months, 3.2 months, 3.3 months, 3.4 months, 3.5 months, 3.6 months, 3.7 months, 3.8 months, 3.9 months, 4.0 months, 4.1 months, 4.2 months, 4.3 months, 4.4 months, 4.5 months, 4.6 months, 4.7 months, 4.8 months, 4.9 months, 5.0 months, 5.1 months, 5.2 months, 5.3 months, 5.4 months, 5.5 months, 5.6 months, 5.7 months, 5.8 months, 5.9 months, 6.0 months, 6.5 months, 7.0 months, 7.5 months, 8.0 months, or 10-12
  • the treatment extends the DOR of the subject by at least about 4 months (e.g., by 4-120 months, by 5-100 months, by 6-80 months, by 7-60 months, by 8-48 months, by 9-36 months, or by 10-24 months, e.g., by at least about 4.0 months, 4.1 months, 4.2 months, 4.3 months, 4.4 months, 4.5 months, 4.6 months, 4.7 months, 4.8 months, 4.9 months, 5.0 months, 5.1 months, 5.2 months, 5.3 months, 5.4 months, 5.5 months, 5.6 months, 5.7 months, 5.8 months, 5.9 months, 6.0 months, 6.5 months, 7.0 months, 7.5 months, 8.0 months, 8.5 months, 9.0 months, 9.5 months, 10 months, 10.5 months, 11 months, 11 .5 months, 12 months, 13 months, 14 months, 15 months, 16 months, 17 months, 18 months, 19 months, 20 months, 21 months, 22 months, 23 months, 24 months, 25 months, 26 months, 27 months,
  • the treatment extends the DOR of the subject by at least about 2 months (e.g., by 2-120 months, by 3-100 months, by 4-80 months, by 6-60 months, by 8-48 months, by 9- 36 months, or by 10-24 months, e.g., by at least about 2.0 months, 2.1 months, 2.2 months, 2.3 months, 2.4 months, 2.5 months, 2.6 months, 2.7 months, 2.8 months, 2.9 months, 3.0 months, 3.1 months, 3.2 months, 3.3 months, 3.4 months, 3.5 months, 3.6 months, 3.7 months, 3.8 months, 3.9 months, 4.0 months, 4.1 months, 4.2 months, 4.3 months, 4.4 months, 4.5 months, 4.6 months, 4.7 months, 4.8 months, 4.9 months, 5.0 months, 5.1 months, 5.2 months, 5.3 months, 5.4 months, 5.5 months, 5.6 months, 5.7 months, 5.8
  • OS is measured as the period of time from the start of treatment to death.
  • the treatment extends the OS of the subject by at least about 2 months (e.g., by 2-120 months, by 3-110 months, by 4-100 months, by 5-80 months, by 6-60 months, by 7-48 months, by 8-36 months, or by 10-24 months, e.g., by at least about 2 months, 2.1 months, 2.2 months, 2.3 months, 2.4 months, 2.5 months, 2.6 months, 2.7 months, 2.8 months, 2.9 months, 3.0 months, 3.1 months, 3.2 months, 3.3 months, 3.4 months, 3.5 months, 3.6 months, 3.7 months, 3.8 months, 3.9 months, 4.0 months, 4.1 months, 4.2 months, 4.3 months, 4.4 months, 4.5 months, 4.6 months, 4.7 months, 4.8 months, 4.9 months, 5.0 months, 5.1 months, 5.2 months, 5.3 months, 5.4 months, 5.5 months, 5.6 months, 5.7 months, 5.8 months, 5.9
  • the treatment extends the OS of the subject by at least about 3.3 months (e.g., by 3.3-120 months, by 4- 100 months, by 5-80 months, by 6-60 months, by 7-48 months, by 8-36 months, or by 10-24 months, e.g., by at least about 3.3 months, 3.4 months, 3.5 months, 3.6 months, 3.7 months, 3.8 months, 3.9 months, 4.0 months, 4.1 months, 4.2 months, 4.3 months, 4.4 months, 4.5 months, 4.6 months, 4.7 months, 4.8 months, 4.9 months, 5.0 months, 5.1 months, 5.2 months, 5.3 months, 5.4 months, 5.5 months, 5.6 months, 5.7 months, 5.8 months, 5.9 months, 6.0 months, 6.5 months, 7.0 months, 7.5 months, 8.0 months, 8.5 months, 9.0 months, 9.5 months, 10 months, 10.5 months, 11 months, 11 .5 months, 12 months, 13 months, 14 months, 15 months, 16 months, 17 months, 18 months, 19 months, 10 months
  • the treatment extends the OS of the subject by at least about 5.3 months (e.g., by 5.3-120, by 6-60 months, by 7-48 months, by 8-36 months, or by 10-24 months, e.g., by at least about 5.3 months, 5.5 months, 6.0 months, 6.5 months, 7.0 months, 7.5 months, 8.0 months, 8.5 months, 9.0 months, 9.5 months, 10 months, 10.5 months, 11 months, 11 .5 months, 12 months, 13 months, 14 months, 15 months, 16 months, 17 months, 18 months, 19 months, 20 months, 21 months, 22 months, 23 months, 24 months, 25 months, 26 months, 27 months, 28 months, 29 months, 30 months, 31 months, 32 months, 33 months, 34 months, 35 months, or 36 months).
  • 5.3 months e.g., by 5.3-120, by 6-60 months, by 7-48 months, by 8-36 months, or by 10-24 months, e.g., by at least about 5.3 months, 5.5 months, 6.0 months
  • Lung cancer remains the leading cause of cancer deaths worldwide. In the United States, it is the most common cancer in both men and women and accounts for 12%- 14% of all new cancer cases.
  • Non-small cell lung cancer is the predominant subtype of lung cancer, accounting for approximately 85% of all cases.
  • Non-small cell lung cancer is the predominant subtype of lung cancer, accounting for approximately 80%-85% of all cases (Osmani et al. Semin Cancer Biol. 52 (Pt 1 ):103-9 (2016)).
  • NSCLC can be divided into two major histologic types: adenocarcinoma and squamous cell carcinoma (Travis et al. 2011 ).
  • Adenocarcinoma histology accounts for approximately 40%-50% of all NSCLC, while squamous cell histology accounts for approximately 20%-30% of NSCLC (Osmani et al. Semin Cancer Biol. 52 (Pt 1 ):103-9 (2016)).
  • the remaining cases of NSCLC are represented by large cell carcinoma, neuroendocrine tumors, sarcomatoid carcinoma, and are of poorly differentiated histology.
  • NSCLC is treated surgically with curative intent.
  • 30%-70% of patients undergoing resection develop recurrence and die as a result of disease progression (Siegel et al. Cancer Statistics. CA Cancer J Clin. 70:7-30 (2020)). Therefore, there is a high unmet need for improved medical intervention for early-stage NSCLC.
  • the overall five-year survival rate is 2%-4%.
  • Poor prognostic factors for survival in patients with NSCLC include advanced stage of disease at the time of initial diagnosis, poor performance status, and a history of unintentional weight loss. More than half of the patients with NSCLC are diagnosed with distant disease, which directly contributes to poor survival prospects.
  • PD-L1/PD-1 blocking antibodies e.g., atezolizumab, nivolumab, and pembrolizumab
  • atezolizumab e.g., atezolizumab, nivolumab, and pembrolizumab
  • PD-L1/PD-1 blocking antibodies provided clinically meaningful benefit in either unselected or PD-L1- selected advanced NSCLC patients; however, a substantial proportion of patients still remained unresponsive or progressed on anti-PD-L1/PD-1 treatment, and the escape mechanisms to such treatment are poorly understood.
  • lung cancer e.g., NSCLC (e.g., non-squamous NSCLC (e.g., locally advanced unresectable or metastatic non-squamous NSCLC (e.g., Stage IV non-squamous NSCLC))
  • NSCLC non-squamous NSCLC
  • metastatic non-squamous NSCLC e.g., Stage IV non-squamous NSCLC
  • SCLC Small cell lung cancer
  • lung cancer e.g., SCLC, e.g., ES-
  • a dosing regimen comprising one or more dosing cycles of an effective amount of an anti-TIG IT antagonist antibody, a PD-1 axis binding antagonist, a platinum-based chemotherapeutic agent, and a topoisomerase II inhibitor, wherein the treatment results in a median PFS of the population of subjects of at least about 6 months (e.g., at least about 6 months (e.g., between 6 months and 24 months (e.g., between about 6 months to about 15 months (e.g., 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months, 13 months, 14 months, or 15 months), e.g., between about 6 months to about 13 months (e.g., 6 months, 6.5 months, 7 months, 7.5 months, 8 months, 8.5 months, 9 months, 9.5 months, 10 months, 10.5 months, 11 months, 11.5 months, 12 months, 1
  • treatment results in a median PFS of the population of subjects of about 8.2 months to about 9.2 months (e.g., about 8.2, 8.4, 8.6, 8.8, 9.0, or 9.2 months, e.g., 8.2-8.4, 8.4-8.6, 8.6-8.8, 8.8-9.0, or 9.0-9.2 months).
  • lung cancer e.g., small cell lung cancer (SCLC), e.g., extensive stage SCLC (ES-SCLC)
  • SCLC small cell lung cancer
  • ES-SCLC extensive stage SCLC
  • an anti-TIG IT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • a PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody, such as atezolizumab
  • a platinum-based chemotherapeutic agent e.g., carboplatin or cisplatin
  • a topoisomerase II inhibitor e.g., etoposide
  • the therapeutic methods and uses of the invention described herein include, in one aspect, administering to a subject or population of subjects having a lung cancer (e.g., SCLC, e.g., ES-SCLC) an effective amount of an anti-TIGIT antagonist antibody (e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab), a PD-1 axis binding antagonist (e.g., an anti-PD-L1 antagonist antibody (e.g., atezolizumab)), a platinum-based chemotherapeutic agent, and a topoisomerase II inhibitor, wherein the treatment extends progression-free survival (PFS) of the subject or population of subjects as compared to treatment with the PD-1 axis binding antagonist, the platinum-based chemotherapeutic agent, and the topoisomerase II inhibitor without the anti-TIGIT antagonist antibody, thereby treating the subject or population of subjects.
  • the treatment extends OS of the subject or population of subjects as compared
  • the PFS of the individual is measured according to RECIST v1 .1 criteria, as described in Eisenhauer et al., Eur. J. Cancer. 2009, 45:228-47. In some embodiments, PFS is measured as the period of time from the start of treatment to the first occurrence of disease progression as determined by RECIST v1 .1 criteria. In some embodiments, PFS is measured as the time from the start of treatment to the time of death.
  • the treatment extends the PFS of the subject or population of subjects by at least about 2.4 months (e.g., by 2.4-120 months, by 2.5-100 months, by 3.0-80 months, by 4.0-60 months, by 5.0-48 months, by 6.0-36 months, by 8.0-24 months, or by 10-12 months, e.g., by at least about 2.4 months, 2.5 months, 2.6 months, 2.7 months, 2.8 months, 2.9 months, 3.0 months, 3.1 months,
  • the treatment extends the PFS of the subject or population of subjects by at least about 4 months (e.g., by 4- 120 months, by 5-100 months, by 6-80 months, by 7-60 months, by 8-48 months, by 9-36 months, or by 10-24 months, e.g., by at least about 4.0 months, 4.1 months, 4.2 months, 4.3 months, 4.4 months, 4.5 months, 4.6 months, 4.7 months, 4.8 months, 4.9 months, 5.0 months, 5.5 months, 6.0 months, 6.5 months, 7.0 months, 7.5 months, 8.0 months, 8.5 months, 9.0 months, 9.5 months, 10 months, 10.5 months, 11 months, 11 .5 months, 12 months, 13 months, 14 months, 15 months, 16 months, 17 months, 18 months, 19 months, 20 months, 21 months, 22 months, 23 months, 24 months, 25 months, 26 months, 27 months, 28 months, 29 months, 30 months, 31 months, 32 months, 33 months, 34 months, 35 months, or 36 months) as compared to
  • the treatment extends the PFS of the subject or population of subjects by at least about 2 months (e.g., by 2-120 months, by 3-100 months, by 4-80 months, by 6-60 months, by 8-48 months, by 9-36 months, or by 10-24 months, e.g., by at least about 2.0 months, 2.1 months, 2.2 months,
  • the treatment extends the PFS of the subject or population of subjects by at least about 3 months to about 4 months as compared to treatment with the PD-1 axis binding antagonist, the platinum-based chemotherapeutic agent, and the topoisomerase II inhibitor without the anti-TIG IT antagonist antibody.
  • the methods and uses of treating a subject or population of subjects having a lung cancer include administering to the subject or population of subjects an effective amount of an anti-TIG IT antagonist antibody (e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab), a PD-1 axis binding antagonist (e.g., an anti-PD-L1 antagonist antibody, such as atezolizumab), a platinum-based chemotherapeutic agent (e.g., carboplatin or cisplatin), and a topoisomerase II inhibitor (e.g., etoposide), wherein the treatment extends OS of the subject or population of subjects as compared to treatment with the PD-1 axis binding antagonist, the platinum-based chemotherapeutic agent, and the topoisomerase II inhibitor without the anti-TIGIT antagonist antibody.
  • an anti-TIG IT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tira
  • OS is measured as the period of time from the start of treatment to death.
  • the treatment extends the OS of the subject or population of subjects by at least about 2 months (e.g., by 2-120 months, by 3-110 months, by 4-100 months, by 5-80 months, by 6-60 months, by 7-48 months, by 8-36 months, or by 10-24 months, e.g., by at least about 2 months, 2.1 months, 2.2 months, 2.3 months, 2.4 months, 2.5 months, 2.6 months, 2.7 months, 2.8 months, 2.9 months, 3.0 months, 3.1 months, 3.2 months, 3.3 months, 3.4 months, 3.5 months, 3.6 months, 3.7 months, 3.8 months, 3.9 months, 4.0 months, 4.1 months, 4.2 months, 4.3 months, 4.4 months, 4.5 months, 4.6 months, 4.7 months, 4.8 months, 4.9 months, 5.0 months, 5.1 months, 5.2 months, 5.3 months, 5.4 months, 5.5 months, 5.6 months, 5.7 months, 5.8
  • the treatment extends the OS of the subject or population of subjects by at least about 3.3 months (e.g., by 3.3-120 months, by 4-100 months, by 5-80 months, by 6-60 months, by 7-48 months, by 8-36 months, or by 10-24 months, e.g., by at least about 3.3 months, 3.4 months, 3.5 months, 3.6 months, 3.7 months, 3.8 months, 3.9 months, 4.0 months, 4.1 months, 4.2 months, 4.3 months, 4.4 months, 4.5 months, 4.6 months, 4.7 months, 4.8 months, 4.9 months, 5.0 months, 5.5 months, 6.0 months, 6.5 months, 7.0 months, 7.5 months, 8.0 months, 8.5 months, 9.0 months, 9.5 months, 10 months, 10.5 months, 11 months, 11 .5 months, 12 months, 13 months, 14 months, 15 months, 16 months, 17 months, 18 months, 19 months, 20 months, 21 months, 22 months, 23 months, 24 months, 25 months, 26 months, 27 months, 28 months,
  • the treatment extends the OS of the subject or population of subjects by at least about 5.3 months (e.g., by 5.3-120, by 6-60 months, by 7-48 months, by 8-36 months, or by 10-24 months, e.g., by at least about 5.3 months, 5.5 months, 6.0 months, 6.5 months, 7.0 months, 7.5 months, 8.0 months, 8.5 months, 9.0 months, 9.5 months, 10 months, 10.5 months, 11 months, 11.5 months, 12 months, 13 months, 14 months, 15 months, 16 months, 17 months, 18 months, 19 months, 20 months, 21 months, 22 months, 23 months, 24 months, 25 months, 26 months, 27 months, 28 months, 29 months, 30 months, 31 months, 32 months, 33 months, 34 months, 35 months, or 36 months) as compared to treatment with the PD-1 axis binding antagonist, the platinum-based chemotherapeutic agent, and the topoisomerase II inhibitor without the anti-TIG IT antagonist antibody.
  • 5.3 months e.g., by
  • the effective amount of the anti-TIGIT antagonist antibody is a dose (e.g. a fixed dose) of between about 30 mg to about 1200 mg (e.g., between about 30 mg to about 1100 mg, e.g., between about 60 mg to about 1000 mg, e.g., between about 100 mg to about 900 mg, e.g., between about 200 mg to about 800 mg, e.g., between about 300 mg to about 800 mg, e.g., between about 400 mg to about 800 mg, e.g., between about 400 mg to about 750 mg, e.g., between about 450 mg to about 750 mg, e.g., between about 500 mg to about 700 mg, e.g., between about 550 mg to about 650 mg, e.g., 600 mg ⁇ 10 mg, e.g., 600 ⁇ 6 mg,
  • a dose e.g. a fixed dose of between about 30 mg to about 1200 mg (e.g., between about 30 mg to about
  • the effective amount of the anti-TIGIT antagonist antibody is a dose (e.g., a fixed dose) of between about 30 mg to about 600 mg (e.g., between about 50 mg to about 600 mg, e.g., between about 60 mg to about 600 mg, e.g., between about 100 mg to about 600 mg, e.g., between about 200 mg to about 600 mg, e.g., between about 200 mg to about 550 mg, e.g., between about 250 mg to about 500 mg, e.g., between about 300 mg to about 450 mg, e.g., between about 350 mg to about 400 mg, e.g., about 375 mg) every three weeks.
  • a dose e.g., a fixed dose of between about 30 mg to about 600 mg (e.g., between about 50 mg to about 600 mg, e.g., between about 60 mg to about 600 mg, e.g., between about 100 mg to about 600 mg, e.g., between about 200 mg to about
  • the effective amount of the anti-TIGIT antagonist antibody is a dose (e.g., a fixed dose) of about 600 mg every three weeks.
  • the effective amount of the anti-TIGIT antagonist antibody is a dose (e.g. a fixed dose) of between 30 mg to 1200 mg (e.g., between 30 mg to 1100 mg, e.g., between 60 mg to 1000 mg, e.g., between 100 mg to 900 mg, e.g., between 200 mg to 800 mg, e.g., between 300 mg to 800 mg, e.g., between 400 mg to 800 mg, e.g., between 400 mg to 750 mg, e.g., between 450 mg to 750 mg, e.g., between 500 mg to 700 mg, e.g., between 550 mg to 650 mg, e.g., 600 mg ⁇ 10 mg, e.g., 600 ⁇ 6 mg, e.g., 600 ⁇ 5 mg, e.g., 600 ⁇ 3 mg
  • the effective amount of the anti-TIGIT antagonist antibody is a dose (e.g., a fixed dose) of between 30 mg to 600 mg (e.g., between 50 mg to 600 mg, e.g., between 60 mg to 600 mg, e.g., between 100 mg to 600 mg, e.g., between 200 mg to 600 mg, e.g., between 200 mg to 550 mg, e.g., between 250 mg to 500 mg, e.g., between 300 mg to 450 mg, e.g., between 350 mg to 400 mg, e.g., 375 mg) every three weeks.
  • a dose e.g., a fixed dose of between 30 mg to 600 mg (e.g., between 50 mg to 600 mg, e.g., between 60 mg to 600 mg, e.g., between 100 mg to 600 mg, e.g., between 200 mg to 600 mg, e.g., between 200 mg to 550 mg, e.g., between 250 mg to 500 mg
  • the effective amount of the anti-TIGIT antagonist antibody is a dose (e.g., a fixed dose) of 600 mg every three weeks.
  • effective amount of the anti-TIGIT antagonist antibody is a dose (e.g., a fixed dose) dose of 600 mg every three weeks.
  • the dose (e.g., fixed dose) of the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • a combination therapy e.g., a combination treatment with a PD-1 axis binding antagonist (e.g., an anti-PD- L1 antagonist antibody, e.g., atezolizumab)), topoisomerase II inhibitor (e.g., etoposide), and/or a platinum-based chemotherapeutic agent (e.g., carboplatin or cisplatin)
  • the effective amount of the PD-1 axis binding antagonist is a dose (e.g., a fixed dose) of between about 80 mg to about 2000 mg (e.g., between about 100 mg to about 1600 mg, e.g., between about 200 mg to about 1600 mg, e.g., between about 300 mg to about 1600 mg, e.g., between about 400 mg to about 1600 mg, e.g., between about 500 mg to about 1600 mg, e.g., between about 600 mg to about 1600 mg, e.g., between about 700 mg to about 1600 mg, e.g., between about 800 mg to about 1600 mg, e.g., between about 900 mg to about 1500 mg, e.g., between about 1000 mg to about 1400 mg, e.g., between about 1050 mg to about 1350 mg, e.g., between about 1100 mg to about 1300 mg,
  • a dose e.g., a fixed dose of between about 80 mg to about 2000 mg (e.g., between
  • the effective amount of the PD-1 axis binding antagonist (e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab)) is a dose (e.g., a fixed dose) of about 840 mg every two weeks. In some instances, the effective amount of the PD-1 axis binding antagonist (e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab)) is a dose (e.g., a fixed dose) of about 1200 mg every three weeks.
  • the effective amount of the PD-1 axis binding antagonist is a dose (e.g., a fixed dose) of between 80 mg to 2000 mg (e.g., between 100 mg to 1600 mg, e.g., between 200 mg to 1600 mg, e.g., between 300 mg to 1600 mg, e.g., between 400 mg to 1600 mg, e.g., between 500 mg to 1600 mg, e.g., between 600 mg to 1600 mg, e.g., between 700 mg to 1600 mg, e.g., between 800 mg to 1600 mg, e.g., between 900 mg to 1500 mg, e.g., between 1000 mg to 1400 mg, e.g., between 1050 mg to 1350 mg, e.g., between 1100 mg to 1300 mg, e.g., between 1150 mg to 1250 mg, e.g., between 1175 mg to
  • the effective amount of the PD-1 axis binding antagonist is a dose (e.g., a fixed dose) of 840 mg every two weeks.
  • the effective amount of the PD-1 axis binding antagonist is a dose (e.g., a fixed dose) of about 1400 mg to 2000 mg every four weeks. In some instances, the effective amount of the PD-1 axis binding antagonist (e.g., anti- PD-L1 antagonist antibody (e.g., atezolizumab)) is a dose (e.g., a fixed dose) of 1400 mg to 2000 mg every four weeks.
  • the effective amount of the PD-1 axis binding antagonist (e.g., anti- PD-L1 antagonist antibody (e.g., atezolizumab)) is a dose (e.g., a fixed dose) of about 1680 mg every four weeks. In some instances, the effective amount of the PD-1 axis binding antagonist (e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab)) is a dose (e.g., a fixed dose) of 1680 mg every four weeks.
  • the dose (e.g., fixed dose) of the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab)
  • a combination therapy e.g., a combination treatment with an anti-TIGIT antagonist antibody, such as an anti-TIGIT antagonist antibody disclosed herein, e.g., tiragolumab
  • a topoisomerase II inhibitor e.g., etoposide
  • a platinum-based chemotherapeutic agent e.g., carboplatin or cisplatin
  • the effective amount of the PD-1 axis binding antagonist is a dose of between about 0.01 mg/kg to about 50 mg/kg of the subject’s body weight (e.g., between about 0.01 mg/kg to about 45 mg/kg, e.g., between about 0.1 mg/kg to about 40 mg/kg, e.g., between about 1 mg/kg to about 35 mg/kg, e.g., between about 2.5 mg/kg to about 30 mg/kg, e.g., between about 5 mg/kg to about 25 mg/kg, e.g., between about 10 mg/kg to about 20 mg/kg, e.g., between about 12.5 mg/kg to about 15 mg/kg, e.g., about 15 ⁇ 2 mg/kg, about 15 ⁇ 1 mg/kg, about 15 ⁇ 0.5 mg/kg, about 15 ⁇ 0.2 mg/kg, or about 15 ⁇
  • the PD-1 axis binding antagonist is a dose of between about 0.01 mg/kg to about 50 mg/kg of the
  • the effective amount of the PD-1 axis binding antagonist is a dose of between about 0.01 mg/kg to about 15 mg/kg of the subject’s body weight (e.g., between about 0.1 mg/kg to about 15 mg/kg, e.g., between about 0.5 mg/kg to about 15 mg/kg, e.g., between about 1 mg/kg to about 15 mg/kg, e.g., between about 2.5 mg/kg to about 15 mg/kg, e.g., between about 5 mg/kg to about 15 mg/kg, e.g., between about 7.5 mg/kg to about 15 mg/kg, e.g., between about 10 mg/kg to about 15 mg/kg, e.g., between about 12.5 mg/kg to about 15 mg/kg, e.g., between about 14 mg/kg to about 15 mg/kg, e.g., about 15 ⁇
  • the effective amount of the PD-1 axis binding antagonist is a dose of between 0.01 mg/kg to 50 mg/kg of the subject’s body weight (e.g., between 0.01 mg/kg to 45 mg/kg, e.g., between 0.1 mg/kg to 40 mg/kg, e.g., between 1 mg/kg to 35 mg/kg, e.g., between 2.5 mg/kg to 30 mg/kg, e.g., between 5 mg/kg to 25 mg/kg, e.g., between 10 mg/kg to 20 mg/kg, e.g., between 12.5 mg/kg to 15 mg/kg, e.g., 15 ⁇ 2 mg/kg, 15 ⁇ 1 mg/kg, 15 ⁇ 0.5 mg/kg, 15 ⁇ 0.2 mg/kg, or 15 ⁇ 0.1 mg/kg, e.g., 15 mg/kg) every three weeks.
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g.,
  • the effective amount of the PD-1 axis binding antagonist is a dose of between 0.01 mg/kg to 15 mg/kg of the subject’s body weight (e.g., between 0.1 mg/kg to 15 mg/kg, e.g., between 0.5 mg/kg to 15 mg/kg, e.g., between 1 mg/kg to 15 mg/kg, e.g., between 2.5 mg/kg to 15 mg/kg, e.g., between 5 mg/kg to 15 mg/kg, e.g., between 7.5 mg/kg to 15 mg/kg, e.g., between 10 mg/kg to 15 mg/kg, e.g., between 12.5 mg/kg to 15 mg/kg, e.g., between 14 mg/kg to 15 mg/kg, e.g., 15 ⁇ 1 mg/kg, e.g., 15 ⁇ 0.5 mg/kg,
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., at
  • the dose of the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab)
  • a combination therapy e.g., a combination treatment with an anti-TIGIT antagonist antibody, such as an anti-TIGIT antagonist antibody disclosed herein, e.g., tiragolumab), a topoisomerase II inhibitor (e.g., etoposide), and/or a platinum-based chemotherapeutic agent (e.g., carboplatin or cisplatin)
  • a combination therapy e.g., a combination treatment with an anti-TIGIT antagonist antibody, such as an anti-TIGIT antagonist antibody disclosed herein, e.g., tiragolumab
  • a topoisomerase II inhibitor e.g., etoposide
  • a platinum-based chemotherapeutic agent e.g., carboplatin or cisplatin
  • the effective amount of the platinum-based chemotherapeutic agent is a dose sufficient to achieve an AUC from 1 -50 mg/ml/min (e.g., 2-25 mg/ml/min, 3-15 mg/ml/min, 4-10 mg/ml/min, or 5 mg/ml/min, e.g., 2 mg/ml/min, 3 mg/ml/min, 4 mg/ml/min, 5 mg/ml/min, 6 mg/ml/min, 7 mg/ml/min, 8 mg/ml/min, 9 mg/ml/min, 10 mg/ml/min, 11 mg/ml/min, 12 mg/ml/min, 13 mg/ml/min, 14 mg/ml/min, 15 mg/ml/min, 20 mg/ml/min, 25 mg/ml/min, 30 mg/ml/min, 35 mg/ml/min, 40 mg/ml/min,
  • 1 -50 mg/ml/min e.g., 2-25 mg
  • AUC can be calculated using the Calvert formula (Calvert et al. , J. Clin. Oncol. 1989, 7:1748-56):
  • Total dose (mg) (target AUC) x (glomerular filtration rate [GFR] + 25)
  • Atezolizumab is equivalent to an average body weight-based dose of 15 m/kg.
  • the effective amount of the platinum-based chemotherapeutic agent is 200 mg-1500 mg (e.g., 300 mg-1200 mg, 400 mg-1100 mg, or 500 mg-1000 mg, e.g., 300 mg-400 mg, 400 mg-500 mg, 500 mg-600 mg, 600 mg-700 mg, 700 mg-750 mg, 750 mg- 800 mg, 800 mg-900 mg, 900 mg-1000 mg, 1000 mg-1100 mg, or 1100 mg-1200 mg, e.g., about 200 mg, about 300 mg, about 400 mg, about 500 mg, about 600 mg, about 700 mg, about 800 mg, about 900 mg, about 1000 mg, about 1100 mg, about 1200 mg, about 1300 mg, about 1400 mg, or about 1500 mg).
  • the platinum-based chemotherapeutic agent e.g., carboplatin or cisplatin
  • 200 mg-1500 mg e.g., 300 mg-1200 mg, 400 mg-1100 mg, or 500 mg-1000 mg, e.g., 300 mg-400 mg
  • the effective amount of the platinum-based chemotherapeutic agent is about 500 mg-1000 mg (e.g., about 500 mg, about 600 mg, about 700 mg, about 800 mg, about 900 mg, or about 1000 mg).
  • the effective amount of the topoisomerase II inhibitor is from 10-1000 mg/m 2 (e.g., from 20-800 mg/m 2 , from 30-700 mg/m 2 , from 40-500 mg/m 2 , from 50-300 mg/m 2 , from 75-200 mg/m 2 , or from 80-150 mg/m 2 , e.g., about 20 mg/m 2 , about 30 mg/m 2 , about 40 mg/m 2 , about 50 mg/m 2 , about 60 mg/m 2 , about 70 mg/m 2 , about 80 mg/m 2 , about 90 mg/m 2 , about 100 mg/m 2 , about 110 mg/m 2 , about 120 mg/m 2 , about 130 mg/m 2 , about 140 mg/m 2 , about 150 mg/m 2 , about 160 mg/m 2 , about 170 mg/m 2 , about 180 mg/m 2 , about 190 mg/m 2 , about
  • 10-1000 mg/m 2 e.g., from
  • the effective amount of the platinum-based chemotherapeutic agent is 200 mg-1500 mg (e.g., 300 mg-1200 mg, 400 mg-1100 mg, or 500 mg-1000 mg, e.g., 300 mg-400 mg, 400 mg-500 mg, 500 mg-600 mg, 600 mg-700 mg, 700 mg-750 mg, 750 mg- 800 mg, 800 mg-900 mg, 900 mg-1000 mg, 1000 mg-1100 mg, or 1100 mg-1200 mg, e.g., 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, 1000 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, or 1500 mg).
  • 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, 1000 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, or 1500 mg is 200 mg-1500 mg (e.g., 300 mg-1200 mg, 400 mg-1100 mg, or 500 mg-1000 mg, e.g.
  • the effective amount of the platinum-based chemotherapeutic agent is 500 mg-1000 mg (e.g., 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, or 1000 mg).
  • the effective amount of the topoisomerase II inhibitor is from 10-1000 mg/m 2 (e.g., from 20-800 mg/m 2 , from 30-700 mg/m 2 , from 40-500 mg/m 2 , from 50-300 mg/m 2 , from 75-200 mg/m 2 , or from 80-150 mg/m 2 , e.g., 20 mg/m 2 , 30 mg/m 2 , 40 mg/m 2 , 50 mg/m 2 , 60 mg/m 2 , 70 mg/m 2 , 80 mg/m 2 , 90 mg/m 2 , 100 mg/m 2 , 110 mg/m 2 , 120 mg/m 2 , 130 mg/m 2 , 140 mg/m 2 , 150 mg/m 2 ,
  • 10-1000 mg/m 2 e.g., from 20-800 mg/m 2 , from 30-700 mg/m 2 , from 40-500 mg/m 2 , from 50-300 mg/m 2 , from 75-200 mg/m 2 , or
  • the effective amount of the topoisomerase II inhibitor is 100 mg/m 2 .
  • the anti-TIGIT antagonist antibody e.g., an anti- TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab)
  • the platinum-based chemotherapeutic agent e.g., carboplatin or cisplatin
  • the topoisomerase II inhibitor e.g., etoposide
  • dosing cycles e.g., 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24, 25, 26, 27, 28, 29, 30, 31 , 32, 33, 34, 35, 36, 37, 38, 39, 40, 41 , 42, 43, 44, 45, 46, 47, 48, 49, or 50 or more dosing cycles).
  • dosing cycles of the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab)
  • the platinum-based chemotherapeutic agent e.g., carboplatin or cisplatin
  • the topoisomerase II inhibitor e.g., etoposide
  • the length of each dosing cycle is about 18 to 24 days (e.g., 15 days, 16 days, 17 days, 18 days, 19 days, 20 days, 21 days, 22 days, 23 days, or 24 days). In some instances, the length of each dosing cycle is about 21 days. In other instances, the length of each dosing cycle is about 14 days. In other instances, the length of each dosing cycle is about 28 days.
  • the anti-TIGIT antagonist antibody (e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab) is administered on about Day 1 (e.g., Day 1 ⁇ 3 days) of each dosing cycle.
  • the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • a dose e.g., a fixed dose
  • 600 mg a dose of about 600 mg on Day 1 of each dosing cycle, e.g., each 21 -day cycle (i.e., at a dose of about 600 mg every three weeks).
  • the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • a dose e.g., a fixed dose
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab)
  • Day 1 e.g., Day 1 ⁇ 3 days
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab)
  • the PD-1 axis binding antagonist is administered intravenously at a dose of about 1200 mg on Day 1 of each 21 -day cycle (i.e., at a dose of about 1200 mg every three weeks).
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab)
  • is administered intravenously at a dose of about 1200 mg on Day 1 of each 21 -day cycle i.e., at a dose of about 1200 mg every three weeks.
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab)
  • the PD-1 axis binding antagonist is administered intravenously at a dose of 1200 mg on Day 1 of each 21 -day cycle (i.e., at a dose of 1200 mg every three weeks).
  • both the anti-TIG IT antagonist antibody e.g., an anti-TIG IT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab)
  • Day 1 e.g., Day 1 ⁇ 3 days
  • the platinum-based chemotherapeutic agent is administered on about Day 1 (e.g., Day 1 ⁇ 3 days) of each dosing cycle.
  • the topoisomerase II inhibitor is on about Day 1 (e.g., Day 1 ⁇ 3 days) of each dosing cycle.
  • the anti-TIGIT antagonist antibody e.g., an anti-TIG IT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab)
  • the platinum-based chemotherapeutic agent e.g., carboplatin or cisplatin
  • AUC 5 mg/ml/min on Day 1 of each of the four initial dosing cycles
  • the topoisomerase II inhibitor e.g., etoposide
  • the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab)
  • the platinum-based chemotherapeutic agent e.g., carboplatin or cisplatin
  • AUC 5 mg/ml/min on Day 1 of each of the four initial dosing cycles
  • the topoisomerase II inhibitor e.g., etoposide
  • the anti-TIGIT antagonist antibody, PD-1 axis binding antagonist, platinum- based chemotherapeutic agent, and topoisomerase II inhibitor are administered in each of four initial dosing cycles.
  • the anti-TIGIT antagonist antibody is administered at a dose from about 30 mg to about 1200 mg on Day 1 of each of the four initial dosing cycles.
  • the anti-TIGIT antagonist antibody is administered at a dose from about 30 mg to about 600 mg on Day 1 of each of the four initial dosing cycles.
  • the anti-TIGIT antagonist antibody is administered at a dose of about 600 mg on Day 1 of each of the four initial dosing cycles.
  • the PD-1 axis binding antagonist is administered at a dose from about 80 mg to about 1600 mg on Day 1 of each of the four initial dosing cycles (e.g., at a dose of about 1200 mg on Day 1 of each of the four initial dosing cycles).
  • the anti-TIGIT antagonist antibody is administered at a dose from 30 mg to 1200 mg on Day 1 of each of the four initial dosing cycles.
  • the anti-TIGIT antagonist antibody is administered at a dose from 30 mg to 600 mg on Day 1 of each of the four initial dosing cycles.
  • the anti-TIGIT antagonist antibody is administered at a dose of 600 mg on Day 1 of each of the four initial dosing cycles.
  • the PD-1 axis binding antagonist is administered at a dose from 80 mg to 1600 mg on Day 1 of each of the four initial dosing cycles (e.g., at a dose of 1200 mg on Day 1 of each of the four initial dosing cycles).
  • the anti-TIG IT antagonist antibody and the PD-1 axis binding antagonist are further administered in one or more additional cycles following the fourth initial dosing cycle.
  • the anti-TIG IT antagonist antibody is administered at a dose from about 30 mg to about 1200 mg on Day 1 of each of the one or more additional dosing cycles (e.g., at a dose from about 30 mg to about 600 mg on Day 1 of each of the one or more additional dosing cycles).
  • the anti- TIGIT antagonist antibody is administered at a dose of about 600 mg on Day 1 of each of the one or more additional dosing cycles.
  • the PD-1 axis binding antagonist is administered at a dose from about 80 mg to about 2000 mg on Day 1 of each of the one or more additional dosing cycles (e.g., at a dose of about 840 mg, 1200 mg, or 1680 mg on Day 1 of each of the one or more additional dosing cycles).
  • the additional dosing cycles include administration of the PD-1 axis binding antagonist (e.g., atezolizumab) at a dose of about 840 mg every two weeks, about 1200 mg every three weeks, or about 1680 mg every four weeks.
  • each of the one or more dosing cycles is about 14 days, and the PD-1 axis binding antagonist (e.g., atezolizumab) is administered at a dose of about 840 mg on Day 1 of each of the one or more additional dosing cycles. In some instances, each of the one or more dosing cycles is about 21 days, and the PD-1 axis binding antagonist (e.g., atezolizumab) is administered at a dose of about 1200 mg on Day 1 of each of the one or more additional dosing cycles.
  • the PD-1 axis binding antagonist e.g., atezolizumab
  • each of the one or more dosing cycles is about 28 days, and the PD-1 axis binding antagonist (e.g., atezolizumab) is administered at a dose of about 1680 mg on Day 1 of each of the one or more additional dosing cycles.
  • the PD-1 axis binding antagonist e.g., atezolizumab
  • the anti-TIG IT antagonist antibody is administered at a dose from 30 mg to 1200 mg on Day 1 of each of the one or more additional dosing cycles (e.g., at a dose from 30 mg to 600 mg on Day 1 of each of the one or more additional dosing cycles). In some instances, the anti-TIGIT antagonist antibody is administered at a dose of 600 mg on Day 1 of each of the one or more additional dosing cycles. In some instances, the PD-1 axis binding antagonist is administered at a dose from 80 mg to 2000 mg on Day 1 of each of the one or more additional dosing cycles (e.g., at a dose of 840 mg, 1200 mg, or 1680 mg on Day 1 of each of the one or more additional dosing cycles).
  • the additional dosing cycles include administration of the PD-1 axis binding antagonist (e.g., atezolizumab) at a dose of 840 mg every two weeks, 1200 mg every three weeks, or 1680 mg every four weeks.
  • the PD-1 axis binding antagonist e.g., atezolizumab
  • each of the one or more dosing cycles is 14 days, and the PD-1 axis binding antagonist (e.g., atezolizumab) is administered at a dose of 840 mg on Day 1 of each of the one or more additional dosing cycles.
  • each of the one or more dosing cycles is 21 days, and the PD-1 axis binding antagonist (e.g., atezolizumab) is administered at a dose of 1200 mg on Day 1 of each of the one or more additional dosing cycles. In some instances, each of the one or more dosing cycles is 28 days, and the PD-1 axis binding antagonist (e.g., atezolizumab) is administered at a dose of 1680 mg on Day 1 of each of the one or more additional dosing cycles.
  • the PD-1 axis binding antagonist e.g., atezolizumab
  • a subject or population of subjects having lung cancer is treated by administering to the subject or population of subjects one or more dosing cycles (e.g., 21 -day dosing cycles) of an anti-TIGIT antagonist antibody (e.g., an anti-TIG IT antagonist antibody as disclosed herein, e.g., tiragolumab) at a dose from about 30 mg to about 1200 mg (e.g., between about 30 mg to about 1100 mg, e.g., between about 60 mg to about 1000 mg, e.g., between about 100 mg to about 900 mg, e.g., between about 200 mg to about 800 mg, e.g., between about 300 mg to about 800 mg, e.g., between about 400 mg to about 800 mg, e.g., between about 400 mg to about 750 mg, e.g., between about 450 mg to about 750 mg, e.g., between
  • a PD-1 axis binding antagonist e.g., anti-PD- L1 antagonist antibody (e.g., atezolizumab)
  • 80 mg to 2000 mg e.g., between 100 mg to 1600 mg, e.g., between 200 mg to 1600 mg, e.g., between 300 mg to 1600 mg, e.g., between 400 mg to
  • 1600 mg e.g., between 500 mg to 1600 mg, e.g., between 600 mg to 1600 mg, e.g., between 700 mg to
  • 1600 mg e.g., between 800 mg to 1600 mg, e.g., between 900 mg to 1500 mg, e.g., between 1000 mg to
  • 1400 mg e.g., between 1050 mg to 1350 mg, e.g., between 1100 mg to 1300 mg, e.g., between 1150 mg to 1250 mg, e.g., between 1175 mg to 1225 mg, e.g., between 1190 mg to 1210 mg, e.g., 1200 mg ⁇ 5 mg, e.g., 1200 ⁇ 2.5 mg, e.g., 1200 ⁇ 1 .0 mg, e.g., 1200 ⁇ 0.5 mg, e.g., 1200 mg) on Day 1 of each dosing cycle), a platinum-based chemotherapeutic agent (e.g., carboplatin or cisplatin) at a dose sufficient to achieve AUC from 1 -50 mg/ml/min (e.g., 2-25 mg/ml/min, 3-15 mg/ml/min, 4-10 mg/ml/min, or 5 mg/ml/min, e.g., 2 mg/m
  • a subject or population of subjects having lung cancer is treated by administering to the subject or population of subjects one or more dosing cycles (e.g., 21 -day dosing cycles) of an anti-TIGIT antagonist antibody (e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab) at a dose from 30 mg to 1200 mg (e.g., between 30 mg to 1100 mg, e.g., between 60 mg to 1000 mg, e.g., between 100 mg to 900 mg, e.g., between 200 mg to 800 mg, e.g., between 300 mg to 800 mg, e.g., between 400 mg to 800 mg, e.g., between 400 mg to 750 mg, e.g., between 450 mg to 750 mg, e.g., between 500 mg to 700 mg, e.g., between 550 mg to
  • an anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as
  • the treatment extends the OS of the subject or population of subjects by at least about 3.3 months (e.g., by 3.3-120 months, by 4-100 months, by 5-80 months, by 6-60 months, by 7-48 months, by 8-36 months, or by 10-24 months, e.g., by at least about 3.3 months, 3.4 months, 3.5 months, 3.6 months, 3.7 months, 3.8 months, 3.9 months, 4.0 months, 4.1 months, 4.2 months, 4.3 months, 4.4 months, 4.5 months, 4.6 months, 4.7 months, 4.8 months, 4.9 months, 5.0 months, 5.5 months, 6.0 months, 6.5 months, 7.0 months, 7.5 months, 8.0 months, 8.5 months, 9.0 months, 9.5 months, 10 months, 10.5 months, 11 months, 11 .5 months, 12 months, 13 months, 14 months, 15 months, 16 months, 17 months, 18 months, 19 months, 20 months, 21 months, 22 months, 23 months, 24 months, 25 months, 26 months, 27 months, 28 months,
  • the treatment extends the OS of the subject or population of subjects by at least about 5.3 months (e.g., by 5.3-120, by 6-60 months, by 7-48 months, by 8-36 months, or by 10-24 months, e.g., by at least about 5.3 months, 5.5 months, 6.0 months, 6.5 months, 7.0 months, 7.5 months, 8.0 months, 8.5 months, 9.0 months, 9.5 months, 10 months, 10.5 months, 11 months, 11 .5 months, 12 months, 13 months, 14 months, 15 months, 16 months, 17 months, 18 months, 19 months, 20 months, 21 months, 22 months, 23 months, 24 months, 25 months, 26 months, 27 months, 28 months, 29 months, 30 months, 31 months, 32 months, 33 months, 34 months, 35 months, or 36 months) as compared to treatment with the PD-1 axis binding antagonist, the platinum-based chemotherapeutic agent, and the topoisomerase II inhibitor without the anti-TIG IT antagonist antibody.
  • 5.3 months e.g.,
  • the treatment extends the PFS of the subject or population of subjects by at least about 2.4 months (e.g., by 2.4-120 months, by 2.5-100 months, by 3.0-80 months, by 4.0-60 months, by 5.0-48 months, by 6.0-36 months, by 8.0-24 months, or by 10-12 months, e.g., by at least about 2.4 months, 2.5 months, 2.6 months, 2.7 months, 2.8 months, 2.9 months, 3.0 months, 3.1 months, 3.2 months, 3.3 months, 3.4 months, 3.5 months, 3.6 months, 3.7 months, 3.8 months, 3.9 months, 4.0 months, 4.1 months, 4.2 months, 4.3 months, 4.4 months, 4.5 months, 4.6 months, 4.7 months, 4.8 months, 4.9 months, 5.0 months, 5.5 months, 6.0 months, 6.5 months, 7.0 months, 7.5 months, 8.0 months, 8.5 months, 9.0 months, 9.5 months, 10 months, 10.5 months, 11 months, 11 .5 months, 12 months,
  • the treatment extends the PFS of the subject or population of subjects by at least about 4 months (e.g., by 4- 120 months, by 5-100 months, by 6-80 months, by 7-60 months, by 8-48 months, by 9-36 months, or by 10-24 months, e.g., by at least about 4.0 months, 4.1 months, 4.2 months, 4.3 months, 4.4 months, 4.5 months, 4.6 months, 4.7 months, 4.8 months, 4.9 months, 5.0 months, 5.5 months, 6.0 months, 6.5 months, 7.0 months, 7.5 months, 8.0 months, 8.5 months, 9.0 months, 9.5 months, 10 months, 10.5 months, 11 months, 11 .5 months, 12 months, 13 months, 14 months, 15 months, 16 months, 17 months, 18 months, 19 months, 20 months, 21 months, 22 months, 23 months, 24 months, 25 months, 26 months, 27 months, 28 months, 29 months, 30 months, 31 months, 32 months, 33 months, 34 months, 35 months, or 36 months) as compared to
  • the subject or population of subjects receives one or more additional dosing cycles (e.g., 21 -day dosing cycles) of the anti-TIGIT antagonist antibody at a dose from about 30 mg to about 1200 mg on Day 1 of each additional dosing cycle and atezolizumab at a dose from about 80 mg to about 2000 mg on Day 1 of each additional dosing cycle, wherein carboplatin and etoposide are omitted from each of the one or more additional dosing cycles.
  • additional dosing cycles e.g., 21 -day dosing cycles
  • the anti-TIG IT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the anti-TIG IT antagonist antibody is administered to the subject or population of subjects by intravenous infusion over about 60 ⁇ 15 minutes (e.g., about 50 minutes, about 51 minutes, about 52 minutes, about 53 minutes, about 54 minutes, about 55 minutes, about 56 minutes, about 57 minutes, about 58 minutes, about 59 minutes, about 60 minutes, about 61 minutes, about 62 minutes, about 63 minutes, about 64 minutes, about 65 minutes, about 66 minutes, about 67 minutes, about 68 minutes, about 69 minutes, or about 70 minutes).
  • about 60 ⁇ 15 minutes e.g., about 50 minutes, about 51 minutes, about 52 minutes, about 53 minutes, about 54 minutes, about 55 minutes, about 56 minutes, about 57 minutes, about 58 minutes, about 59 minutes, about 60 minutes, about 61 minutes, about 62 minutes, about 63 minutes, about 64 minutes, about 65
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab)
  • the PD-1 axis binding antagonist is administered to the subject or population of subjects by intravenous infusion over about 60 ⁇ 15 minutes (e.g., about 45 minutes, about 46 minutes, about 47 minutes, about 48 minutes, about 49 minutes, about 50 minutes, about 51 minutes, about 52 minutes, about 53 minutes, about 54 minutes, about 55 minutes, about 56 minutes, about 57 minutes, about 58 minutes, about 59 minutes, about 60 minutes, about 61 minutes, about 62 minutes, about 63 minutes, about 64 minutes, about 65 minutes, about 66 minutes, about 67 minutes, about 68 minutes, about 69 minutes, about 70 minutes, about 71 minutes, about 72 minutes, about 73 minutes, about 74 minutes, or about 75 minutes).
  • anti-PD-L1 antagonist antibody e.g., atezolizumab
  • the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD- 1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab)
  • the method includes an intervening first observation period.
  • the method further includes a second observation period following administration of the PD-1 axis binding antagonist.
  • the method includes both a first observation period following administration of the anti-TIGIT antagonist antibody and second observation period following administration of PD-1 axis binding antagonist.
  • the first and second observation periods are each between about 30 minutes to about 60 minutes in length.
  • the method may include recording the subject’s vital signs (e.g., pulse rate, respiratory rate, blood pressure, and temperature) at about 30 ⁇ 10 minutes after administration of the anti-TIGIT antagonist antibody and PD-1 axis binding antagonist during the first and second observation periods, respectively.
  • the method may include recording the subject’s vital signs (e.g., pulse rate, respiratory rate, blood pressure, and temperature) at about 15 ⁇ 10 minutes after administration of the anti-TIGIT antagonist antibody and PD-1 axis binding antagonist during the first and second observation periods, respectively.
  • vital signs e.g., pulse rate, respiratory rate, blood pressure, and temperature
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab)
  • the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab.
  • the method includes an intervening first observation period.
  • the method includes a second observation period following administration of the anti-TIGIT antagonist antibody.
  • the method includes both a first observation period following administration of the PD-1 axis binding antagonist and second observation period following administration of the anti-TIGIT antagonist antibody.
  • the first and second observation periods are each between about 30 minutes to about 60 minutes in length.
  • the method may include recording the subject’s vital signs (e.g., pulse rate, respiratory rate, blood pressure, and temperature) at about 30 ⁇ 10 minutes after administration of the PD-1 axis binding antagonist and anti- TIGIT antagonist antibody during the first and second observation periods, respectively.
  • the method may include recording the subject’s vital signs (e.g., pulse rate, respiratory rate, blood pressure, and temperature) at about 15 ⁇ 10 minutes after administration of the PD-1 axis binding antagonist and anti- TIGIT antagonist antibody during the first and second observation periods, respectively.
  • vital signs e.g., pulse rate, respiratory rate, blood pressure, and temperature
  • the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 (atezolizumab) antagonist antibody
  • the method includes an observation period. In some instances, the observation period is between about 30 minutes to about 60 minutes in length.
  • the method may include recording the subject’s vital signs (e.g., pulse rate, respiratory rate, blood pressure, and temperature) at about 30 ⁇ 10 minutes after administration of the PD-1 axis binding antagonist (e.g., anti-PD-L1 antagonist antibody) and anti-TIGIT antagonist antibody during the observation period.
  • the method may include recording the subject’s vital signs (e.g., pulse rate, respiratory rate, blood pressure, and temperature) at about 15 ⁇ 10 minutes after administration of the PD-1 axis binding antagonist (e.g., anti-PD-L1 antagonist antibody) and anti-TIGIT antagonist antibody during the observation period.
  • the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • PD-1 axis binding antagonist e.g., anti-PD-L1 antibody (e.g., atezolizumab)
  • platinum-based chemotherapeutic agent e.g., carboplatin or cisplatin
  • topoisomerase II inhibitor e.g., etoposide
  • a medicament thereof may be administered in conjunction with (either separately or together), one or more additional anti-cancer therapeutic agent(s) (e.g., an immunomodulatory agent (e.g., an agent that decreases or inhibits one or more immune co-inhibitory receptors (e.g., one or more immune co-inhibitory receptors selected from TIGIT, PD-L1 , PD-1 , CTLA-4, LAG 3, TIM3, BTLA
  • an immunomodulatory agent e.g., an agent that
  • the lung cancer is a small cell lung cancer (SCLC), such as extensive stage SCLC (ES-SCLC).
  • SCLC small cell lung cancer
  • ES-SCLC extensive stage SCLC
  • the subject or population of subjects is treatment-naive for ES- SCLC (e.g., chemotherapy-naive for ES-SCLC).
  • the lung cancer is unselected for PD-L1 expression. In other instances, the lung cancer is selected for PD-L1 expression. In some instances, the lung cancer is selected for PD-L1 expression by an immunohistochemical (IHC) assay comprising staining with an anti-PD-L1 antibody, such as SP263, 22C3, SP142, or 28-8.
  • IHC immunohistochemical
  • the anti-PD-L1 antibody is SP263 and the IHC assay is the Ventana SP263 IHC assay; the anti-PD-L1 antibody is 22C3 and the IHC assay is the pharmDx 22C3 IHC assay; the anti-PD-L1 antibody is SP142 and the IHC assay is the Ventana SP142 IHC assay, or the anti-PD-L1 antibody is 28-8 and the IHC assay is the pharmDx 28-8 IHC assay.
  • a tumor sample obtained from the individual has a detectable nucleic acid expression level of PD-L1 .
  • the detectable nucleic acid expression level of PD-L1 has been determined by RNA-seq, RT-qPCR, qPCR, multiplex qPCR or RT-qPCR, microarray analysis, SAGE, MassARRAY technique, ISH, or a combination thereof.
  • the sample is selected from the group consisting of a tissue sample, a whole blood sample, a serum sample, and a plasma sample.
  • the tissue sample is a tumor sample.
  • the tumor sample comprises tumor-infiltrating immune cells, tumor cells, stromal cells, and any combinations thereof.
  • the lung cancer is small cell lung cancer (SCLC).
  • SCLC small cell lung cancer
  • the SCLC is extensive-stage small cell lung cancer (ES-SCLC), also referred to as stage 4 (IV) SCLC.
  • ES-SCLC extensive-stage small cell lung cancer
  • the SCLC is histologically or cytologically confirmed ES-SCLC, according to or as defined by the Veterans Administration Lung Study Group (VALG) staging system (see, e.g., Micke et al. Lung Cancer 2002, 37:271 -6).
  • VOG Veterans Administration Lung Study Group
  • SCLC is classified as ES-SCLC if the individual is inoperable and cannot be classified as having limited or limited stage SCLC (L-SCLC or LS-SCLC).
  • the ES-SCLC is detectable and/or has spread outside the originally affected lung.
  • the ESSCLC is detectable and/or has spread further into other (e.g., distant) organs, such as (but not limited to) the liver, adrenal glands, lymph nodes and/or brain.
  • the ESSCLC is difficult to treat.
  • the subject or population of subjects has a poor prognosis.
  • the subject or population of subjects is a treatment-naive subject or population of subjects (e.g., a chemotherapy-naive subject or population of subjects).
  • a treatment-naive subject is a subject who has not received prior treatment, e.g., for cancer, for SCLC, or for ES-SCLC.
  • the treatment naive subject is a subject who has not received prior treatment for ES SCLC.
  • the treatment-naive subject is chemotherapy naive, e.g., a subject who has not received prior chemotherapy for the treatment of, e.g., cancer, SCLC, and/or ES-SCLC.
  • the subject or population of subjects has not received treatment for ES-SCLC.
  • the subject or population of subjects has not received prior systemic treatment for ES SCLC.
  • the subject or population of subjects has received prior chemoradiotherapy for limited stage SCLC (LS-SCLC) with curative intent, and has experienced a treatment-free cycle of at least six months since the last chemotherapy, radiotherapy, or chemoradiotherapy cycle from the diagnosis of ES-SCLC.
  • LS-SCLC limited stage SCLC
  • the subject or population of subjects has asymptomatic supratentorial or cerebellar central nervous system (CNS) metastases. In some embodiments, the subject or population of subjects does not have metastases to the midbrain, pons, medulla, or spinal cord. In some embodiments, the subject or population of subjects has CNS disease and does not require corticosteroid treatment for CNS disease. In some embodiments, the subject or population of subjects has new asymptomatic metastases and has received radiation therapy and/or surgery for CNS metastases. In some embodiments, the subject or population of subjects has measurable disease, according to/as defined by RECIST v1 .1 criteria (see, e.g., Eisenhauer et al., Eur. J. Cancer 2009, 45: 228-247). In some embodiments, the subject or population of subjects has not received prior treatment with a CD137 agonist or an immune checkpoint blockade therapy.
  • CNS central nervous system
  • the treatment results in a CR or a PR.
  • the PFS of the subject or population of subjects is increased as compared to a reference PFS time.
  • the reference PFS time is the median PFS time of a population of subjects who have received a treatment with (e.g., anti-PD-L1 antibody (e.g., atezolizumab)), platinum-based chemotherapeutic agent (e.g., carboplatin or cisplatin), and topoisomerase II inhibitor (e.g., etoposide) without the anti-TIGIT antagonist antibody (e.g., tiragolumab).
  • anti-PD-L1 antibody e.g., atezolizumab
  • platinum-based chemotherapeutic agent e.g., carboplatin or cisplatin
  • topoisomerase II inhibitor e.g., etoposide
  • the anti-TIGIT antagonist antibody e.g., tiragolumab
  • the methods further comprise an additional therapy.
  • the additional therapy may be radiation therapy, surgery (e.g., lumpectomy and a mastectomy), chemotherapy, gene therapy, DNA therapy, viral therapy, RNA therapy, immunotherapy, bone marrow transplantation, nanotherapy, monoclonal antibody therapy, or a combination of the foregoing.
  • the additional therapy may be in the form of adjuvant or neoadjuvant therapy.
  • the additional therapy is the administration of small molecule enzymatic inhibitor or anti-metastatic agent.
  • the additional therapy is the administration of side-effect limiting agents (e.g., agents intended to lessen the occurrence and/or severity of side effects of treatment, such as anti-nausea agents, etc.).
  • the additional therapy is radiation therapy.
  • the additional therapy is surgery.
  • the additional therapy is a combination of radiation therapy and surgery.
  • the additional therapy is gamma irradiation.
  • Additional therapeutic antibodies contemplated for use herein include, without limitation, alemtuzumab (Campath), bevacizumab (AVASTIN®, Genentech); cetuximab (ERBITUX®, Imclone); panitumumab (VECTIBIX®, Amgen), rituximab (RITUXAN®, Genentech/Biogen plec), pertuzumab (OMNITARG®, 2C4, Genentech), trastuzumab (HERCEPTIN®, Genentech), tositumomab (Bexxar, Corixia), the antibody drug conjugate gemtuzumab ozogamicin (MYLOTARG®, Wyeth), apolizumab, aselizumab, atlizumab, bapineuzumab, bivatuzumab mertansine, cantuzumab mertansine, cedelizumab, certolizumab pegol, cidfusituzum
  • the additional therapy is therapy targeting PI3K/AKT/mTOR pathway, HSP90 inhibitor, tubulin inhibitor, apoptosis inhibitor, and/or chemopreventative agent.
  • the additional therapy is CTLA-4 (also known as CD152), e.g., a blocking antibody, ipilimumab (also known as MDX-010, MDX-101 , or Yervoy®), tremelimumab (also known as ticilimumab or CP-675,206), an antagonist directed against B7-H3 (also known as CD276), e.g., a blocking antibody, MGA271 , an antagonist directed against TGF beta, e.g., metelimumab (also known as CAT-192), fresolimumab (also known as GC1008), or LY2157299, a treatment comprising adoptive transfer of a T cell (e.g., a cytotoxic T cell or CTL)
  • a T cell
  • TLR agonist e.g., Poly-ICLC (also known as Hiltonol®), LPS, MPL, or CpG ODN, tumor necrosis factor (TNF) alpha, IL-1 , HMGB1 , an IL-10 antagonist, an IL-4 antagonist, an IL-13 antagonist, an HVEM antagonist, an ICOS agonist, e.g., by administration of ICOS-L, or an agonistic antibody directed against ICOS, a treatment targeting CX3CL1 , a treatment targeting CXCL10, a treatment targeting CCL5, an LFA-1 or ICAM1 agonist, a Selectin agonist, a targeted therapy, an inhibitor of B-Raf, vemurafenib (also known as Zelboraf®, dabrafenib (also known as Tafinlar®), erlotinib (also known as Tarceva®), an inhibitor of B-Raf, vemurafenib (also known as Zelboraf®
  • cobimetinib also known as GDC-0973 or XL-518
  • trametinib also known as Mekinist®
  • K-Ras an inhibitor of K-Ras
  • an inhibitor of c-Met an inhibitor of c-Met, onartuzumab (also known as MetMAb)
  • Aik an inhibitor of Aik
  • AF802 also known as CH5424802 or alectinib
  • an inhibitor of a phosphatidylinositol 3-kinase PI3K
  • BKM120 idelalisib
  • perifosine also known as KRX-0401
  • an Akt Akt
  • MK2206 GSK690693
  • GDC-0941 an inhibitor of mTOR
  • sirolimus also known as rapamycin
  • temsirolimus also known as CCI-779 or Torisel®
  • everolimus also known as RAD001
  • ridaforolimus also known as
  • lung cancer e.g., non-small cell lung cancer (NSCLC), which includes squamous NSCLC or non-squamous NSCLC, including locally advanced unresectable NSCLC (e.g., Stage NIB NSCLC), or recurrent or metastatic NSCLC (e.g., Stage IV NSCLC), small cell lung cancer (SCLC), which includes extensive stage SCLC (ES-SCLC), and adenocarcinoma of the lung) in a subject or population of subjects comprising administering to the subject or population of subjects one or more dosing cycles of an effective amount of an anti-TIG IT antagonist antibody (e.g., an anti-TIG IT antagonist antibody as disclosed herein, e.g., tiragolumab), a PD-1 axis binding antagonist (e.g., an anti-PD-L1 antagonist antibody, such as atezolizumab), and a first and second chemotherapeutic agent (e.g., a
  • NSCLC non-small cell
  • the present invention includes methods and uses involving administration of an effective amount of an anti-TIGIT antagonist antibody (e.g., an anti-TIG IT antagonist antibody as disclosed herein, e.g., tiragolumab), a PD-1 axis binding antagonist (e.g., an anti-PD-L1 antagonist antibody, such as atezolizumab), and a chemotherapy combination to a subject or population of subjects in need thereof.
  • an anti-TIGIT antagonist antibody e.g., an anti-TIG IT antagonist antibody as disclosed herein, e.g., tiragolumab
  • a PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody, such as atezolizumab
  • the anti-TIGIT antagonist antibody e.g., anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody, e.g., atezolizumab
  • the anti-TIGIT antagonist antibody is administered every three weeks (e.g., on Day 1 of each 21 -day dosing cycle).
  • the invention includes methods and uses involving administration of an effective amount of an anti-TIGIT antagonist antibody (e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab) and a PD-1 axis binding antagonist (e.g., an anti-PD-L1 antagonist antibody, such as atezolizumab) based on body weight (BW) or body surface area (BSA) of a subject or population of subjects every three weeks (e.g., on Day 1 of each 21 -day dosing cycle).
  • an anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • a PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody, such as atezolizumab
  • BW body weight
  • BSA body surface area
  • the invention includes methods and uses involving administration of an effective amount of an anti-TIGIT antagonist antibody (e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab), a PD-1 axis binding antagonist (e.g., an anti-PD-L1 antagonist antibody, such as atezolizumab), and a chemotherapy combination to a subject or population of subjects in need thereof, wherein the chemotherapy combination includes an effective amount of a platinum-based chemotherapeutic agent and an effective amount of a non-platinum-based chemotherapeutic agent.
  • an anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • a PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody, such as atezolizumab
  • a chemotherapy combination includes an effective amount of a platinum-based chemotherapeutic agent and an effective amount of a
  • the anti-TIGIT antagonist antibody e.g., anti-TIG IT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody, e.g., atezolizumab
  • the platinum-based chemotherapeutic agent is carboplatin or cisplatin and the non- platinum-based chemotherapeutic agent is an antimetabolite (e.g., pemetrexed).
  • the method involves administration of an effective amount of an anti- TIGIT antagonist antibody (e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab), a PD-1 axis binding antagonist (e.g., an anti-PD-L1 antagonist antibody, e.g., atezolizumab), a platinum- based chemotherapeutic agent (e.g., carboplatin or cisplatin), and an antimetabolite (e.g., pemetrexed) to a subject or population of subjects in need thereof, wherein the anti-TIGIT antagonist antibody (e.g., anti- TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab) and the PD-1 axis binding antagonist (e.g., an anti-PD-L1 antagonist antibody, e.g., atezolizumab) are administered every three weeks (e.g., on Day 1 of each 21 -day dosing
  • the dosing continues for four-to-six induction dosing cycles (e.g., four induction dosing cycles, five induction dosing cycles, or six induction dosing cycles).
  • maintenance therapy can be administered in one or more subsequent (maintenance) dosing cycles.
  • the one or more maintenance dosing cycles does not include the platinum-based chemotherapeutic agent.
  • the present invention includes methods and uses involving administration of an effective amount of an anti-TIGIT antagonist antibody (e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab) and a PD-1 axis binding antagonist (e.g., an anti-PD-L1 antagonist antibody, such as atezolizumab) to a subject or population of subjects in need thereof every four weeks (e.g., on Day 1 of each 28-day dosing cycle).
  • an anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • a PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody, such as atezolizumab
  • administering results in a CR or a PR.
  • administration of the effective amount of the anti-TIGIT antagonist antibody results in an increase in PFS or DOR.
  • administering results in an increase in OS.
  • the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody, such as atezolizumab
  • administering results in an increase in progression-free survival of the subject or population of subjects, e.g., as compared to treatment with the PD-1 axis binding antagonist without the anti-TIGIT antagonist antibody or as compared to treatment with the anti-TIGIT antagonist antibody without the PD-1 axis binding antagonist.
  • the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody, such as atezolizumab
  • the effective amount of the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody, such as atezolizumab
  • the effective amount of the anti-TIGIT antagonist antibody extends OS of the subject or population of subjects, e.g., as compared to treatment with the PD-1 axis binding antagonist without the anti-TIGIT antagonist antibody or as compared to treatment with the anti-TIGIT antagonist antibody without the PD-1 axis binding antagonist.
  • an anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • a PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody, such as atezolizumab
  • a chemotherapy combination e.g., a combination of a platinum- based chemotherapeutic agent (e.g., carboplatin or cisplatin) and an antimetabolite (e.g., pemetrexed)
  • results in an increase in a median PFS of the subject or population of subjects as compared to treatment with pembrolizumab and the chemotherapy combination e.g., the antimetabolite (e.g., pemetrexed) and the platinum-based chemotherapeutic agent (e.g., carboplatin or cisplatin)).
  • the treatment extends the PFS of the subject or population of subjects by at least about 3.5 months or about 4.7 months (e.g., at least about 3.5, 3.6, 3.7, 3.8, 3.9, 4.0, 4.1 , 4.2, 4.3, 4.4, 4.5, 4.6, or 4.7 months, e.g., at least about 3.5-3.7 months, 3.7-3.9 months, 3.9-4.1 months, 4.1 -4.3 months, 4.3-4.5 months, or 4.5-4.7 months).
  • at least about 3.5-3.7 months, 3.7-3.9 months, 3.9-4.1 months, 4.1 -4.3 months, 4.3-4.5 months, or 4.5-4.7 months e.g., at least about 3.5-3.7 months, 3.7-3.9 months, 3.9-4.1 months, 4.1 -4.3 months, 4.3-4.5 months, or 4.5-4.7 months.
  • the administration of the effective amount of an anti-TIGIT antagonist antibody results in a median PFS of greater than 8.8 months (e.g., at least 8.9 months, at least 9.0 months, at least 9.2 months, at least 9.5 months, at least 10 months, at least 11 months, at least 12 months, at least 13 months, at least 14 months, at least 15 months
  • an anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • a PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody, such as atezolizumab
  • a chemotherapy combination e.g., a combination of a platinum-based chemotherapeutic agent (e.g., carboplatin or cisplatin) and an antimetabolite (e.g., pembrolizumab)
  • a subject or population of subjects having a lung cancer e.g., an NSCLC
  • the treatment results in a median PFS of the population of subjects of at least about 8 months (e.g., between 8 months and 36 months, e.g., between 8 months and 24 months (e.g., 8 months, 9 months, 10 months, 12 months, 13 months, 14 months, 15 months, 16 months, 17 months, 18 months, 19 months, 20 months, 21 months, 22 months, 23 months, or 24 months).
  • the treatment results in a median PFS of the population of subjects of about 12.5 months to about 14.7 months (e.g., 12.5, 12.7, 12.9, 13.1 , 13.3, 13.5, 13.7, 13.9, 14.1 , 14.3, 14.5, or 14.7 months, e.g., about 12.5-13 months, 13-13.5 months, 13.5-14 months, or 14-14.7 months.
  • 14.7 months e.g., 12.5, 12.7, 12.9, 13.1 , 13.3, 13.5, 13.7, 13.9, 14.1 , 14.3, 14.5, or 14.7 months, e.g., about 12.5-13 months, 13-13.5 months, 13.5-14 months, or 14-14.7 months.
  • an anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • a PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody, such as atezolizumab
  • a chemotherapy combination e.g., a combination of a platinum-based chemotherapeutic agent (e.g., carboplatin or cisplatin) and an antimetabolite (e.g., pembrolizumab)
  • a subject or population of subjects having a lung cancer e.g., an NSCLC
  • the administration of the effective amount of an anti-TIGIT antagonist antibody results in a median PFS of at least 12 months.
  • an anti-TIGIT antagonist antibody e.g., an anti-TIG IT antagonist antibody as disclosed herein, e.g., tiragolumab
  • a PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody, such as atezolizumab
  • a chemotherapy combination e.g., a combination of a platinum-based chemotherapeutic agent (e.g., carboplatin or cisplatin) and an antimetabolite (e.g., pembrolizumab)
  • a subject or population of subjects having a lung cancer e.g., an NSCLC
  • an anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • a PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody, such as atezolizumab
  • a chemotherapy combination to a subject or population of subjects having a lung cancer (e.g., a combination of a platinum-based chemotherapeutic agent (e.g., carboplatin or cisplatin) and an antimetabolite (e.g., pemetrexed)) results in an increase in a median OS (OS) of the subject or population of subjects as compared to treatment with pembrolizumab and the chemotherapy combination (e.g., the antimetabolite (e.g., pemetrexed) and the platinum-based chemotherapeutic agent (e.g., carboplatin or cisplatin)).
  • OS median OS
  • the antimetabolite e.g
  • the treatment extends the OS of the subject or population of subjects by at least about 4 months (e.g., between 4 and 12 months (e.g., 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, or 12 months)). In some instances, the treatment extends the OS of the subject or population of subjects by at least about 5.5 months to about 8.0 months (e.g., 5.5., 6.0, 6.5,
  • 7.0, 7.5, or 8.0 months e.g., 5.5-6.5, 6.5-7.5, or 7.5-8.0 months).
  • the administration of the effective amount of an anti-TIGIT antagonist antibody results in a median OS of greater than 22 months (e.g., at least 23, at least 24, at least 25, at least 26, at least 27, at least 28, at least 29, at least 30, at least 31 , at least 32, at least 33, at least 34, at least 35, at least 36, at least 42, at least
  • the treatment results in a median OS of the population of subjects of at least about 24 months (e.g., between 24 months and 42 months (e.g., between 24 months and 36 months (e.g., 24 months, 25 months, 26 months, 27 months, 28 months, 29 months, 30 months, 31 months, 32 months, 33 months, 34 months, 35 months, or 36 months))).
  • 24 months and 42 months e.g., between 24 months and 36 months (e.g., 24 months, 25 months, 26 months, 27 months, 28 months, 29 months, 30 months, 31 months, 32 months, 33 months, 34 months, 35 months, or 36 months)
  • the treatment results in a median OS of the population of subjects of about 27.5 months to about 32.0 months (e.g., 27.5, 28.0, 28.5, 29.0, 29.5, 30.0, 30.5, 31 .0, 31 .5, or 32.0 months (e.g., 27.5-28.5, 28.5-29.5, 29.5-30.5, 30.5-31 .5, or 31 .5-32 months).
  • a median OS of the population of subjects of about 27.5 months to about 32.0 months (e.g., 27.5, 28.0, 28.5, 29.0, 29.5, 30.0, 30.5, 31 .0, 31 .5, or 32.0 months (e.g., 27.5-28.5, 28.5-29.5, 29.5-30.5, 30.5-31 .5, or 31 .5-32 months).
  • an anti-TIGIT antagonist antibody e.g., an anti-TIG IT antagonist antibody as disclosed herein, e.g., tiragolumab
  • a PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody, such as atezolizumab
  • a chemotherapy combination e.g., a combination of a platinum-based chemotherapeutic agent (e.g., carboplatin or cisplatin) and an antimetabolite (e.g., pembrolizumab)
  • a subject or population of subjects having a lung cancer e.g., an NSCLC
  • an anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • a PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody, such as atezolizumab
  • a chemotherapy combination e.g., a combination of a platinum-based chemotherapeutic agent (e.g., carboplatin or cisplatin) and an antimetabolite (e.g., pembrolizumab)
  • a subject or population of subjects having a lung cancer e.g., an NSCLC
  • an anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • a PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody, such as atezolizumab
  • a chemotherapy combination e.g., a combination of a platinum- based chemotherapeutic agent (e.g., carboplatin or cisplatin) and an antimetabolite (e.g., pemetrexed)
  • ORR overall response rate
  • the antimetabolite e.g., pemetrexed
  • the platinum-based chemotherapeutic agent e.g., carboplatin or cisplatin
  • an anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • a PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody, such as atezolizumab
  • a chemotherapy combination e.g., a combination of a platinum-based chemotherapeutic agent (e.g., carboplatin or cisplatin) and an antimetabolite (e.g., pembrolizumab)
  • a subject or population of subjects having a lung cancer e.g., an NSCLC
  • an ORR of greater than 47.5% (e.g., at least 48%, at least 49%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%
  • an anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • a PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody, such as atezolizumab
  • a chemotherapy combination e.g., a combination of a platinum- based chemotherapeutic agent (e.g., carboplatin or cisplatin) and an antimetabolite (e.g., pembrolizumab)
  • a subject or population of subjects having a lung cancer e.g., an NSCLC
  • an anti-TIGIT antagonist antibody e.g., an anti-TIG IT antagonist antibody as disclosed herein, e.g., tiragolumab
  • a PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody, such as atezolizumab
  • a chemotherapy combination e.g., a combination of a platinum-based chemotherapeutic agent (e.g., carboplatin or cisplatin) and an antimetabolite (e.g., pembrolizumab)
  • a subject or population of subjects having a lung cancer e.g., an NSCLC
  • an anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • a PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody, such as atezolizumab
  • a chemotherapy combination e.g., a combination of a platinum-based chemotherapeutic agent (e.g., carboplatin or cisplatin) and an antimetabolite (e.g., pembrolizumab)
  • a subject or population of subjects having a lung cancer e.g., an NSCLC
  • the present invention includes methods and uses involving administration of an effective amount of an anti-TIGIT antagonist antibody (e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab) to a subject or population of subjects in need thereof every four weeks (e.g., on Day 1 of each 28-day dosing cycle).
  • an anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • administration of the effective amount of the anti-TIGIT antagonist antibody results in a CR or a PR.
  • administration of the effective amount of the anti-TIGIT antagonist antibody results in an increase in progression-free survival of the subject or population of subjects compared to a reference.
  • administration of the effective amount of the anti-TIGIT antagonist antibody results in an increase in DOR.
  • administration of the effective amount of the anti-TIGIT antagonist antibody extends OS of the subject or population of subjects.
  • the present invention includes methods and uses involving administration of an effective amount of an anti-TIGIT antagonist antibody (e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab) and a PD-1 axis binding antagonist (e.g., an anti-PD-L1 antagonist antibody, such as atezolizumab) to a subject or population of subjects in need thereof every two weeks (e.g., on Days 1 and 15 of each 28-day dosing cycle).
  • an anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • a PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody, such as atezolizumab
  • administering results in a CR or a PR.
  • the anti- TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody, such as atezolizumab
  • administering results in an increase in progression-free survival of the subject or population of subjects, e.g., as compared to treatment with the PD-1 axis binding antagonist without the anti-TIG IT antagonist antibody or as compared to treatment with the anti-TIGIT antagonist antibody without the PD-1 axis binding antagonist.
  • the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody, such as atezolizumab
  • administering extends OS of the subject or population of subjects, e.g., as compared to treatment with the PD-1 axis binding antagonist without the anti-TIGIT antagonist antibody or as compared to treatment with the anti-TIGIT antagonist antibody without the PD-1 axis binding antagonist.
  • the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody, such as atezolizumab
  • the present invention includes methods and uses involving administration of an effective amount of an anti-TIGIT antagonist antibody (e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab) to a subject or population of subjects in need thereof every two weeks (e.g., on Days 1 and 15 of each 28-day dosing cycle).
  • administration of the effective amount of the anti-TIGIT antagonist antibody results in a CR or a PR.
  • administration of the effective amount of the anti-TIGIT antagonist antibody results in an increase in progression-free survival of the subject or population of subjects compared to a reference.
  • administration of the effective amount of the anti-TIGIT antagonist antibody extends OS of the subject or population of subjects.
  • the subject or population of subjects has not received prior systemic therapy (e.g., e.g., prior systemic therapy with curative intent, e.g., chemotherapy) within the month prior to the administration with the PD-1 axis binding antagonist and the anti-TIGIT antagonist antibody (e.g., within the two months prior, three months prior, four months prior, six months prior, one year prior, two years prior, three years prior, four years prior, five years prior, or ten years prior to the administration with the PD-1 axis binding antagonist and the anti-TIGIT antagonist antibody).
  • the subject or population of subjects is chemotherapy naive.
  • the PD-1 axis binding antagonist and the anti-TIGIT antagonist antibody are administered in conjunction with a chemotherapy.
  • a once-every-two-weeks (Q2W), once-every-three-weeks (Q3W), or once-every-four-weeks (Q4W) dosing regimen of the PD-1 axis binding antagonist and the anti-TIGIT antagonist antibody can be administered in conjunction with one or more chemotherapeutic agents.
  • the one or more chemotherapeutic agents can be administered at the same frequency as the frequency of administration of the PD-1 axis binding antagonist and the anti-TIGIT antagonist antibody (Q2W, Q3W, or Q4W) or at a different frequency (e.g., 3-weeks on/1 -week off schedule).
  • the PD-1 axis binding antagonist and the anti-TIGIT antagonist antibody are administered every two weeks and the one or more chemotherapeutic agents is administered every week, 3-weeks on/1 -week off, every two weeks, every three weeks, or every four weeks.
  • the PD-1 axis binding antagonist and the anti-TIGIT antagonist antibody are administered every three weeks and the one or more chemotherapeutic agents is administered every week, two weeks, every three weeks, or every four weeks.
  • the PD-1 axis binding antagonist and the anti-TIG IT antagonist antibody are administered every four weeks and the one or more chemotherapeutic agents is administered every week, 3-weeks on/1 -week off, every two weeks, every three weeks, or every four weeks.
  • a chemotherapeutic agent is administered multiple times per week (e.g., 2, 3, 4, 5, 6 or 7 times per week (e.g., at Days 1 , 2, and 3 of a dosing cycle)).
  • the dose of a chemotherapeutic agent is reduced after one or more initial doses (e.g., after one, two, three, four, or more initial doses).
  • a subsequent dose of the chemotherapeutic agent e.g., a platinum-based chemotherapeutic agent (e.g., carboplatin or cisplatin) and/or one or more non-platinum-based chemotherapeutic agents (e.g., an antimetabolite (e.g., pemetrexed or gemcitabine) can be administered at about 95%, 90%, 85%, 80%, 75%, 70%, 65%, 60%, 55%, 50%, 45%, 40%, 35%, 30%, 25%, 20%, 15%, 10%, or 5% of the initial dose.
  • a platinum-based chemotherapeutic agent e.g., carboplatin or cisplatin
  • non-platinum-based chemotherapeutic agents e.g., an antimetabolite (e.g., pe
  • administering results in a CR or a PR.
  • the anti-TIG IT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody, such as atezolizumab
  • the platinum-based chemotherapeutic agent e.g., carboplatin or cisplatin
  • the antimetabolite e.g., pemetrexed
  • administering results in an increase in progression-free survival of the subject or population of subjects.
  • the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody, such as atezolizumab
  • the platinum-based chemotherapeutic agent e.g., carboplatin or cisplatin
  • the antimetabolite e.g., pemetrexed
  • administering extends OS of the subject or population of subjects.
  • the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody, such as atezolizumab
  • the platinum-based chemotherapeutic agent e.g., carboplatin or cisplatin
  • the antimetabolite e.g., pemetrexed
  • the subject or population of subjects receiving the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody, such as atezolizumab
  • the platinum-based chemotherapeutic agent e.g., carboplatin or cisplatin
  • the antimetabolite e.g., pemetrexed
  • a lung cancer e.g., an NSCLC (e.g., non-squamous NSCLC (e.g., locally advanced unresectable or metastatic non-squamous NSCLC (e.g., Stage IV non-squamous NSCLC))).
  • NSCLC e.g., non-squamous NSCLC (e.g., locally advanced unresectable or metastatic non-squamous NSCLC (e.g., Stage IV non
  • Dosing of agents Dosing of anti-TIG IT antagonist antibodies, PD-1 axis binding antagonists, and chemotherapeutic agents is described in Section lll(K).
  • the lung cancer may be an NSCLC (e.g., non-squamous NSCLC (e.g., locally advanced unresectable or metastatic non- squamous NSCLC (e.g., Stage IV non-squamous NSCLC))).
  • NSCLC non-squamous NSCLC
  • locally advanced unresectable or metastatic non- squamous NSCLC e.g., Stage IV non-squamous NSCLC
  • the subject or population of subjects has not received prior systemic therapy for the lung cancer.
  • the subject has no epidermal growth factor receptor ( EGFR ) or anaplastic lymphoma kinase ( ALK) genomic tumor aberrations.
  • EGFR epidermal growth factor receptor
  • ALK anaplastic lymphoma kinase
  • the subject does not have an EGFR gene mutation (e.g., a sensitizing EGFR gene mutation) or ALK gene rearrangement.
  • the subject has an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1 .
  • ECOG Eastern Cooperative Oncology Group
  • Methods for detecting the mutational status EGFR and ALK are well known in the art, and include, but are not limited to, sequencing DNA from clinical samples (e.g., tumor biopsies or blood samples (e.g., circulating tumor DNA in blood)) using a next-generation sequencing method, such as the targeted gene pulldown and sequencing method described in Frampton et al. ( Nature Biotechnology. 31 (11): 1023-1033, 2013), which is incorporated by reference herein in its entirety.
  • Such a next- generation sequencing method can be used with any of the methods disclosed herein to detect various mutations (e.g., insertions, deletions, base substitutions, focal gene amplifications, and/or homozygous gene deletions), while enabling the use of small samples (e.g., from small-core needle biopsies, fine- needle aspirations, and/or cell blocks) or fixed samples (e.g., formalin-fixed and paraffin-embedded (FFPE) samples).
  • Other methods for the detection of the mutational status of EGFR and ALK " include fluorescence in situ hybridization (FISH) and immunohistochemical (IHC) methods. Exemplary methods for the detection of the mutational status of ALK are disclosed in U.S. Patent No: 9,651 ,555, which is herein incorporated by reference in its entirety. In some instances, the VENTANA ® anti-ALK " (D5F3) IHC assay is used to determine the mutational status of the ALK gene.
  • the mutation is a sensitizing EGFR mutation.
  • Sensitizing EGFR mutations are well known in the art and include those described in U.S. Publication No: US 2018/0235968 and in Juan et al. (Therapeutic Advances in Medical Oncology. 9(3): 201-216, 2017), which are incorporated by reference herein in their entireties.
  • the sensitizing EGFR mutation is a mutation in any one of exons 18-21 (e.g., a mutation in exon 18, exon 19, exon 20, and/or exon 21 ).
  • the sensitizing EGFR mutation is a deletion of exon 19 (dell 9).
  • sensitizing EGFR mutation is a L858R point mutation in exon 21 .
  • the sensitizing EGFR mutation is a G719X point mutation in exon 18, wherein “X” is most commonly C, A, or S.
  • the sensitizing EGFR mutation is a G719S point mutation in exon 18.
  • the sensitizing EGFR mutation is a G719A point mutation in exon 18.
  • the sensitizing EGFR mutation is a S720F point mutation in exon 18.
  • the sensitizing EGFR mutation is a L861 Q point mutation in exon 21 .
  • the sensitizing EGFR mutation is a L861 R point mutation in exon 21 . In other instances, the sensitizing EGFR mutation is a T790M point mutation. In some instances, the sensitizing EGFR mutation is an E709X point mutation, where “X” is most commonly K, A, or H. In some instances, the sensitizing EGFR mutation is a S768I point mutation.
  • the mutation is an ALK gene rearrangement.
  • ALK gene rearrangements are well known in the art and include those described in U.S. Patent No: 9,651 ,555 and in Du et al. ( Thoracic Cancer. 9: 423-430, 2018), which are incorporated herein by reference in their entireties.
  • the ALK gene rearrangement results in the creation of an oncogenic ALK tyrosine kinase that activates downstream signaling pathways resulting in increased cell proliferation and survival.
  • the ALK " gene rearrangement is an ALK " rearrangement with a gene selected from the group consisting of EML4, KIF5B, KLC1, TFG, TPR, HIP1, STRN, DCTN1, SQSTM1, NPM1, BCL11A, BIRC6, RANBP2, ARC, CLTC, TMP4, and MSN resulting in the formation of a fusion oncogene.
  • the ALK " gene rearrangement is an EML4 rearrangement with ALK resulting in the formation of the fusion oncogene EML4-ALK.
  • the subject does not have a pulmonary lymphoepithelioma-like carcinoma subtype of NSCLC.
  • Methods for detecting the subtype of NSCLC are well known in the art, and include, but are not limited to, methods of determination by histopathological criteria, or by molecular features (e.g., a subtype characterized by expression of one or a combination of biomarkers (e.g., particular genes or proteins encoded by said genes)).
  • the sample is selected from the group consisting of a tissue sample, a whole blood sample, a serum sample, and a plasma sample.
  • the tissue sample is a tumor sample.
  • the subject does not have an active Epstein-Barr virus (EBV) infection or a known or suspected chronic active EBV infection.
  • Indicators of active or chronic active EBV infections for use in the methods described herein can include, but are not limited to, EBV IgM, EBV IgG, Epstein-Barr nuclear antigen (EBNA), and Epstein- Barr viral particles detected in a sample from the subject (e.g., a blood or serum sample).
  • EBV IgM EBV IgG
  • Epstein-Barr nuclear antigen (EBNA) Epstein-Barr viral particles
  • EBNA Epstein-Barr nuclear antigen
  • Epstein-Barr viral particles in a sample from a subject are well known in the art, and include, but are not limited to, methods involving serological diagnosis (e.g., the detection of EBV DNA (e.g., by PCR analysis of a blood sample for the detection of EBV viral particles) or EBV antigens or anti-EBV antibodies (e.g., detection of EBNA, EBV IgM, or EBV IgG using heterophilic antibodies).
  • the sample is selected from the group consisting of a whole blood sample, a serum sample, and a plasma sample.
  • the subject is negative for EBV IgM and/or negative by EBV PCR.
  • the subject is negative for EBV IgM and/or negative by EBV PCR and is positive for EBV IgG and/or positive for Epstein-Barr nuclear antigen (EBNA).
  • EBNA Epstein-Barr nuclear antigen
  • the subject is negative for EBV IgG and/or negative for EBNA.
  • the subject has a PD-L1 selected tumor (e.g., a tumor PD-L1 expression with a minimum PD-L1 -positive tumor cell fraction or TPS > 30% (e.g., > 50%) as determined by an IHC with the SP263 or 22C3 antibody or a proportion of tumor area occupied by PD-L1 expressing tumor- infiltrating immune cells (ICs) is greater than or equal to 1% in the tumor sample as determined by an IHC with the SP142 antibody).
  • a PD-L1 selected tumor e.g., a tumor PD-L1 expression with a minimum PD-L1 -positive tumor cell fraction or TPS > 30% (e.g., > 50%) as determined by an IHC with the SP263 or 22C3 antibody or a proportion of tumor area occupied by PD-L1 expressing tumor- infiltrating immune cells (ICs) is greater than or equal to 1% in the tumor sample as determined by an IHC with the SP142 antibody).
  • ICs
  • the PD-L1 selected tumor is a tumor that has been determined to have a PD-L1 -positive tumor cell fraction or PD-L1 TPS of greater than, or equal to, 30% (e.g., greater than, or equal to, 50%) by an immunohistochemical (IHC) assay.
  • the PD-L1 selected tumor is a tumor that has been determined to have a proportion of tumor area occupied by PD-L1 expressing immune cells (ICs) greater than or equal to 1% by an immunohistochemical (IHC) assay.
  • the IHC assay uses the anti-PD-L1 antibody SP263, 22C3, SP142, or 28-8.
  • the IHC assay uses anti-PD-L1 antibody SP263. In some instances, the IHC assay uses anti-PD-L1 antibody SP142. In some instances, the IHC assay uses anti-PD-L1 antibody 22C3. In some instances, the tumor sample has been determined to have a TPS of greater than, or equal to, 50%.
  • the PD-L1 -positive tumor cell fraction is greater than, or equal to, 50% (e.g., as determined by positive staining with the anti-PD-L1 antibody SP263 (e.g., using the Ventana assay), as determined by positive staining with the anti-PD-L1 antibody 22C3 (e.g., using the pharmDx assay), or as determined by positive staining with the anti-PD-L1 antibody 28-8). In some embodiments, the PD-L1 - positive tumor cell fraction is greater than, or equal to, 30%, as determined by positive staining with the anti-PD-L1 antibody SP142.
  • the ICs has been determined to be greater than, or equal to, 1% (e.g., as determined using the Ventana (SP142) PD-L1 IHC assay). In some instances, the ICs has been determined to be greater than, or equal to, 5% (e.g., as determined using the Ventana (SP142) PD-L1 IHC assay). In some instances, the ICs has been determined to be greater than, or equal to, 10% (e.g., as determined using the Ventana (SP142) PD-L1 IHC assay).
  • the ICs has been determined to be greater than, or equal to, 1% and less than 50% (e.g., as determined using the Ventana (SP142) PD-L1 IHC assay). In some instances, the ICs has been determined to be greater than, or equal to, 1% and less than 30% (e.g., as determined using the Ventana (SP142) PD-L1 IHC assay).
  • a tumor sample obtained from the individual has a detectable protein expression level of PD-L1 .
  • the detectable protein expression level of PD-L1 has been determined by an IHC assay.
  • the IHC assay uses anti-PD-L1 antibody SP142.
  • the tumor sample has been determined to have a detectable expression level of PD-L1 in greater than, or equal to, 1% of the tumor cells in the tumor sample.
  • the tumor sample has been determined to have a detectable expression level of PD-L1 in greater than, or equal to, 1% and less than 5% of the tumor cells in the tumor sample.
  • the tumor sample has been determined to have a detectable expression level of PD-L1 in greater than, or equal to, 5% and less than 50% of the tumor cells in the tumor sample. In some instances, the tumor sample has been determined to have a detectable expression level of PD-L1 in greater than, or equal to, 50% of the tumor cells in the tumor sample. In some instances, the tumor sample has been determined to have a detectable expression level of PD-L1 in tumor-infiltrating immune cells that comprise greater than, or equal to, 1% of the tumor sample. In some instances, the tumor sample has been determined to have a detectable expression level of PD-L1 in tumor-infiltrating immune cells that comprise greater than, or equal to, 1% and less than 5% of the tumor sample.
  • the tumor sample has been determined to have a detectable expression level of PD-L1 in tumor-infiltrating immune cells that comprise greater than, or equal to, 5% and less than 10% of the tumor sample. In some instances, the tumor sample has been determined to have a detectable expression level of PD-L1 in tumor-infiltrating immune cells that comprise greater than, or equal to, 10% of the tumor sample.
  • the subject has a lung cancer (e.g., NSCLC (e.g., non-squamous NSCLC (e.g., locally advanced unresectable or metastatic non-squamous NSCLC (e.g., Stage IV non-squamous NSCLC))) that has not been evaluated from PD-L1 expression.
  • NSCLC non-squamous NSCLC
  • metastatic non-squamous NSCLC e.g., Stage IV non-squamous NSCLC
  • the subject having a lung cancer has not been determined to have a PD-L1 -positive tumor cell fraction greater than, or equal to, 50% (e.g., the subject has not been determined to have a PD-L1 -positive tumor cell fraction greater than, or equal to, 45%, 40%, 35%, or 30%).
  • the subject has not been determined to have a TPS of greater than, or equal to, 50% PD-L1 -positive (e.g., the subject has not been determined to have a TPS of greater than, or equal to, 45% PD-L1 -positive,
  • PD-L1 -positive 40% PD-L1 -positive, 35% PD-L1 -positive, or 30% PD-L1 -positive), e.g., as assessed using any of the IHC methods described herein or known in the art.
  • the subject having a lung cancer e.g., NSCLC (e.g., non-squamous NSCLC (e.g., locally advanced unresectable or metastatic non-squamous NSCLC (e.g., Stage IV non-squamous NSCLC))
  • NSCLC e.g., non-squamous NSCLC (e.g., locally advanced unresectable or metastatic non-squamous NSCLC (e.g., Stage IV non-squamous NSCLC)
  • a PD-L1 -positive tumor cell fraction of less than 50% (e.g., from 1 % to 50%, from 1 % to 49%, from 5% to 45%, from 10% to 40%, from 15% to 35%, or from 20% to 30%, e.g., from 1 % to 5%, from 5% to 10%, from 10% to 15%, from 15% to 20%, from 20% to 25%, from 25% to 30%, from 30% to 35%, from 35% to 40%, from 40%
  • the subject having a lung cancer has been determined to have a PD-L1 -positive tumor cell fraction from 1 - 49% (e.g., from 1 % to 5%, from 5% to 10%, from 10% to 15%, from 15% to 20%, from 20% to 25%, from 25% to 30%, from 30% to 35%, from 35% to 40%, from 40% to 45%, or from 45% to 49%).
  • the subject having a lung cancer has been determined to have a PD-L1 -positive tumor cell fraction of less than 1% (e.g., about 0%, or an undetectable PD-L1 expression).
  • the subject having a lung cancer e.g., NSCLC (e.g., non- squamous NSCLC (e.g., locally advanced unresectable or metastatic non-squamous NSCLC (e.g., Stage IV non-squamous NSCLC))
  • NSCLC non- squamous NSCLC
  • a TPS of less than 50% PD-L1 -positive (e.g., from 1 % to 50%, from 1 % to 49%, from 5% to 45%, from 10% to 40%, from 15% to 35%, or from 20% to 30% PD-L1 -positive, e.g., from 1% to 5%, from 5% to 10%, from 10% to 15%, from 15% to 20%, from 20% to 25%, from 25% to 30%, from 30% to 35%, from 35% to 40%, from 40% to 45%, or from 45% to 49% PD-L1 -positive, e.g., less than 49%, less than 45%, less than 40%,
  • the subject having a lung cancer has been determined to have a TPS from 1 -49% PD-L1 -positive (e.g., from 1 % to 5%, from 5% to 10%, from 10% to 15%, from 15% to 20%, from 20% to 25%, from 25% to 30%, from 30% to 35%, from 35% to 40%, from 40% to 45%, or from 45% to 49% PD-L1 -positive).
  • the subject having a lung cancer has been determined to have a TPS of less than 1% PD-L1 -positive (e.g., about 0%, or an undetectable PD-L1 expression).
  • the subject has an NSCLC (e.g., non-squamous NSCLC (e.g., locally advanced unresectable or metastatic non-squamous NSCLC (e.g., Stage IV non-squamous NSCLC))) that has not been evaluated from PD-L1 expression.
  • NSCLC non-squamous NSCLC
  • the subject having an NSCLC has not been determined to have a PD-L1 -positive tumor cell fraction greater than, or equal to, 50% (e.g., the subject has not been determined to have a PD-L1 -positive tumor cell fraction greater than, or equal to, 45%, 40%, 35%, or 30%).
  • the subject has not been determined to have a TPS of greater than, or equal to, 50% PD-L1 -positive (e.g., the subject has not been determined to have a TPS of greater than, or equal to, 45% PD-L1 -positive, 40% PD-L1 -positive, 35% PD-L1 -positive, or 30% PD-L1 -positive), e.g., as assessed using any of the IHC methods described herein or known in the art.
  • the subject having an NSCLC has been determined to have a PD-L1 -positive tumor cell fraction of less than 50% (e.g., from 1% to 50%, from 1 % to 49%, from 5% to 45%, from 10% to 40%, from 15% to 35%, or from 20% to 30%, e.g., from 1% to 5%, from 5% to 10%, from 10% to 15%, from 15% to 20%, from 20% to 25%, from 25% to 30%, from 30% to 35%, from 35% to 40%, from 40% to 45%, or from 45% to 49%, e.g., less than 49%, less than 45%, less than 40%, less than 35%, less than 30%, less than 25%, less than 20%, less than 15%, less than 10%, less than 9%, less than 8%
  • the subject having an NSCLC has been determined to have a PD-L1 -positive tumor cell fraction from 1 -49% (e.g., from 1% to 5%, from 5% to 10%, from 10% to 15%, from 15% to 20%, from 20% to 25%, from 25% to 30%, from 30% to 35%, from 35% to 40%, from 40% to 45%, or from 45% to 49%).
  • the subject having an NSCLC has been determined to have a PD-L1 -positive tumor cell fraction of less than 1% (e.g., about 0%, or an undetectable PD-L1 expression).
  • the subject having an NSCLC has been determined to have a TPS from 1 -49% PD-L1 -positive (e.g., from 1 % to 5%, from 5% to 10%, from 10% to 15%, from 15% to 20%, from 20% to 25%, from 25% to 30%, from 30% to 35%, from 35% to 40%, from 40% to 45%, or from 45% to 49% PD-L1 -positive).
  • the subject having an NSCLC has been determined to have a TPS of less than 1% PD-L1 -positive (e.g., about 0%, or an undetectable PD-L1 expression).
  • a tumor sample obtained from the individual has a detectable nucleic acid expression level of PD-L1 .
  • the detectable nucleic acid expression level of PD-L1 has been determined by RNA-seq, RT-qPCR, qPCR, multiplex qPCR or RT-qPCR, microarray analysis,
  • the sample is selected from the group consisting of a tissue sample, a whole blood sample, a serum sample, and a plasma sample.
  • the tissue sample is a tumor sample.
  • the tumor sample comprises tumor-infiltrating immune cells, tumor cells, stromal cells, and any combinations thereof.
  • a tumor sample obtained from a subject having a lung cancer e.g., NSCLC (e.g., non-squamous NSCLC (e.g., locally advanced unresectable or metastatic non-squamous NSCLC (e.g., Stage IV non-squamous NSCLC))
  • NSCLC non-squamous NSCLC
  • metastatic non-squamous NSCLC e.g., Stage IV non-squamous NSCLC
  • the nucleic acid expression level of PD-L1 has been determined by RNA-seq, RT- qPCR, qPCR, multiplex qPCR or RT-qPCR, microarray analysis, SAGE, MassARRAY technique, ISH, or a combination thereof.
  • the sample is selected from the group consisting of a tissue sample, a whole blood sample, a serum sample, and a plasma sample.
  • the tissue sample is a tumor sample.
  • the tumor sample comprises tumor-infiltrating immune cells, tumor cells, stromal cells, and any combinations thereof.
  • the subject having a lung cancer has received no prior systemic treatment for the lung cancer (e.g., no prior systemic treatment with curative intent).
  • NSCLC e.g., non-squamous NSCLC (e.g., locally advanced unresectable or metastatic non-squamous NSCLC (e.g., Stage IV non-squamous NSCLC)
  • the subject has a locally advanced lung cancer and has received no prior systemic treatment for the locally advanced lung cancer.
  • the subject has an NSCLC (e.g., a non-squamous NSCLC, e.g., a locally advanced unresectable or metastatic non-squamous NSCLC) and has received no prior systemic treatment for the NSCLC (e.g., a non-squamous NSCLC, e.g., a locally advanced unresectable or metastatic non-squamous NSCLC).
  • NSCLC e.g., a non-squamous NSCLC, e.g., a locally advanced unresectable or metastatic non-squamous NSCLC
  • Prior systemic treatments include prior neo-adjuvant, adjuvant chemotherapy, radiotherapy, and chemoradiotherapy with curative intent for non-metastatic disease.
  • the subject having a lung cancer e.g., NSCLC (e.g., non-squamous NSCLC (e.g., locally advanced unresectable or metastatic non-squamous NSCLC (e.g., Stage IV non-squamous NSCLC))
  • NSCLC e.g., non-squamous NSCLC (e.g., locally advanced unresectable or metastatic non-squamous NSCLC (e.g., Stage IV non-squamous NSCLC)
  • a lung cancer e.g., NSCLC (e.g., non-squamous NSCLC (e.g., locally advanced unresectable or metastatic non-squamous NSCLC (e.g., Stage IV non-squamous NSCLC)
  • a lung cancer e.g., NSCLC (e.g., non-squamous NSCLC (e.g., locally advanced unresectable or metastatic non
  • lung cancer e.g., early stage lung cancer (e.g., resectable lung cancer (e.g., NSCLC (e.g., squamous or non-squamous NSCLC))
  • resectable lung cancer e.g., NSCLC (e.g., squamous or non-squamous NSCLC)
  • an anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • a PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody, such as atezolizumab, or an anti- PD-1 antagonist antibody, such as pembrolizumab.
  • At least one dosing cycle is administered as a neoadjuvant treatment.
  • the treatment is a neoadjuvant treatment.
  • at least one dosing cycle is administered as an adjuvant treatment.
  • the treatment is an adjuvant treatment.
  • the treatment comprises a neoadjuvant treatment and an adjuvant treatment.
  • the lung cancer is a resectable lung cancer.
  • the lung cancer is an early stage lung cancer (e.g., stage II, MIA, or NIB lung cancer).
  • the lung cancer is an NSCLC (e.g., a squamous or non-squamous NSCLC).
  • the lung cancer is PD-L1 positive (e.g., PD-L1 high).
  • the lung cancer has no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumor aberrations.
  • the subject has not been previously treated for lung cancer (e.g., a prior surgery, a prior immunotherapy, a prior chemotherapy, or a prior radiotherapy).
  • the subject is eligible to receive a platinum-based chemotherapy regimen.
  • the subject is eligible for an R0 resection with curative intent.
  • the subject is preferably a human.
  • the present invention includes methods and uses for treating a subject having a resectable lung cancer (e.g., a resectable NSCLC (e.g., a resectable squamous or non-squamous NSCLC)), the method comprising administering to the subject one or more dosing cycles of an anti-TIGIT antagonist antibody (e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab) at a dose (e.g., a fixed dose) of between about 30 mg to about 1200 mg every three weeks (e.g., on Day 1 of each 21 -day dosing cycle) and a PD-1 axis binding antagonist (e.g., an anti-PD-L1 antagonist antibody, such as atezolizumab, or an anti-PD-1 antagonist antibody, such as e.g., pembrolizumab) at a dose (e.g., a fixed dose) of between about 80 mg to about 1600 mg
  • the method comprises administering to the subject one or more dosing cycles of an anti-TIGIT antagonist antibody (e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab) at a dose (e.g., a fixed dose) of between 30 mg to 1200 mg every three weeks (e.g., on Day 1 of each 21 -day dosing cycle) and a PD-1 axis binding antagonist (e.g., an anti-PD-L1 antagonist antibody, such as atezolizumab, or an anti-PD-1 antagonist antibody, such as e.g., pembrolizumab) at a dose (e.g., a fixed dose) of between 80 mg to 1600 mg every three weeks (e.g., on Day 1 of each 21 -day dosing cycle).
  • an anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • a dose
  • the present invention includes methods and uses involving administration of an effective amount of an anti-TIGIT antagonist antibody (e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab) and a PD-1 axis binding antagonist (e.g., an anti-PD-L1 antagonist antibody, such as atezolizumab, or an anti-PD-1 antagonist antibody, such as e.g., pembrolizumab) to a subject in need thereof every three weeks (e.g., on Day 1 of each 21 -day dosing cycle).
  • an anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • a PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody, such as atezolizumab, or an anti-PD-1 antagonist antibody, such as e.g., pembrolizumab
  • At least one of the dosing cycles comprises administering to the subject the anti-TIGIT antagonist antibody at a dose (e.g., a fixed dose) of between about 30 mg to about 1200 mg every three weeks (e.g., a dose of 600 mg every three weeks) and the PD-1 axis binding antagonist at a dose (e.g., a fixed dose) of between about 80 mg to about 1600 mg every three weeks (e.g., a dose of about 1200 mg every three weeks) as a neoadjuvant treatment.
  • a dose e.g., a fixed dose
  • a dose e.g., a fixed dose of between about 30 mg to about 1200 mg every three weeks (e.g., a dose of 600 mg every three weeks) and the PD-1 axis binding antagonist at a dose (e.g., a fixed dose) of between about 80 mg to about 1600 mg every three weeks (e.g., a dose of about 1200 mg every three weeks) as a n
  • At least one of the dosing cycles comprises administering to the subject the anti-TIGIT antagonist antibody at a dose (e.g., a fixed dose) of between about 30 mg to about 1200 mg every three weeks (e.g., a dose of 600 mg every three weeks) and the PD-1 axis binding antagonist at a dose (e.g., a fixed dose) of between about 80 mg to about 1600 mg every three weeks (e.g., a dose of about 1200 mg every three weeks) as an adjuvant treatment.
  • a dose e.g., a fixed dose
  • At least one of the dosing cycles comprises administering to the subject the anti-TIGIT antagonist antibody at a dose (e.g., a fixed dose) of between 30 mg to 1200 mg every three weeks (e.g., a dose of 600 mg every three weeks) and the PD-1 axis binding antagonist at a dose (e.g., a fixed dose) of between 80 mg to 1600 mg every three weeks (e.g., a dose of 1200 mg every three weeks) as a neoadjuvant treatment.
  • a dose e.g., a fixed dose
  • the PD-1 axis binding antagonist at a dose (e.g., a fixed dose) of between 80 mg to 1600 mg every three weeks (e.g., a dose of 1200 mg every three weeks) as a neoadjuvant treatment.
  • At least one of the dosing cycles comprises administering to the subject the anti-TIGIT antagonist antibody at a dose (e.g., a fixed dose) of between 30 mg to 1200 mg every three weeks (e.g., a dose of 600 mg every three weeks) and the PD-1 axis binding antagonist at a dose (e.g., a fixed dose) of between 80 mg to 1600 mg every three weeks (e.g., a dose of 1200 mg every three weeks) as an adjuvant treatment.
  • a dose e.g., a fixed dose
  • the subject receiving the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody, such as atezolizumab
  • a lung cancer e.g., an early stage lung cancer (e.g., a resectable lung cancer (e.g., an NSCLC (e.g., a squamous or non-squamous NSCLC))
  • a lung cancer e.g., an early stage lung cancer (e.g., a resectable lung cancer (e.g., an NSCLC (e.g., a squamous or non-squamous NSCLC))
  • NSCLC e.g., a squamous or non-squamous NSCLC
  • the PD-1 axis binding antagonist anti-TIGIT antagonist antibody may be administered in any suitable manner known in the art.
  • the PD-1 axis binding antagonist and anti-TIGIT antagonist antibody may be administered sequentially (on different days) or concurrently (on the same day or during the same treatment cycle).
  • the anti-TIGIT antagonist antibody and/or the PD-1 axis binding antagonist are administered on about Day 1 (e.g., Day -3, Day -2, Day -1 , Day 1 , Day 2, or Day 3) of a dosing cycle.
  • the PD-1 axis binding antagonist and anti-TIGIT antagonist antibody may be administered on the same day.
  • the PD-1 axis binding antagonist is administered before the anti-TIGIT antagonist antibody. In some instances, the PD-1 axis binding antagonist is administered after the anti-TIGIT antagonist antibody. In some instances, the PD-1 axis binding antagonist is administered simultaneously with the anti-TIGIT antagonist antibody. In some instances, the PD-1 axis binding antagonist may be administered prior to an anti-TIGIT antagonist antibody that is administered on the same day. In some instances, the PD-1 axis binding antagonist may be administered after to an anti-TIGIT antagonist antibody that is administered on the same day. In yet other instances, the PD-1 axis binding antagonist is administered at the same time as the anti-TIGIT antagonist antibody.
  • the PD-1 axis binding antagonist is in a separate composition as the anti-TIGIT antagonist antibody. In some instances, the PD-1 axis binding antagonist is in the same composition as the anti-TIGIT antagonist antibody. In some instances, the PD-1 axis binding antagonist is administered through a separate intravenous line from any other therapeutic agent administered to the patient on the same day.
  • the PD-1 axis binding antagonist and anti-TIGIT antagonist antibody may be administered by the same route of administration or by different routes of administration.
  • the PD-1 axis binding antagonist is administered intravenously, intramuscularly, subcutaneously, topically, orally, transdermally, intraperitoneally, intraorbitally, by implantation, by inhalation, intrathecally, intraventricularly, or intranasally. In some instances, the PD-1 axis binding antagonist is administered intravenously. In some instances, the anti-TIGIT antagonist antibody is administered intravenously, intramuscularly, subcutaneously, topically, orally, transdermally, intraperitoneally, intraorbitally, by implantation, by inhalation, intrathecally, intraventricularly, or intranasally. In some instances, the anti-TIGIT antagonist antibody is administered intravenously.
  • the observation period is between about 30 minutes to about 60 minutes in length.
  • the anti-TIGIT antagonist antibody and/or PD-1 axis binding antagonist are administered intravenously or subcutaneously. In some instances, the intravenous infusion is over 30 ⁇ 10 minutes and/or over 60 ⁇ 15 minutes.
  • Atezolizumab may be administered intravenously over 60 minutes; if the first infusion is tolerated, all subsequent infusions may be delivered over 30 minutes.
  • the PD-1 axis binding antagonist is not administered as an intravenous push or bolus.
  • tiragolumab may be administered intravenously over 60 minutes; if the first infusion is tolerated, all subsequent infusions may be delivered over 30 minutes.
  • the anti-TIGIT antagonist antibody is not administered as an intravenous push or bolus.
  • each dosing cycle may have any suitable length, e.g., about 7 days (about 5, 6, 7, 8, or 9 days), about 14 days (e.g., about 12, 13, 14, 15, or 16 days), about 21 days (e.g., about 18, 19, 20, 21 , 22, 23, or 24 days), about 28 days (about 25, 26, 27, 28, 29, 30, or 31 days), or longer. In some instances, each dosing cycle is about 21 days.
  • a PD-L1 expression level of a sample e.g., a tumor sample, a blood sample (e.g., a plasma sample), or a lymph sample
  • the sample has been determined to have a detectable expression level of PD-L1 (e.g., a detectable protein and/or nucleic acid expression level of PD-L1).
  • the detectable expression level of PD-L1 is a detectable protein expression level of PD-L1 .
  • the detectable expression level of PD-L1 is a PD-L1 -positive tumor cell fraction (e.g., a PD-L1 -positive tumor cell fraction of greater than or equal to 50%).
  • the detectable protein expression level of PD-L1 has been determined by an immunohistochemical (IHC) assay comprising staining with an anti- PD-L1 antibody suitable for staining (e.g., anti-PD-L1 antibody SP263).
  • the IHC assay is a Ventana SP263 IHC assay.
  • the detectable expression level of PD-L1 is a detectable nucleic acid expression level of PD-L1 .
  • the mutational status of epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) is determined.
  • the method further comprises obtaining a sample from the subject.
  • the method further comprises determining the expression level of PD-L1 .
  • the first dosing cycle is initiated prior to a surgery (e.g., a segmentectomy, a lobectomy, a bilobectomy, or a pneumonectomy).
  • a surgery e.g., a segmentectomy, a lobectomy, a bilobectomy, or a pneumonectomy.
  • one or more dosing cycles are completed prior to a surgery.
  • at least 1 , 2, 3, or 4 dosing cycles e.g., 1 , 2, 3, 4, 5, 6,
  • dosing cycles are completed prior to a surgery. In some instances, 4 dosing cycles are completed prior to a surgery. In some instances, one or more dosing cycles (e.g., 1 , 2, 3, 4, 5, 6, 7, 8, 9,
  • the treatment includes a surgery.
  • the surgery is a segmentectomy, a lobectomy, a bilobectomy, or a pneumonectomy.
  • the treatment includes a radiotherapy (e.g., a post-operative radiotherapy).
  • the treating results in an increase in major pathological response (MPR) rate as compared to a reference MPR rate. In some instances, the treating results in a pathological complete response (pCR) and/or an increase in pCR rate as compared to a reference pCR rate. In some instances, the treating results in an increase in event-free survival (EFS) as compared to a reference EFS time. In some instances, the treating results in an increase in OS as compared to a reference OS time.
  • MPR major pathological response
  • pCR pathological complete response
  • EFS event-free survival
  • the reference MPR rate, reference pCR rate, and/or reference EFS time are an MPR rate, a pCR rate, and/or an EFS time of a population of subjects who have received a treatment comprising: (a) a PD-1 axis binding antagonist without an anti-TIGIT antagonist antibody; and/or (b) cisplatin and docetaxel or cisplatin, docetaxel, and bevacizumab.
  • administering results in an increase in MPR rate.
  • administration of the effective amount of the anti-TIGIT antagonist antibody results in a pCR.
  • administering results in an increase in EFS.
  • administration of the effective amount of the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody, such as atezolizumab
  • the treatment further comprises one or more chemotherapeutic agents (e.g., a platinum-based chemotherapeutic agent (e.g., carboplatin or cisplatin) and/or one or more non-platinum- based chemotherapeutic agents (e.g., an antimetabolite (e.g., pemetrexed or gemcitabine) and/or a taxane (e.g., paclitaxel, e.g., nab-paclitaxel)).
  • chemotherapeutic agents e.g., a platinum-based chemotherapeutic agent (e.g., carboplatin or cisplatin) and/or one or more non-platinum- based chemotherapeutic agents (e.g., an antimetabolite (e.g., pemetrexed or gemcitabine) and/or a taxane (e.g., paclitaxel, e.g., nab-paclitaxe
  • the neoadjuvant and/or adjuvant treatment further comprises one or more chemotherapeutic agents (e.g., a platinum-based chemotherapeutic agent (e.g., carboplatin or cisplatin) and/or one or more non-platinum-based chemotherapeutic agents (e.g., an antimetabolite (e.g., pemetrexed or gemcitabine) and/or a taxane (e.g., paclitaxel, e.g., nab-paclitaxel)).
  • chemotherapeutic agents e.g., a platinum-based chemotherapeutic agent (e.g., carboplatin or cisplatin) and/or one or more non-platinum-based chemotherapeutic agents (e.g., an antimetabolite (e.g., pemetrexed or gemcitabine) and/or a taxane (e.g., paclitaxel, e
  • the one or more chemotherapeutic agents are one or more platinum-based chemotherapeutic agents and/or one or more non-platinum-based chemotherapeutic agents.
  • the platinum-based chemotherapeutic agent is carboplatin or cisplatin.
  • the non-platinum-based chemotherapeutic agents are an antimetabolite (e.g., pemetrexed or gemcitabine) and/or a taxane (e.g., paclitaxel, e.g., nab-paclitaxel).
  • the one or more chemotherapeutic agents are a platinum-based chemotherapeutic agent (e.g., carboplatin or cisplatin) and a non-platinum-based chemotherapeutic agent (e.g., an antimetabolite (e.g., pemetrexed or gemcitabine) and/or a taxane (e.g., paclitaxel, e.g., nab-paclitaxel)).
  • a platinum-based chemotherapeutic agent e.g., carboplatin or cisplatin
  • a non-platinum-based chemotherapeutic agent e.g., an antimetabolite (e.g., pemetrexed or gemcitabine) and/or a taxane (e.g., paclitaxel, e.g., nab-paclitaxel)
  • At least one or more chemotherapeutic agents are: (a) carboplatin and pemetrexed; (b) carboplatin and paclitaxel; (c) cisplatin and pemetrexed; (d) carboplatin and gemcitabine; or (e) cisplatin and gemcitabine.
  • the one or more chemotherapeutic agents used in a treatment for non-squamous NSCLC are (a) carboplatin and pemetrexed, (b) carboplatin and paclitaxel, or (c) cisplatin and pemetrexed.
  • the one or more chemotherapeutic agents used in a treatment for squamous NSCLC are (a) carboplatin and gemcitabine, (b) carboplatin and paclitaxel, or (c) cisplatin and gemcitabine.
  • the treatment further comprises administering one or more chemotherapeutic agents (e.g., a platinum-based chemotherapeutic agent (e.g., carboplatin or cisplatin) and/or one or more non-platinum-based chemotherapeutic agents (e.g., an antimetabolite (e.g., pemetrexed or gemcitabine) and/or a taxane (e.g., paclitaxel, e.g., nab-paclitaxel)).
  • the one or more chemotherapeutic agents are administered every three weeks.
  • the one or more chemotherapeutic agents are administered on about Day 1 (e.g., Day -3, Day -2, Day -1 ,
  • the one or more chemotherapeutic agents are administered on about Day 1 (e.g., Day -3, Day -2, Day -1 , Day 1 , Day 2, or Day 3) and on about Day 8 (e.g., Day 5, Day 6, Day 7, Day 8, Day 9, Day 10, or Day 11 ) of one or more dosing cycles.
  • Day 1 e.g., Day -3, Day -2, Day -1 , Day 1 , Day 2, or Day 3
  • Day 8 e.g., Day 5, Day 6, Day 7, Day 8, Day 9, Day 10, or Day 11
  • the dosing cycles are, e.g., about 7 days (about 5, 6, 7, 8, or 9 days), about 14 days (e.g., about 12, 13, 14, 15, or 16 days), about 21 days (e.g., about 18, 19, 20, 21 , 22, 23, or 24 days), about 28 days (about 25, 26, 27, 28, 29, 30, or 31 days), or longer. In some instances, each dosing cycle is about 21 days.
  • the one or more chemotherapeutic agents are administered intravenously, intramuscularly, subcutaneously, topically, orally, transdermally, intraperitoneally, intraorbitally, by implantation, by inhalation, intrathecally, intraventricularly, or intranasally.
  • the one or more chemotherapeutic agents are administered after the PD-1 axis binding antagonist (e.g., atezolizumab) and/or anti-TIGIT antagonist antibody (e.g., an anti- TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab).
  • the PD-1 axis binding antagonist e.g., atezolizumab
  • anti-TIGIT antagonist antibody e.g., an anti- TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab.
  • the non-platinum- based chemotherapeutic agent e.g., an antimetabolite (e.g., pemetrexed or gemcitabine) and/or a taxane (e.g., paclitaxel, e.g., nab-paclitaxel)
  • the platinum-based chemotherapeutic agent e.g., carboplatin or cisplatin.
  • the present invention includes methods and uses for treating a subject having a resectable lung cancer (e.g., an early stage resectable lung cancer (e.g., a resectable NSCLC (e.g., a resectable squamous or non-squamous NSCLC))), the method comprising administering to the subject one or more dosing cycles of an anti-TIGIT antagonist antibody (e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab) at a dose (e.g., a fixed dose) of between about 30 mg to about 600 mg every three weeks, a PD-1 axis binding antagonist (e.g., an anti-PD-L1 antagonist antibody, such as atezolizumab, or an anti-PD-1 antagonist antibody, such as e.g., pembrolizumab) at a dose (e.g., a fixed dose) of between about 80 mg to about 1600 mg every three weeks,
  • the method comprising administering to the subject one or more dosing cycles of an anti-TIGIT antagonist antibody (e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab) at a dose (e.g., a fixed dose) of between 30 mg to 600 mg every three weeks, a PD-1 axis binding antagonist (e.g., an anti-PD-L1 antagonist antibody, such as atezolizumab, or an anti-PD-1 antagonist antibody, such as e.g., pembrolizumab) at a dose (e.g., a fixed dose) of between 80 mg to 1600 mg every three weeks, a platinum-based chemotherapeutic agent (e.g., cisplatin or carboplatin), and a non-platinum- based chemotherapeutic agent (e.g., an antimetabolite (e.g., pemetrexed or gemcitabine) or a taxane (e.g.
  • the present invention includes methods and uses for treating a subject having a lung cancer (e.g., an early stage lung cancer (e.g., a resectable lung cancer (e.g., an NSCLC (e.g., a squamous or non-squamous NSCLC))), the method comprising administering to the subject one or more dosing cycles of an anti-TIGIT antagonist antibody (e.g., an anti-TIG IT antagonist antibody as disclosed herein, e.g., tiragolumab), a PD-1 axis binding antagonist (e.g., an anti-PD-L1 antagonist antibody, such as atezolizumab, or an anti-PD-1 antagonist antibody, such as e.g., pembrolizumab), a platinum-based chemotherapeutic agent (e.g., cisplatin or carboplatin), and a non-platinum-based chemotherapeutic agent (e.g., an antimetabolite (e.g.
  • At least one of the dosing cycles comprises administering to the subject the anti-TIGIT antagonist antibody at a dose (e.g., a fixed dose) of between 30 mg to 600 mg every three weeks, the PD-1 axis binding antagonist at a dose (e.g., a fixed dose) of between 80 mg to 1600 mg every three weeks, a platinum-based chemotherapeutic agent (e.g., cisplatin or carboplatin), and a non-platinum- based chemotherapeutic agent (e.g., an antimetabolite (e.g., pemetrexed or gemcitabine) or a taxane (e.g., paclitaxel or nab-paclitaxel)) as a neoadjuvant treatment.
  • a dose e.g., a fixed dose
  • the PD-1 axis binding antagonist at a dose (e.g., a fixed dose) of between 80 mg to 1600 mg every three weeks
  • the present invention includes methods and uses for treating a subject having a resectable lung cancer (e.g., an early stage resectable lung cancer (e.g., a resectable NSCLC (e.g., a resectable squamous or non-squamous NSCLC))), the method comprising administering to the subject one or more dosing cycles of an anti-TIGIT antagonist antibody (e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab) at a dose (e.g., a fixed dose) of between about 30 mg to about 600 mg every three weeks, a PD-1 axis binding antagonist (e.g., an anti-PD-L1 antagonist antibody, such as atezolizumab, or an anti-PD-1 antagonist antibody, such as e.g., pembrolizumab) at a dose (e.g., a fixed dose) of between about 80 mg to about 1600 mg every three weeks, and
  • the method comprises administering to the subject one or more dosing cycles of an anti-TIGIT antagonist antibody (e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab) at a dose (e.g., a fixed dose) of between 30 mg to 600 mg every three weeks, a PD-1 axis binding antagonist (e.g., an anti-PD-L1 antagonist antibody, such as atezolizumab, or an anti-PD-1 antagonist antibody, such as e.g., pembrolizumab) at a dose (e.g., a fixed dose) of between 80 mg to 1600 mg every three weeks, and: (a) (i) a platinum-based chemotherapeutic agent (e.g., cisplatin or carboplatin) at a dose targeted to achieve an AUC of 5 mg/mL/min or an AUC of 6 mg/mL/min every three weeks; or (ii) a platinum-based chemotherapeut
  • the present invention includes methods and uses for treating a subject having a lung cancer (e.g., an early stage lung cancer (e.g., a resectable lung cancer (e.g., an NSCLC (e.g., a squamous or non-squamous NSCLC))), the method comprising administering to the subject one or more dosing cycles of an anti-TIGIT antagonist antibody (e.g., an anti-TIG IT antagonist antibody as disclosed herein, e.g., tiragolumab), a PD-1 axis binding antagonist (e.g., an anti-PD-L1 antagonist antibody, such as atezolizumab, or an anti-PD-1 antagonist antibody, such as e.g., pembrolizumab), a platinum-based chemotherapeutic agent (e.g., cisplatin or carboplatin), and a non-platinum-based chemotherapeutic agent (e.g., an antimetabolite (e.g.
  • At least one of the dosing cycles comprises administering to the subject: (a) the anti-TIGIT antagonist antibody at a dose (e.g., a fixed dose) of between 30 mg to 600 mg every three weeks; (b) the PD-1 axis binding antagonist at a dose (e.g., a fixed dose) of between 80 mg to 1600 mg every three weeks; (c) the platinum-based chemotherapeutic agent: (i) at a dose targeted to achieve an AUC of 5 mg/mL/min or an AUC of 6 mg/mL/min every three weeks; or (ii) at a dose of 75 mg/m 2 every three weeks; and (d) the non-platinum- based chemotherapeutic agent, wherein the non-platinum-based chemotherapeutic agent is: (i) an antimetabolite at a dose of 500 mg/m 2 every three weeks or 1000 mg/m 2 or 1250 mg/m 2 on Days 1 and 8 of each dosing cycle; or (ii)
  • the present invention includes methods and uses for treating a subject having a lung cancer (e.g., an early stage lung cancer (e.g., a resectable lung cancer (e.g., an NSCLC (e.g., a squamous or non-squamous NSCLC))), the method comprising administering to the subject one or more dosing cycles of an anti-TIGIT antagonist antibody and a PD-1 axis binding antagonist, wherein: (a) at least one of the dosing cycles comprises administering to the subject the anti-TIGIT antagonist antibody at a dose (e.g., a fixed dose) of between about 30 mg to about 1200 mg every three weeks and the PD-1 axis binding antagonist at a dose (e.g., a fixed dose) of between about 80 mg to about 1600 mg every three weeks as a neoadjuvant treatment; and (b) at least one of the dosing cycles comprises administering to the subject the anti-TIGIT antagonist antibody at a dose (
  • the method comprises administering to the subject one or more dosing cycles of an anti-TIGIT antagonist antibody and a PD-1 axis binding antagonist, wherein: (a) at least one of the dosing cycles comprises administering to the subject the anti-TIGIT antagonist antibody at a dose (e.g., a fixed dose) of between 30 mg to 1200 mg every three weeks and the PD-1 axis binding antagonist at a dose (e.g., a fixed dose) of between 80 mg to 1600 mg every three weeks as a neoadjuvant treatment; and (b) at least one of the dosing cycles comprises administering to the subject the anti-TIGIT antagonist antibody at a dose (e.g., a fixed dose) of between 30 mg to 1200 mg every three weeks and the PD-1 axis binding antagonist at a dose (e.g., a fixed dose) of between 80 mg to 1600 mg every three weeks as an adjuvant treatment.
  • a dose e.g., a fixed dose
  • the present invention includes methods and uses for treating a subject having a lung cancer (e.g., an early stage lung cancer (e.g., a resectable lung cancer (e.g., an NSCLC (e.g., a squamous or non-squamous NSCLC))), the method comprising administering to the subject one or more dosing cycles of an anti-TIGIT antagonist antibody and a PD-1 axis binding antagonist, wherein: (I) at least one of the dosing cycles is a neoadjuvant treatment and comprises administering to the subject: (a) the anti-TIGIT antagonist antibody at a dose (e.g., a fixed dose) of between about 30 mg to about 1200 mg every three weeks; (b) the PD-1 axis binding antagonist at a dose (e.g., a fixed dose) of between about 80 mg to about 1600 mg every three weeks as a neoadjuvant treatment; (c) a platinum-based chemotherapeut
  • the method comprises administering to the subject: (a) the anti-TIGIT antagonist antibody at a dose (e.g., a fixed dose) of between 30 mg to 1200 mg every three weeks; (b) the PD-1 axis binding antagonist at a dose (e.g., a fixed dose) of between 80 mg to 1600 mg every three weeks as a neoadjuvant treatment; (c) a platinum-based chemotherapeutic agent: (i) at a dose targeted to achieve an AUC of 5 mg/mL/min or an AUC of 6 mg/mL/min every three weeks; or (ii) at a dose of 75 mg/m 2 every three weeks; and (d) a non-platinum-based chemotherapeutic agent, wherein the non-platinum-based chemotherapeutic agent is: (i) an antimetabolite at a dose of 500 mg/m 2 every three weeks or 1000 mg/m 2 or 1250 mg/m 2 on Days 1 and 8 of each dosing cycle
  • the treatment may further comprise an additional therapy.
  • Any suitable additional therapy known in the art or described herein may be used.
  • the additional therapy may be radiation therapy (e.g., a post-operative radiotherapy), surgery, gene therapy, DNA therapy, viral therapy, RNA therapy, immunotherapy, bone marrow transplantation, nanotherapy, monoclonal antibody therapy, gamma irradiation, or a combination of the foregoing.
  • the additional therapy is the administration of side-effect limiting agents (e.g., agents intended to lessen the occurrence and/or severity of side effects of treatment, such as anti-nausea agents, a corticosteroid (e.g., prednisone or an equivalent, e.g., at a dose of 1-2 mg/kg/day), hormone replacement medicine(s), and the like).
  • side-effect limiting agents e.g., agents intended to lessen the occurrence and/or severity of side effects of treatment, such as anti-nausea agents, a corticosteroid (e.g., prednisone or an equivalent, e.g., at a dose of 1-2 mg/kg/day), hormone replacement medicine(s), and the like.
  • Also provided herein are methods for treating lung cancer in a subject comprising administering to the subject a treatment regimen comprising an effective amount of a PD-1 axis binding antagonist (e.g., atezolizumab) and/or anti-TIG IT antagonist antibody (e.g., an anti-TIG IT antagonist antibody as disclosed herein, e.g., tiragolumab) in combination with one or more chemotherapeutic agents (e.g., a platinum-based chemotherapeutic agent (e.g., carboplatin or cisplatin) and/or one or more non-platinum- based chemotherapeutic agents (e.g., an antimetabolite (e.g., pemetrexed or gemcitabine) and/or a taxane (e.g., paclitaxel, e.g., nab-paclitaxel))) and/or cancer therapy (e.g., a surgery and/or a radiotherapy).
  • a PD-1 axis binding antagonist may be administered in combination with an additional chemotherapy or chemotherapeutic agent (see definition above); a targeted therapy or targeted therapeutic agent; an immunotherapy or immunotherapeutic agent, for example, a monoclonal antibody; one or more cytotoxic agents (see definition above); or combinations thereof.
  • the lung cancer e.g., early-stage lung cancer (e.g., resectable lung cancer (e.g., NSCLC (e.g., squamous or non-squamous NSCLC))) is resectable (e.g., eligible for R0 resection with curative intent).
  • the lung cancer is an NSCLC.
  • the NSCLC is a squamous or non- squamous NSCLC.
  • the lung cancer is PD-L1 positive. In some instances, the lung cancer is PD-L1 high.
  • the lung cancer has no epidermal growth factor receptor ( EGFR ) or anaplastic lymphoma kinase ( ALK) genomic tumor aberrations.
  • the lung cancer is a stage II, IMA, or NIB lung cancer.
  • the subject in any of the methods, uses, or compositions for use described herein, is eligible for platinum-based chemotherapy. In some instances, the subject has an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1 . In some instances, the subject has not received a prior therapy (e.g., an immunotherapy, a chemotherapy, or a radiotherapy) for lung cancer.
  • ECOG Eastern Cooperative Oncology Group
  • PS Performance Status
  • the subject has not received a prior therapy (e.g., an immunotherapy, a chemotherapy, or a radiotherapy) for lung cancer.
  • ctDNA circulating tumor DNA
  • a sample e.g., a blood sample (e.g., a plasma sample)
  • ctDNA is assessed in a sample from the subject prior to day 1 of the first dosing cycle (e.g., the first dosing cycle of an anti-TIGIT antagonist antibody and a PD-1 axis binding antagonist).
  • ctDNA is assessed in a sample from the subject prior to surgery.
  • ctDNA is assessed in a sample from the subject after surgery.
  • the presence or level of immune cells may be assessed.
  • the presence or level of immune cells is assessed in a sample (e.g., a blood sample, a tumor tissue sample, or a lymph node sample) from the subject.
  • the presence or level of immune cells is assessed in a sample from the subject prior to surgery.
  • the presence or level of immune cells is assessed in a sample from the subject after surgery.
  • PD-L1 The expression of PD-L1 may be assessed as described in Section lll(L).
  • a subject’s response to the therapy can be characterized by one or more measures.
  • the treatment results in an increase in major pathological response (MPR) rate.
  • the treatment results in a pCR.
  • the treatment results in an increase in event-free survival (EFS).
  • EFS event-free survival
  • the treatment results in an improvement in patient-reported outcomes.
  • the treatment results in an improvement in patient-reported physical functioning, role functioning, or GHS/QoL, as measured by the EORTC-QLQ-C30.
  • the treatment results in an improvement in patient-reported lung cancer symptoms for cough, dyspnea, and chest pain, as measured through the use of the EORTC-QLQ-LC13.
  • the treatment results in an increase in MPR rate of the subject, e.g., as compared to treatment with the PD-1 axis binding antagonist without the anti-TIGIT antagonist antibody or as compared to treatment with the anti-TIGIT antagonist antibody without the PD-1 axis binding antagonist.
  • the treatment results in an increase in MPR rate of the subject, e.g., as compared to treatment with the PD-1 axis binding antagonist and the anti-TIGIT antagonist antibody without chemotherapy (e.g., a platinum-based doublet chemotherapy (e.g., a platinum-based chemotherapeutic agent (e.g., carboplatin or cisplatin) and a non-platinum-based chemotherapeutic agent (e.g., an antimetabolite (e.g., pemetrexed or gemcitabine) or a taxane (e.g., paclitaxel or nab- paclitaxel)))).
  • a platinum-based doublet chemotherapy e.g., a platinum-based chemotherapeutic agent (e.g., carboplatin or cisplatin) and a non-platinum-based chemotherapeutic agent (e.g., an antimetabolite (e.g., pemetrexed or gemcita
  • the treatment results in an increase in pCR of the subject, e.g., as compared to treatment with the PD-1 axis binding antagonist without the anti-TIG IT antagonist antibody or as compared to treatment with the anti-TIGIT antagonist antibody without the PD-1 axis binding antagonist.
  • the treatment results in an increase in pCR of the subject, e.g., as compared to treatment with the PD-1 axis binding antagonist and the anti-TIGIT antagonist antibody without chemotherapy (e.g., a platinum-based doublet chemotherapy (e.g., a platinum-based chemotherapeutic agent (e.g., carboplatin or cisplatin) and a non-platinum-based chemotherapeutic agent (e.g., an antimetabolite (e.g., pemetrexed or gemcitabine) or a taxane (e.g., paclitaxel or nab-paclitaxel)))).
  • a platinum-based doublet chemotherapy e.g., a platinum-based chemotherapeutic agent (e.g., carboplatin or cisplatin) and a non-platinum-based chemotherapeutic agent (e.g., an antimetabolite (e.g., pemetrexed or gemcitabine
  • the treatment extends OS of the subject, e.g., as compared to treatment with the PD-1 axis binding antagonist without the anti-TIGIT antagonist antibody or as compared to treatment with the anti-TIGIT antagonist antibody without the PD-1 axis binding antagonist.
  • the treatment extends OS of the subject, e.g., as compared to treatment with the PD-1 axis binding antagonist and the anti-TIGIT antagonist antibody without chemotherapy (e.g., a platinum-based doublet chemotherapy (e.g., a platinum-based chemotherapeutic agent (e.g., carboplatin or cisplatin) and a non- platinum-based chemotherapeutic agent (e.g., an antimetabolite (e.g., pemetrexed or gemcitabine) or a taxane (e.g., paclitaxel or nab-paclitaxel)))).
  • a platinum-based doublet chemotherapy e.g., a platinum-based chemotherapeutic agent (e.g., carboplatin or cisplatin) and a non- platinum-based chemotherapeutic agent (e.g., an antimetabolite (e.g., pemetrexed or gemcitabine) or a taxane (e
  • the treatment extends EFS of the subject, e.g., as compared to treatment with the PD-1 axis binding antagonist without the anti-TIGIT antagonist antibody or as compared to treatment with the anti-TIGIT antagonist antibody without the PD-1 axis binding antagonist.
  • the treatment extends EFS of the subject, e.g., as compared to treatment with the PD-1 axis binding antagonist and the anti-TIGIT antagonist antibody without chemotherapy (e.g., a platinum-based doublet chemotherapy (e.g., a platinum-based chemotherapeutic agent (e.g., carboplatin or cisplatin) and a non-platinum-based chemotherapeutic agent (e.g., an antimetabolite (e.g., pemetrexed or gemcitabine) or a taxane (e.g., paclitaxel or nab-paclitaxel)))).
  • a platinum-based doublet chemotherapy e.g., a platinum-based chemotherapeutic agent (e.g., carboplatin or cisplatin) and a non-platinum-based chemotherapeutic agent (e.g., an antimetabolite (e.g., pemetrexed or gemcitabine) or a
  • a treatment described increases the MPR rate by at least 1% (e.g., by 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100%).
  • a treatment described herein extends the pCR of the subject by at least about 2 months (e.g., by 2-120 months, by 2.5-100 months, by 3.0-80 months, by 4.0-60 months, by 5.0- 48 months, by 6.0-36 months, by 8.0-24 months, or by 10-12 months, e.g., by at least about 2.4 months, 2.5 months, 2.6 months, 2.7 months, 2.8 months, 2.9 months, 3.0 months, 3.1 months, 3.2 months, 3.3 months, 3.4 months, 3.5 months, 3.6 months, 3.7 months, 3.8 months, 3.9 months, 4.0 months, 4.1 months, 4.2 months, 4.3 months, 4.4 months, 4.5 months, 4.6 months, 4.7 months, 4.8 months, 4.9 months, 5.0 months, 5.5 months, 6.0 months, 6.5 months, 7.0 months, 7.5 months, 8.0 months, 8.5 months, 9.0 months, 9.5 months, 10 months, 10.5 months, 11 months, 11 .5 months, 12 months, 13 months, 10 months,
  • the treatment extends the pCR of the subject by at least about 4 months (e.g., by 4-120 months, by 5-100 months, by 6-80 months, by 7-60 months, by 8-48 months, by 9-36 months, or by 10-24 months, e.g., by at least about 4.0 months, 4.1 months, 4.2 months, 4.3 months, 4.4 months, 4.5 months, 4.6 months, 4.7 months, 4.8 months, 4.9 months, 5.0 months, 5.5 months, 6.0 months, 6.5 months, 7.0 months, 7.5 months, 8.0 months, 8.5 months, 9.0 months, 9.5 months, 10 months, 10.5 months, 11 months, 11 .5 months, 12 months, 13 months, 14 months, 15 months, 16 months, 17 months, 18 months, 19 months, 20 months, 21 months, 22 months, 23 months, 24 months, 25 months, 26 months, 27 months, 28 months, 29 months, 30 months, 31 months, 32 months, 33 months, 34 months, 35 months, or 36 months).
  • 4 months e.g., by
  • a treatment described herein extends the EFS of the subject by at least about 2 months (e.g., by 2-120 months, by 2.5-100 months, by 3.0-80 months, by 4.0-60 months, by 5.0- 48 months, by 6.0-36 months, by 8.0-24 months, or by 10-12 months, e.g., by at least about 2.4 months, 2.5 months, 2.6 months, 2.7 months, 2.8 months, 2.9 months, 3.0 months, 3.1 months, 3.2 months, 3.3 months, 3.4 months, 3.5 months, 3.6 months, 3.7 months, 3.8 months, 3.9 months, 4.0 months, 4.1 months, 4.2 months, 4.3 months, 4.4 months, 4.5 months, 4.6 months, 4.7 months, 4.8 months, 4.9 months, 5.0 months, 5.5 months, 6.0 months, 6.5 months, 7.0 months, 7.5 months, 8.0 months, 8.5 months, 9.0 months, 9.5 months, 10 months, 10.5 months, 11 months, 11 .5 months, 12 months, 13 months,
  • the treatment extends the EFS of the subject by at least about 4 months (e.g., by 4-120 months, by 5-100 months, by 6-80 months, by 7-60 months, by 8-48 months, by 9-36 months, or by 10-24 months, e.g., by at least about 4.0 months, 4.1 months, 4.2 months, 4.3 months, 4.4 months, 4.5 months, 4.6 months, 4.7 months, 4.8 months, 4.9 months, 5.0 months, 5.5 months, 6.0 months, 6.5 months, 7.0 months, 7.5 months, 8.0 months, 8.5 months, 9.0 months, 9.5 months, 10 months, 10.5 months, 11 months, 11 .5 months, 12 months, 13 months, 14 months, 15 months, 16 months, 17 months, 18 months, 19 months, 20 months, 21 months, 22 months, 23 months, 24 months, 25 months, 26 months, 27 months, 28 months, 29 months, 30 months, 31 months, 32 months, 33 months, 34 months, 35 months, or 36 months).
  • 4 months e.g., by 4-
  • OS is measured as the period of time from the start of treatment to death.
  • the treatment extends the OS of the subject by at least about 2 months (e.g., by 2-120 months, by 3-110 months, by 4-100 months, by 5-80 months, by 6-60 months, by 7-48 months, by 8-36 months, or by 10-24 months, e.g., by at least about 2 months, 2.1 months, 2.2 months, 2.3 months, 2.4 months, 2.5 months, 2.6 months, 2.7 months, 2.8 months, 2.9 months, 3.0 months, 3.1 months, 3.2 months, 3.3 months, 3.4 months, 3.5 months, 3.6 months, 3.7 months, 3.8 months, 3.9 months, 4.0 months, 4.1 months, 4.2 months, 4.3 months, 4.4 months, 4.5 months, 4.6 months, 4.7 months, 4.8 months, 4.9 months, 5.0 months, 5.5 months, 6.0 months, 6.5 months, 7.0 months, 7.5 months, 8.0 months, 8.5 months, 9.0 months, 9.5
  • the treatment extends the OS of the subject by at least about 3.3 months (e.g., by 3.3-120 months, by 4- 100 months, by 5-80 months, by 6-60 months, by 7-48 months, by 8-36 months, or by 10-24 months, e.g., by at least about 3.3 months, 3.4 months, 3.5 months, 3.6 months, 3.7 months, 3.8 months, 3.9 months, 4.0 months, 4.1 months, 4.2 months, 4.3 months, 4.4 months, 4.5 months, 4.6 months, 4.7 months, 4.8 months, 4.9 months, 5.0 months, 5.5 months, 6.0 months, 6.5 months, 7.0 months, 7.5 months, 8.0 months, 8.5 months, 9.0 months, 9.5 months, 10 months, 10.5 months, 11 months, 11 .5 months, 12 months, 13 months, 14 months, 15 months, 16 months, 17 months, 18 months, 19 months, 20 months, 21 months, 22 months, 23 months, 24 months, 25 months, 26 months, 27 months, 28 months, 29 months, 30
  • the treatment extends the OS of the subject by at least about 5.3 months (e.g., by 5.3-120, by 6-60 months, by 7-48 months, by 8-36 months, or by 10-24 months, e.g., by at least about 5.3 months, 5.5 months, 6.0 months, 6.5 months, 7.0 months, 7.5 months, 8.0 months, 8.5 months, 9.0 months, 9.5 months, 10 months, 10.5 months, 11 months, 11 .5 months, 12 months, 13 months, 14 months, 15 months, 16 months, 17 months, 18 months, 19 months, 20 months, 21 months, 22 months, 23 months, 24 months, 25 months, 26 months, 27 months, 28 months, 29 months, 30 months, 31 months, 32 months, 33 months, 34 months, 35 months, or 36 months).
  • 5.3 months e.g., by 5.3-120, by 6-60 months, by 7-48 months, by 8-36 months, or by 10-24 months, e.g., by at least about 5.3 months, 5.5 months, 6.0 months
  • Cervical cancer is the fourth most frequently diagnosed cancer and the fourth leading cause of cancer-related death. More than 500,000 women are diagnosed with cervical cancer annually worldwide, resulting in more than 300,000 deaths. Almost 90% of cervical cancer deaths occur in developing countries. In the United States, there are 13,000 new cases of invasive cervical cancer and approximately 4000 cancer-related deaths each year.
  • Treatment for early and locally advanced cervical cancer consists of surgery and definitive chemoradiotherapy, respectively, and can be quite effective in eliciting a remission.
  • prognosis is quite poor with 5-year survival rates of approximately 15%, which is comparable to that of patients with de novo metastatic disease.
  • the standard of care for recurrent, persistent, or de novo metastatic disease is chemotherapy plus bevacizumab based on the Gynecology Oncology Group 240 trial, which showed that bevacizumab added to chemotherapy improved median OS compared with chemotherapy alone (17 vs. 13.3 months, respectively).
  • cytotoxic chemotherapy agents administered as either a single agent or in combination.
  • increasing focus has been given to whether cytotoxic chemotherapies represent an acceptable standard of care over best supportive care given the impact and burden such agents can impart on patient quality of life.
  • a detectable expression level of PD-L1 e.g., cervical cancer, e.g., Stage IVB, metastatic, recurrent, or persistent cervical cancer, e.g., a metastatic and/or recurrent PD-L1 -positive cervical carcinoma
  • a detectable expression level of PD-L1 e.g., cervical cancer, e.g., Stage IVB, metastatic, recurrent, or persistent cervical cancer, e.g., a metastatic and/or recurrent PD-L1 -positive cervical carcinoma
  • an anti-TIG IT antagonist antibody and a PD-1 axis binding antagonist e.g., an anti- PD-L1 antagonist antibody (e.g., atezolizumab) or an anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab)
  • an anti-PD-L1 antagonist antibody e.
  • the therapeutic methods and uses of the invention described herein include, in one aspect, administering to a subject or population of subjects having a cancer with a detectable expression level of PD-L1 (e.g., cervical cancer, e.g., Stage IVB, metastatic, recurrent, or persistent cervical cancer, e.g., a metastatic and/or recurrent PD-L1 -positive cervical carcinoma) one or more dosing cycles of an effective amount of an anti-TIG IT antagonist antibody (e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab) and an effective amount of a PD-1 axis binding antagonist (e.g., an anti-PD-L1 antagonist antibody (e.g., atezolizumab) or an anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab))), thereby treating the subject
  • the effective amount of the anti-TIGIT antagonist antibody is a dose (e.g., a fixed dose) of between about 30 mg to about 1200 mg (e.g., between about 30 mg to about 1100 mg, e.g., between about 60 mg to about 1000 mg, e.g., between about 100 mg to about 900 mg, e.g., between about 200 mg to about 800 mg, e.g., between about 300 mg to about 800 mg, e.g., between about 400 mg to about 800 mg, e.g., between about 400 mg to about 750 mg, e.g., between about 450 mg to about 750 mg, e.g., between about 500 mg to about 700 mg, e.g., between about 550 mg to about 650 mg, e.g., 600 mg ⁇ 10 mg, e.g., 600 ⁇ 6 mg,
  • a dose e.g., a fixed dose of between about 30 mg to about 1200 mg (e.g., between about 30 mg
  • the effective amount of the anti-TIGIT antagonist antibody is a dose (e.g., a fixed dose) of between about 30 mg to about 600 mg (e.g., between about 50 mg to between 600 mg, e.g., between about 60 mg to about 600 mg, e.g., between about 100 mg to about 600 mg, e.g., between about 200 mg to about 600 mg, e.g., between about 200 mg to about 550 mg, e.g., between about 250 mg to about 500 mg, e.g., between about 300 mg to about 450 mg, e.g., between about 350 mg to about 400 mg, e.g., about 375 mg) every three weeks.
  • a dose e.g., a fixed dose of between about 30 mg to about 600 mg (e.g., between about 50 mg to between 600 mg, e.g., between about 60 mg to about 600 mg, e.g., between about 100 mg to about 600 mg, e.g., between about 200 mg to about
  • the effective amount of the anti-TIGIT antagonist antibody is a dose (e.g., a fixed dose) of about 600 mg every three weeks.
  • the effective amount of the anti-TIG IT antagonist antibody is a dose (e.g., a fixed dose) of between 30 mg to 1200 mg (e.g., between 30 mg to 1100 mg, e.g., between 60 mg to 1000 mg, e.g., between 100 mg to 900 mg, e.g., between 200 mg to 800 mg, e.g., between 300 mg to 800 mg, e.g., between 400 mg to 800 mg, e.g., between 400 mg to 750 mg, e.g., between 450 mg to 750 mg, e.g., between 500 mg to 700 mg, e.g., between 550 mg to 650 mg, e.g., 600 mg ⁇ 10 mg, e.g., 600 ⁇ 6 mg, e.g., 600 ⁇ 5 mg, e.g., 600 ⁇ 3
  • a dose e.g., a fixed dose of between 30 mg to 1200 mg (e.g., between 30 mg to 1100
  • the effective amount of the anti-TIGIT antagonist antibody is a dose (e.g., a fixed dose) of between 30 mg to 600 mg (e.g., between 50 mg to between 600 mg, e.g., between 60 mg to 600 mg, e.g., between 100 mg to 600 mg, e.g., between 200 mg to 600 mg, e.g., between 200 mg to 550 mg, e.g., between 250 mg to 500 mg, e.g., between 300 mg to 450 mg, e.g., between 350 mg to 400 mg, e.g., 375 mg) every three weeks.
  • a dose e.g., a fixed dose of between 30 mg to 600 mg (e.g., between 50 mg to between 600 mg, e.g., between 60 mg to 600 mg, e.g., between 100 mg to 600 mg, e.g., between 200 mg to 600 mg, e.g., between 200 mg to 550 mg, e.g., between 250 mg to
  • the effective amount of the anti-TIGIT antagonist antibody is a dose (e.g., a fixed dose) of 600 mg every three weeks.
  • effective amount of the anti-TIGIT antagonist antibody is a dose (e.g., a fixed dose) of 600 mg every three weeks.
  • the dose of the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • a combination therapy e.g., a combination treatment with a PD-1 axis binding antagonist (e.g., an anti-PD- L1 antagonist antibody (e.g., atezolizumab) or an anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab))
  • a combination therapy e.g., a combination treatment with a PD-1 axis binding antagonist
  • an anti-PD- L1 antagonist antibody e.g., atezolizumab
  • an anti-PD-1 antagonist antibody e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab)
  • the effective amount of the PD-1 axis binding antagonist is a dose (e.g., a fixed dose) of between about 80 mg to about 2000 mg (e.g., between about 80 mg to about 1950 mg, e.g., between about 80 mg to about 1900 mg, e.g., between about 80 mg to about 1800 mg, e.g., between about 100 mg to about 1700 mg, e.g., between about 200 mg to about 1600 mg, e.g., between about 300 mg to about 1400 mg, e.g., between about 400 mg to about 1300 mg, e.g., between about 500 mg to about 1200 mg, e.g., between about 600 mg to about 1100 mg, e.g., between about 700 mg to about 1000 mg, e.g., between about 740 mg to about 940 mg, e.g., between about 790 mg to about 8
  • a dose e.g., a fixed dose of between about 80 mg to about 2000 mg (e.g., between
  • the effective amount of the PD-1 axis binding antagonist is a dose of between about 80 mg to about 2000 mg (e.g., between about 100 mg to about 2000 mg, e.g., between about 200 mg to about 1900 mg, e.g., between about 300 mg to about 1700 mg, e.g., between about 400 mg to about 1600 mg, e.g., between about 500 mg to about 1600 mg, e.g., between about 600 mg to about 1600 mg, e.g., between about 700 mg to about 1600 mg, e.g., between about 800 mg to about 1600 mg, e.g., between about 900 mg to about 1500 mg, e.g., between about 1000 mg to about 1400 mg, e.g., between about 1050
  • the effective amount of the PD-1 axis binding antagonist is a dose of between about 80 mg to about 2000 mg (e.g., between about 100 mg to about 2000 mg, e.g., between about 200 mg to about 2000 mg, e.g., between about 300 mg to about 2000 mg, e.g., between about 400 mg to about 2000 mg, e.g., between about 500 mg to about 2000 mg, e.g., between about 600 mg to about 1900 mg, e.g., between about 700 mg to about 1800 mg, e.g., between about 800 mg to about 1800 mg, e.g., between about 900 mg to about 1800 mg, e.g., between about 1000 mg to about 1800 mg, e.g., between about 1100 mg to about 1800 mg, e.g., between about 1200 mg to about 1800 mg, e.g., between about 1300 mg to about 1800
  • the effective amount of the PD-1 axis binding antagonist is a dose of about 840 mg every two weeks. In some instances, the effective amount of the PD-1 axis binding antagonist (e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab)) is a dose of 840 mg every two weeks. In some instances, the effective amount of the PD-1 axis binding antagonist (e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab)) is a dose of about 1200 mg every three weeks.
  • the effective amount of the PD-1 axis binding antagonist is a dose (e.g., a fixed dose) of between 80 mg to 2000 mg (e.g., between 80 mg to 1950 mg, e.g., between 80 mg to 1900 mg, e.g., between 80 mg to 1800 mg, e.g., between 100 mg to 1700 mg, e.g., between 200 mg to 1600 mg, e.g., between 300 mg to 1400 mg, e.g., between 400 mg to 1300 mg, e.g., between 500 mg to 1200 mg, e.g., between 600 mg to 1100 mg, e.g., between 700 mg to 1000 mg, e.g., between 740 mg to 940 mg, e.g., between 790 mg to 890 mg, e.g., between 815 mg to 865 mg, e.g., between 8
  • the effective amount of the PD-1 axis binding antagonist is a dose of between 80 mg to 2000 mg (e.g., between 100 mg to 2000 mg, e.g., between 200 mg to 1900 mg, e.g., between 300 mg to 1700 mg, e.g., between 400 mg to 1600 mg, e.g., between 500 mg to 1600 mg, e.g., between 80 mg to 2000 mg (e.g., between 100 mg to 2000 mg, e.g., between 200 mg to 1900 mg, e.g., between 300 mg to 1700 mg, e.g., between 400 mg to 1600 mg, e.g., between 500 mg to 1600 mg, e.g., between 80 mg to 2000 mg (e.g., between 100 mg to 2000 mg, e.g., between 200 mg to 1900 mg, e.g., between 300 mg to 1700 mg, e.g., between 400 mg to 1600 mg, e.g., between 500 mg to 1600 mg, e.g., between
  • 600 mg to 1600 mg e.g., between 700 mg to 1600 mg, e.g., between 800 mg to 1600 mg, e.g., between
  • 900 mg to 1500 mg e.g., between 1000 mg to 1400 mg, e.g., between 1050 mg to 1350 mg, e.g., between 1100 mg to 1300 mg, e.g., between 1150 mg to 1250 mg, e.g., between 1175 mg to 1225 mg, e.g., between 1190 mg to 1210 mg, e.g., 1200 mg ⁇ 5 mg, e.g., 1200 ⁇ 2.5 mg, e.g., 1200 ⁇ 1 .0 mg, e.g., 1200 ⁇ 0.5 mg, e.g., 1200 mg) every three weeks.
  • the effective amount of the PD-1 axis binding antagonist is a dose of between 80 mg to 2000 mg (e.g., between 100 mg to 2000 mg, e.g., between 200 mg to 2000 mg, e.g., between 300 mg to 2000 mg, e.g., between 400 mg to 2000 mg, e.g., between 500 mg to 2000 mg, e.g., between 80 mg to 2000 mg (e.g., between 100 mg to 2000 mg, e.g., between 200 mg to 2000 mg, e.g., between 300 mg to 2000 mg, e.g., between 400 mg to 2000 mg, e.g., between 500 mg to 2000 mg, e.g., between 80 mg to 2000 mg (e.g., between 100 mg to 2000 mg, e.g., between 200 mg to 2000 mg, e.g., between 300 mg to 2000 mg, e.g., between 400 mg to 2000 mg, e.g., between 500 mg to 2000 mg, e.g., between 80 mg to 2000
  • 600 mg to 1900 mg e.g., between 700 mg to 1800 mg, e.g., between 800 mg to 1800 mg, e.g., between
  • 900 mg to 1800 mg e.g., between 1000 mg to 1800 mg, e.g., between 1100 mg to 1800 mg, e.g., between 1200 mg to 1800 mg, e.g., between 1300 mg to 1800 mg, e.g., between 1400 mg to 1800 mg, e.g., between 1500 mg to 1800 mg, e.g., between 1580 mg to 1780 mg, e.g., between 1630 mg to 1730 mg, e.g., between 1655 mg to 1705 mg, e.g., between 1670 mg to 1690 mg, e.g., 1680 mg ⁇ 5 mg, e.g., 1680 ⁇ 2.5 mg, e.g., 1680 ⁇ 1 .0 mg, e.g., 1680 ⁇ 0.5 mg, e.g., 1680 mg) every four weeks.
  • the effective amount of the PD-1 axis binding antagonist (e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab)) is a dose of 840 mg every two weeks. In some instances, the effective amount of the PD-1 axis binding antagonist (e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab)) is a dose of 840 mg every two weeks. In some instances, the effective amount of the PD-1 axis binding antagonist (e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab)) is a dose of 1200 mg every three weeks.
  • the effective amount of the PD-1 axis binding antagonist (e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab)) is a dose of 1200 mg every three weeks. In some instances, the effective amount of the PD-1 axis binding antagonist (e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab)) is a dose of about 1680 mg every four weeks. In some instances, the effective amount of the PD-1 axis binding antagonist (e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab)) is a dose of 1680 mg every four weeks.
  • the dose of the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab)
  • a combination therapy e.g., a combination treatment with an anti-TIG IT antagonist antibody, such as an anti-TIG IT antagonist antibody disclosed herein, e.g., tiragolumab
  • a combination therapy e.g., a combination treatment with an anti-TIG IT antagonist antibody, such as an anti-TIG IT antagonist antibody disclosed herein, e.g., tiragolumab
  • a combination therapy e.g., a combination treatment with an anti-TIG IT antagonist antibody, such as an anti-TIG IT antagonist antibody disclosed herein, e.g., tiragolumab
  • the effective amount of the PD-1 axis binding antagonist is a dose of between about 0.01 mg/kg to about 50 mg/kg of the subject’s body weight (e.g., between about 0.01 mg/kg to about 45 mg/kg, e.g., between about 0.1 mg/kg to about 40 mg/kg, e.g., between about 1 mg/kg to about 35 mg/kg, e.g., between about 2.5 mg/kg to about 30 mg/kg, e.g., between about 5 mg/kg to about 25 mg/kg, e.g., between about 10 mg/kg to about 20 mg/kg, e.g., between about 12.5 mg/kg to about 15 mg/kg, e.g., about 15 ⁇ 2 mg/kg, about 15 ⁇ 1 mg/kg, about 15 ⁇ 0.5 mg/kg, about 15 ⁇ 0.2 mg/kg, or about 15 ⁇
  • the PD-1 axis binding antagonist is a dose of between about 0.01 mg/kg to about 50 mg/kg of the
  • the effective amount of the PD-1 axis binding antagonist is a dose of between about 0.01 mg/kg to about 15 mg/kg of the subject’s body weight (e.g., between about 0.1 mg/kg to about 15 mg/kg, e.g., between about 0.5 mg/kg to about 15 mg/kg, e.g., between about 1 mg/kg to about 15 mg/kg, e.g., between about 2.5 mg/kg to about 15 mg/kg, e.g., between about 5 mg/kg to about 15 mg/kg, e.g., between about 7.5 mg/kg to about 15 mg/kg, e.g., between about 10 mg/kg to about 15 mg/kg, e.g., between about 12.5 mg/kg to about 15 mg/kg, e.g., between about 14 mg/kg to about 15 mg/kg, e.g., about 15 ⁇
  • the effective amount of anti-PD-L1 antagonist antibody is a dose of about 15 mg/kg administered every three weeks.
  • the effective amount of the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab)
  • is a dose of between 0.01 mg/kg to 50 mg/kg of the subject’s body weight e.g., between 0.01 mg/kg to 45 mg/kg, e.g., between 0.1 mg/kg to 40 mg/kg, e.g., between 1 mg/kg to 35 mg/kg, e.g., between 2.5 mg/kg to 30 mg/kg, e.g., between 5 mg/kg to 25 mg/kg, e.g., between 10 mg/kg to 20 mg/kg, e.g., between 12.5 mg/kg to 15 mg/kg, e.g., 15 ⁇ 2 mg/kg, 15 ⁇ 1 mg/kg
  • the effective amount of the PD-1 axis binding antagonist is a dose of between 0.01 mg/kg to 15 mg/kg of the subject’s body weight (e.g., between 0.1 mg/kg to 15 mg/kg, e.g., between 0.5 mg/kg to 15 mg/kg, e.g., between 1 mg/kg to 15 mg/kg, e.g., between 2.5 mg/kg to 15 mg/kg, e.g., between 5 mg/kg to 15 mg/kg, e.g., between 7.5 mg/kg to 15 mg/kg, e.g., between 10 mg/kg to 15 mg/kg, e.g., between 12.5 mg/kg to 15 mg/kg, e.g., between 14 mg/kg to 15 mg/kg, e.g., 15 ⁇ 1 mg/kg, e.g., 15 ⁇ 0.5 mg/kg,
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., at
  • the effective amount of anti-PD-L1 antagonist antibody is a dose of 15 mg/kg administered every three weeks.
  • the dose of the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab)
  • a combination therapy e.g., a combination treatment with an anti-TIGIT antagonist antibody, such as an anti-TIGIT antagonist antibody disclosed herein, e.g., tiragolumab
  • a combination therapy e.g., a combination treatment with an anti-TIGIT antagonist antibody, such as an anti-TIGIT antagonist antibody disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab) or anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambroli
  • the effective amount of the PD-1 axis binding antagonist is a dose (e.g., a fixed dose) of between about 20 mg to about 1000 mg (e.g., between about 40 mg to about 900 mg, e.g., between about 60 mg to about 800 mg, e.g., between about 80 mg to about 700 mg, e.g., between about 80 mg to about 600 mg, e.g., between about 100 mg to about 500 mg, e.g., between about 120 mg to about 400 mg, e.g., between about 140 mg to about 300 mg, e.g., between about 160 mg to about 350 mg, e.g., between about 180 mg to about 300 mg, e.g., between about 180 mg to about 250 mg, e.g., between about 180 mg to about 220 mg, e.g., between about 190 mg to about 210 mg, e.g.
  • the effective amount of the PD-1 axis binding antagonist is a dose (e.g., a fixed dose) of between 20 mg to 1000 mg (e.g., between 40 mg to 900 mg, e.g., between 60 mg to 800 mg, e.g., between 80 mg to 700 mg, e.g., between 80 mg to 600 mg, e.g., between 100 mg to 500 mg, e.g., between 120 mg to 400 mg, e.g., between 140 mg to 300 mg, e.g., between 160 mg to 350 mg, e.g., between 180 mg to 300 mg, e.g., between 180 mg to 250 mg, e.g., between 180 mg to 220 mg, e.g., between 190 mg to 210 mg, e.g., 200 mg ⁇ 5 mg, e.g., 200 ⁇ 2.5 mg, e.g.
  • a dose e.g., a fixed dose of between 20 mg to 1000 mg (e.g., between
  • the effective amount of the PD-1 axis binding antagonist is a dose (e.g., a fixed dose) of 200 mg every three weeks.
  • the dose of the PD-1 axis binding antagonist e.g., anti- PD-1 antagonist antibody (e.g., pembrolizumab)
  • administered in a combination therapy e.g., a combination treatment with an anti-TIGIT antagonist antibody, such as an anti-TIGIT antagonist antibody disclosed herein, e.g., tiragolumab
  • a combination therapy e.g., a combination treatment with an anti-TIGIT antagonist antibody, such as an anti-TIGIT antagonist antibody disclosed herein, e.g., tiragolumab
  • an anti-TIGIT antagonist antibody such as an anti-TIGIT antagonist antibody disclosed herein, e.g., tiragolumab
  • the effective amount of the PD-1 axis binding antagonist is a dose (e.g., a fixed dose) of between about 20 mg to about 1000 mg (e.g., between about 40 mg to about 900 mg, e.g., between about 60 mg to about 800 mg, e.g., between about 80 mg to about 700 mg, e.g., between about 80 mg to about 600 mg, e.g., between about 100 mg to about 500 mg, e.g., between about 120 mg to about 400 mg, e.g., between about 140 mg to about 300 mg, e.g., between about 160 mg to about 350 mg, e.g., between about 180 mg to about 300 mg, e.g., between about 200 mg to about 280 mg, e.g., between about 220 mg to about 260 mg, e.g., between about 230 mg to about 250 mg, e
  • a dose e.g., a fixed dose of between about 20 mg to about 1000 mg (e.g.,
  • the effective amount of the PD-1 axis binding antagonist is a dose of 240 mg every two weeks.
  • the effective amount of the PD-1 axis binding antagonist is a dose of between about 100 mg to about 1000 mg (e.g., between about 200 mg to about 900 mg, e.g., between about 300 mg to about 800 mg, e.g., between about 400 mg to about 700 mg, e.g., between about 400 mg to about 600 mg, e.g., between about 400 mg to about 550 mg, e.g., between about 420 mg to about 540 mg, e.g., between about 440 mg to about 520 mg, e.g., between about 460 mg to about 500 mg, e.g., between about 470 mg to about 490
  • the effective amount of the PD-1 axis binding antagonist is a dose (e.g., a fixed dose) of between 20 mg to 1000 mg (e.g., between 40 mg to 900 mg, e.g., between 60 mg to 800 mg, e.g., between 80 mg to 700 mg, e.g., between 80 mg to 600 mg, e.g., between 100 mg to 500 mg, e.g., between 120 mg to 400 mg, e.g., between 140 mg to 300 mg, e.g., between 160 mg to 350 mg, e.g., between 180 mg to 300 mg, e.g., between 200 mg to 280 mg, e.g., between 220 mg to 260 mg, e.g., between 230 mg to 250 mg, e.g., 240 mg ⁇ 5 mg, e.g., 240 ⁇ 2.5 mg,
  • a dose e.g., a fixed dose of between 20 mg to 1000 mg (e.g., between 40 mg
  • the effective amount of the PD-1 axis binding antagonist is a dose of 240 mg every two weeks.
  • the effective amount of the PD-1 axis binding antagonist is a dose of between 100 mg to 1000 mg (e.g., between 200 mg to 900 mg, e.g., between 300 mg to 800 mg, e.g., between 400 mg to 700 mg, e.g., between 400 mg to 600 mg, e.g., between 400 mg to 550 mg, e.g., between 420 mg to 540 mg, e.g., between 440 mg to 520 mg, e.g., between 460 mg to 500 mg, e.g., between 470 mg to 490 mg, e.g., 480 mg ⁇ 5 mg, e.g.
  • the dose of the PD-1 axis binding antagonist e.g., anti-PD-1 antagonist antibody (e.g., nivolumab)
  • a combination therapy e.g., a combination treatment with an anti-TIGIT antagonist antibody, such as an anti-TIGIT antagonist antibody disclosed herein, e.g., tiragolumab
  • a combination therapy e.g., a combination treatment with an anti-TIGIT antagonist antibody, such as an anti-TIGIT antagonist antibody disclosed herein, e.g., tiragolumab
  • the anti-TIGIT antagonist antibody e.g., an anti- TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab) or anti-PD-1 antagonist antibody (e.g., MDX- 1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab)
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab) or anti-PD-1 antagonist antibody (e.g., MDX- 1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab)
  • dosing cycles e.g., 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 ,
  • the dosing cycles of the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab) or anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab)
  • a loss of clinical benefit e.g., confirmed disease progression, drug resistance, death, or unacceptable toxicity.
  • the length of each dosing cycle is about 14 to 28 days (e.g., 14 days, 15 days, 16 days, 17 days, 18 days, 19 days, 20 days, 21 days, 22 days, 23 days, 24 days, 25 days, 26 days, 27 days, or 28 days). In some instances, the length of each dosing cycle is about 21 days. In some instances, the length of each dosing cycle is about 14 days. In some instances, the length of each dosing cycle is about 28 days. In some instances, the anti-TIGIT antagonist antibody (e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab) is administered on about Day 1 (e.g., Day 1 ⁇ 3 days) of each dosing cycle.
  • Day 1 e.g., Day 1 ⁇ 3 days
  • the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • a dose e.g., a fixed dose
  • the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • a dose e.g., a fixed dose
  • 600 mg on Day 1 of each 21 -day cycle i.e., at a dose of 600 mg every three weeks.
  • the PD-1 axis binding antagonist e.g., an anti- PD-L1 antagonist antibody (e.g., atezolizumab) or an anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab)
  • the PD-1 axis binding antagonist is administered on about Day 1 (e.g., Day 1 ⁇ 3 days) of each dosing cycle.
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab)
  • the PD-1 axis binding antagonist is administered intravenously at a dose of about 1200 mg on Day 1 of each 21 -day cycle (i.e., at a dose of about 1200 mg every three weeks).
  • the PD-1 axis binding antagonist e.g., anti-PD-1 antagonist antibody (e.g., pembrolizumab)
  • is administered intravenously at a dose of about 200 mg on Day 1 of each 21 -day cycle i.e., at a dose of about 200 mg every three weeks.
  • the PD-1 axis binding antagonist e.g., anti-PD-1 antagonist antibody (e.g., nivolumab)
  • the PD-1 axis binding antagonist is administered intravenously at a dose of about 240 mg on Day 1 of each 14-day cycle (i.e., at a dose of about 240 mg every two weeks).
  • the PD-1 axis binding antagonist e.g., anti-PD-1 antagonist antibody (e.g., nivolumab)
  • is administered intravenously at a dose of about 480 mg on Day 1 of each 28-day cycle i.e., at a dose of about 480 mg every four weeks).
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab)
  • the PD-1 axis binding antagonist is administered intravenously at a dose of about 1200 mg on Day 1 of each 21 -day cycle (i.e., at a dose of about 1200 mg every three weeks).
  • the PD-1 axis binding antagonist e.g., anti-PD-1 antagonist antibody (e.g., pembrolizumab)
  • is administered intravenously at a dose of about 200 mg on Day 1 of each 21 -day cycle i.e., at a dose of about 200 mg every three weeks.
  • the PD-1 axis binding antagonist e.g., anti-PD-1 antagonist antibody (e.g., nivolumab)
  • the PD-1 axis binding antagonist is administered intravenously at a dose of about 240 mg on Day 1 of each 14-day cycle (i.e., at a dose of about 240 mg every two weeks).
  • the PD-1 axis binding antagonist e.g., anti-PD-1 antagonist antibody (e.g., nivolumab)
  • is administered intravenously at a dose of about 480 mg on Day 1 of each 28-day cycle i.e. , at a dose of about 480 mg every four weeks).
  • both the anti-TIGIT antagonist antibody e.g., an anti-TIG IT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab) or anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab)
  • Day 1 e.g., Day 1 ⁇ 3 days
  • the anti-TIGIT antagonist antibody e.g., an anti- TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • a dose e.g., a fixed dose
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab)
  • a dose e.g., a fixed dose
  • the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., pembrolizumab)
  • the PD-1 axis binding antagonist is administered intravenously at a dose of about 200 mg on Day 1 of each 21 -day cycle (i.e., at a dose of about 200 mg every three weeks).
  • the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • a dose e.g., a fixed dose
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab)
  • a dose e.g., a fixed dose
  • 1200 mg on Day 1 of each 21 -day cycle i.e., at a dose of 1200 mg every three weeks.
  • the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., pembrolizumab)
  • the PD-1 axis binding antagonist is administered intravenously at a dose of 200 mg on Day 1 of each 21 -day cycle (i.e., at a dose of 200 mg every three weeks).
  • both the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab) or anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab)
  • Day 1 e.g., Day 1 ⁇ 3 days
  • the anti-TIGIT antagonist antibody e.g., an anti- TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • a dose e.g., a fixed dose
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., nivolumab)
  • a dose e.g., a fixed dose
  • the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., nivolumab)
  • the PD-1 axis binding antagonist is administered intravenously at a dose of about 480 mg on Day 1 of each 28-day cycle (i.e., at a dose of about 480 mg every four weeks).
  • the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • a dose e.g., a fixed dose
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., nivolumab)
  • a dose e.g., a fixed dose
  • 240 mg e.g., a fixed dose
  • the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., nivolumab)
  • the PD-1 axis binding antagonist is administered intravenously at a dose of 480 mg on Day 1 of each 28-day cycle (i.e., at a dose of 480 mg every four weeks).
  • the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the anti-TIGIT antagonist antibody is administered to the subject or population of subjects by intravenous infusion over about 60 ⁇ 15 minutes (e.g., about 50 minutes, about 51 minutes, about 52 minutes, about 53 minutes, about 54 minutes, about 55 minutes, about 56 minutes, about 57 minutes, about 58 minutes, about 59 minutes, about 60 minutes, about 61 minutes, about 62 minutes, about 63 minutes, about 64 minutes, about 65 minutes, about 66 minutes, about 67 minutes, about 68 minutes, about 69 minutes, or about 70 minutes).
  • about 60 ⁇ 15 minutes e.g., about 50 minutes, about 51 minutes, about 52 minutes, about 53 minutes, about 54 minutes, about 55 minutes, about 56 minutes, about 57 minutes, about 58 minutes, about 59 minutes, about 60 minutes, about 61 minutes, about 62 minutes, about 63 minutes, about 64 minutes, about 65
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab) or anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab)
  • the PD-1 axis binding antagonist is administered to the subject or population of subjects by intravenous infusion over about 60 ⁇ 15 minutes (e.g., about 45 minutes, about 46 minutes, about 47 minutes, about 48 minutes, about 49 minutes, about 50 minutes, about 51 minutes, about 52 minutes, about 53 minutes, about 54 minutes, about 55 minutes, about 56 minutes, about 57 minutes, about 58 minutes, about 59 minutes, about 60 minutes, about 61 minutes, about 62 minutes, about 63 minutes, about 64 minutes, about 65 minutes, about 66 minutes, about 67 minutes, about 68 minutes, about 69 minutes, about 70 minutes, about 71 minutes, about 72 minutes, about 73 minutes, about
  • the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the anti-TIGIT antagonist antibody is administered to the subject or population of subjects by intravenous infusion over about 30 ⁇ 10 minutes (e.g., about 20 minutes, about 21 minutes, about 22 minutes, about 23 minutes, about 24 minutes, about 25 minutes, about 26 minutes, about 27 minutes, about 28 minutes, about 29 minutes, about 30 minutes, about 31 minutes, about 32 minutes, about 33 minutes, about 34 minutes, about 35 minutes, about 36 minutes, about 37 minutes, about 38 minutes, about 39 minutes, or about 40 minutes).
  • ⁇ 10 minutes e.g., about 20 minutes, about 21 minutes, about 22 minutes, about 23 minutes, about 24 minutes, about 25 minutes, about 26 minutes, about 27 minutes, about 28 minutes, about 29 minutes, about 30 minutes, about 31 minutes, about 32 minutes, about 33 minutes, about 34 minutes, about 35 minutes, about 36 minutes, about 37 minutes, about 38 minutes, about 39 minutes,
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab) or anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab)
  • the PD-1 axis binding antagonist is administered to the subject or population of subjects by intravenous infusion over about 30 ⁇ 10 minutes (e.g., about 20 minutes, about 21 minutes, about 22 minutes, about 23 minutes, about 24 minutes, about 25 minutes, about 26 minutes, about 27 minutes, about 28 minutes, about 29 minutes, about 30 minutes, about 31 minutes, about 32 minutes, about 33 minutes, about 34 minutes, about 35 minutes, about 36 minutes, about 37 minutes, about 38 minutes, about 39 minutes, or about 40 minutes).
  • anti-PD-L1 antagonist antibody e.g., atezolizumab
  • anti-PD-1 antagonist antibody e.g., MDX-1106 (nivolum
  • the anti-TIG IT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD- 1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab) or anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab)
  • the method includes an intervening first observation period.
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab) or anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab)
  • the method includes an intervening first observation period.
  • the method further includes a second observation period following administration of the PD-1 axis binding antagonist (e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab) or anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab))).
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab) or anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab)
  • the method includes both a first observation period following administration of the anti-TIGIT antagonist antibody and second observation period following administration of the PD-1 axis binding antagonist (e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab) or anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab))).
  • the first and second observation periods are each between about 30 minutes to about 60 minutes in length.
  • the method may include recording the subject or population of subjects’ vital signs (e.g., pulse rate, respiratory rate, blood pressure, and temperature) at about 30 ⁇ 10 minutes after administration of the anti-TIGIT antagonist antibody and PD-1 axis binding antagonist (e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab) or anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab))) during the first and second observation periods, respectively.
  • vital signs e.g., pulse rate, respiratory rate, blood pressure, and temperature
  • PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab) or anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab)
  • the method may include recording the subject or population of subjects’ vital signs (e.g., pulse rate, respiratory rate, blood pressure, and temperature) at about 15 ⁇ 10 minutes after administration of the anti-TIGIT antagonist antibody and PD-1 axis binding antagonist (e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab) or anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab))) during the first and second observation periods, respectively.
  • vital signs e.g., pulse rate, respiratory rate, blood pressure, and temperature
  • PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab) or anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab)
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab) or anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab)
  • anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab.
  • the method includes an intervening first observation period.
  • the method includes a second observation period following administration of the anti-TIGIT antagonist antibody.
  • the method includes both a first observation period following administration of the PD-1 axis binding antagonist (e.g., anti-PD- L1 antagonist antibody (e.g., atezolizumab) or anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab))) and second observation period following administration of the anti-TIGIT antagonist antibody.
  • the first and second observation periods are each between about 30 minutes to about 60 minutes in length.
  • the method may include recording the subject or population of subjects’ vital signs (e.g., pulse rate, respiratory rate, blood pressure, and temperature) at about 30 ⁇ 10 minutes after administration of the PD-1 axis binding antagonist (e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab) or anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab))) and anti-TIGIT antagonist antibody during the first and second observation periods, respectively.
  • vital signs e.g., pulse rate, respiratory rate, blood pressure, and temperature
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab) or anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab
  • the method may include recording the subject or population of subjects’ vital signs (e.g., pulse rate, respiratory rate, blood pressure, and temperature) at about 15 ⁇ 10 minutes after administration of the PD-1 axis binding antagonist (e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab) or anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab))) and anti-TIGIT antagonist antibody during the first and second observation periods, respectively.
  • vital signs e.g., pulse rate, respiratory rate, blood pressure, and temperature
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab) or anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab
  • the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab) or anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab)
  • MDX-1106 nivolumab
  • MK-3475 pembrolizumab, previously known as lambrolizumab
  • the method includes an observation period.
  • the observation period is between about 30 minutes to about 60 minutes in length.
  • the method may include recording the subject or population of subjects’ vital signs (e.g., pulse rate, respiratory rate, blood pressure, and temperature) at about 30 ⁇ 10 minutes after administration of the PD-1 axis binding antagonist (e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab) or anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab))) and anti-TIGIT antagonist antibody during the observation period.
  • vital signs e.g., pulse rate, respiratory rate, blood pressure, and temperature
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab) or anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab)
  • the method may include recording the subject or population of subjects’ vital signs (e.g., pulse rate, respiratory rate, blood pressure, and temperature) at about 15 ⁇ 10 minutes after administration of the PD-1 axis binding antagonist (e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab) or anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab))) and anti-TIG IT antagonist antibody during the observation period.
  • vital signs e.g., pulse rate, respiratory rate, blood pressure, and temperature
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab) or anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab)
  • the invention provides a method of treating a subject or population of subjects having a Stage IVB, metastatic, recurrent, or persistent cervical cancer by administering to the subject or population of subjects one or more dosing cycles of an anti-TIGIT antagonist antibody at a dose (e.g., a fixed dose) of 600 mg every three weeks and atezolizumab at a dose (e.g., a fixed dose) of 1200 mg every three weeks, wherein the anti-TIGIT antagonist antibody has a VH domain having the amino acid sequence of SEQ ID NO: 17 or 18 and a VL domain having the amino acid sequence of SEQ ID NO: 19, as described in further detail below.
  • a dose e.g., a fixed dose
  • atezolizumab atezolizumab
  • a dose e.g., a fixed dose
  • the anti-TIGIT antagonist antibody has a VH domain having the amino acid sequence of SEQ ID NO: 17 and a VL domain having the amino acid sequence of SEQ ID NO: 19. In some instances, the anti-TIGIT antagonist antibody has a VH domain having the amino acid sequence of SEQ ID NO: 18 and a VL domain having the amino acid sequence of SEQ ID NO: 19.
  • the invention provides a method of treating a subject or population of subjects having a Stage IVB, metastatic, recurrent, or persistent cervical cancer by administering to the subject or population of subjects one or more dosing cycles of tiragolumab at a dose (e.g., a fixed dose) of 600 mg every three weeks and atezolizumab at a dose (e.g., a fixed dose) of 1200 mg every three weeks.
  • a dose e.g., a fixed dose
  • atezolizumab e.g., a fixed dose
  • the invention provides a method of treating a subject or population of subjects having a Stage IVB, metastatic, recurrent, or persistent cervical cancer by administering to the subject or population of subjects one or more dosing cycles of tiragolumab at a dose (e.g., a fixed dose) of 600 mg every three weeks and pembrolizumab at a dose (e.g., a fixed dose) of 200 mg every three weeks.
  • a dose e.g., a fixed dose
  • pembrolizumab e.g., a fixed dose
  • the invention provides a method of treating a subject or population of subjects having a Stage IVB, metastatic, recurrent, or persistent cervical cancer by administering to the subject or population of subjects one or more dosing cycles of tiragolumab at a dose (e.g., a fixed dose) of 600 mg every three weeks and nivolumab at a dose (e.g., a fixed dose) of 240 mg every two weeks.
  • a dose e.g., a fixed dose
  • nivolumab e.g., a fixed dose
  • the invention provides a method of treating a subject or population of subjects having a Stage IVB, metastatic, recurrent, or persistent cervical cancer by administering to the subject or population of subjects one or more dosing cycles of tiragolumab at a dose (e.g., a fixed dose) of 600 mg every three weeks and nivolumab at a dose (e.g., a fixed dose) of 480 mg every four weeks.
  • a dose e.g., a fixed dose
  • nivolumab e.g., a fixed dose
  • the invention provides an anti-TIGIT antagonist antibody (e.g., an anti-TIGIT antagonist antibody disclosed herein, e.g., tiragolumab) and an PD-1 axis binding antagonist (e.g., an anti-PD-L1 antagonist antibody (e.g., atezolizumab) or an anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab))) for use in a method of treating a subject or population of subjects having a cancer with a detectable expression level of PD-L1 (e.g., cervical cancer, e.g., Stage IVB, metastatic, recurrent, or persistent cervical cancer, e.g., a metastatic and/or recurrent PD-L1 -positive cervical carcinoma), wherein the method comprises administering to the subject or population of subjects one or more dosing cycles of an effective amount of an anti-L1
  • the effective amount of the anti-TIGIT antagonist antibody is a dose (e.g., a fixed dose) of between about 30 mg to about 1200 mg (e.g., between about 30 mg to about 1100 mg, e.g., between about 60 mg to about 1000 mg, e.g., between about 100 mg to about 900 mg, e.g., between about 200 mg to about 800 mg, e.g., between about 300 mg to about 800 mg, e.g., between about 400 mg to about 800 mg, e.g., between about 400 mg to about 750 mg, e.g., between about 450 mg to about 750 mg, e.g., between about 500 mg to about 700 mg, e.g., between about 550 mg to about 650 mg, e.g., 600 mg ⁇ 10 mg, e.g., 600 ⁇ 6 mg,
  • a dose e.g., a fixed dose of between about 30 mg to about 1200 mg (e.g., between about 30 mg
  • the effective amount of the anti-TIGIT antagonist antibody is a dose of between about 30 mg to about 600 mg (e.g., between about 50 mg to between 600 mg, e.g., between about 60 mg to about 600 mg, e.g., between about 100 mg to about 600 mg, e.g., between about 200 mg to about 600 mg, e.g., between about 200 mg to about 550 mg, e.g., between about 250 mg to about 500 mg, e.g., between about 300 mg to about 450 mg, e.g., between about 350 mg to about 400 mg, e.g., about 375 mg) every three weeks.
  • the effective amount of the anti-TIGIT antagonist antibody is a dose (e.g., a fixed dose) of between 30 mg to 1200 mg (e.g., between 30 mg to 1100 mg, e.g., between 60 mg to 1000 mg, e.g., between 100 mg to 900 mg, e.g., between 200 mg to 800 mg, e.g., between 300 mg to 800 mg, e.g., between 400 mg to 800 mg, e.g., between 400 mg to 750 mg, e.g., between 450 mg to 750 mg, e.g., between 500 mg to 700 mg, e.g., between 550 mg to 650 mg, e.g., 600 mg ⁇ 10 mg, e.g., 600 ⁇ 6 mg, e.g., 600 ⁇ 5 mg, e.g., 600 ⁇ 3
  • a dose e.g., a fixed dose of between 30 mg to 1200 mg (e.g., between 30 mg to 1100
  • the effective amount of the anti-TIGIT antagonist antibody is a dose of between 30 mg to 600 mg (e.g., between 50 mg to between 600 mg, e.g., between 60 mg to 600 mg, e.g., between 100 mg to 600 mg, e.g., between 200 mg to 600 mg, e.g., between 200 mg to 550 mg, e.g., between 250 mg to 500 mg, e.g., between 300 mg to 450 mg, e.g., between 350 mg to 400 mg, e.g., 375 mg) every three weeks.
  • the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • a dose of between 30 mg to 600 mg e.g., between 50 mg to between 600 mg, e.g., between 60 mg to 600 mg, e.g., between 100 mg to 600 mg, e.g., between 200 mg to 600 mg, e.g
  • the effective amount of the anti-TIGIT antagonist antibody is a dose of about 600 mg every three weeks. In some instances, effective amount of the anti-TIGIT antagonist antibody (e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab) is a dose of 600 mg every three weeks.
  • the dose of the anti-TIGIT antagonist antibody is to be administered in a combination therapy (e.g., a combination treatment with a PD-1 axis binding antagonist (e.g., an anti-PD-L1 antagonist antibody (e.g., atezolizumab) or an anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab))
  • a combination therapy e.g., a combination treatment with a PD-1 axis binding antagonist (e.g., an anti-PD-L1 antagonist antibody (e.g., atezolizumab) or an anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab))
  • a combination therapy e.g., a combination treatment with a PD-1 axis binding antagonist (
  • the effective amount of the PD-1 axis binding antagonist is a dose (e.g., a fixed dose) of between about 80 mg to about 2000 mg (e.g., between about 80 mg to about 1950 mg, e.g., between about 80 mg to about 1900 mg, e.g., between about 80 mg to about 1800 mg, e.g., between about 100 mg to about 1700 mg, e.g., between about 200 mg to about 1600 mg, e.g., between about 300 mg to about 1400 mg, e.g., between about 400 mg to about 1300 mg, e.g., between about 500 mg to about 1200 mg, e.g., between about 600 mg to about 1100 mg, e.g., between about 700 mg to about 1000 mg, e.g., between about 740 mg to about 940 mg, e.g., between about 790 mg to about 8
  • a dose e.g., a fixed dose of between about 80 mg to about 2000 mg (e.g., between
  • the effective amount of the PD-1 axis binding antagonist is a dose of between about 80 mg to about 2000 mg (e.g., between about 100 mg to about 2000 mg, e.g., between about 200 mg to about 1900 mg, e.g., between about 300 mg to about 1700 mg, e.g., between about 400 mg to about 1600 mg, e.g., between about 500 mg to about 1600 mg, e.g., between about 600 mg to about 1600 mg, e.g., between about 700 mg to about 1600 mg, e.g., between about 800 mg to about 1600 mg, e.g., between about 900 mg to about 1500 mg, e.g., between about 1000 mg to about 1400 mg, e.g., between about 1050
  • the effective amount of the PD-1 axis binding antagonist is a dose of between about 80 mg to about 2000 mg (e.g., between about 100 mg to about 2000 mg, e.g., between about 200 mg to about 2000 mg, e.g., between about 300 mg to about 2000 mg, e.g., between about 400 mg to about 2000 mg, e.g., between about 500 mg to about 2000 mg, e.g., between about 600 mg to about 1900 mg, e.g., between about 700 mg to about 1800 mg, e.g., between about 800 mg to about 1800 mg, e.g., between about 900 mg to about 1800 mg, e.g., between about 1000 mg to about 1800 mg, e.g., between about 1100 mg to about 1800 mg, e.g., between about 1200 mg to about 1800 mg, e.g., between about 1300 mg to about 1800
  • the effective amount of the PD-1 axis binding antagonist is a dose (e.g., a fixed dose) of between 80 mg to 2000 mg (e.g., between 80 mg to 1950 mg, e.g., between 80 mg to 1900 mg, e.g., between 80 mg to 1800 mg, e.g., between 100 mg to 1700 mg, e.g., between 200 mg to 1600 mg, e.g., between 300 mg to 1400 mg, e.g., between 400 mg to 1300 mg, e.g., between 500 mg to 1200 mg, e.g., between 600 mg to 1100 mg, e.g., between 700 mg to 1000 mg, e.g., between 740 mg to 940 mg, e.g., between 790 mg to 890 mg, e.g., between 815 mg to 865 mg, e.g., between 8
  • the effective amount of the PD-1 axis binding antagonist is a dose of between 80 mg to 2000 mg (e.g., between 100 mg to 2000 mg, e.g., between 200 mg to 1900 mg, e.g., between 300 mg to 1700 mg, e.g., between 400 mg to 1600 mg, e.g., between 500 mg to 1600 mg, e.g., between 600 mg to 1600 mg, e.g., between 700 mg to 1600 mg, e.g., between 800 mg to 1600 mg, e.g., between 900 mg to 1500 mg, e.g., between 1000 mg to 1400 mg, e.g., between 1050 mg to 1350 mg, e.g., between 1100 mg to 1300 mg, e.g., between 1150 mg to 1250 mg, e.g., between 1175 mg to 1225 mg, e.g.,
  • the effective amount of the PD-1 axis binding antagonist is a dose of between 80 mg to 2000 mg (e.g., between 100 mg to 2000 mg, e.g., between 200 mg to 2000 mg, e.g., between 300 mg to 2000 mg, e.g., between 400 mg to 2000 mg, e.g., between 500 mg to 2000 mg, e.g., between 600 mg to 1900 mg, e.g., between 700 mg to 1800 mg, e.g., between 800 mg to 1800 mg, e.g., between 900 mg to 1800 mg, e.g., between 1000 mg to 1800 mg, e.g., between 1100 mg to 1800 mg, e.g., between 1200 mg to 1800 mg, e.g., between 1300 mg to 1800 mg, e.g., between 1400 mg to 1800 mg, e.g., between 1500 mg to 1800 mg
  • 80 mg to 2000 mg e.g., between 100 mg to 2000 mg, e.g., between 200 mg to 2000
  • the effective amount of the PD-1 axis binding antagonist (e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab)) is a dose of 840 mg every two weeks. In some instances, the effective amount of the PD-1 axis binding antagonist (e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab)) is a dose of about 1200 mg every three weeks. In some instances, the effective amount of the PD-1 axis binding antagonist (e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab)) is a dose of 1200 mg every three weeks.
  • the effective amount of the PD-1 axis binding antagonist (e.g., anti-PD- L1 antagonist antibody (e.g., atezolizumab)) is a dose of about 1680 mg every four weeks. In some instances, the effective amount of the PD-1 axis binding antagonist (e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab)) is a dose of 1680 mg every four weeks.
  • the dose of the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab)
  • a combination therapy e.g., a combination treatment with an anti-TIG IT antagonist antibody, such as an anti-TIG IT antagonist antibody disclosed herein, e.g., tiragolumab
  • an anti-TIG IT antagonist antibody such as an anti-TIG IT antagonist antibody disclosed herein, e.g., tiragolumab
  • a combination therapy e.g., a combination treatment with an anti-TIG IT antagonist antibody, such as an anti-TIG IT antagonist antibody disclosed herein, e.g., tiragolumab
  • the effective amount of the PD-1 axis binding antagonist is a dose (e.g., a fixed dose) of between about 20 mg to about 1000 mg (e.g., between about 40 mg to about 900 mg, e.g., between about 60 mg to about 800 mg, e.g., between about 80 mg to about 700 mg, e.g., between about 80 mg to about 600 mg, e.g., between about 100 mg to about 500 mg, e.g., between about 120 mg to about 400 mg, e.g., between about 140 mg to about 300 mg, e.g., between about 160 mg to about 350 mg, e.g., between about 180 mg to about 300 mg, e.g., between about 180 mg to about 250 mg, e.g., between about 180 mg to about 220 mg, e.g., between about 190 mg to about 210 mg, e.g.
  • the effective amount of the PD-1 axis binding antagonist is a dose (e.g., a fixed dose) of between 20 mg to 1000 mg (e.g., between 40 mg to 900 mg, e.g., between 60 mg to 800 mg, e.g., between 80 mg to 700 mg, e.g., between 80 mg to 600 mg, e.g., between 100 mg to 500 mg, e.g., between 120 mg to 400 mg, e.g., between 140 mg to 300 mg, e.g., between 160 mg to 350 mg, e.g., between 180 mg to 300 mg, e.g., between 180 mg to 250 mg, e.g., between 180 mg to 220 mg, e.g., between 190 mg to 210 mg, e.g., 200 mg ⁇ 5 mg, e.g., 200 ⁇ 2.5 mg, e.g.
  • a dose e.g., a fixed dose of between 20 mg to 1000 mg (e.g., between
  • the effective amount of the PD-1 axis binding antagonist (e.g., anti-PD-1 antagonist antibody (e.g., pembrolizumab)) is a dose of about 200 mg every three weeks. In some instances, the effective amount of the PD-1 axis binding antagonist (e.g., anti-PD-1 antagonist antibody (e.g., pembrolizumab)) is a dose of 200 mg every three weeks.
  • the dose of the PD-1 axis binding antagonist e.g., anti-PD-1 antagonist antibody (e.g., pembrolizumab)
  • a combination therapy e.g., a combination treatment with an anti-TIG IT antagonist antibody, such as an anti-TIG IT antagonist antibody disclosed herein, e.g., tiragolumab
  • a combination therapy e.g., a combination treatment with an anti-TIG IT antagonist antibody, such as an anti-TIG IT antagonist antibody disclosed herein, e.g., tiragolumab
  • the effective amount of the PD-1 axis binding antagonist is a dose (e.g., a fixed dose) of between about 20 mg to about 1000 mg (e.g., between about 40 mg to about 900 mg, e.g., between about 60 mg to about 800 mg, e.g., between about 80 mg to about 700 mg, e.g., between about 80 mg to about 600 mg, e.g., between about 100 mg to about 500 mg, e.g., between about 120 mg to about 400 mg, e.g., between about 140 mg to about 300 mg, e.g., between about 160 mg to about 350 mg, e.g., between about 180 mg to about 300 mg, e.g., between about 200 mg to about 280 mg, e.g., between about 220 mg to about 260 mg, e.g., between about 230 mg to about 250 mg, e
  • a dose e.g., a fixed dose of between about 20 mg to about 1000 mg (e.g.,
  • the effective amount of the PD-1 axis binding antagonist (e.g., anti-PD-1 antagonist antibody (e.g., nivolumab)) is a dose of about 240 mg every two weeks. In some instances, the effective amount of the PD-1 axis binding antagonist (e.g., anti- PD-1 antagonist antibody (e.g., nivolumab)) is a dose of 240 mg every two weeks.
  • the effective amount of the PD-1 axis binding antagonist is a dose of between about 100 mg to about 1000 mg (e.g., between about 200 mg to about 900 mg, e.g., between about 300 mg to about 800 mg, e.g., between about 400 mg to about 700 mg, e.g., between about 400 mg to about 600 mg, e.g., between about 400 mg to about 550 mg, e.g., between about 420 mg to about 540 mg, e.g., between about 440 mg to about 520 mg, e.g., between about 460 mg to about 500 mg, e.g., between about 470 mg to about 490 mg, e.g., 480 mg ⁇ 5 mg, e.g., 480 ⁇ 2.5 mg, e.g., 480 ⁇ 1 .0 mg, e.g., 480 ⁇
  • the effective amount of the PD-1 axis binding antagonist is a dose (e.g., a fixed dose) of between 20 mg to 1000 mg (e.g., between 40 mg to 900 mg, e.g., between 60 mg to 800 mg, e.g., between 80 mg to 700 mg, e.g., between 80 mg to 600 mg, e.g., between 100 mg to 500 mg, e.g., between 120 mg to 400 mg, e.g., between 140 mg to 300 mg, e.g., between 160 mg to 350 mg, e.g., between 180 mg to 300 mg, e.g., between 200 mg to 280 mg, e.g., between 220 mg to 260 mg, e.g., between 230 mg to 250 mg, e.g., 240 mg ⁇ 5 mg, e.g., 240 ⁇ 2.5 mg,
  • a dose e.g., a fixed dose of between 20 mg to 1000 mg (e.g., between 40 mg
  • the effective amount of the PD-1 axis binding antagonist (e.g., anti-PD-1 antagonist antibody (e.g., nivolumab)) is a dose of 240 mg every two weeks. In some instances, the effective amount of the PD-1 axis binding antagonist (e.g., anti-PD-1 antagonist antibody (e.g., nivolumab)) is a dose of 240 mg every two weeks.
  • the effective amount of the PD-1 axis binding antagonist is a dose of between 100 mg to 1000 mg (e.g., between 200 mg to 900 mg, e.g., between 300 mg to 800 mg, e.g., between 400 mg to 700 mg, e.g., between 400 mg to 600 mg, e.g., between 400 mg to 550 mg, e.g., between 420 mg to 540 mg, e.g., between 440 mg to 520 mg, e.g., between 460 mg to 500 mg, e.g., between 470 mg to 490 mg, e.g., 480 mg ⁇ 5 mg, e.g., 480 ⁇ 2.5 mg, e.g., 480 ⁇ 1 .0 mg, e.g., 480 ⁇ 0.5 mg, e.g., 480 mg) every four weeks.
  • 100 mg to 1000 mg e.g., between 200 mg to 900 mg, e.g., between 300 mg to 800 mg
  • the effective amount of the PD-1 axis binding antagonist (e.g., anti-PD-1 antagonist antibody (e.g., nivolumab)) is a dose of about 480 mg every four weeks. In some instances, the effective amount of the PD-1 axis binding antagonist (e.g., anti-PD-1 antagonist antibody (e.g., nivolumab)) is a dose of 480 mg every four weeks.
  • the dose of the PD-1 axis binding antagonist e.g., anti-PD-1 antagonist antibody (e.g., nivolumab)
  • a combination therapy e.g., a combination treatment with an anti-TIG IT antagonist antibody, such as an anti-TIG IT antagonist antibody disclosed herein, e.g., tiragolumab
  • a combination therapy e.g., a combination treatment with an anti-TIG IT antagonist antibody, such as an anti-TIG IT antagonist antibody disclosed herein, e.g., tiragolumab
  • the effective amount of the PD-1 axis binding antagonist is a dose of between about 0.01 mg/kg to about 50 mg/kg of the subject’s body weight (e.g., between about 0.01 mg/kg to about 45 mg/kg, e.g., between about 0.1 mg/kg to about 40 mg/kg, e.g., between about 1 mg/kg to about 35 mg/kg, e.g., between about 2.5 mg/kg to about 30 mg/kg, e.g., between about 5 mg/kg to about 25 mg/kg, e.g., between about 10 mg/kg to about 20 mg/kg, e.g., between about 12.5 mg/kg to about 15 mg/kg, e.g., about 15 ⁇ 2 mg/kg, about 15 ⁇ 1 mg/kg, about 15 ⁇ 0.5 mg/kg, about 15 ⁇ 0.2 mg/kg, or about 15 ⁇
  • the PD-1 axis binding antagonist is a dose of between about 0.01 mg/kg to about 50 mg/kg of the
  • the effective amount of the PD-1 axis binding antagonist is a dose of between about 0.01 mg/kg to about 15 mg/kg of the subject’s body weight (e.g., between about 0.1 mg/kg to about 15 mg/kg, e.g., between about 0.5 mg/kg to about 15 mg/kg, e.g., between about 1 mg/kg to about 15 mg/kg, e.g., between about 2.5 mg/kg to about 15 mg/kg, e.g., between about 5 mg/kg to about 15 mg/kg, e.g., between about 7.5 mg/kg to about 15 mg/kg, e.g., between about 10 mg/kg to about 15 mg/kg, e.g., between about 12.5 mg/kg to about 15 mg/kg, e.g., between about 14 mg/kg to about 15 mg/kg, e.g., about 15 ⁇
  • effective amount of anti-PD-L1 antagonist antibody is a dose of about 15 mg/kg to be administered every three weeks.
  • the effective amount of the PD-1 axis binding antagonist is a dose of between 0.01 mg/kg to 50 mg/kg of the subject’s body weight (e.g., between 0.01 mg/kg to 45 mg/kg, e.g., between 0.1 mg/kg to 40 mg/kg, e.g., between 1 mg/kg to 35 mg/kg, e.g., between 2.5 mg/kg to 30 mg/kg, e.g., between 5 mg/kg to 25 mg/kg, e.g., between 10 mg/kg to 20 mg/kg, e.g., between 12.5 mg/kg to 15 mg/kg, e.g., 15 ⁇ 2 mg/kg, 15 ⁇ 1 mg/
  • the effective amount of the PD-1 axis binding antagonist is a dose of between 0.01 mg/kg to 15 mg/kg of the subject’s body weight (e.g., between 0.1 mg/kg to 15 mg/kg, e.g., between 0.5 mg/kg to 15 mg/kg, e.g., between 1 mg/kg to 15 mg/kg, e.g., between 2.5 mg/kg to 15 mg/kg, e.g., between 5 mg/kg to 15 mg/kg, e.g., between 7.5 mg/kg to 15 mg/kg, e.g., between 10 mg/kg to 15 mg/kg, e.g., between 12.5 mg/kg to 15 mg/kg, e.g., between 14 mg/kg to 15 mg/kg, e.g., 15 ⁇ 1 mg/kg, e.g., 15 ⁇ 0.5 mg/kg,
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., at
  • effective amount of anti-PD-L1 antagonist antibody is a dose of 15 mg/kg to be administered every three weeks.
  • the dose of the PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody (e.g., atezolizumab) or an anti-PD-1 antagonist antibody (e.g., MDX- 1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab)
  • a combination therapy e.g., a combination treatment with an anti-TIG IT antagonist antibody, such as an anti-TIG IT antagonist antibody disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab) or anti-PD-1 antagonist antibody (e.g.
  • the anti-TIGIT antagonist antibody e.g., an anti-TIG IT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody (e.g., atezolizumab) or an anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab)
  • dosing cycles e.g., 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24, 25, 26, 27, 28, 29, 30, 31 , 32, 33, 34, 35, 36, 37, 38, 39, 40, 41 , 42, 43, 44, 45, 46, 47, 48, 49, or 50 or more dosing cycles).
  • the dosing cycles of the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody (e.g., atezolizumab) or an anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab)
  • a loss of clinical benefit e.g., confirmed disease progression, drug resistance, death, or unacceptable toxicity.
  • the length of each dosing cycle is about 14 to 28 days (e.g., 14 days, 15 days, 16 days, 17 days, 18 days, 19 days, 20 days, 21 days, 22 days, 23 days, 24 days, 25 days, 26 days, 27 days, or 28 days). In some instances, the length of each dosing cycle is about 21 days. In some instances, the length of each dosing cycle is about 14 days. In some instances, the length of each dosing cycle is about 28 days.
  • the anti-TIGIT antagonist antibody (e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab) is to be administered on about Day 1 (e.g., Day 1 ⁇ 3 days) of each dosing cycle.
  • the anti-TIGIT antagonist antibody e.g., an anti- TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • a dose e.g., a fixed dose
  • 600 mg on Day 1 of each 21 -day cycle
  • the PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody (e.g., atezolizumab) or an anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab))
  • an anti-PD-L1 antagonist antibody e.g., atezolizumab
  • an anti-PD-1 antagonist antibody e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab)
  • Day 1 e.g., Day 1 ⁇ 3 days
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab)
  • a dose e.g., a fixed dose
  • the PD-1 axis binding antagonist e.g., anti-PD-1 antagonist antibody (e.g., pembrolizumab)
  • the PD-1 axis binding antagonist is to be administered intravenously at a dose of about 200 mg on Day 1 of each 21 -day cycle (i.e., at a dose of about 200 mg every three weeks).
  • the PD-1 axis binding antagonist e.g., anti-PD-1 antagonist antibody (e.g., nivolumab)
  • the PD-1 axis binding antagonist is to be administered intravenously at a dose of about 240 mg on Day 1 of each 14-day cycle (i.e., at a dose of about 240 mg every two weeks).
  • the PD-1 axis binding antagonist e.g., anti-PD-1 antagonist antibody (e.g., nivolumab)
  • is to be administered intravenously at a dose of about 480 mg on Day 1 of each 28-day cycle i.e., at a dose of about 480 mg every four weeks).
  • both the anti-TIGIT antagonist antibody e.g., an anti-TIG IT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody (e.g., atezolizumab) or an anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab)
  • Day 1 e.g., Day 1 ⁇ 3 days
  • both the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody (e.g., atezolizumab) or an anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK- 3475 (pembrolizumab, previously known as lambrolizumab)
  • Day 1 e.g., Day 1 ⁇ 3 days
  • the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the anti-TIGIT antagonist antibody is to be administered intravenously at a dose of about 600 mg on Day 1 of each 21 -day cycle (i.e., at a dose of about 600 mg every three weeks)
  • thePD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., nivolumab)
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., nivolumab)
  • the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., nivolumab)
  • the PD-1 axis binding antagonist is administered intravenously at a dose of about 480 mg on Day 1 of each 28-day cycle (i.e., at a dose of about 480 mg every four weeks).
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab)
  • a dose e.g., a fixed dose
  • the PD-1 axis binding antagonist e.g., anti-PD-1 antagonist antibody (e.g., pembrolizumab)
  • the PD-1 axis binding antagonist is to be administered intravenously at a dose of 200 mg on Day 1 of each 21 -day cycle (i.e., at a dose of 200 mg every three weeks).
  • the PD-1 axis binding antagonist e.g., anti-PD-1 antagonist antibody (e.g., nivolumab)
  • the PD-1 axis binding antagonist is to be administered intravenously at a dose of 240 mg on Day 1 of each 14-day cycle (i.e., at a dose of 240 mg every two weeks).
  • the PD-1 axis binding antagonist e.g., anti-PD-1 antagonist antibody (e.g., nivolumab)
  • is to be administered intravenously at a dose of 480 mg on Day 1 of each 28-day cycle i.e., at a dose of 480 mg every four weeks).
  • both the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody (e.g., atezolizumab) or an anti- PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab)
  • Day 1 e.g., Day 1 ⁇ 3 days
  • both the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody (e.g., atezolizumab) or an anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK- 3475 (pembrolizumab, previously known as lambrolizumab)
  • Day 1 e.g., Day 1 ⁇ 3 days
  • the anti-TIG IT antagonist antibody e.g., an anti-TIG IT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the anti-TIG IT antagonist antibody is to be administered intravenously at a dose of 600 mg on Day 1 of each 21 -day cycle (i.e. , at a dose of 600 mg every three weeks)
  • thePD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., nivolumab)
  • a dose of 240 mg on Day 1 of each 14-day cycle i.e., at a dose of 240 mg every two weeks.
  • the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., nivolumab)
  • the PD-1 axis binding antagonist is administered intravenously at a dose of 480 mg on Day 1 of each 28-day cycle (i.e., at a dose of 480 mg every four weeks).
  • the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the anti-TIGIT antagonist antibody is to be administered to the subject or population of subjects by intravenous infusion over about 60 ⁇ 15 minutes (e.g., about 50 minutes, about 51 minutes, about 52 minutes, about 53 minutes, about 54 minutes, about 55 minutes, about 56 minutes, about 57 minutes, about 58 minutes, about 59 minutes, about 60 minutes, about 61 minutes, about 62 minutes, about 63 minutes, about 64 minutes, about 65 minutes, about 66 minutes, about 67 minutes, about 68 minutes, about 69 minutes, or about 70 minutes).
  • about 60 ⁇ 15 minutes e.g., about 50 minutes, about 51 minutes, about 52 minutes, about 53 minutes, about 54 minutes, about 55 minutes, about 56 minutes, about 57 minutes, about 58 minutes, about 59 minutes, about 60 minutes, about 61 minutes, about 62 minutes, about 63 minutes, about 64 minutes,
  • the PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody (e.g., atezolizumab) or an anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab))
  • an anti-PD-L1 antagonist antibody e.g., atezolizumab
  • an anti-PD-1 antagonist antibody e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab)
  • the PD-1 axis binding antagonist is to be administered to the subject or population of subjects by intravenous infusion over about 60 ⁇ 15 minutes (e.g., about 45 minutes, about 46 minutes, about 47 minutes, about 48 minutes, about 49 minutes, about 50 minutes, about 51 minutes, about 52 minutes, about 53 minutes, about 54 minutes, about 55 minutes, about 56 minutes, about 57
  • the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the anti-TIGIT antagonist antibody is to be administered to the subject or population of subjects by intravenous infusion over about 30 ⁇ 10 minutes (e.g., about 20 minutes, about 21 minutes, about 22 minutes, about 23 minutes, about 24 minutes, about 25 minutes, about 26 minutes, about 27 minutes, about 28 minutes, about 29 minutes, about 30 minutes, about 31 minutes, about 32 minutes, about 33 minutes, about 34 minutes, about 35 minutes, about 36 minutes, about 37 minutes, about 38 minutes, about 39 minutes, or about 40 minutes).
  • ⁇ 10 minutes e.g., about 20 minutes, about 21 minutes, about 22 minutes, about 23 minutes, about 24 minutes, about 25 minutes, about 26 minutes, about 27 minutes, about 28 minutes, about 29 minutes, about 30 minutes, about 31 minutes, about 32 minutes, about 33 minutes, about 34 minutes, about 35 minutes, about 36 minutes, about 37 minutes, about 38 minutes, about 39
  • the PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody (e.g., atezolizumab) or an anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab))
  • an anti-PD-L1 antagonist antibody e.g., atezolizumab
  • an anti-PD-1 antagonist antibody e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab)
  • the PD-1 axis binding antagonist is to be administered to the subject or population of subjects by intravenous infusion over about 30 ⁇ 10 minutes (e.g., about 20 minutes, about 21 minutes, about 22 minutes, about 23 minutes, about 24 minutes, about 25 minutes, about 26 minutes, about 27 minutes, about 28 minutes, about 29 minutes, about 30 minutes, about 31 minutes, about 32 minutes
  • the anti-TIG IT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody (e.g., atezolizumab) or an anti- PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab)
  • the PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody (e.g., atezolizumab) or an anti- PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab)
  • the method includes an intervening first observation period.
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab) or anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab)
  • the method includes an intervening first observation period.
  • the method further includes a second observation period following administration of the PD-1 axis binding antagonist (e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab) or anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab))).
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab) or anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab)
  • the method includes both a first observation period following administration of the anti-TIGIT antagonist antibody and second observation period following administration of the PD-1 axis binding antagonist (e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab) or anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab))).
  • the first and second observation periods are each between about 30 minutes to about 60 minutes in length.
  • the method may include recording the subject or population of subjects’ vital signs (e.g., pulse rate, respiratory rate, blood pressure, and temperature) at about 30 ⁇ 10 minutes after administration of the anti-TIGIT antagonist antibody and PD-1 axis binding antagonist (e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab) or anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab))) during the first and second observation periods, respectively.
  • vital signs e.g., pulse rate, respiratory rate, blood pressure, and temperature
  • PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab) or anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab)
  • the method may include recording the subject or population of subjects’ vital signs (e.g., pulse rate, respiratory rate, blood pressure, and temperature) at about 15 ⁇ 10 minutes after administration of the anti-TIGIT antagonist antibody and PD-1 axis binding antagonist (e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab) or anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab))) during the first and second observation periods, respectively.
  • vital signs e.g., pulse rate, respiratory rate, blood pressure, and temperature
  • PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab) or anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab)
  • the PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody (e.g., atezolizumab) or an anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab))
  • an anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab.
  • the method includes an intervening first observation period.
  • the method includes a second observation period following administration of the anti-TIGIT antagonist antibody.
  • the method includes both a first observation period following administration of the PD-1 axis binding antagonist (e.g., anti-PD- L1 antagonist antibody (e.g., atezolizumab) or anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab))) and second observation period following administration of the anti-TIGIT antagonist antibody.
  • the first and second observation periods are each between about 30 minutes to about 60 minutes in length.
  • the method may include recording the subject or population of subjects’ vital signs (e.g., pulse rate, respiratory rate, blood pressure, and temperature) at about 30 ⁇ 10 minutes after administration of the PD-1 axis binding antagonist (e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab) or anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab))) and anti-TIGIT antagonist antibody during the first and second observation periods, respectively.
  • vital signs e.g., pulse rate, respiratory rate, blood pressure, and temperature
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab) or anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab
  • the method may include recording the subject or population of subjects’ vital signs (e.g., pulse rate, respiratory rate, blood pressure, and temperature) at about 15 ⁇ 10 minutes after administration of the PD-1 axis binding antagonist (e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab) or anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab))) and anti-TIGIT antagonist antibody during the first and second observation periods, respectively.
  • vital signs e.g., pulse rate, respiratory rate, blood pressure, and temperature
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab) or anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab
  • the anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab) or anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab)
  • MDX-1106 nivolumab
  • MK-3475 pembrolizumab, previously known as lambrolizumab
  • the method includes an observation period.
  • the observation period is between about 30 minutes to about 60 minutes in length.
  • the method may include recording the subject’s vital signs (e.g., pulse rate, respiratory rate, blood pressure, and temperature) at about 30 ⁇ 10 minutes after administration of the PD-1 axis binding antagonist (e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab) or anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab))) and anti-TIGIT antagonist antibody during the observation period.
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab) or anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab)
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.
  • the method may include recording the subject’s vital signs (e.g., pulse rate, respiratory rate, blood pressure, and temperature) at about 15 ⁇ 10 minutes after administration of the PD-1 axis binding antagonist (e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab) or anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab))) and anti-TIGIT antagonist antibody during the observation period.
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab) or anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab)
  • the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.
  • the invention provides an anti-TIG IT antagonist antibody (e.g., an anti-TIGIT antagonist antibody disclosed herein, e.g., tiragolumab) and PD-1 axis binding antagonist (e.g., anti-PD- L1 antagonist antibody (e.g., atezolizumab)) for use in a method of treating a subject or population of subjects having a cancer with a detectable expression level of PD-L1 (e.g., cervical cancer, e.g., Stage IVB, metastatic, recurrent, or persistent cervical cancer, e.g., a metastatic and/or recurrent PD-L1 -positive cervical carcinoma), wherein the method comprises administering to the subject or population of subjects one or more dosing cycles of an anti-TIGIT antagonist antibody at a dose (e.g., a fixed dose) of 600 mg every three weeks and atezolizumab at a dose (e.g., a fixed dose) of 1200 mg every three weeks, where
  • the anti-TIGIT antagonist antibody has a VH domain having the amino acid sequence of SEQ ID NO: 17 and a VL domain having the amino acid sequence of SEQ ID NO: 19. In some instances, the anti-TIGIT antagonist antibody has a VH domain having the amino acid sequence of SEQ ID NO: 18 and a VL domain having the amino acid sequence of SEQ ID NO: 19.
  • the invention provides an anti-TIGIT antagonist antibody (e.g., an anti-TIGIT antagonist antibody disclosed herein, e.g., tiragolumab) and PD-1 axis binding antagonist (e.g., anti-PD-1 antagonist antibody (e.g., pembrolizumab)) for use in a method of treating a subject or population of subjects having a cancer with a detectable expression level of PD-L1 (e.g., cervical cancer, e.g., Stage IVB, metastatic, recurrent, or persistent cervical cancer, e.g., a metastatic and/or recurrent PD-L1 -positive cervical carcinoma), wherein the method comprises administering to the subject or population of subjects one or more dosing cycles of an anti-TIGIT antagonist antibody at a dose (e.g., a fixed dose) of 600 mg every three weeks and pembrolizumab at a dose (e.g., a fixed dose) of 200 mg every three weeks, wherein the anti-TIG
  • the anti-TIGIT antagonist antibody has a VH domain having the amino acid sequence of SEQ ID NO: 17 and a VL domain having the amino acid sequence of SEQ ID NO: 19. In some instances, the anti-TIGIT antagonist antibody has a VH domain having the amino acid sequence of SEQ ID NO: 18 and a VL domain having the amino acid sequence of SEQ ID NO: 19.
  • the invention provides an anti-TIGIT antagonist antibody (e.g., an anti-TIGIT antagonist antibody disclosed herein, e.g., tiragolumab) and PD-1 axis binding antagonist (e.g., anti-PD-1 antagonist antibody (e.g., nivolumab)) for use in a method of treating a subject or population of subjects having a cancer with a detectable expression level of PD-L1 (e.g., cervical cancer, e.g., Stage IVB, metastatic, recurrent, or persistent cervical cancer, e.g., a metastatic and/or recurrent PD-L1 -positive cervical carcinoma), wherein the method comprises administering to the subject or population of subjects one or more dosing cycles of an anti-TIGIT antagonist antibody at a dose (e.g., a fixed dose) of 600 mg every three weeks and nivolumab at a dose (e.g., a fixed dose) of 240 mg every two weeks, where
  • the anti-TIGIT antagonist antibody has a VH domain having the amino acid sequence of SEQ ID NO: 17 and a VL domain having the amino acid sequence of SEQ ID NO: 19. In some instances, the anti-TIGIT antagonist antibody has a VH domain having the amino acid sequence of SEQ ID NO: 18 and a VL domain having the amino acid sequence of SEQ ID NO: 19.
  • the invention provides an anti-TIGIT antagonist antibody (e.g., an anti-TIGIT antagonist antibody disclosed herein, e.g., tiragolumab) and PD-1 axis binding antagonist (e.g., anti-PD-1 antagonist antibody (e.g., nivolumab)) for use in a method of treating a subject or population of subjects having a cancer with a detectable expression level of PD-L1 (e.g., cervical cancer, e.g., Stage IVB, metastatic, recurrent, or persistent cervical cancer, e.g., a metastatic and/or recurrent PD-L1 -positive cervical carcinoma), wherein the method comprises administering to the subject or population of subjects one or more dosing cycles of an anti-TIGIT antagonist antibody at a dose (e.g., a fixed dose) of 600 mg every three weeks and nivolumab at a dose (e.g., a fixed dose) of 480 mg every four weeks, where
  • the anti-TIGIT antagonist antibody has a VH domain having the amino acid sequence of SEQ ID NO: 17 and a VL domain having the amino acid sequence of SEQ ID NO: 19. In some instances, the anti-TIGIT antagonist antibody has a VH domain having the amino acid sequence of SEQ ID NO: 18 and a VL domain having the amino acid sequence of SEQ ID NO: 19.
  • the invention provides an anti-TIGIT antagonist antibody (e.g., an anti-TIGIT antagonist antibody disclosed herein, e.g., tiragolumab) and PD-1 axis binding antagonist (e.g., anti-PD- L1 antagonist antibody (e.g., atezolizumab)) for use in a method of treating a subject or population of subjects having a cancer with a detectable expression level of PD-L1 (e.g., cervical cancer, e.g., Stage IVB, metastatic, recurrent, or persistent cervical cancer, e.g., a metastatic and/or recurrent PD-L1 -positive cervical carcinoma), wherein the method comprises administering to the subject or population of subjects one or more dosing cycles of tiragolumab at a dose (e.g., a fixed dose) of 600 mg every three weeks and atezolizumab at a dose (e.g., a fixed dose) of 1200 mg every three weeks.
  • a dose
  • the invention provides an anti-TIGIT antagonist antibody (e.g., an anti-TIGIT antagonist antibody disclosed herein, e.g., tiragolumab) and PD-1 axis binding antagonist (e.g., anti-PD-1 antagonist antibody (e.g., MK-3475 (pembrolizumab, previously known as lambrolizumab)) for use in a method of treating a subject or population of subjects having a cancer with a detectable expression level of PD-L1 (e.g., cervical cancer, e.g., Stage IVB, metastatic, recurrent, or persistent cervical cancer, e.g., a metastatic and/or recurrent PD-L1 -positive cervical carcinoma), wherein the method comprises administering to the subject or population of subjects one or more dosing cycles of tiragolumab at a dose (e.g., a fixed dose) of 600 mg every three weeks and pembrolizumab at a dose (e.g., a dose (e
  • the invention provides an anti-TIGIT antagonist antibody (e.g., an anti-TIGIT antagonist antibody disclosed herein, e.g., tiragolumab) and PD-1 axis binding antagonist (e.g., anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab)) for use in a method of treating a subject or population of subjects having a cancer with a detectable expression level of PD-L1 (e.g., cervical cancer, e.g., Stage IVB, metastatic, recurrent, or persistent cervical cancer, e.g., a metastatic and/or recurrent PD-L1 -positive cervical carcinoma), wherein the method comprises administering to the subject or population of subjects one or more dosing cycles of tiragolumab at a dose (e.g., a fixed dose) of 600 mg every three weeks and nivolumab at a dose (e.g., a fixed dose) of 240 mg every two weeks
  • the invention provides an anti-TIG IT antagonist antibody (e.g., an anti-TIGIT antagonist antibody disclosed herein, e.g., tiragolumab) and PD-1 axis binding antagonist (e.g., anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab)) for use in a method of treating a subject or population of subjects having a cancer with a detectable expression level of PD-L1 (e.g., cervical cancer, e.g., Stage IVB, metastatic, recurrent, or persistent cervical cancer, e.g., a metastatic and/or recurrent PD-L1 -positive cervical carcinoma), wherein the method comprises administering to the subject or population of subjects one or more dosing cycles of tiragolumab at a dose (e.g., a fixed dose) of 600 mg every three weeks and nivolumab at a dose (e.g., a fixed dose) of 480 mg every four weeks
  • the invention provides uses of an anti-TIGIT antagonist antibody (e.g., an anti- TIGIT antagonist antibody disclosed herein, e.g., tiragolumab) and PD-1 axis binding antagonist (e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab) or anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab))) in the manufacture or preparation of a medicament for use in a method of treating a subject or population of subjects having a cancer with a detectable expression level of PD-L1 (e.g., cervical cancer, e.g., Stage IVB, metastatic, recurrent, or persistent cervical cancer, e.g., a metastatic and/or recurrent PD-L1 -positive cervical carcinoma), wherein the method comprises administering to the subject or population of subjects one or more dosing cycles
  • the invention provides uses of an anti-TIGIT antagonist antibody in the manufacture of a medicament for use in a method of treating a subject or population of subjects having a cancer with a detectable expression level of PD-L1 (e.g., cervical cancer, e.g., Stage IVB, metastatic, recurrent, or persistent cervical cancer, e.g., a metastatic and/or recurrent PD-L1 -positive cervical carcinoma), wherein the method comprises administering to the subject or population of subjects one or more dosing cycles of the medicament and a PD-1 axis binding antagonist (e.g., an anti-PD-L1 antagonist antibody (e.g., atezolizumab) or an anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK- 3475 (pembrolizumab, previously known as lambrolizumab))), and wherein the medicament is formulated for administration of an effective amount of the anti-TIGIT antagonist antibody and an effective
  • the invention provides uses of a PD-1 axis binding antagonist (e.g., an anti- PD-L1 antagonist antibody (e.g., atezolizumab) or an anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab))) in the manufacture of a medicament for use in a method of treating a subject or population of subjects having a cancer with a detectable expression level of PD-L1 (e.g., cervical cancer, e.g., Stage IVB, metastatic, recurrent, or persistent cervical cancer, e.g., a metastatic and/or recurrent PD-L1 -positive cervical carcinoma), wherein the method comprises administering to the subject or population of subjects one or more dosing cycles of the medicament and an anti-TIGIT antagonist antibody, and wherein the medicament is formulated for administration an effective amount of the PD-1 axis binding antagonist (
  • the effective amount of the anti-TIGIT antagonist antibody is a dose (e.g., a fixed dose) of between about 30 mg to about 1200 mg (e.g., between about 30 mg to about 1100 mg, e.g., between about 60 mg to about 1000 mg, e.g., between about 100 mg to about 900 mg, e.g., between about 200 mg to about 800 mg, e.g., between about 300 mg to about 800 mg, e.g., between about 400 mg to about 800 mg, e.g., between about 400 mg to about 750 mg, e.g., between about 450 mg to about 750 mg, e.g., between about 500 mg to about 700 mg, e.g., between about 550 mg to about 650 mg, e.g., 600 mg ⁇ 10 mg, e.g., 600 ⁇ 6 mg,
  • a dose e.g., a fixed dose of between about 30 mg to about 1200 mg (e.g., between about 30 mg
  • an effective amount of the anti-TIGIT antagonist antibody is a dose of between about 30 mg to about 600 mg (e.g., between about 50 mg to between 600 mg, e.g., between about 60 mg to about 600 mg, e.g., between about 100 mg to about 600 mg, e.g., between about 200 mg to about 600 mg, e.g., between about 200 mg to about 550 mg, e.g., between about 250 mg to about 500 mg, e.g., between about 300 mg to about 450 mg, e.g., between about 350 mg to about 400 mg, e.g., about 375 mg) (e.g., between 30 mg to 1200 mg (e.g., between 30 mg to 1100 mg, e.g., between 60 mg to 1000 mg, e.g., between 100 mg to 900 mg, e.g., between
  • an effective amount of the anti-TIGIT antagonist antibody is a dose of between 30 mg to 600 mg (e.g., between 50 mg to between 600 mg, e.g., between 60 mg to 600 mg, e.g., between 100 mg to 600 mg, e.g., between 200 mg to 600 mg, e.g., between 200 mg to 550 mg, e.g., between 250 mg to 500 mg, e.g., between 300 mg to 450 mg, e.g., between 350 mg to 400 mg, e.g., 375 mg)) every three weeks.
  • an effective amount of the anti-TIGIT antagonist antibody is a dose of between 30 mg to 600 mg (e.g., between 50 mg to between 600 mg, e.g., between 60 mg to 600 mg, e.g., between 100 mg to 600 mg, e.g., between 200 mg to 600 mg, e.g., between 200 mg to 550 mg, e.g., between 250 mg to 500 mg, e.
  • the effective amount of the anti-TIGIT antagonist antibody is a dose of about 600 mg every three weeks. In some instances, effective amount of the anti-TIGIT antagonist antibody (e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab) is a dose of 600 mg every three weeks.
  • the dose of the anti-TIGIT antagonist antibody (e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab) is to be administered in a combination therapy (e.g., a combination treatment with a PD-1 axis binding antagonist (e.g., an anti-PD-L1 antagonist antibody (e.g., atezolizumab) or an anti-PD- 1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab))))
  • a combination therapy e.g., a combination treatment with a PD-1 axis binding antagonist (e.g., an anti-PD-L1 antagonist antibody (e.g., atezolizumab) or an anti-PD- 1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as
  • the effective amount of the PD-1 axis binding antagonist is a dose (e.g., a fixed dose) of between about 80 mg to about 2000 mg (e.g., between about 80 mg to about 1950 mg, e.g., between about 80 mg to about 1900 mg, e.g., between about 80 mg to about 1800 mg, e.g., between about 100 mg to about 1700 mg, e.g., between about 200 mg to about 1600 mg, e.g., between about 300 mg to about 1400 mg, e.g., between about 400 mg to about 1300 mg, e.g., between about 500 mg to about 1200 mg, e.g., between about 600 mg to about 1100 mg, e.g., between about 700 mg to about 1000 mg, e.g., between about 740 mg to about 940 mg, e.g., between about 790 mg to about 8
  • a dose e.g., a fixed dose of between about 80 mg to about 2000 mg (e.g., between
  • 1.0 mg, e.g., 840 ⁇ 0.5 mg, e.g., 840 mg) (e.g., between 80 mg to 2000 mg (e.g., between 80 mg to 1950 mg, e.g., between 80 mg to 1900 mg, e.g., between 80 mg to 1800 mg, e.g., between 100 mg to 1700 mg, e.g., between 200 mg to 1600 mg, e.g., between 300 mg to 1400 mg, e.g., between 400 mg to 1300 mg, e.g., between 500 mg to 1200 mg, e.g., between 600 mg to 1100 mg, e.g., between 700 mg to 1000 mg, e.g., between 740 mg to 940 mg, e.g., between 790 mg to 890 mg, e.g., between 815 mg to 865 mg, e.g., between 830 mg to 850 mg, e.g., 840 mg ⁇ 5 mg, e.g.
  • the effective amount of the PD-1 axis binding antagonist is a dose of between about 80 mg to about 2000 mg (e.g., between about 100 mg to about 2000 mg, e.g., between about 200 mg to about 1900 mg, e.g., between about 300 mg to about 1700 mg, e.g., between about 400 mg to about 1600 mg, e.g., between about 500 mg to about 1600 mg, e.g., between about 600 mg to about 1600 mg, e.g., between about 700 mg to about 1600 mg, e.g., between about 800 mg to about 1600 mg, e.g., between about 900 mg to about 1500 mg, e.g., between about 1000 mg to about 1400 mg, e.g., between about 1050 mg to about 1350 mg, e.g., between about 1100 mg to about 1300 mg, e.g., between about 1150
  • 1600 mg e.g., between 500 mg to 1600 mg, e.g., between 600 mg to 1600 mg, e.g., between 700 mg to
  • 1600 mg e.g., between 800 mg to 1600 mg, e.g., between 900 mg to 1500 mg, e.g., between 1000 mg to
  • 1400 mg e.g., between 1050 mg to 1350 mg, e.g., between 1100 mg to 1300 mg, e.g., between 1150 mg to 1250 mg, e.g., between 1175 mg to 1225 mg), e.g., between about 1190 mg to about 1210 mg (e.g., between 1190 mg to 1210 mg), e.g., 1200 mg ⁇ 5 mg, e.g., 1200 ⁇ 2.5 mg, e.g., 1200 ⁇ 1 .0 mg, e.g.,
  • the effective amount of the PD-1 axis binding antagonist is a dose of between about 80 mg to about 2000 mg (e.g., between about 100 mg to about 2000 mg, e.g., between about 200 mg to about 2000 mg, e.g., between about 300 mg to about 2000 mg, e.g., between about 400 mg to about 2000 mg, e.g., between about 500 mg to about 2000 mg, e.g., between about 600 mg to about 1900 mg, e.g., between about 700 mg to about 1800 mg, e.g., between about 800 mg to about 1800 mg, e.g., between about 900 mg to about 1800 mg, e.g., between about 1000 mg to about 1800 mg, e.g., between about 1100 mg to about 1800 mg, e.g., between about
  • the effective amount of the PD-1 axis binding antagonist is a dose of about 840 mg every two weeks. In some instances, the effective amount of the PD-1 axis binding antagonist (e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab)) is a dose of 840 mg every two weeks. In some instances, the effective amount of the PD- 1 axis binding antagonist (e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab)) is a dose of about 1200 mg every three weeks.
  • the effective amount of the PD-1 axis binding antagonist (e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab)) is a dose of 1200 mg every three weeks. In some instances, the effective amount of the PD-1 axis binding antagonist (e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab)) is a dose of about 1680 mg every four weeks. In some instances, the effective amount of the PD-1 axis binding antagonist (e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab)) is a dose of 1680 mg every four weeks.
  • the dose of the PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody (e.g., atezolizumab) or an anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab))
  • a combination therapy e.g., a combination treatment with an anti- TIGIT antagonist antibody, such as an anti-TIG IT antagonist antibody disclosed herein, e.g., tiragolumab
  • a combination therapy e.g., a combination treatment with an anti- TIGIT antagonist antibody, such as an anti-TIG IT antagonist antibody disclosed herein, e.g., tiragolumab
  • a combination therapy e.g., a combination treatment with an anti- TIGIT antagonist antibody, such as an anti-TIG IT antagonist antibody disclosed herein, e.g., tiragolumab
  • the effective amount of the PD-1 axis binding antagonist is a dose (e.g., a fixed dose) of between about 20 mg to about 1000 mg (e.g., between about 40 mg to about 900 mg, e.g., between about 60 mg to about 800 mg, e.g., between about 80 mg to about 700 mg, e.g., between about 80 mg to about 600 mg, e.g., between about 100 mg to about 500 mg, e.g., between about 120 mg to about 400 mg, e.g., between about 140 mg to about 300 mg, e.g., between about 160 mg to about 350 mg, e.g., between about 180 mg to about 300 mg, e.g., between about 180 mg to about 250 mg, e.g., between about 180 mg to about 220 mg, e.g., between about 190 mg to about 210 mg (e.g.
  • the effective amount of the PD-1 axis binding antagonist (e.g., anti-PD-1 antagonist antibody (e.g., pembrolizumab)) is a dose of about 200 mg every three weeks. In some instances, the effective amount of the PD-1 axis binding antagonist (e.g., anti-PD-1 antagonist antibody (e.g., pembrolizumab)) is a dose of 200 mg every three weeks.
  • the dose of the PD-1 axis binding antagonist e.g., anti-PD-1 antagonist antibody (e.g., pembrolizumab)
  • a combination therapy e.g., a combination treatment with an anti-TIG IT antagonist antibody, such as an anti-TIG IT antagonist antibody disclosed herein, e.g., tiragolumab
  • a combination therapy e.g., a combination treatment with an anti-TIG IT antagonist antibody, such as an anti-TIG IT antagonist antibody disclosed herein, e.g., tiragolumab
  • the effective amount of the PD-1 axis binding antagonist is a dose (e.g., a fixed dose) of between about 20 mg to about 1000 mg (e.g., 20 mg to 1000 mg) (e.g., between about 40 mg to about 900 mg, e.g., between about 60 mg to about 800 mg, e.g., between about 80 mg to about 700 mg, e.g., between about 80 mg to about 600 mg, e.g., between about 100 mg to about 500 mg, e.g., between about 120 mg to about 400 mg, e.g., between about 140 mg to about 300 mg, e.g., between about 160 mg to about 350 mg, e.g., between about 180 mg to about 300 mg, e.g., between about 200 mg to about 280 mg, e.g., between about 220 mg to about 260 mg, e.g., a dose (e.g., a fixed dose) of between about 20 mg to about 1000 mg (e.g., 20
  • the effective amount of the PD-1 axis binding antagonist (e.g., anti-PD-1 antagonist antibody (e.g., nivolumab)) is a dose of about 240 mg every two weeks. In some instances, the effective amount of the PD-1 axis binding antagonist (e.g., anti-PD-1 antagonist antibody (e.g., nivolumab)) is a dose of 240 mg every two weeks.
  • the effective amount of the PD-1 axis binding antagonist is a dose of between about 100 mg to about 1000 mg (e.g., between 100 mg to 1000 mg) (e.g., between about 200 mg to about 900 mg, e.g., between about 300 mg to about 800 mg, e.g., between about 400 mg to about 700 mg, e.g., between about 400 mg to about 600 mg, e.g., between about 400 mg to about 550 mg, e.g., between about 420 mg to about 540 mg, e.g., between about 440 mg to about 520 mg, e.g., between about 460 mg to about 500 mg, e.g., between about 470 mg to about 490 mg (e.g., between 200 mg to 900 mg, e.g., between 300 mg to 800 mg, e.g., between 400 mg to 700 mg, e
  • the effective amount of the PD-1 axis binding antagonist (e.g., anti- PD-1 antagonist antibody (e.g., nivolumab)) is a dose of about 480 mg every four weeks. In some instances, the effective amount of the PD-1 axis binding antagonist (e.g., anti-PD-1 antagonist antibody (e.g., nivolumab)) is a dose of 480 mg every four weeks.
  • the dose of the PD-1 axis binding antagonist e.g., anti-PD-1 antagonist antibody (e.g., nivolumab)
  • a combination therapy e.g., a combination treatment with an anti-TIGIT antagonist antibody, such as an anti-TIGIT antagonist antibody disclosed herein, e.g., tiragolumab
  • a combination therapy e.g., a combination treatment with an anti-TIGIT antagonist antibody, such as an anti-TIGIT antagonist antibody disclosed herein, e.g., tiragolumab
  • the effective amount of the PD-1 axis binding antagonist is a dose of between about 0.01 mg/kg to about 50 mg/kg of the subject’s body weight (e.g., between about 0.01 mg/kg to about 45 mg/kg, e.g., between about 0.1 mg/kg to about 40 mg/kg, e.g., between about 1 mg/kg to about 35 mg/kg, e.g., between about 2.5 mg/kg to about 30 mg/kg, e.g., between about 5 mg/kg to about 25 mg/kg, e.g., between about 10 mg/kg to about 20 mg/kg, e.g., between about 12.5 mg/kg to about 15 mg/kg, e.g., about 15 ⁇ 2 mg/kg, about 15 ⁇ 1 mg/kg, about 15 ⁇ 0.5 mg/kg, about 15 ⁇ 0.2 mg/kg, or about 15 ⁇
  • the PD-1 axis binding antagonist is a dose of between about 0.01 mg/kg to about 50 mg/kg of the
  • the effective amount of the PD-1 axis binding antagonist is a dose of between about 0.01 mg/kg to about 15 mg/kg of the subject’s body weight (e.g., between about 0.1 mg/kg to about 15 mg/kg, e.g., between about 0.5 mg/kg to about 15 mg/kg, e.g., between about 1 mg/kg to about 15 mg/kg, e.g., between about 2.5 mg/kg to about 15 mg/kg, e.g., between about 5 mg/kg to about 15 mg/kg, e.g., between about 7.5 mg/kg to about 15 mg/kg, e.g., between about 10 mg/kg to about 15 mg/kg, e.g., between about 12.5 mg/kg to about 15 mg/kg, e.g., between about 14 mg/kg to about 15 mg/kg, e.g., about 15 ⁇
  • the effective amount of anti-PD-L1 antagonist antibody is a dose of about 15 mg/kg to be administered every three weeks.
  • the dose of the PD- 1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody (e.g., atezolizumab) or an anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab)
  • a combination therapy e.g., a combination treatment with an anti-TIG IT antagonist antibody, such as an anti-TIG IT antagonist antibody disclosed herein, e.g., tiragolumab
  • an anti-TIG IT antagonist antibody such as an anti-TIG IT antagonist antibody disclosed herein, e.g., tiragolumab
  • the medicament comprising the anti-TIGIT antagonist antibody (e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab) and the PD-1 axis binding antagonist (e.g., an anti-PD-L1 antagonist antibody (e.g., atezolizumab) or an anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab)))
  • PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody (e.g., atezolizumab) or an anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab)
  • dosing cycles e.g., 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16,
  • the dosing cycles of the medicament comprising anti-TIGIT antagonist antibody (e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab) and the PD-1 axis binding antagonist (e.g., an anti-PD-L1 antagonist antibody (e.g., atezolizumab) or an anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK- 3475 (pembrolizumab, previously known as lambrolizumab)))
  • an anti-PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody (e.g., atezolizumab) or an anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK- 3475 (pembrolizumab, previously known as lambrolizumab)
  • a loss of clinical benefit e.g., confirmed disease progression, drug resistance, death, or unacceptable
  • the length of each dosing cycle is about 14 to 28 days (e.g., 14 days,15 days, 16 days, 17 days, 18 days, 19 days, 20 days, 21 days, 22 days, 23 days, 24 days, 25 days, 26 days, 27 days, or 28 days). In some instances, the length of each dosing cycle is about 21 days.
  • the medicament comprising the anti-TIGIT antagonist antibody e.g., an anti-TIG IT antagonist antibody as disclosed herein, e.g., tiragolumab
  • Day 1 e.g., Day 1 ⁇ 3 days
  • the medicament comprising the anti-TIGIT antagonist antibody is to be administered intravenously at a dose (e.g., a fixed dose) of about 600 mg on Day 1 of each 21 -day cycle (i.e. , at a dose of about 600 mg every three weeks).
  • a dose e.g., a fixed dose
  • the medicament comprising the PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody (e.g., atezolizumab) or an anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab))
  • the PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody (e.g., atezolizumab) or an anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab)
  • Day 1 e.g., Day 1 ⁇ 3 days
  • the medicament comprising the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab)
  • the medicament comprising the PD-1 axis binding antagonist is to be administered intravenously at a dose of about 1200 mg on Day 1 of each 21 -day cycle (i.e., at a dose of about 1200 mg every three weeks).
  • the medicament comprising the PD-1 axis binding antagonist e.g., anti-PD-1 antagonist antibody (e.g., pembrolizumab)
  • is to be administered intravenously at a dose of about 200 mg on Day 1 of each 21 -day cycle i.e., at a dose of about 200 mg every three weeks).
  • the medicament comprising the PD-1 axis binding antagonist e.g., anti-PD-1 antagonist antibody (e.g., nivolumab)
  • the medicament comprising the PD-1 axis binding antagonist is to be administered intravenously at a dose of about 240 mg on Day 1 of each 14-day cycle (i.e., at a dose of about 240 mg every two weeks).
  • the medicament comprising the PD-1 axis binding antagonist e.g., anti- PD-1 antagonist antibody (e.g., nivolumab)
  • is to be administered intravenously at a dose of about 480 mg on Day 1 of each 28-day cycle i.e., at a dose of about 480 mg every four weeks).
  • the medicament comprising both the anti-TIGIT antagonist antibody (e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab) and the PD-1 axis binding antagonist (e.g., an anti-PD-L1 antagonist antibody (e.g., atezolizumab) or an anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab)))
  • Day 1 e.g., Day 1 ⁇ 3 days
  • the medicament comprising the anti-TIGIT antagonist antibody is to be administered intravenously at a dose of about 600 mg on Day 1 of each 21 -day cycle (i.e., at a dose of about 600 mg every three weeks)
  • the medicament comprising the PD-1 axis binding antagonist e.g., anti-PD-L1 antagonist antibody (e.g., atezolizumab)
  • the PD-1 axis binding antagonist is to be administered intravenously at a dose of about 1200 mg on Day 1 of each 21 -day cycle (i.e., at a dose of about 1200 mg every three weeks).
  • the medicament comprising the anti-TIGIT antagonist antibody is to be administered intravenously at a dose of about 600 mg on Day 1 of each 21 -day cycle (i.e., at a dose of about 600 mg every three weeks)
  • the medicament comprising the PD-1 axis binding antagonist e.g., anti-PD-1 antagonist antibody (e.g., pembrolizumab)
  • the medicament comprising the PD-1 axis binding antagonist is to be administered intravenously at a dose of about 200 mg on Day 1 of each 21 -day cycle (i.e., at a dose of about 200 mg every three weeks).
  • the medicament comprising the anti-TIGIT antagonist antibody is to be administered intravenously at a dose of about 600 mg on Day 1 of each 21 -day cycle (i.e., at a dose of about 600 mg every three weeks)
  • the medicament comprising the PD-1 axis binding antagonist e.g., anti-PD-1 antagonist antibody (e.g., nivolumab)
  • the PD-1 axis binding antagonist is to be administered intravenously at a dose of about 240 mg on Day 1 of each 14-day cycle (i.e., at a dose of about 240 mg every two weeks).
  • the medicament comprising the anti-TIGIT antagonist antibody is to be administered intravenously at a dose of about 600 mg on Day 1 of each 21 -day cycle (i.e., at a dose of about 600 mg every three weeks)
  • the medicament comprising the PD-1 axis binding antagonist e.g., anti-PD-1 antagonist antibody (e.g., nivolumab)
  • the PD-1 axis binding antagonist is to be administered intravenously at a dose of about 480 mg on Day 1 of each 28-day cycle (i.e., at a dose of about 480 mg every four weeks).
  • the medicament comprising the anti-TIGIT antagonist antibody e.g., an anti- TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the medicament comprising the anti-TIGIT antagonist antibody is administered to the subject or population of subjects by intravenous infusion over about 60 ⁇ 15 minutes (e.g., about 50 minutes, about 51 minutes, about 52 minutes, about 53 minutes, about 54 minutes, about 55 minutes, about 56 minutes, about 57 minutes, about 58 minutes, about 59 minutes, about 60 minutes, about 61 minutes, about 62 minutes, about 63 minutes, about 64 minutes, about 65 minutes, about 66 minutes, about 67 minutes, about 68 minutes, about 69 minutes, or about 70 minutes).
  • the anti-TIGIT antagonist antibody e.g., an anti- TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the medicament comprising the PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody (e.g., atezolizumab) or an anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab))
  • an anti-PD-L1 antagonist antibody e.g., atezolizumab
  • an anti-PD-1 antagonist antibody e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab)
  • the PD-1 axis binding antagonist is to be administered to the subject or population of subjects by intravenous infusion over about 60 ⁇ 15 minutes (e.g., about 45 minutes, about 46 minutes, about 47 minutes, about 48 minutes, about 49 minutes, about 50 minutes, about 51 minutes, about 52 minutes, about 53 minutes, about 54 minutes, about 55 minutes, about 56 minutes
  • the medicament comprising the anti-TIGIT antagonist antibody e.g., an anti- TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the medicament comprising the anti-TIGIT antagonist antibody is administered to the subject or population of subjects by intravenous infusion over about 30 ⁇ 10 minutes (e.g., about 20 minutes, about 21 minutes, about 22 minutes, about 23 minutes, about 24 minutes, about 25 minutes, about 26 minutes, about 27 minutes, about 28 minutes, about 29 minutes, about 30 minutes, about 31 minutes, about 32 minutes, about 33 minutes, about 34 minutes, about 35 minutes, about 36 minutes, about 37 minutes, about 38 minutes, about 39 minutes, or about 40 minutes).
  • the anti-TIGIT antagonist antibody e.g., an anti- TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • intravenous infusion e.g., about 30 minutes, about 31 minutes, about 32 minutes, about 33 minutes, about 34 minutes, about 35 minutes, about 36 minutes, about 37
  • the medicament comprising the PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody (e.g., atezolizumab) or an anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab))
  • an anti-PD-L1 antagonist antibody e.g., atezolizumab
  • an anti-PD-1 antagonist antibody e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab)
  • the PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody (e.g., atezolizumab) or an anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab
  • the medicament comprising the anti-TIG IT antagonist antibody e.g., an anti- TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the PD-1 axis binding antagonist e.g., an anti- PD-L1 antagonist antibody (e.g., atezolizumab) or an anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab)
  • the PD-1 axis binding antagonist e.g., an anti- PD-L1 antagonist antibody (e.g., atezolizumab) or an anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab)
  • the method includes an intervening first observation period.
  • the method further includes a second observation period following administration of the anti-PD-L1 antagonist antibody.
  • the method includes both a first observation period following administration of the medicament comprising the anti-TIGIT antagonist antibody and second observation period following administration of the medicament comprising the anti-PD-L1 antagonist antibody.
  • the first and second observation periods are each between about 30 minutes to about 60 minutes in length.
  • the method may include recording the subject’s vital signs (e.g., pulse rate, respiratory rate, blood pressure, and temperature) at about 30 ⁇ 10 minutes after administration of the medicament comprising the anti-TIGIT antagonist antibody and the medicament comprising the anti-PD-L1 antagonist antibody during the first and second observation periods, respectively.
  • the method may include recording the subject’s vital signs (e.g., pulse rate, respiratory rate, blood pressure, and temperature) at about 15 ⁇ 10 minutes after administration of the medicament comprising the anti-TIGIT antagonist antibody and the medicament comprising the anti-PD-L1 antagonist antibody during the first and second observation periods, respectively.
  • the medicament comprising the PD-1 axis binding antagonist e.g., an anti- PD-L1 antagonist antibody (e.g., atezolizumab) or an anti-PD-1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab))
  • an anti-TIGIT antagonist antibody e.g., an anti-TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab.
  • the method includes an intervening first observation period.
  • the method includes a second observation period following administration of the medicament comprising the anti-TIGIT antagonist antibody.
  • the method includes both a first observation period following administration of the medicament comprising the anti-PD-L1 antagonist antibody and second observation period following administration of the medicament comprising the anti-TIGIT antagonist antibody.
  • the first and second observation periods are each between about 30 minutes to about 60 minutes in length.
  • the method may include recording the subject’s vital signs (e.g., pulse rate, respiratory rate, blood pressure, and temperature) at about 30 ⁇ 10 minutes after administration of the medicament comprising the anti-PD-L1 antagonist antibody and the medicament comprising the anti-TIGIT antagonist antibody during the first and second observation periods, respectively.
  • the method may include recording the subject’s vital signs (e.g., pulse rate, respiratory rate, blood pressure, and temperature) at about 15 ⁇ 10 minutes after administration of the medicament comprising the anti-PD-L1 antagonist antibody and the medicament comprising the anti-TIGIT antagonist antibody during the first and second observation periods, respectively.
  • the medicament comprising the anti-TIGIT antagonist antibody e.g., an anti- TIGIT antagonist antibody as disclosed herein, e.g., tiragolumab
  • the medicament comprising the PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody (e.g., atezolizumab) or an anti-PD- 1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab))
  • the PD-1 axis binding antagonist e.g., an anti-PD-L1 antagonist antibody (e.g., atezolizumab) or an anti-PD- 1 antagonist antibody (e.g., MDX-1106 (nivolumab) or MK-3475 (pembrolizumab, previously known as lambrolizumab)
  • MDX-1106 nivolumab
  • MK-3475 pembrolizumab

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EP21705841.1A 2020-01-27 2021-01-26 Methoden zur behandlung von krebs mit einem antitigit-antagonistischen antikörper Pending EP4096646A1 (de)

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US202062966448P 2020-01-27 2020-01-27
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US202063059054P 2020-07-30 2020-07-30
US202063059960P 2020-07-31 2020-07-31
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US202063085890P 2020-09-30 2020-09-30
US202063105198P 2020-10-23 2020-10-23
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Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
MX2022015877A (es) * 2020-06-16 2023-01-24 Genentech Inc Metodos y composiciones para tratar cancer de mama triple negativo.
TW202309078A (zh) * 2021-07-02 2023-03-01 美商建南德克公司 治療癌症之方法及組成物
TW202320848A (zh) * 2021-07-28 2023-06-01 美商建南德克公司 治療癌症之方法及組成物
WO2023018675A1 (en) * 2021-08-10 2023-02-16 Merck Sharp & Dohme Llc A therapeutic combination comprising a tigit antagonist, a pd-1 antagonist, and lenvatinib
WO2023018677A1 (en) * 2021-08-10 2023-02-16 Merck Sharp & Dohme Llc A therapeutic combination comprising a t1git antagonist, a pd-1 antagonist, and a chemotherapeutic agent(s)
CN118103067A (zh) * 2021-09-14 2024-05-28 信达生物制药(苏州)有限公司 抗pd-1抗体和化疗药的药物组合及其使用方法
TW202328195A (zh) * 2021-09-15 2023-07-16 大陸商江蘇恆瑞醫藥股份有限公司 特異性結合ｐｄ－１的蛋白及其醫藥用途
WO2023122665A1 (en) * 2021-12-22 2023-06-29 Genentech, Inc. Clinical formulations of anti-tigit antibodies
CN114181310B (zh) * 2022-02-14 2022-07-05 中山康方生物医药有限公司 抗tigit抗体、其药物组合物及用途

Family Cites Families (38)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4816567A (en) 1983-04-08 1989-03-28 Genentech, Inc. Recombinant immunoglobin preparations
US6548640B1 (en) 1986-03-27 2003-04-15 Btg International Limited Altered antibodies
DE3920358A1 (de) 1989-06-22 1991-01-17 Behringwerke Ag Bispezifische und oligospezifische, mono- und oligovalente antikoerperkonstrukte, ihre herstellung und verwendung
US6075181A (en) 1990-01-12 2000-06-13 Abgenix, Inc. Human antibodies derived from immunized xenomice
US6150584A (en) 1990-01-12 2000-11-21 Abgenix, Inc. Human antibodies derived from immunized xenomice
JPH07501451A (ja) 1991-11-25 1995-02-16 エンゾン・インコーポレイテッド 多価抗原結合タンパク質
GB9300059D0 (en) 1992-01-20 1993-03-03 Zeneca Ltd Quinazoline derivatives
GB9314893D0 (en) 1993-07-19 1993-09-01 Zeneca Ltd Quinazoline derivatives
US5679683A (en) 1994-01-25 1997-10-21 Warner-Lambert Company Tricyclic compounds capable of inhibiting tyrosine kinases of the epidermal growth factor receptor family
IL112249A (en) 1994-01-25 2001-11-25 Warner Lambert Co Pharmaceutical compositions containing di and tricyclic pyrimidine derivatives for inhibiting tyrosine kinases of the epidermal growth factor receptor family and some new such compounds
IL112248A0 (en) 1994-01-25 1995-03-30 Warner Lambert Co Tricyclic heteroaromatic compounds and pharmaceutical compositions containing them
CZ18497A3 (en) 1994-07-21 1997-07-16 Akzo Nobel Nv Cyclic ketoneperoxidic compounds
US5804396A (en) 1994-10-12 1998-09-08 Sugen, Inc. Assay for agents active in proliferative disorders
PT817775E (pt) 1995-03-30 2002-01-30 Pfizer Derivados de quinazolina
US5641870A (en) 1995-04-20 1997-06-24 Genentech, Inc. Low pH hydrophobic interaction chromatography for antibody purification
GB9508565D0 (en) 1995-04-27 1995-06-14 Zeneca Ltd Quiazoline derivative
GB9508538D0 (en) 1995-04-27 1995-06-14 Zeneca Ltd Quinazoline derivatives
US5747498A (en) 1996-05-28 1998-05-05 Pfizer Inc. Alkynyl and azido-substituted 4-anilinoquinazolines
HUP9900330A3 (en) 1995-07-06 2001-08-28 Novartis Ag Pyrrolopyrimidines and processes for the preparation thereof
US5760041A (en) 1996-02-05 1998-06-02 American Cyanamid Company 4-aminoquinazoline EGFR Inhibitors
GB9603095D0 (en) 1996-02-14 1996-04-10 Zeneca Ltd Quinazoline derivatives
JP3370340B2 (ja) 1996-04-12 2003-01-27 ワーナー―ランバート・コンパニー チロシンキナーゼの不可逆的阻害剤
ES2186908T3 (es) 1996-07-13 2003-05-16 Glaxo Group Ltd Compuestos heterociciclos condensados como inhibidores de pproteina-tirosina-quinasas.
ID18494A (id) 1996-10-02 1998-04-16 Novartis Ag Turunan pirazola leburan dan proses pembuatannya
US6002008A (en) 1997-04-03 1999-12-14 American Cyanamid Company Substituted 3-cyano quinolines
UA73073C2 (uk) 1997-04-03 2005-06-15 Уайт Холдінгз Корпорейшн Заміщені 3-ціанохіноліни, спосіб їх одержання та фармацевтична композиція
ATE241986T1 (de) 1997-05-06 2003-06-15 Wyeth Corp Verwendung von chinazolin verbindungen zur behandlung von polyzystischer nierenkrankheit
ZA986729B (en) 1997-07-29 1999-02-02 Warner Lambert Co Irreversible inhibitors of tyrosine kinases
ZA986732B (en) 1997-07-29 1999-02-02 Warner Lambert Co Irreversible inhibitiors of tyrosine kinases
TW436485B (en) 1997-08-01 2001-05-28 American Cyanamid Co Substituted quinazoline derivatives
CN1278176A (zh) 1997-11-06 2000-12-27 美国氰胺公司 喹唑啉衍生物作为用于治疗结肠息肉的酪氨酸激酶抑制剂的应用
EP1034298B1 (de) 1997-12-05 2011-11-02 The Scripps Research Institute Humanisierung von nager-antikörpern
CZ20011759A3 (cs) 1998-11-19 2002-01-16 Warner-Lambert Company N-[4-(3-chlor-4-fluor-fenylamino)-7-(3-morfolin-4-yl-propoxy)-chinazolin-6-yl]-akrylamid, ireversibilní inhibitor tyrosin-kinas
CA2569520C (en) 2004-06-04 2023-03-14 Genentech, Inc. Kras mutations for identifying colorectal tumors responsive to cetuximab or panitumumab
ES2633864T3 (es) 2012-09-24 2017-09-25 Ventana Medical Systems, Inc. Procedimiento para identificar cáncer de pulmón de células no pequeñas que responde al tratamiento usando quinasa de linfoma anaplásico (alk) como marcador
JP7048319B2 (ja) 2015-05-12 2022-04-05 ジェネンテック， インコーポレイテッド 癌のための治療方法及び診断方法
IL255372B (en) 2015-05-29 2022-07-01 Genentech Inc Therapeutic and diagnostic methods for cancer
KR20200135313A (ko) * 2018-02-26 2020-12-02 제넨테크, 인크. 항-tigit 및 항-pd-l1 길항제 항체에 의한 치료를 위한 투약

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CA3165187A1 (en) 2021-08-05
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