EP4688854A2

EP4688854A2 - Methods of treating tumors with anti-tigit antibodies

Info

Publication number: EP4688854A2
Application number: EP24722380.3A
Authority: EP
Inventors: Ian Chung-ti SHIEH; Ann Marie WOYS; Katherine Laura TSCHUDI; Robyn Mariah SUHLING; Rucha Sudhakar SANE; Hui Min Phyllis CHAN; Xiaohui Wen; Isabelle Anne ROONEY
Original assignee: Genentech Inc
Current assignee: Genentech Inc
Priority date: 2023-03-31
Filing date: 2024-03-29
Publication date: 2026-02-11
Also published as: JP2026513259A; WO2024206868A3; TW202448506A; CN121241067A; WO2024206868A2

Abstract

The present disclosure relates to methods of treating or the manufacture of a medicament for treating cancer by using pharmaceutical formulations or medicaments comprising anti-TIGIT monoclonal antibodies that are suitable for co‑administration or co-formulation with anti-PD-L1 monoclonal antibodies. The present disclosure also relates to articles of manufacture comprising single doses of anti-TIGIT monoclonal antibodies or both anti-TIGIT and anti-PD-L1 monoclonal antibodies and methods of treating cancer using such articles of manufacture and the formulations contained therein.

Description

METHODS OF TREATING TUMORS WITH ANTI-TIGIT ANTIBODIES

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to and benefit of United States Provisional Application No. 63/493,691, filed March 31, 2023, and United States Provisional Application No. 63/494,982, filed April 7, 2023, the contents of each of which are hereby incorporated by reference in their entireties.

TECHNICAL FIELD

[0002] The present disclosure pertains to the field of treating tumors with anti-TIGIT monoclonal antibodies, either as a monotherapy or in combination with an anti-PD-Ll monoclonal antibody.

SEQUENCE LISTING

[0003] The instant disclosure contains a Sequence Listing which has been submitted electronically in XML format and is hereby incorporated by reference in its entirety. Said XML copy, created on March 29, 2024, is named 000218-0072-W01_SL.xml and is 26,376 bytes in size.

BACKGROUND

[0004] Cancer is a leading cause of death worldwide with approximately 9,958, 130 deaths globally in 2020. In North America, the number of new cases were estimated to be 2,556,860 (1,372,000 cases in men and 1,184,860 new cases in women) and 699,274 cancer deaths.

Similar data for Central and Eastern Europe estimated in 2020 showing 1,314,193 new cases (657,259 in men; 656,934 in women) and 695,828 cancer deaths (the Global Cancer Observatory, December, 2020). For most malignancies, the impact of current therapy on improving the quality of live, slowing progression of disease, prolonging survival, or curing patients is inadequate.

[0005] Immunotherapy has become an established strategy for treating cancer, improving the prognosis of many patients suffering from a broad variety of cancers. Further, combinations of immunotherapies have proven more effective at treating cancer. Indeed, the FDA has granted the combination of tiragolumab and atezolizumab Breakthrough Therapy Designation for the first line-treatment of non-small cell lung cancer. Immunotherapies are typically infused into a patient over the course of hours. Patients receiving combination therapies receive two separate infusions, requiring patients to be available for longer periods of time (if the therapies are administered on the same day) or more frequently (if the therapies are administered on separate days). There is a need in the art for therapies, including combination therapies, that can be administered more rapidly than by intravenous infusion, e.g. by subcutaneous injection.

SUMMARY OF THE DISCLOSURE

[0006] In one aspect, the present disclosure provides a method of treating cancer in a subject in need thereof comprising subcutaneously administering to the subject a dose of an anti-TIGIT monoclonal antibody of about 1,000 mg; wherein the anti-TIGIT monoclonal antibody is a full-length antibody comprising a heavy chain variable region comprising a HVR-H1 comprising the amino acid sequence of SEQ ID NO: 1; a HVR-H2 comprising the amino acid sequence of SEQ ID NO: 2; and a HVR-H3 comprising the amino acid sequence of SEQ ID NO: 3; and a light chain variable region comprising a HVR-L1 comprising the amino acid sequence of SEQ ID NO: 4; a HVR-L2 comprising the amino acid sequence of SEQ ID NO: 5; and a HVR-L3 comprising the amino acid sequence of SEQ ID NO: 6.

[0007] In another aspect, the present disclosure provides the use of about 1,000 mg of an anti-TIGIT monoclonal antibody in the manufacture of a medicament for treating cancer in a subject in need thereof; wherein the medicament is formulated for subcutaneous administration, and wherein the anti-TIGIT monoclonal antibody is a full-length antibody comprising a heavy chain variable region comprising a HVR-H1 comprising the amino acid sequence of SEQ ID NO: 1; a HVR-H2 comprising the amino acid sequence of SEQ ID NO: 2; and a HVR-H3 comprising the amino acid sequence of SEQ ID NO: 3; and a light chain variable region comprising a HVR-L1 comprising the amino acid sequence of SEQ ID NO: 4; a HVR-L2 comprising the amino acid sequence of SEQ ID NO: 5; and a HVR-L3 comprising the amino acid sequence of SEQ ID NO: 6.

[0008] In another aspect, the present disclosure provides an anti-TIGIT monoclonal antibody for use in treating cancer in a subject in need thereof, wherein the anti-TIGIT monoclonal antibody is a full-length antibody comprising a heavy chain variable region comprising a HVR-H1 comprising the amino acid sequence of SEQ ID NO: 1; a HVR-H2 comprising the amino acid sequence of SEQ ID NO: 2; and a HVR-H3 comprising the amino acid sequence of SEQ ID NO: 3; and a light chain variable region comprising a HVR-L1 comprising the amino acid sequence of SEQ ID NO: 4; a HVR-L2 comprising the amino acid sequence of SEQ ID NO: 5; and a HVR-L3 comprising the amino acid sequence of SEQ ID NO: 6 and is subcutaneously administered at a dose of about 1,000 mg.

[0009] In some embodiments of any of the above-identified aspects, the anti-TIGIT monoclonal antibody is administered in the thigh or the abdomen. In some embodiments of any of the above-identified aspects, the anti-TIGIT monoclonal antibody is administered in the thigh. In some embodiments of any of the above-identified aspects, the anti-TIGIT monoclonal antibody is administered in the abdomen. In some embodiments of any of the above-identified aspects, the anti-TIGIT monoclonal antibody is administered every three weeks (Q3W).

[0010] In another aspect, the present disclosure provides a method of treating cancer in a subject in need thereof comprising subcutaneously administering to the subject a dose of an anti-TIGIT monoclonal antibody of about 1,000 mg and administering to the subject about 1,875 mg to about 2,000 mg of an anti-PD-Ll monoclonal antibody; wherein the anti-TIGIT monoclonal antibody is a full-length antibody comprising a heavy chain variable region comprising a HVR-H1 comprising the amino acid sequence of SEQ ID NO: 1; a HVR-H2 comprising the amino acid sequence of SEQ ID NO: 2; and a HVR-H3 comprising the amino acid sequence of SEQ ID NO: 3; and a light chain variable region comprising a HVR-L1 comprising the amino acid sequence of SEQ ID NO: 4; a HVR-L2 comprising the amino acid sequence of SEQ ID NO: 5; and a HVR-L3 comprising the amino acid sequence of SEQ ID NO: 6; and wherein the anti-PD-Ll monoclonal antibody is a full-length antibody comprising a heavy chain variable region comprising a HVR-H1 comprising the amino acid sequence of SEQ ID NO: 10; a HVR-H2 comprising the amino acid sequence of SEQ ID NO: 11; and a HVR-H3 comprising the amino acid sequence of SEQ ID NO: 12; and a light chain variable region comprising a HVR-L1 comprising the amino acid sequence of SEQ ID NO: 13; a HVR-L2 comprising the amino acid sequence of SEQ ID NO: 14; and a HVR-L3 comprising the amino acid sequence of SEQ ID NO: 15.

[0011] In another aspect, the present disclosure provides the use of about 1,000 mg of an anti-TIGIT monoclonal antibody and about 1,875 mg to about 2,000 mg of an anti-PD-Ll monoclonal antibody in the manufacture of a medicament for treating cancer in a subject in need thereof; wherein the medicament is formulated for subcutaneous administration, and wherein the anti-TIGIT monoclonal antibody is a full-length antibody comprising a heavy chain variable region comprising a HVR-H1 comprising the amino acid sequence of SEQ ID NO: 1; a HVR-H2 comprising the amino acid sequence of SEQ ID NO: 2; and a HVR-H3 comprising the amino acid sequence of SEQ ID NO: 3; and a light chain variable region comprising a HVR-L1 comprising the amino acid sequence of SEQ ID NO: 4; a HVR-L2 comprising the amino acid sequence of SEQ ID NO: 5; and a HVR-L3 comprising the amino acid sequence of SEQ ID NO: 6; and wherein the anti-PD-Ll monoclonal antibody is a full- length antibody comprising a heavy chain variable region comprising a HVR-H1 comprising the amino acid sequence of SEQ ID NO: 10; a HVR-H2 comprising the amino acid sequence of SEQ ID NO: 11; and a HVR-H3 comprising the amino acid sequence of SEQ ID NO: 12; and a light chain variable region comprising a HVR-L1 comprising the amino acid sequence of SEQ ID NO: 13; a HVR-L2 comprising the amino acid sequence of SEQ ID NO: 14; and a HVR-L3 comprising the amino acid sequence of SEQ ID NO: 15.

[0012] In another aspect, the present disclosure provides an anti-TIGIT monoclonal antibody and an anti-PD-Ll monoclonal antibody for use in treating cancer in a subject in need thereof, wherein the anti-TIGIT monoclonal antibody is a full-length antibody comprising a heavy chain variable region comprising a HVR-H1 comprising the amino acid sequence of SEQ ID NO: 1; a HVR-H2 comprising the amino acid sequence of SEQ ID NO: 2; and a HVR-H3 comprising the amino acid sequence of SEQ ID NO: 3; and a light chain variable region comprising a HVR-L1 comprising the amino acid sequence of SEQ ID NO: 4; a HVR-L2 comprising the amino acid sequence of SEQ ID NO: 5; and a HVR-L3 comprising the amino acid sequence of SEQ ID NO: 6 and is subcutaneously administered at a dose of about 1,000 mg; and wherein the anti-PD-Ll monoclonal antibody is a full-length antibody comprising a heavy chain variable region comprising a HVR-H1 comprising the amino acid sequence of SEQ ID NO: 10; a HVR-H2 comprising the amino acid sequence of SEQ ID NO: 11; and a HVR-H3 comprising the amino acid sequence of SEQ ID NO: 12; and a light chain variable region comprising a HVR-L1 comprising the amino acid sequence of SEQ ID NO: 13; a HVR-L2 comprising the amino acid sequence of SEQ ID NO: 14; and a HVR-L3 comprising the amino acid sequence of SEQ ID NO: 15 and is administered at a dose of about 1,875 mg to about 2,000 mg.

[0013] In some embodiments of any of the above-identified aspects, the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody, are administered simultaneously. In some embodiments of any of the above-identified aspects, the anti-TIGIT monoclonal and the anti-PD-Ll monoclonal antibody are co-formulated. In some embodiments of any of the above-identified aspects, the anti-TIGIT monoclonal and the anti- PD-Ll monoclonal antibody are mixed 24 hours or less prior to administration to the subject. In some embodiments of any of the above-identified aspects, the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody are mixed during administration to the subject. In some embodiments of any of the above-identified aspects, the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody, are administered sequentially.

[0014] In some embodiments of any of the above-identified aspects, the anti-PD-Ll monoclonal antibody is administered intravenously. In some embodiments of any of the above-identified aspects, the anti-PD-Ll monoclonal antibody is administered subcutaneously.

[0015] In some embodiments of any of the above-identified aspects, the anti-TIGIT monoclonal antibody is administered every three weeks (Q3W).

[0016] In some embodiments of any of the above-identified aspects, the cancer is selected from the group consisting of a lung cancer, a non-small cell lung cancer, a renal cell cancer, a urothelial cancer, a ureter cancer, a urethral cancer, a colorectal cancer, a colon cancer, a rectal cancer, a kidney cancer, a sarcoma, an ovarian cancer, a breast cancer, a cervical cancer, a fallopian tube cancer, an endometrial cancer, a uterine cancer, a pancreatic cancer, a gastric carcinoma, a bladder cancer, an esophageal cancer, a mesothelioma, a melanoma, a head and neck cancer, a thyroid cancer, a sarcoma, a prostate cancer, a penile cancer, a glioblastoma, a thymic carcinoma, an esophageal carcinoma, a nasopharyngeal cancer, a mesothelioma, a liver cancer, a biliary tract cancer, a HPV-positive cancer, a leukemia, a lymphoma, a brain cancer, a neuroendocrine cancer, a myeloma, a mycosis fungoides, a Merkel cell cancer, a hematologic malignancy, a deficient mismatch repair (dMMR) cancer, and a microsatellite instability -high (MSI-H) cancer.

[0017] In some embodiments of any of the above-identified aspects, the cancer is selected from the group consisting of a bladder cancer, a muscle-invasive bladder cancer, a urothelial carcinoma, a ureter cancer, a urethral cancer, a ureter urothelial carcinoma, a urethral urothelial carcinoma, a renal cancer, a renal pelvis cancer, a renal cell carcinoma, a clear-cell renal carcinoma, a rectal cancer, a colon cancer, a colorectal cancer, a sarcoma, an osteosarcoma, a leiomyosarcoma, a pleomorphic sarcoma, a myxofibrosarcoma, a liposarcoma, a chondrosarcoma, a lung cancer, a non-small cell lung cancer, a fallopian tube cancer, a peritoneal carcinoma, an esophageal cancer, an esophageal squamous cell carcinoma, a mesothelioma, a pleural mesothelioma, a peritoneal mesothelioma, an ovarian cancer, a cervical cancer, a cervical adenosquamous carcinoma, a breast cancer, a triplenegative breast cancer, a HER2 -positive breast cancer, a HER2-negative breast cancer, an estrogen receptor-positive breast cancer, a progesterone receptor-positive breast cancer, a luminal B breast cancer, a lymphoma, a T-cell lymphoma, a B-cell lymphoma, a nasal -type lymphoma, non-Hodgkin’s lymphoma, a follicular lymphoma, a penile carcinoma, a prostate cancer, a castration-resistant prostate cancer, an endometrial cancer, a uterine cancer, a myeloma, a multiple myeloma, a head and neck cancer, a prostate cancer, a melanoma, a cutaneous melanoma, a Merkel cell carcinoma, a pancreatic cancer, hepatocellular carcinoma, gastric cancer, a gastroesophageal junction adenocarcinoma, a glioblastoma, a glioblastoma multiforme, a mycosis fungoides, an HPV-positive cancer, a HPV-related cervical carcinoma, a HPV-related anal squamous cell carcinoma, a HPV-related penile squamous cell carcinoma, a HPV-related vulvar squamous cell carcinoma, a vulvar cancer, a vaginal cancer, an anal cancer, an oropharyngeal cancer, an oropharyngeal squamous cell carcinoma, a leukemia, an acute myeloid leukemia, a bone cancer, a solitary bone plasmacytoma, a squamous cell carcinoma, a cutaneous squamous cell carcinoma, a thyroid cancer, a microsatellite stability/proficient mismatch repair (MSS/pMMR) metastatic colorectal cancer, a deficient mismatch repair (dMMR) cancer, a microsatellite instability-high (MSI-H) cancer, a nasaltype extranodal NK/T-Cell lymphoma, a neuroendocrine cancer, a biliary tract cancer, a cholangiocarcinoma, and an intrahepatic cholangiocarcinoma.

[0018] In some embodiments of any of the above-identified aspects, the cancer is selected from the group consisting of a Merkel cell carcinoma, a urothelial carcinoma, a renal cell carcinoma, non-small cell lung cancer, a breast cancer, a triple-negative breast cancer, a hepatocellular carcinoma, a melanoma, a Hodgkin’s lymphoma, a head and neck cancer, a colorectal cancer, a gastric cancer, a cervical cancer, a primary mediastinal large B-cell lymphoma, a cutaneous squamous-cell carcinoma, a basal cell carcinoma, a bladder cancer, an endometrial cancer, an esophageal cancer, a malignant pleural mesothelioma, a tumor mutational burden (TMB)-high cancer, a deficient mismatch repair (dMMR) cancer, and a microsatellite instability-high (MSI-H) cancer.

[0019] In some embodiments of any of the above-identified aspects, the cancer is selected from the group consisting of a lung cancer, a non-small cell lung cancer, a bronchogenic carcinoma, a breast cancer, a triple-negative breast cancer, an estrogen receptor-positive breast cancer, a HER2 -positive breast cancer, a lobular metastatic breast cancer, a ductal breast carcinoma, a cervical cancer, a fallopian tube cancer, a fallopian tube serous adenocarcinoma, an ovarian cancer, an ovarian endometrioid tumor, an ovarian serous adenocarcinoma, an ovarian seromucinous carcinoma, a uterine cancer, an endometrial cancer, a skin cancer, a melanoma, a cutaneous melanoma, a Merkel cell carcinoma, a head and neck cancer, squamous cell carcinoma of head and neck, a hematologic malignancy, a leukemia, a myeloid leukemia, an acute myeloid leukemia, a chronic lymphocytic leukemia, a myelomonocytic leukemia, a thyroid cancer, thyroid gland carcinoma, a thymic carcinoma, a neuroendocrine cancer, a pheochromocytoma, a glioma, a glioblastoma multiforme, a paraganglioma, a lymphoma, a B-cell lymphoma, a Hodgkin lymphoma, a B-cell nonHodgkin lymphoma, a non-Hodgkin’s lymphoma, a cutaneous T-cell lymphoma, a diffuse large B-cell lymphoma, a follicular lymphoma, a marginal zone lymphoma, a pancreatic cancer, a pancreatic ductal adenocarcinoma, a rectal cancer, a colon cancer, a colorectal cancer, a urinary tract cancer, a genitourinary cancer, a mesothelioma, a pleural mesothelioma, a peritoneal mesothelioma, a sarcoma, a chondrosarcoma, a clear cell sarcoma, a liposarcoma, a myxoid/round cell liposarcoma, a synovial sarcoma, an alveolar soft part sarcoma, a gliosarcoma, a uterine carcinosarcoma, a kidney cancer, a non-clear cell kidney cancer, a renal cell carcinoma, a bladder cancer, a urothelial carcinoma, a muscle- invasive bladder cancer, a non-muscle invasive bladder cancer, a HER2-positive bladder cancer, a gallbladder carcinoma, a gastric cancer, an esophageal cancer, an esophageal squamous cell carcinoma, a gastrointestinal cancer, a gastroesophageal cancer, a gastroesophageal junction cancer, a HER2-positive gastric cancer, a primary peritoneal cancer, a cutaneous squamous cell carcinoma, a prostate cancer, a prostate adenocarcinoma, a castration-resistant prostate cancer, a urogenital cancer, a ureter urothelial carcinoma, a renal pelvis urothelial carcinoma, a urethral urothelial carcinoma, an appendix carcinoma, a penile cancer, an anal canal cancer, a hepatocellular carcinoma, a hepatobiliary cancer, an unresectable liver and intrahepatic bile duct carcinoma, a biliary tract cancer, a cholangiocarcinoma, an intrahepatic cholangiocarcinoma, an extrahepatic cholangiocarcinoma, an HPV-related cancer, an HPV-related anal squamous cell carcinoma, an HPV-related cervical squamous cell carcinoma, an HPV-related penile squamous cell carcinoma, an HPV-related vulvar squamous cell carcinoma, a nasopharynx carcinoma, a nasopharyngeal carcinoma, a laryngeal squamous cell carcinoma, a hypopharyngeal squamous cell carcinoma, an oral cavity squamous cell carcinoma, and a mycosis fungoides. [0020] In some embodiments of any of the above-identified aspects, the cancer is selected from the group consisting of urothelial carcinoma, non-small cell lung cancer (NSCLC), breast cancer, triple-negative breast cancer, hepatocellular carcinoma and melanoma. In some embodiments of any of the above-identified aspects, the cancer is selected from the group consisting of a multiple myeloma, a cervical cancer, an esophageal cancer, an esophageal squamous cell carcinoma, a lung cancer, a non-small cell lung cancer, a glioblastoma, an endometrial cancer, an ovarian cancer, a squamous cell cancer, a head and neck cancer. In some embodiments of any of the above-identified aspects, the cancer is selected from the group consisting of a cervical cancer, a squamous cell carcinoma of head and neck, a head and neck cancer, a non-small cell lung cancer, a non-squamous non-small cell lung cancer, an esophageal squamous cell carcinoma, an esophageal cancer, a breast cancer, a triple-negative breast cancer, a gastric cancer, a gastroesophageal junction adenocarcinoma, a multiple myeloma, a non-Hodgkin lymphoma, a B-cell lymphoma, a liver cancer, a bladder cancer, a urothelial carcinoma, a pancreatic cancer, and a pancreatic adenocarcinoma. In some embodiments of any of the above-identified aspects, the cancer is a solid tumor. In some embodiments of any of the above-identified aspects, the cancer is a hematological cancer.

[0021] In some embodiments of any of the above-identified aspects, the heavy chain variable region of the anti-PD-Ll monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 16. In some embodiments of any of the above-identified aspects, the light chain variable region of the anti-PD-Ll monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 17. In some embodiments of any of the above-identified aspects, the heavy chain variable region of the anti-PD-Ll monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 16 and the light chain variable region of the anti-PD-Ll monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 17. In some embodiments of any of the above-identified aspects, the anti-PD-Ll monoclonal antibody is an IgG antibody. In some embodiments of any of the above-identified aspects, the anti-PD- Ll monoclonal antibody is an IgGl or an IgG4 antibody. In some embodiments of any of the above-identified aspects, the anti-PD-Ll monoclonal antibody or the anti-TIGIT monoclonal antibody is a human antibody. In some embodiments of any of the above-identified aspects, the anti-PD-Ll monoclonal antibody or the anti-TIGIT monoclonal antibody is a humanized antibody. In some embodiments of any of the above-identified aspects, the anti-PD-Ll monoclonal antibody is selected from the group consisting of atezolizumab (MPDL3280A), durvalumab (MED 14736), avelumab, and MDX-1105.

[0022] In some embodiments of any of the above-identified aspects, the heavy chain variable region of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 7 or SEQ ID NO: 8. In some embodiments of any of the above-identified aspects, the light chain variable region of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 9. In some embodiments of any of the above-identified aspects, the heavy chain variable region of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 7 or SEQ ID NO: 8 and the light chain variable region of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 9. In some embodiments of any of the above-identified aspects, the heavy chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 18 or SEQ ID NO: 24. In some embodiments of any of the above-identified aspects, the heavy chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 19 or SEQ ID NO: 25. In some embodiments of any of the above-identified aspects, the light chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 20. In some embodiments of any of the above-identified aspects, the heavy chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 18 or SEQ ID NO: 24, and the light chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 20. In some embodiments of any of the above-identified aspects, the heavy chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 19 or SEQ ID NO: 25, and the light chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 20. In some embodiments of any of the above-identified aspects, the anti-TIGIT monoclonal antibody is an IgG antibody. In some embodiments of any of the above-identified aspects, the anti-TIGIT monoclonal antibody is an IgGl or an IgG4 antibody. In some embodiments of any of the above-identified aspects, the anti-TIGIT monoclonal antibody is a human antibody. In some embodiments of any of the above-identified aspects, the anti-TIGIT monoclonal antibody is a humanized antibody. In some embodiments of any of the aboveidentified aspects, the anti-TIGIT monoclonal antibody inhibits or blocks the interaction of CD226 with TIGIT. In some embodiments of any of the above-identified aspects, the anti- TIGIT monoclonal antibody is tiragolumab.

[0023] In some embodiments of any of the above-identified aspects, the anti-TIGIT monoclonal antibody is in a liquid pharmaceutical composition comprising 160 mg/mL of tiragolumab and 2000 U/mL hyaluronidase in 20 mM histidine acetate, 240 mM sucrose, 10 mM methionine, 0.06% polysorbate 20, pH 5.5. In some embodiments of any of the aboveidentified aspects, the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody are in a liquid pharmaceutical formulation comprising 40 mg/ml of tiragolumab, 80 mg/ml of atezolizumab, 2000 U/ml hyaluronidase in 20 mM histidine acetate, 240 mM sucrose, 10 mM methionine, 0.06% polysorbate 20, pH 5.8.

[0024] In another aspect, the present disclosure provides an article of manufacture comprising a formulation that comprises 1,000 mg of tiragolumab.

[0025] In some embodiments of any of the above-identified aspects, the formulation further comprises 1,875 mg or 2,000 mg of atezolizumab. In certain embodiments, the formulation further comprises 1,875 mg of atezolizumab. In other embodiments, the formulation further comprises 2,000 mg of atezolizumab. In certain embodiments, the formulation further comprises hyaluronidase.

[0026] In another aspect, the present disclosure provides an article of manufacture comprising a formulation that comprises 1,000 mg of tiragolumab and 1,875 mg or 2,000 mg of atezolizumab. In certain embodiments of the above-identified aspects, the formulation comprises 1,875 mg of atezolizumab. In other embodiments, the formulation comprises 2,000 mg of atezolizumab. In some of the above embodiments, the formulation further comprises hyaluronidase.

[0027] In some embodiments of any of the above-identified aspects, the concentration of the hyaluronidase is 2000 U/mL. In some embodiments of any of the above-identified aspects, the hyaluronidase is a recombinant human hyaluronidase. In some embodiments of any of the above-identified aspects, the recombinant hyaluronidase is a human soluble PH20 hyaluronidase glycoprotein, such as rHuPH20.

[0028] In some embodiments of any of the above-identified aspects, the article of manufacture is a vial. In some embodiments of any of the above-identified aspects, the vial is a single dosage vial. In some embodiments of any of the above-identified aspects, the vial is stoppered with a chlorobutyl elastomer stopper.

[0029] In some embodiments of any of the above-identified aspects, the article of manufacture is a pre-filled syringe. In some embodiments of any of the above-identified aspects, the article of manufacture is a syringe pump.

[0030] In some embodiments of any of the above-identified aspects, the article of manufacture is a subcutaneous administration device. In some embodiments of any of the above-identified aspects, the subcutaneous administration device is selected from the group consisting of a syringe, a syringe pump, an injection device, an infusion pump, an injector pen, a needleless device, an autoinjector, and a subcutaneous patch delivery system.

[0031] In another aspect, the present disclosure provides an article of manufacture comprising a subcutaneous administration device, wherein the subcutaneous administration device contains and delivers to a patient a 1,000 mg fixed dose of tiragolumab. In some embodiments of this aspect, the subcutaneous administration device further contains and delivers to the patient a 1,875 mg or 2,000 mg fixed dose of atezolizumab. In one embodiment, the subcutaneous administration device further contains and delivers to the patient a 1,875 mg fixed dose of atezolizumab. In another embodiment, the subcutaneous administration device further contains and delivers to the patient a 2,000 mg fixed dose of atezolizumab. In some embodiments of this aspect, the subcutaneous administration device further contains and delivers to the patient hyaluronidase. In one embodiment, the hyaluronidase is a human soluble PH20 hyaluronidase glycoprotein, such as rHuPH20.

[0032] In some embodiments of the above-identified aspect, the subcutaneous administration device is selected from the group consisting of a syringe, a syringe pump, an injection device, an infusion pump, an injector pen, a needleless device, an autoinjector, and a subcutaneous patch delivery system. In one embodiment, the subcutaneous administration device is a syringe. In another embodiment, the subcutaneous administration device is a syringe pump.

[0033] In some embodiments of any of the above aspects, the article of manufacture comprises about 3 mL to about 60 mL of the anti-TIGIT full-length monoclonal antibody, and one or more of hyaluronidase, a histidine buffer, sucrose, and polysorbate 20. In some embodiments of any of the above aspects, the article of manufacture comprises about 10 mL of tiragolumab, and one or more of hyaluronidase, a histidine buffer, sucrose, and polysorbate 20. In some embodiments of any of the above aspects, the article of manufacture comprises about 7 mL of tiragolumab, and one or more of hyaluronidase, a histidine buffer, sucrose, and polysorbate 20. In some embodiments of any of the above aspects, the article of manufacture comprises about 6.5 mL of tiragolumab, and one or more of hyaluronidase, a histidine buffer, sucrose, and polysorbate 20. In some embodiments of any of the above aspects, the article of manufacture comprises about 21 mL of tiragolumab, and one or more of hyaluronidase, a histidine buffer, sucrose, and polysorbate 20.

BRIEF DESCRIPTION OF THE DRAWINGS

[0034] The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.

[0035] Fig. 1 provides a treatment protocol using a combination therapy comprising tiragolumab and atezolizumab. Fig. 1 uses the following abbreviations: Atezo = atezolizumab; ECOG = Eastern Cooperative Oncology Group; IV = intravenous; PD = progressive disease; PK = pharmacokinetic; PS = Performance Status; Q3W = every 3 weeks; SC = subcutaneous; TBD = to be determined; Tira = tiragolumab [0036] Figs. 2A and Fig. 2B provide pharmacokinetic model fit over time (days) in two representative subjects in Cohort 1 A who were subcutaneously administered a single dose of 880 mg of tiragolumab in the abdomen (Fig. 2A), followed by intravenous administration of 600 mg tiragolumab, and in two representative subjects in Cohort IB who were subcutaneously administered a single dose of 880 mg of tiragolumab in the thigh (Fig. 2B). filled circle = directly observed value; Solid line = individual model-predicted concentration. Dashed line = Model-predicted value.

DETAILED DESCRIPTION

General

[0037] Practice of the methods, as well as preparation and use of the compositions disclosed herein employ, unless otherwise indicated, conventional techniques in molecular biology, biochemistry, chromatin structure and analysis, computational chemistry, cell culture, recombinant DNA and related fields as are within the skill of the art. These techniques are fully explained in the literature. See, e.g., Current Protocols in Molecular Biology or Current Protocols in Immunology, John Wiley & Sons, New York, N.Y.(2009); Ausubel et al., Short Protocols in Molecular Biology, 5th ed., Wiley & Sons, 2002; Sambrook and Russell, Molecular Cloning: A Laboratory Manual (4th Edition, 2012); and other like references.

[0038] The term “herein” means the entire disclosure.

[0039] It should be understood that any of the embodiments described herein, including those described under different aspects of the disclosure and different parts of the specification (including embodiments described only in the Examples) can be combined with one or more other embodiments disclosed herein, unless explicitly disclaimed or improper. Combinations of embodiments are not limited to those specific combinations claimed via the dependent (including multiple dependent) claims.

[0040] Any publications, patents and published patent applications referred to in this disclosure are specifically incorporated by reference herein. In case of conflict, the present specification, including its specific definitions, will control.

[0041] Throughout this specification, the word “comprise” or variations such as “comprises” or “comprising,” which is synonymous with “including,” “containing,” or “characterized by,” is inclusive or open-ended and does not exclude additional, unrecited elements or method steps. [0042] Throughout the specification, where compositions are described as having, including, or comprising (or variations thereof), specific components, it is contemplated that compositions also may consist essentially of, or consist of, the recited components.

Similarly, where methods or processes are described as having, including, or comprising specific process steps, the processes also may consist essentially of, or consist of, the recited processing steps. Further, it should be understood that, unless otherwise indicated or the context clearly indicates otherwise, the order of steps or order for performing certain actions is immaterial so long as the compositions and methods described herein remains operable. Moreover, two or more steps or actions can be conducted simultaneously.

[0043] The term “consisting of’ excludes any element, step, or ingredient not specifically recited.

[0044] The term “consisting essentially of’ limits the scope of a disclosure to the specified materials or steps and those that do not materially affect the basic and novel characteristic(s) of the disclosure.

[0045] Any example(s) following the term “e.g.” or “for example” is not meant to be exhaustive or limiting.

[0046] The articles “a,” “an” and “the” are used herein to refer to one or to more than one (z.e., to at least one) of the grammatical object of the article. By way of example, “an element” means one element or more than one element.

[0047] As used herein, the term “about” modifying the quantity of an ingredient, parameter, calculation, or measurement in the compositions employed in the methods of the disclosure refers to the variation in the numerical quantity that can occur, for example, through typical measuring and liquid handling procedures used for making isolated polypeptides or pharmaceutical compositions in the real world; through inadvertent error in these procedures; through differences in the manufacture, source, or purity of the ingredients employed to make the compositions or carry out the methods; and the like without having a substantial effect on the chemical or physical attributes of the compositions or methods of the disclosure. Such variation can be within 5%, of a given value or range. The term “about” also encompasses amounts that differ due to different equilibrium conditions for a composition resulting from a particular initial mixture. Whether or not modified by the term “about,” the paragraphs include equivalents to the quantities. Reference to “about” a value or parameter herein includes (and describes) in particular embodiments that are directed to that value or parameter per se. For example, description referring to “about X” includes description of “X.” Numeric ranges are inclusive of the numbers defining the range. [0048] The term “or” as used herein should be understood to mean “and/or,” unless the context clearly indicates otherwise.

[0049] Notwithstanding that the numerical ranges and parameters setting forth the broad scope of the disclosure are approximations, the numerical values set forth in the specific examples are reported as precisely as possible. Any numerical value, however, inherently contains certain errors necessarily resulting from the standard deviation found in their respective testing measurements. Also, recitations of numerical values are not limited to specifically the recited value, but also include numbers that the skilled artisan would normally round to that value in the context of significant digits. Moreover, all ranges disclosed herein are to be understood to encompass any and all subranges subsumed therein. For example, a stated range of “1 to 10” should be considered to include any and all subranges between (and inclusive of) the minimum value of 1 and the maximum value of 10; that is, all subranges beginning with a minimum value of 1 or more, e.g., 1 to 6.1, and ending with a maximum value of 10 or less, e.g., 5.5 to 10. The disclosure of a range should also be considered as disclosure of the endpoints of that range.

[0050] Exemplary methods and materials are described herein, although methods and materials similar or equivalent to those described herein can also be used in the practice or testing of the present disclosure. The materials, methods, and examples are illustrative only and not intended to be limiting.

Definitions

[0051] “Administering” or “administration of’ a substance, a compound, an agent, or a composition to a subject, as used herein, refers to the contact of that substance, compound, agent, or composition to the subject or a cell, tissue, organ or bodily fluid of the subject. Such administration can be carried out using one of a variety of methods known to those skilled in the art. For example, a substance, compound, agent, or composition can be administered parenterally, such as by injection. In some embodiments, a substance, compound, agent or composition is administered subcutaneously. In some embodiments, a substance, compound, agent or composition is administered intravenously. Administering can also be performed, for example, once, a plurality of times, and/or over one or more extended periods. In some embodiments, the administration includes both direct administration, including self-administration, and indirect administration, including the act of prescribing a drug. For example, as used herein, a physician who instructs a subject to self- administer a drug, or to have the drug administered by another and/or who provides a subject with a prescription for a drug is administering the drug to the subject.

[0052] As used herein, the term “antibody” or “Ab” is used in the broadest sense and specifically covers monoclonal antibodies (including full length monoclonal antibodies), polyclonal antibodies, and multispecific antibodies (e.g., bispecific antibodies), and antibody fragments so long as they exhibit the desired biological activity. An "isolated" antibody is one which has been identified and separated and/or recovered from a component of its natural environment. Contaminant components of its natural environment are materials which would interfere with research, diagnostic or therapeutic uses for the antibody, and may include enzymes, hormones, and other proteinaceous or nonproteinaceous solutes. In some embodiments, an antibody is purified (1) to greater than 95% by weight of antibody as determined by, for example, the Lowry method, and in some embodiments, to greater than 99% by weight; (2) to a degree sufficient to obtain at least 15 residues of N-terminal or internal amino acid sequence by use of, for example, a spinning cup sequenator, or (3) to homogeneity by SDS-PAGE under reducing or nonreducing conditions using, for example, Coomassie blue or silver stain. Isolated antibody includes the antibody in situ within recombinant cells since at least one component of the antibody's natural environment will not be present. Ordinarily, however, isolated antibody will be prepared by at least one purification step.

[0053] The terms “anti-TIGIT antibody,” “anti-TIGIT monoclonal antibody,” and “an antibody that specifically binds to TIGIT” are used interchangeably herein and refer to an antibody that is capable of binding TIGIT with sufficient affinity such that the antibody is useful as a diagnostic and/or therapeutic agent in targeting TIGIT. In some embodiments, the extent of binding of an anti-TIGIT 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). In certain embodiments, an antibody that binds to TIGIT has a dissociation constant (Kd) of < IpM, < 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). In certain embodiments, an anti-TIGIT 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, such as an epitope comprising amino acid residues Ser78, Ser80, and Lys82.

[0054] The terms “anti-PD-Ll antibody,” “anti-PD-Ll monoclonal antibody,” and “an antibody that specifically binds to PD-L1” are used interchangeably herein and refer to an antibody that is capable of binding PD-L1 with sufficient affinity such that the antibody is useful as a diagnostic and/or therapeutic agent in targeting PD-L1. In some embodiments, the extent of binding of an anti-PD-Ll antibody to an unrelated, non-PD-Ll protein is less than about 10% of the binding of the antibody to PD-L1 as measured, e.g., by a radioimmunoassay (RIA). In certain embodiments, an antibody that binds to PD-L1 has a dissociation constant (Kd) of < IpM, < 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). In certain embodiments, an anti-PD-Ll 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. [0055] The term “atezolizumab,” as used herein, refers to anti-PD-Ll monoclonal antagonist antibody having the International Nonproprietary Names for Pharmaceutical Substances (INN) List 112 (WHO Drug Information, Vol. 28, No. 4, 2014, p. 488), or the CAS Registry Number 1380723-44-3.

[0056] The term “cancer,” as used herein, refers to a disease caused by an uncontrolled division of abnormal cells in a part of the body. The cancer may be locally advanced or metastatic. In some instances, the cancer is locally advanced. In some instances, the cancer is metastatic. In some instances, the cancer is recurrent. In some instances, the cancer may be unresectable (e.g., unresectable locally advanced or metastatic cancer).

[0057] The term “chimeric,” as used herein, antibody refers to an antibody in which a portion of the heavy and/or light chain is derived from a particular source or species, while the remainder of the heavy and/or light chain is derived from a different source or species. [0058] The terms “full-length antibody” “intact antibody” and “whole antibody” are used interchangeably herein and refer to an antibody in its substantially intact form, as opposed to an antibody fragment. Specifically, 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. It is known in the art that during antibody expression C-terminal clipping of the antibody by carboxypeptidases occurs. Such clipped antibodies are considered to be in substantially intact form and, thus, full-length antibodies, despite the removal of one or more C-terminal amino acid residues. In some cases, the intact antibody may have one or more effector functions. In some embodiments, the intact antibody retains all effector functions. Optionally, one or more effector functions of the antibody may have been modified or eliminated. [0059] As used herein, the term “effector function” refers to a biochemical event that results from the interaction of an antibody Fc region with an Fc receptor or another effector molecule (e.g., Fc receptor-Like (FcRL) molecules, complement component Clq, and Tripartite motifcontaining protein 21 (TRIM21)). Effector functions include, but are not limited to, antibody dependent cell-mediated cytotoxicity (ADCC), antibody dependent cell-mediated phagocytosis (ADCP) and complement-dependent cellular cytotoxicity (CDC). The term “ADCC” or “antibody dependent cell-mediated cytotoxicity,” as used herein, refers to the cell-mediated reaction wherein nonspecific cytotoxic cells that express FcyRs recognize bound antibody on a target cell and subsequently cause lysis of the target cell. ADCC is correlated with binding to FcyRIIIa; increased binding to FcyRIIIa leads to an increase in ADCC activity. The term “ADCP” or “antibody dependent cell-mediated phagocytosis,” as used herein, refers to the cell- mediated reaction wherein nonspecific cytotoxic cells that express FcyRs recognize bound antibody on a target cell and subsequently cause phagocytosis of the target cell. The term “CDC” or “complement-dependent cellular cytotoxicity,” as used herein, refers to an effector function which leads to the activation of the classical complement pathway, which is triggered by the binding of an antibody to an antigen on the target cell, which activates a series of cascades containing complement-related protein groups in blood.

[0060] The term “human antibody” as used herein refers to 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 known in the art for making human antibodies. 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, mouse hybridoma, transgenic animals (e.g., mice) and single B cell technique. See, e.g., Lu et al, J. Biomed. Sci., 27: 1 (2020);

Hoogenboom and Winter, J. Mol. Biol., 227:381 (1991); Marks et al., J. Mol. Biol., 222:581 (1991), each of which is incorporated by reference herein in its entirety. Also available for the preparation of human monoclonal antibodies are methods described in Cole et al., Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, p. 77 (1985); Boerner et al., J. Immunol., 147(1): 86-95 (1991). See also van Dijk and van de Winkel, Curr. Opin.

Pharmacol., 5: 368-74 (2001). Human antibodies can be prepared by administering the antigen to a transgenic animal that has been modified to produce human antibodies in response to antigenic challenge, e.g., immunized xenomice (see, e.g., U.S. Pat. Nos. 6,075,181 and 6,150,584 regarding XENOMOUSE™ technology). Other transgenic animals for producing human antibodies are also known in the art, including, e.g., the HuMAb mouse, the UntiMAb mouse, the Transchromo mouse, the Veloclmmune mice, the OmniRat, the OmniMouse, the Harbour Mouse, the Kymouse, the MeMo mouse, the AlivaMab mouse, etc. See, e.g., Briiggemann et al., Arch. Immunol. Ther. Exp. (Warsz.) 2015, vol. 63(2): 101-108. Additional techniques are also known the art. See also, for example, Li et al., Proc. Natl. Acad. Sci. USA, 103:3557-3562 (2006) regarding human antibodies generated via a human B-cell hybridoma technology.

[0061] “Humanized” antibodies, as used herein, refer to chimeric antibodies that contain both human and non-human antibody sequences. Typically, humanized antibodies comprise minimal sequence derived from the non-human immunoglobulin. For example, humanized antibodies include human immunoglobulins (recipient antibody) in which residues from a hypervariable region of the recipient are replaced by residues from a hypervariable region of a non-human species (donor antibody) such as mouse, rat, rabbit or nonhuman primate having the desired specificity, affinity, and capacity. In some instances, certain framework region (FR) residues of the human immunoglobulin are replaced by corresponding non- human residues. Furthermore, humanized antibodies may comprise residues that are not found in the recipient antibody or in the donor antibody. These modifications are made to further refine antibody performance. In general, the 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 and all or substantially all of the FRs are those of a human immunoglobulin sequence. The humanized antibody, optionally, will also comprise at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin. For further details, see Jones et al, Nature 321 :522-525 (1986); Riechmann et al, Nature 332:323-329 (1988); and Presta, Curr. Op. Struct. Biol. 2:593-596 (1992). See also, Vaswani and Hamilton, Ann. Allergy, Asthma & Immunol. 1 : 105-115 (1998); Harris, Biochem. Soc. Transactions 23 : 1035-1038 (1995); Hurle and Gross, Curr. Op. Biotech. 5:428-433 (1994).

[0062] The term “hyaluronidase,” as used herein, refers to an enzyme that catalyzes the degradation of hyaluronic acid (also referred to as hyaluronan). Hyaluronidase transiently hydrolyzes hyaluronic acid, which is a component of the subcutaneous matrix, and reduces the viscosity of the extracellular matrix of the hypodermis to improve delivery of subcutaneously administered drugs in the systemic circulation. In some embodiments, hyaluronidase is a recombinant human hyaluronidase. In some embodiments, recombinant human hyaluronidase is administered subcutaneously.

[0063] The term “hypervariable region,” “HVR,” or “HV,” as used herein refers to the regions of an antibody variable domain which are hypervariable in sequence and/or form structurally defined loops. Generally, antibodies comprise six HVRs; three in the VH (Hl, H2, H3), and three in the VL (LI, L2, L3). In native antibodies, H3 and L3 display the most diversity of the six HVRs, and H3, in particular, is believed to play a unique role in conferring fine specificity to antibodies. See, e.g., Xu et ah, Immunity 13:37-45 (2000); Johnson and Wu, Methods in Molecular Biology 248: 1-25 (Lo, ed., Human Press, Totowa, NJ, 2003). For example, naturally occurring camelid antibodies consisting of only a heavy chain are functional and stable in the absence of light chain. See, e.g., Hamers-Casterman et al, Nature 363:446- 448 (1993); Sheriff et al, Nature Struct. Biol. 3:733-736 (1996).

[0064] A number of HVR delineations are used in the art and are encompassed herein. The Kabat Complementarity Determining Regions (CDRs) are based on sequence variability and are one of the most commonly used definitions (Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD. (1991)). Chothia refers, instead, to the location of the structural loops (Chothia and Lesk, J. Mol. Biol. 196:901-917 (1987)). The AbM HVRs represent a compromise between the Kabat HVRs and Chothia structural loops and are used by Oxford Molecular’s AbM antibody modeling software. The “contact” HVRs are based on an analysis of the available complex crystal structures. The IMGT numbering system was created by taking into account the high conservation of the structure of the V domain and by integrating the knowledge acquired by the analysis of multiple sources: alignment of more than 5000 sequences, literature data on the framework (FR) and complementarity determining regions (CDR), structural data from X-ray diffraction studies and characterization of the CDR hypervariable loops . The residues from each of these HVRs are noted below in Table 1. Table 1.

Loop Kabat AbM Chothia Contact IMGT

LI L24-L34 L24- L26- L30-L36 L27-

L34 L32 L32

L2 L50-L56 L50- L50- L46-L55 L50-

L56 L52 L51

L3 L89-L97 L89- L91- L89-L96 L89-

L97 L96 L97

Hl H31-H35B H26- H26- H30- H26-

(Kabat Numbering) H35B H32 H35B H35B

Hl H31-H35 H26- H26- H30-H35 H26-

(Chothia Numbering) H35 H32 H33

H2 H50-H65 H50- H53- H47-H58 H51-

H58 H55 H56

H3 H95-H102 H95- H96- H93- H93-

H102 H101 H101 H102

[0065] Unless otherwise indicated, the HVRs are determined according to Kabat et al., supra. HVRs may comprise “extended HVRs” as follows: residues 24-36 or 24-34 (LI), residues 46-56 or 50-56 (L2) and residues 89-97 or 89-96 (L3) in the VL and residues 26-35 (Hl), residues 50-65 or 49-65 (H2) and residues 93-102, 94-102, or 95-102 (H3) in the VH, each according to Kabat numbering.

[0066] The term “monoclonal antibody,” as used herein, refers to an antibody obtained from a single clone of cells or a cell line that produce a population of substantially homogeneous antibodies, i.e., the individual antibodies produced by the cells are identical except for possible naturally occurring mutations that may be present in minor amounts. Monoclonal antibodies are highly specific and are directed against a single antigen. Furthermore, in contrast to polyclonal antibody preparations that typically include different antibodies directed against different determinants (epitopes), each monoclonal antibody is directed against a single determinant on the antigen. Monoclonal antibodies may be human, humanized or chimeric antibodies. [0067] The terms “subject” and “patient” are used interchangeably herein and refer to a human in need of treatment. Accordingly, the term “subject” or “patient,” as used herein, means a human patient or subject to which the compositions of the disclosure may be administered. In some embodiments, the subject is in need of treatment of cancer.

[0068] The term “effective amount,” as used herein, refers to at least the minimum amount of a substance, compound, agent or composition, such as an antibody, required to affect a measurable improvement of a particular disorder. A therapeutically 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 substance, compound, agent or composition, such as an antibody, to elicit a desired response in the individual. The appropriate amount and dosage regimen can be determined using routine skill in the art. A therapeutically effective amount is also one in which any toxic or detrimental effects of the treatment are outweighed by the therapeutically beneficial effects. A beneficial or desired result include clinical results such as decreasing one or more 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, enhancing effect of another medication such as via targeting, delaying the progression of the disease, and/or prolonging survival. In the case of cancer or tumor, a therapeutically 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; relieving to some extent one or more of the symptoms associated with the disorder and/or maintaining remission. A therapeutically effective amount can be administered in one or more administrations. For purposes of this disclosure, a therapeutically effective amount of drug, compound, or pharmaceutical composition is an amount sufficient to accomplish therapeutic treatment either directly or indirectly. As is understood in the clinical context, a therapeutically effective amount of a drug, compound, or pharmaceutical composition may or may not be achieved in conjunction with another drug, compound, or pharmaceutical composition. Thus, a “therapeutically 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 a therapeutically effective amount if, in conjunction with one or more other agents, a desirable result may be or is achieved.

[0069] The term “tiragolumab,” as used herein, refers to anti-TIGIT monoclonal antagonist antibody described in WHO Drug Information (International Nonproprietary Names for Pharmaceutical Substances), Proposed ESIN: List 117, Vol. 31, No. 2, published June 9, 2017 (see p. 343). In some embodiments, tiragolumab has the CAS Registry Number 1918185-84- 8.

[0070] The term “treatment” (and variations thereof such as “treat” or “treating”), as used herein, 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 decreasing the rate of disease progression, ameliorating or palliating the disease state, preventing recurrence of cancer, preventing metastasis, and remission or improved prognosis. For example, an individual suffering from cancer is successfully “treated” if one or more symptoms associated with the cancer are mitigated or eliminated, including, but are not limited to, reducing the proliferation of (or destroying) cancerous cells, decreasing symptoms resulting from the cancer, increasing the quality of life of those suffering from the cancer, decreasing the dose of other medications required to treat the cancer, delaying the progression of the cancer, and/or prolonging survival of individuals.

[0071] The term “variable region” or “variable domain,” as used herein, refers to the domain of an antibody heavy or light chain that is involved in binding the antibody to antigen. The variable domains of the heavy chain and light chain (VH and VL, respectively) of a native antibody generally have similar structures, with each domain comprising four conserved framework regions (FRs) and three hypervariable regions (HVRs). (See, e.g., Kindt et al. Kuby Immunology, 6th ed., W.H. Freeman and Co., page 91 (2007).) While a VH domain is typically paired with a VL domain, a single VH or VL domain may be sufficient to confer antigen-binding specificity. Furthermore, antibodies that bind a particular antigen may be isolated using a VH or VL domain from an antibody that binds the antigen to screen a library of complementary VL or VH domains, respectively. See, e.g., Portolano et al, J. Immunol. 150:880-887 (1993); Clarkson et al, Nature 352:624-628 (1991).

Overview

[0072] The present disclosure relates to methods of treating cancer with an anti-TIGIT full-length monoclonal antibody, either as a monotherapy or in combination with an anti-PD- L1 full-length antibody, and articles of manufacture for use in such methods. Methods of treating cancer

[0073] In one aspect, the disclosure provides a method of treating cancer in a subject in need thereof comprising administering to the subject an anti-TIGIT monoclonal antibody. [0074] In some embodiments, the method comprises administering to the subject the anti-TIGIT monoclonal antibody at a fixed dose of about 1,000 mg. In some embodiments, the method comprises subcutaneously administering to the subject a fixed dose of about 1,000 mg of the anti-TIGIT monoclonal antibody In some embodiments, the method comprises administering to the subject a fixed dose of about 1,000 mg of the anti-TIGIT monoclonal antibody and a fixed dose of about 1,875 mg or about 2,000 mg of an anti-PD-Ll monoclonal antibody. In some embodiments, the method comprises subcutaneously administering to the subject a fixed dose of about 1,000 mg of the anti-TIGIT monoclonal antibody and a fixed dose of about 1,875 mg or about 2,000 mg of an anti-PD-Ll monoclonal antibody. In some embodiments, the method comprises administering to the subject a fixed dose of about 1,000 mg of the anti-TIGIT monoclonal antibody and a fixed dose of about 1,875 mg of an anti-PD-Ll monoclonal antibody. In some embodiments, the method comprises subcutaneously administering to the subject a fixed dose of about 1,000 mg of the anti-TIGIT monoclonal antibody and a fixed dose of about 1,875 mg of an anti-PD-Ll monoclonal antibody. In some embodiments, the method comprises administering to the subject a fixed dose of about 1,000 mg of the anti-TIGIT monoclonal antibody and a fixed dose of about 2,000 mg of an anti-PD-Ll monoclonal antibody. In some embodiments, the method comprises subcutaneously administering to the subject a fixed dose of about 1,000 mg of the anti-TIGIT monoclonal antibody and a fixed dose of about 2,000 mg of an anti-PD- Ll monoclonal antibody.

[0075] In some embodiments, the method comprises administering to the subject the anti- TIGIT monoclonal antibody at a fixed dose of 1,000 mg. In some embodiments, the method comprises subcutaneously administering to the subject a fixed dose of 1,000 mg of the anti- TIGIT monoclonal antibody In some embodiments, the method comprises administering to the subject a fixed dose of 1,000 mg of the anti-TIGIT monoclonal antibody and a fixed dose of 1,875 mg or 2,000 mg of an anti-PD-Ll monoclonal antibody. In some embodiments, the method comprises subcutaneously administering to the subject a fixed dose of 1,000 mg of the anti-TIGIT monoclonal antibody and a fixed dose of 1,875 mg or 2,000 mg of an anti-PD- Ll monoclonal antibody. In some embodiments, the method comprises administering to the subject a fixed dose of 1,000 mg of the anti-TIGIT monoclonal antibody and a fixed dose of 1,875 mg of an anti-PD-Ll monoclonal antibody. In some embodiments, the method comprises subcutaneously administering to the subject a fixed dose of 1,000 mg of the anti- TIGIT monoclonal antibody and a fixed dose of 1,875 mg of an anti-PD-Ll monoclonal antibody. In some embodiments, the method comprises administering to the subject a fixed dose of 1,000 mg of the anti-TIGIT monoclonal antibody and a fixed dose of 2,000 mg of an anti-PD-Ll monoclonal antibody. In some embodiments, the method comprises subcutaneously administering to the subject a fixed dose of 1,000 mg of the anti-TIGIT monoclonal antibody and a fixed dose of 2,000 mg of an anti-PD-Ll monoclonal antibody. [0076] In another aspect, the disclosure provides use of an anti-TIGIT monoclonal antibody in the manufacture of a medicament for treating cancer.

[0077] In some embodiments, the medicament is configured for administration of a fixed dose of about 1,000 mg of the anti-TIGIT monoclonal antibody. In some embodiments, the medicament is formulated for subcutaneous administration to the subject and configured for administration of a fixed dose of about 1,000 mg of the anti-TIGIT monoclonal antibody [0078] In some embodiments, the medicament is configured for administration of a fixed dose of 1,000 mg of the anti-TIGIT monoclonal antibody. In some embodiments, the medicament is formulated for subcutaneous administration to the subject and configured for administration of a fixed dose of 1,000 mg of the anti-TIGIT monoclonal antibody.

[0079] In another aspect, the disclosure provides use of an anti-TIGIT monoclonal antibody and an anti-PD-Ll antibody in the manufacture of a medicament for treating cancer.

[0080] In some embodiments, the medicament is configured for administration of a fixed dose of about 1,000 mg of the anti-TIGIT monoclonal antibody and a fixed dose of about 1,875 mg or about 2,000 mg of the anti-PD-Ll monoclonal antibody. In some embodiments, the medicament is formulated for subcutaneous administration to the subject and configured for administration of a fixed dose of about 1,000 mg of the anti-TIGIT monoclonal antibody and a fixed dose of about 1,875 mg or about 2,000 mg of the anti-PD-Ll monoclonal antibody. In some embodiments, the medicament is configured for administering to the subject a fixed dose of about 1,000 mg of the anti-TIGIT monoclonal antibody and a fixed dose of about 1,875 mg of the anti-PD-Ll monoclonal antibody. In some embodiments, the medicament is formulated for subcutaneous administration to the subject and configured for administration of a fixed dose of about 1,000 mg of the anti-TIGIT monoclonal antibody and a fixed dose of about 1,875 mg of the anti-PD-Ll monoclonal antibody. In some embodiments, the medicament is configured for administering to the subject a fixed dose of about 1,000 mg of the anti-TIGIT monoclonal antibody and a fixed dose of about 2,000 mg of the anti-PD-Ll monoclonal antibody. In some embodiments, the medicament is formulated for subcutaneous administration to the subject and configured for administering a fixed dose of about 1,000 mg of the anti-TIGIT monoclonal antibody and a fixed dose of about 2,000 mg of the anti-PD-Ll monoclonal antibody.

[0081] In some embodiments, the medicament is configured for administration of a fixed dose of 1,000 mg of the anti-TIGIT monoclonal antibody and a fixed dose of 1,875 mg or 2,000 mg of the anti-PD-Ll monoclonal antibody. In some embodiments, the medicament is formulated for subcutaneous administration to the subject and configured for administration of a fixed dose of 1,000 mg of the anti-TIGIT monoclonal antibody and a fixed dose of 1,875 mg or 2,000 mg of the anti-PD-Ll monoclonal antibody. In some embodiments, the medicament is configured for administering to the subject a fixed dose of 1,000 mg of the anti-TIGIT monoclonal antibody and a fixed dose of 1,875 mg of the anti-PD-Ll monoclonal antibody. In some embodiments, the medicament is formulated for subcutaneous administration to the subject and configured for administration of a fixed dose of 1,000 mg of the anti-TIGIT monoclonal antibody and a fixed dose of 1,875 mg of the anti-PD-Ll monoclonal antibody. In some embodiments, the medicament is configured for administering to the subject a fixed dose of 1,000 mg of the anti-TIGIT monoclonal antibody and a fixed dose of 2,000 mg of the anti-PD-Ll monoclonal antibody. In some embodiments, the medicament is formulated for subcutaneous administration to the subject and configured for administering a fixed dose of 1,000 mg of the anti-TIGIT monoclonal antibody and a fixed dose of 2,000 mg of the anti-PD-Ll monoclonal antibody.

[0082] In another aspect, the disclosure provides an anti-TIGIT monoclonal antibody for use in treating cancer.

[0083] In some embodiments, the anti-TIGIT monoclonal antibody is administered at a fixed dose of about 1,000 mg. In some embodiments, the anti-TIGIT monoclonal antibody is subcutaneously administered at a fixed dose of about 1,000 mg.

[0084] In some embodiments, the anti-TIGIT monoclonal antibody is administered at a fixed dose of 1,000 mg. In some embodiments, the anti-TIGIT monoclonal antibody is subcutaneously administered at a fixed dose of 1,000 mg.

[0085] In another aspect, the disclosure provides an anti-TIGIT monoclonal antibody and an anti-PD-Ll antibody for use in treating cancer.

[0086] In some embodiments, the anti-TIGIT monoclonal antibody is administered at a fixed dose of about 1,000 mg, and the anti-PD-Ll monoclonal antibody is administered at a fixed dose of about 1,875 mg or about 2,000 mg. In some embodiments, the anti-TIGIT monoclonal antibody is subcutaneously administered at a fixed dose of about 1,000 mg, and the anti-PD-Ll monoclonal antibody is subcutaneously administered at a fixed dose of about 1,875 mg or about 2,000 mg. In some embodiments, the anti-TIGIT monoclonal antibody is administered at a fixed dose of about 1,000 mg, and the anti-PD-Ll monoclonal antibody is administered at a fixed dose of about 1,875 mg. In some embodiments, the anti-TIGIT monoclonal antibody is subcutaneously administered at a fixed dose of about 1,000 mg, and the anti-PD-Ll monoclonal antibody is subcutaneously administered at a fixed dose of about 1,875 mg. In some embodiments, the anti-TIGIT monoclonal antibody is administered at a fixed dose of about 1,000 mg, and the anti-PD-Ll monoclonal antibody is administered at a fixed dose of about 2,000 mg. In some embodiments, the anti-TIGIT monoclonal antibody is subcutaneously administered at a fixed dose of about 1,000 mg, and the anti-PD-Ll monoclonal antibody is subcutaneously administered at a fixed dose of about 2,000 mg. [0087] In some embodiments, the anti-TIGIT monoclonal antibody is administered at a fixed dose of 1,000 mg, and the anti-PD-Ll monoclonal antibody is administered at a fixed dose of 1,875 mg or 2,000 mg. In some embodiments, the anti-TIGIT monoclonal antibody is subcutaneously administered at a fixed dose of 1,000 mg, and the anti-PD-Ll monoclonal antibody is subcutaneously administered at a fixed dose of 1,875 mg or 2,000 mg. In some embodiments, the anti-TIGIT monoclonal antibody is administered at a fixed dose of 1,000 mg, and the anti-PD-Ll monoclonal antibody is administered at a fixed dose of 1,875 mg. In some embodiments, the anti-TIGIT monoclonal antibody is subcutaneously administered at a fixed dose of 1,000 mg, and the anti-PD-Ll monoclonal antibody is subcutaneously administered at a fixed dose of 1,875 mg. In some embodiments, the anti-TIGIT monoclonal antibody is administered at a fixed dose of 1,000 mg, and the anti-PD-Ll monoclonal antibody is administered at a fixed dose of 2,000 mg. In some embodiments, the anti-TIGIT monoclonal antibody is subcutaneously administered at a fixed dose of 1,000 mg, and the anti-PD-Ll monoclonal antibody is subcutaneously administered at a fixed dose of 2,000 mg. [0088] In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody comprises a heavy chain variable region (VH) comprising a HVR-H1 comprising the amino acid sequence of SEQ ID NO: 1; a HVR-H2 comprising the amino acid sequence of SEQ ID NO: 2; and a HVR-H3 comprising the amino acid sequence of SEQ ID NO: 3; and a light chain variable region (VL) comprising a HVR-L1 comprising the amino acid sequence of SEQ ID NO: 4; a HVR-L2 comprising the amino acid sequence of SEQ ID NO: 5; and a HVR-L3 comprising the amino acid sequence of SEQ ID NO: 6. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody comprises a VH comprising the HVR-H1, the HVR-H2, and the HVR-H3 of tiragolumab; and a VL comprising the HVR- Ll, the HVR-L2, and the HVR-L3 of tiragolumab.

[0089] In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 7. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody comprises a VL comprising the amino acid sequence of SEQ ID NO: 9. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 7 and a VL comprising the amino acid sequence of SEQ ID NO: 9. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody comprises the VH of tiragolumab. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody comprises the VL of tiragolumab. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody comprises the VH and the VL of tiragolumab.

[0090] In some embodiments of any of the above aspects, the heavy chain of the anti- TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 18. In some embodiments of any of the above aspects, the heavy chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 19. In some embodiments of any of the above aspects, the heavy chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 24. In some embodiments of any of the above aspects, the heavy chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 25. In some embodiments of any of the above aspects, the light chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 20. In some embodiments of any of the above aspects, the heavy chain of the anti- TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 18 and the light chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 20. In some embodiments of any of the above aspects, the heavy chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 19 and the light chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 20. In some embodiments of any of the above aspects, the heavy chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 24 and the light chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 20. In some embodiments of any of the above aspects, the heavy chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 25 and the light chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 20. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody comprises the heavy chain of tiragolumab. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody comprises the light chain of tiragolumab. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody comprises the heavy chain and the light chain of tiragolumab. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody is tiragolumab. Tiragolumab is described in WHO Drug Information (International Nonproprietary Names for Pharmaceutical Substances), Proposed INN: List 117, Vol. 31, No. 2, published June 9, 2017 (see p. 343). In some embodiments of any of the above aspects, tiragolumab has the CAS Registry Number 1918185-84-8.

[0091] In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody is an IgG antibody. The anti-TIGIT monoclonal antibody may be an IgGl antibody, an IgG2 antibody, an IgG3 antibody, or an IgG4 antibody. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody is an IgGl or an IgG4 antibody. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody is an IgGl antibody. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody is a wild-type IgGl antibody. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody comprises a human IgGl Fc region that comprises one or more amino acid modifications. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody is an IgG4 antibody. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody is a wild-type IgG4 antibody. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody comprises a human IgG4 Fc region that comprises one or more amino acid modifications. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody is an antagonist antibody In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody may have one or more effector functions. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody retains all effector functions. Optionally, one or more effector functions of the anti-TIGIT monoclonal antibody may have been modified or eliminated.

[0092] In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody is a human antibody. In some embodiments of any of the above aspects, the anti- TIGIT monoclonal antibody is a humanized antibody. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody is a full-length antibody. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody is a full- length IgG antibody. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody is a full-length IgGl antibody. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody is a full-length human IgGl antibody. The anti-TIGIT monoclonal antibody may be an antibody fragment.

[0093] In some embodiments of any of the above aspects, the anti-PD-Ll monoclonal antibody comprises a heavy chain variable region (VH) comprising a HVR-H1 comprising the amino acid sequence of SEQ ID NO: 10; a HVR-H2 comprising the amino acid sequence of SEQ ID NO: 11; and a HVR-H3 comprising the amino acid sequence of SEQ ID NO: 12; and a light chain variable region (VL) comprising a HVR-L1 comprising the amino acid sequence of SEQ ID NO: 13; a HVR-L2 comprising the amino acid sequence of SEQ ID NO: 14; and a HVR-L3 comprising the amino acid sequence of SEQ ID NO: 15. In some embodiments of any of the above aspects, the anti-PD-Ll monoclonal antibody comprises a VH comprising the HVR-H1, the HVR-H2, and the HVR-H3 of atezolizumab; and a VL comprising the HVR-L1, the HVR-L2, and the HVR-L3 of atezolizumab.

[0094] In some embodiments of any of the above aspects, the anti-PD-Ll monoclonal antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 16. In some embodiments of any of the above aspects, the anti-PD-Ll monoclonal antibody comprises a light chain variable region comprising the amino acid sequence of SEQ ID NO: 17. In some embodiments of any of the above aspects, the anti-PD- Ll monoclonal antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 16 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 17. In some embodiments of any of the above aspects, the anti-PD- Ll monoclonal antibody comprises the VH of atezolizumab. In some embodiments of any of the above aspects, the anti-PD-Ll monoclonal antibody comprises the VL of atezolizumab. In some embodiments of any of the above aspects, the anti-PD-Ll monoclonal antibody comprises the VH and the VL of atezolizumab.

[0095] In some embodiments of any of the above aspects, the heavy chain of the anti-PD- Ll monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 21. In some embodiments of any of the above aspects, the heavy chain of the anti-PD-Ll monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 22. In some embodiments of any of the above aspects, the light chain of the anti-PD-Ll monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 23. In some embodiments of any of the above aspects, the heavy chain of the anti-PD-Ll monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 21, and the light chain of the anti-PD-Ll monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 23. In some embodiments of any of the above aspects, the heavy chain of the anti-PD-Ll monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 22, and the light chain of the anti-PD-Ll monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 23. In some embodiments of any of the above aspects, the anti-PD-Ll monoclonal antibody comprises the heavy chain of atezolizumab. In some embodiments of any of the above aspects, the anti-PD-Ll monoclonal antibody comprises the light chain of atezolizumab. In some embodiments of any of the above aspects, the anti-PD-Ll monoclonal antibody comprises the heavy chain and the light chain of atezolizumab. In some embodiments of any of the above aspects, the anti-PD-Ll monoclonal antibody is atezolizumab.

[0096] In some embodiments of any of the above aspects, the anti-PD-Ll monoclonal antibody is an IgG antibody. The anti-PD-Ll monoclonal antibody may be an IgGl antibody, an IgG2 antibody, an IgG3 antibody, or an IgG4 antibody. In some embodiments of any of the above aspects, the anti-PD-Ll monoclonal antibody is an IgGl or an IgG4 antibody. In some embodiments of any of the above aspects, the anti-PD-Ll monoclonal antibody is an IgGl antibody. In some embodiments of any of the above aspects, the anti- PD-Ll monoclonal antibody is an IgG4 antibody. In some embodiments of any of the above aspects, the anti-PD-Ll monoclonal antibody is an antagonist antibody. In some cases, the anti-PD-Ll monoclonal antibody may have one or more effector functions. In some embodiments of any of the above aspects, the anti-PD-Ll monoclonal antibody retains all effector functions. Optionally, one or more effector functions of the anti-PD-Ll monoclonal antibody may have been modified or eliminated.

[0097] In some embodiments of any of the above aspects, the anti-PD-Ll monoclonal antibody is a human antibody. In some embodiments of any of the above aspects, the anti-PD-Ll monoclonal antibody is a humanized antibody. In some embodiments of any of the above aspects, the anti-PD-Ll monoclonal antibody is a full-length antibody. In some embodiments of any of the above aspects, the anti-PD-Ll monoclonal antibody is a full- length IgG antibody. In some embodiments of any of the above aspects, the anti-PD-Ll monoclonal antibody is a full-length IgGl antibody. In some embodiments of any of the above aspects, the anti-PD-Ll monoclonal antibody is a full-length human IgGl antibody. In some embodiments of any of the above aspects, the anti-PD-Ll monoclonal antibody is a full-length humanized IgGl antibody. The anti-PD-Ll monoclonal antibody may be an antibody fragment. In some embodiments of any of the above aspects, the anti-PD-Ll monoclonal antibody is atezolizumab, marketed as TECENTRIQ®. Atezolizumab is described in WHO Drug Information (International Nonproprietary Names for Pharmaceutical Substances), Proposed INN: List 112, Vol. 28, No. 4, 2014 (see page 488). In some embodiments of any of the above aspects, atezolizumab has the CAS Registry Number 1380723-44-3.

[0098] In some embodiments, the method comprises administering to the subject a fixed dose of about 1,000 mg of tiragolumab. In some embodiments, the method comprises subcutaneously administering to the subject a fixed dose of about 1,000 mg of tiragolumab. In some embodiments, the method comprises administering to the subject a fixed dose of about 1,000 mg of tiragolumab and a fixed dose of about 1,875 mg or 2,000 mg of atezolizumab. In some embodiments, the method comprises subcutaneously administering to the subject a fixed dose of about 1,000 mg of tiragolumab and a fixed dose of about 1,875 mg or 2,000 mg of atezolizumab. In some embodiments, the method comprises administering to the subject a fixed dose of about 1,000 mg of tiragolumab and a fixed dose of about 1,875 mg of atezolizumab. In some embodiments, the method comprises subcutaneously administering to the subject a fixed dose of about 1,000 mg of tiragolumab and a fixed dose of about of atezolizumab. In some embodiments, the method comprises administering to the subject a fixed dose of about 1,000 mg of tiragolumab and a fixed dose of about 2,000 mg of atezolizumab. In some embodiments, the method comprises subcutaneously administering to the subject a fixed dose of about 1,000 mg of tiragolumab and a fixed dose of about 2,000 mg of atezolizumab.

[0099] In some embodiments, the method comprises administering to the subject a fixed dose of 1,000 mg of tiragolumab. In some embodiments, the method comprises subcutaneously administering to the subject a fixed dose of 1,000 mg of tiragolumab. In some embodiments, the method comprises administering to the subject a fixed dose of 1,000 mg of tiragolumab and a 1,875 mg or 2,000 mg fixed dose of atezolizumab. In some embodiments, the method comprises subcutaneously administering to the subject a fixed dose of 1,000 mg of tiragolumab and a 1,875 mg or 2,000 mg fixed dose of atezolizumab. In some embodiments, the method comprises administering to the subject a fixed dose of 1,000 mg of tiragolumab and a 1,875 mg fixed dose of atezolizumab. In some embodiments, the method comprises subcutaneously administering to the subject a fixed dose of 1,000 mg of tiragolumab and a 1,875 mg fixed dose of atezolizumab. In some embodiments, the method comprises administering to the subject a fixed dose of 1,000 mg of tiragolumab and a 2,000 mg fixed dose of atezolizumab. In some embodiments, the method comprises subcutaneously administering to the subject a fixed dose of 1,000 mg of tiragolumab and a 2,000 mg fixed dose of atezolizumab.

[0100] In some embodiments, the medicament is configured for administration of a fixed dose of about 1,000 mg of tiragolumab. In some embodiments, the medicament is formulated for subcutaneous administration to the subject and configured for administration of a fixed dose of about 1,000 mg of tiragolumab. In some embodiments, the medicament is configured for administration of a fixed dose of about 1,000 mg of tiragolumab and a fixed dose of about 1,875 mg or about 2,000 mg of atezolizumab. In some embodiments, the medicament is formulated for subcutaneous administration to the subject and configured for administration of a fixed dose of about 1,000 mg of tiragolumab and a fixed dose of about 1,875 mg or about 2,000 mg of atezolizumab. In some embodiments, the medicament is configured for administering to the subject a fixed dose of about 1,000 mg of tiragolumab and a fixed dose of about 1,875 mg of atezolizumab. In some embodiments, the medicament is formulated for subcutaneous administration to the subject and configured for administration of a fixed dose of about 1,000 mg of tiragolumab and a fixed dose of about 1,875 mg of atezolizumab. In some embodiments, the medicament is configured for administering to the subject a fixed dose of about 1,000 mg of the anti TIGIT monoclonal antibody and a fixed dose of about 2,000 mg of atezolizumab. In some embodiments, the medicament is formulated for subcutaneous administration to the subject and configured for administering a fixed dose of about 1,000 mg of tiragolumab and a fixed dose of about 2,000 mg of atezolizumab.

[0101] In some embodiments, the medicament is configured for administration of a fixed dose of 1,000 mg of tiragolumab. In some embodiments, the medicament is formulated for subcutaneous administration to the subject and configured for administration of a fixed dose of 1,000 mg of tiragolumab. In some embodiments, the medicament is configured for administration of a fixed dose of 1,000 mg of tiragolumab and a fixed dose of 1,875 mg or 2,000 mg of atezolizumab. In some embodiments, the medicament is formulated for subcutaneous administration to the subject and configured for administration of a fixed dose of 1,000 mg of tiragolumab and a fixed dose of 1,875 mg or 2,000 mg of atezolizumab. In some embodiments, the medicament is configured for administering to the subject a fixed dose of 1,000 mg of tiragolumab and a fixed dose of 1,875 mg of atezolizumab. In some embodiments, the medicament is formulated for subcutaneous administration to the subject and configured for administration of a fixed dose of 1,000 mg of tiragolumab and a fixed dose of 1,875 mg of atezolizumab. In some embodiments, the medicament is configured for administering to the subject a fixed dose of 1,000 mg of the anti TIGIT monoclonal antibody and a fixed dose of 2,000 mg of atezolizumab. In some embodiments, the medicament is formulated for subcutaneous administration to the subject and configured for administering a fixed dose of 1,000 mg of tiragolumab and a fixed dose of 2,000 mg of atezolizumab.

[0102] In some embodiments, tiragolumab is administered at a fixed dose of about 1,000 mg. In some embodiments, tiragolumab is subcutaneously administered at a fixed dose of about 1,000 mg. In some embodiments, tiragolumab is administered at a fixed dose of about 1,000 mg, and atezolizumab is administered at a fixed dose of about 1,875 mg or about 2,000 mg. In some embodiments, tiragolumab is subcutaneously administered at a fixed dose of about 1,000 mg, and atezolizumab is subcutaneously administered at a fixed dose of about 1,875 mg or about 2,000 mg. In some embodiments, tiragolumab is administered at a fixed dose of about 1,000 mg, and atezolizumab is administered at a fixed dose of about 1,875 mg. In some embodiments, tiragolumab is subcutaneously administered at a fixed dose of about 1,000 mg, and atezolizumab is subcutaneously administered at a fixed dose of about 1,875 mg. In some embodiments, tiragolumab is administered at a fixed dose of about 1,000 mg, and atezolizumab is administered at a fixed dose of about 2,000 mg. In some embodiments, tiragolumab is subcutaneously administered at a fixed dose of about 1,000 mg, and atezolizumab is subcutaneously administered at a fixed dose of about 2,000 mg.

[0103] In some embodiments, tiragolumab is administered at a fixed dose of 1,000 mg. In some embodiments, tiragolumab is subcutaneously administered at a fixed dose of 1,000 mg. In some embodiments, tiragolumab is administered at a fixed dose of 1,000 mg, and atezolizumab is administered at a fixed dose of 1,875 mg or 2,000 mg. In some embodiments, tiragolumab is subcutaneously administered at a fixed dose of 1,000 mg, and atezolizumab is subcutaneously administered at a fixed dose of 1,875 mg or 2,000 mg. In some embodiments, tiragolumab is administered at a fixed dose of 1,000 mg, and atezolizumab is administered at a fixed dose of 1,875 mg. In some embodiments, tiragolumab is subcutaneously administered at a fixed dose of 1,000 mg, and atezolizumab is subcutaneously administered at a fixed dose of 1,875 mg. In some embodiments, tiragolumab is administered at a fixed dose of 1,000 mg, and atezolizumab is administered at a fixed dose of 2,000 mg. In some embodiments, tiragolumab is subcutaneously administered at a fixed dose of 1,000 mg, and atezolizumab is subcutaneously administered at a fixed dose of 2,000 mg.

[0104] In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody may be administered parenterally. In some embodiments, the anti-TIGIT monoclonal antibody is administered by injection. In some embodiments, the anti-TIGIT monoclonal antibody is administered intravenously or subcutaneously. In some embodiments, the anti-TIGIT monoclonal antibody is administered intravenously. In some embodiments, the anti-TIGIT monoclonal antibody is administered subcutaneously.

[0105] In some embodiments of any of the above aspects, the anti-PD-Ll monoclonal antibody may be administered parenterally. In some embodiments, the anti-PD-Ll monoclonal antibody is administered by injection. In some embodiments, the anti-PD-Ll monoclonal antibody is administered intravenously or subcutaneously. In some embodiments, the anti-PD-Ll monoclonal antibody is administered intravenously. In some embodiments, the anti-PD-Ll monoclonal antibody is administered subcutaneously.

[0106] In some embodiments, the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody are co-mixed. In some embodiments, the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody are coformulated.

[0107] In some embodiments of any of the above aspects, the subject is human. In some embodiments of any of the above aspects, the subject has not received prior checkpoint inhibitor treatment (i.e. is CPI-Naive). In some embodiments of any of the above aspects, the subject has not received prior treatment with an anti-PD-Ll monoclonal antibody, an anti- PD-1 antibody, an anti-CTLl-4 antibody, or an anti-TIGIT monoclonal antibody. In some embodiments of any of the above aspects, the subject has not received prior treatment with an anti-PD-Ll monoclonal antibody. In some embodiments of any of the above aspects, the subject has not received prior treatment with an anti-PD-1 antibody. In some embodiments of any of the above aspects, the subject has not received prior treatment with an anti-CTLl-4 antibody. In some embodiments of any of the above aspects, the subject has not received prior treatment with an anti-TIGIT monoclonal antibody. In some embodiments of any of the above aspects, the subject is cancer immunotherapy (CIT) naive (i.e. is CIT -Naive).

[0108] In some embodiments of any of the above aspects, the cancer is selected from the group consisting of a lung cancer, a non-small cell lung cancer, a renal cell cancer, a urothelial cancer, a ureter cancer, a urethral cancer, a colorectal cancer, a colon cancer, a rectal cancer, a kidney cancer, a sarcoma, an ovarian cancer, a breast cancer, a cervical cancer, a fallopian tube cancer, an endometrial cancer, a uterine cancer, a pancreatic cancer, a gastric carcinoma, a bladder cancer, an esophageal cancer, a mesothelioma, a melanoma, a head and neck cancer, a thyroid cancer, a sarcoma, a prostate cancer, a penile cancer, a glioblastoma, a thymic carcinoma, an esophageal carcinoma, a nasopharyngeal cancer, a mesothelioma, a liver cancer, a biliary tract cancer, a HPV-positive cancer, a leukemia, a lymphoma, a brain cancer, a neuroendocrine cancer, a myeloma, a mycosis fungoides, a Merkel cell cancer, a hematologic malignancy, a deficient mismatch repair (dMMR) cancer, and a microsatellite instability -high (MSI-H) cancer. In some embodiments of any of the above aspects, the cancer is a lung cancer. In some embodiments of any of the above aspects, the cancer is a non-small cell lung cancer. In some embodiments of any of the above aspects, the cancer is a renal cell cancer. In some embodiments of any of the above aspects, the cancer is a urothelial cancer. In some embodiments of any of the above aspects, the cancer is a ureter cancer. In some embodiments, the cancer is a urethral cancer. In some embodiments of any of the above aspects, the cancer is a colorectal cancer. In some embodiments of any of the above aspects, the cancer is a colon cancer. In some embodiments of any of the above aspects, the cancer is a rectal cancer. In some embodiments of any of the above aspects, the cancer is a kidney cancer. In some embodiments of any of the above aspects, the cancer is a sarcoma. In some embodiments of any of the above aspects, the cancer is an ovarian cancer. In some embodiments of any of the above aspects, the cancer is a breast cancer. In some embodiments of any of the above aspects, the cancer is a cervical cancer. In some embodiments of any of the above aspects, the cancer is a fallopian tube cancer. In some embodiments of any of the above aspects, the cancer is an endometrial cancer. In some embodiments of any of the above aspects, the cancer is a uterine cancer. In some embodiments of any of the above aspects, the cancer is a pancreatic cancer. In some embodiments of any of the above aspects, the cancer is a gastric carcinoma. In some embodiments of any of the above aspects, the cancer is a bladder cancer. In some embodiments of any of the above aspects, the cancer is an esophageal cancer. In some embodiments of any of the above aspects, the cancer is a mesothelioma. In some embodiments of any of the above aspects, the cancer is a melanoma. In some embodiments of any of the above aspects, the cancer is a head and neck cancer. In some embodiments of any of the above aspects, the cancer is a thyroid cancer. In some embodiments of any of the above aspects, the cancer is a sarcoma. In some embodiments of any of the above aspects, the cancer is a prostate cancer. In some embodiments of any of the above aspects, the cancer is a penile cancer. In some embodiments of any of the above aspects, the cancer is a glioblastoma. In some embodiments of any of the above aspects, the cancer is a thymic carcinoma. In some embodiments of any of the above aspects, the cancer is an esophageal carcinoma. In some embodiments of any of the above aspects, the cancer is a nasopharyngeal cancer. In some embodiments of any of the above aspects, the cancer is a mesothelioma. In some embodiments of any of the above aspects, the cancer is a liver cancer. In some embodiments of any of the above aspects, the cancer is a biliary tract cancer. In some embodiments of any of the above aspects, the cancer is a HPV-positive cancer. In some embodiments of any of the above aspects, the cancer is a leukemia. In some embodiments of any of the above aspects, the cancer is a lymphoma. In some embodiments of any of the above aspects, the cancer is a brain cancer. In some embodiments of any of the above aspects, the cancer is a neuroendocrine cancer. In some embodiments of any of the above aspects, the cancer is a myeloma. In some embodiments of any of the above aspects, the cancer is a mycosis fungoides. In some embodiments of any of the above aspects, the cancer is a Merkel cell cancer. In some embodiments of any of the above aspects, the cancer is a hematologic malignancy. In some embodiments of any of the above aspects, the cancer is a deficient mismatch repair (dMMR) cancer. In some embodiments of any of the above aspects, the cancer is a microsatellite instability-high (MSI-H) cancer.

[0109] In some embodiments of any of the above aspects, the cancer is selected from the group consisting of a bladder cancer, a muscle-invasive bladder cancer, a urothelial carcinoma, a ureter cancer, a urethral cancer, a ureter urothelial carcinoma, a urethral urothelial carcinoma, a renal cancer, a renal pelvis cancer, a renal cell carcinoma, a clear-cell renal carcinoma, a rectal cancer, a colon cancer, a colorectal cancer, a sarcoma, an osteosarcoma, a leiomyosarcoma, a pleomorphic sarcoma, a myxofibrosarcoma, a liposarcoma, a chondrosarcoma, a lung cancer, a non-small cell lung cancer, a fallopian tube cancer, a peritoneal carcinoma, an esophageal cancer, an esophageal squamous cell carcinoma, a mesothelioma, a pleural mesothelioma, a peritoneal mesothelioma, an ovarian cancer, a cervical cancer, a cervical adenosquamous carcinoma, a breast cancer, a triplenegative breast cancer, a HER2 -positive breast cancer, a HER2-negative breast cancer, an estrogen receptor-positive breast cancer, a progesterone receptor-positive breast cancer, a luminal B breast cancer, a lymphoma, a T-cell lymphoma, a B-cell lymphoma, a nasal -type lymphoma, non-Hodgkin’s lymphoma, a follicular lymphoma, a penile carcinoma, a prostate cancer, a castration-resistant prostate cancer, an endometrial cancer, a uterine cancer, a myeloma, a multiple myeloma, a head and neck cancer, a prostate cancer, a melanoma, a cutaneous melanoma, a Merkel cell carcinoma, a pancreatic cancer, hepatocellular carcinoma, gastric cancer, a gastroesophageal junction adenocarcinoma, a glioblastoma, a glioblastoma multiforme, a mycosis fungoides, an HPV-positive cancer, a HPV-related cervical carcinoma, a HPV-related anal squamous cell carcinoma, a HPV-related penile squamous cell carcinoma, a HPV-related vulvar squamous cell carcinoma, a vulvar cancer, a vaginal cancer, an anal cancer, an oropharyngeal cancer, an oropharyngeal squamous cell carcinoma, a leukemia, an acute myeloid leukemia, a bone cancer, a solitary bone plasmacytoma, a squamous cell carcinoma, a cutaneous squamous cell carcinoma, a thyroid cancer, a microsatellite stability/proficient mismatch repair (MSS/pMMR) metastatic colorectal cancer, a deficient mismatch repair (dMMR) cancer, a microsatellite instability-high (MSI-H) cancer, a nasaltype extranodal NK/T-Cell lymphoma, a neuroendocrine cancer, a biliary tract cancer, a cholangiocarcinoma, and an intrahepatic cholangiocarcinoma.

[0110] In some embodiments of any of the above aspects, the breast cancer is a triplenegative breast cancer, a HER2 -positive breast cancer, a HER2-negative breast cancer, an estrogen receptor-positive breast cancer, a progesterone receptor-positive breast cancer, or a luminal B breast cancer.

[0111] In some embodiments of any of the above aspects, the lymphoma is a T-cell lymphoma, a B-cell lymphoma, a nasal -type lymphoma, non-Hodgkin’s lymphoma, or a follicular lymphoma.

[0112] In some embodiments of any of the above aspects, the cancer is selected from the group consisting of a Merkel cell carcinoma, a urothelial carcinoma, a renal cell carcinoma, non-small cell lung cancer, a breast cancer, a triple-negative breast cancer, a hepatocellular carcinoma, a melanoma, a Hodgkin’s lymphoma, a head and neck cancer, a colorectal cancer, a gastric cancer, a cervical cancer, a primary mediastinal large B-cell lymphoma, a cutaneous squamous-cell carcinoma, a basal cell carcinoma, a bladder cancer, an endometrial cancer, an esophageal cancer, a malignant pleural mesothelioma, a tumor mutational burden (TMB)- high cancer, a deficient mismatch repair (dMMR) cancer, and a microsatellite instability-high (MSI-H) cancer.

[0113] In some embodiments of any of the above aspects, the cancer is selected from the group consisting of a lung cancer, a non-small cell lung cancer, a bronchogenic carcinoma, a breast cancer, a triple-negative breast cancer, an estrogen receptor-positive breast cancer, a HER2 -positive breast cancer, a lobular metastatic breast cancer, a ductal breast carcinoma, a cervical cancer, a fallopian tube cancer, a fallopian tube serous adenocarcinoma, an ovarian cancer, an ovarian endometrioid tumor, an ovarian serous adenocarcinoma, an ovarian seromucinous carcinoma, a uterine cancer, an endometrial cancer, a skin cancer, a melanoma, a cutaneous melanoma, a Merkel cell carcinoma, a head and neck cancer, squamous cell carcinoma of head and neck, a hematologic malignancy, a leukemia, a myeloid leukemia, an acute myeloid leukemia, a chronic lymphocytic leukemia, a myelomonocytic leukemia, a thyroid cancer, thyroid gland carcinoma, a thymic carcinoma, a neuroendocrine cancer, a pheochromocytoma, a glioma, a glioblastoma multiforme, a paraganglioma, a lymphoma, a B-cell lymphoma, a Hodgkin lymphoma, a B-cell non-Hodgkin lymphoma, a non-Hodgkin’s lymphoma, a cutaneous T-cell lymphoma, a diffuse large B-cell lymphoma, a follicular lymphoma, a marginal zone lymphoma, a pancreatic cancer, a pancreatic ductal adenocarcinoma, a rectal cancer, a colon cancer, a colorectal cancer, a urinary tract cancer, a genitourinary cancer, a mesothelioma, a pleural mesothelioma, a peritoneal mesothelioma, a sarcoma, a chondrosarcoma, a clear cell sarcoma, a liposarcoma, a myxoid/round cell liposarcoma, a synovial sarcoma, an alveolar soft part sarcoma, a gliosarcoma, a uterine carcinosarcoma, a kidney cancer, a non-clear cell kidney cancer, a renal cell carcinoma, a bladder cancer, a urothelial carcinoma, a muscle-invasive bladder cancer, a non-muscle invasive bladder cancer, a HER2-positive bladder cancer, a gallbladder carcinoma, a gastric cancer, an esophageal cancer, an esophageal squamous cell carcinoma, a gastrointestinal cancer, a gastroesophageal cancer, a gastroesophageal junction cancer, a HER2-positive gastric cancer, a primary peritoneal cancer, a cutaneous squamous cell carcinoma, a prostate cancer, a prostate adenocarcinoma, a castration-resistant prostate cancer, a urogenital cancer, a ureter urothelial carcinoma, a renal pelvis urothelial carcinoma, a urethral urothelial carcinoma, an appendix carcinoma, a penile cancer, an anal canal cancer, a hepatocellular carcinoma, a hepatobiliary cancer, an unresectable liver and intrahepatic bile duct carcinoma, a biliary tract cancer, a cholangiocarcinoma, an intrahepatic cholangiocarcinoma, an extrahepatic cholangiocarcinoma, an HPV-related cancer, an HPV-related anal squamous cell carcinoma, an HPV-related cervical squamous cell carcinoma, an HPV-related penile squamous cell carcinoma, an HPV-related vulvar squamous cell carcinoma, a nasopharynx carcinoma, a nasopharyngeal carcinoma, a laryngeal squamous cell carcinoma, a hypopharyngeal squamous cell carcinoma, an oral cavity squamous cell carcinoma, and a mycosis fungoides.

[0114] In some embodiments of any of the above aspects, the caner is selected from the group consisting of urothelial carcinoma, non-small cell lung cancer (NSCLC), breast cancer, triple-negative breast cancer, hepatocellular carcinoma and melanoma.

[0115] In some embodiments of any of the above aspects, the cancer is selected from the group consisting of a multiple myeloma, a cervical cancer, an esophageal cancer, an esophageal squamous cell carcinoma, a lung cancer, a non-small cell lung cancer, a glioblastoma, an endometrial cancer, an ovarian cancer, a squamous cell cancer, a head and neck cancer.

[0116] In some embodiments of any of the above aspects, the cancer is selected from the group consisting of a cervical cancer, a squamous cell carcinoma of head and neck, a head and neck cancer, a non-small cell lung cancer, a non-squamous non-small cell lung cancer, an esophageal squamous cell carcinoma, an esophageal cancer, a breast cancer, a triple-negative breast cancer, a gastric cancer, a gastroesophageal junction adenocarcinoma, a multiple myeloma, a non-Hodgkin lymphoma, a B-cell lymphoma, a liver cancer, a bladder cancer, a urothelial carcinoma, a pancreatic cancer, and a pancreatic adenocarcinoma.

[0117] In some embodiments of any of the above aspects, the cancer is a solid tumor. In some embodiments of any of the above aspects, the solid tumor is PD-L1 positive. In some embodiments of any of the above aspects, the solid tumor is a histologically-confirmed PD- L1 solid tumor. In some embodiments of any of the above aspects, the solid tumor is locally advanced, recurrent, or metastatic.

[0118] In some embodiments of any of the above aspects, the cancer is a hematological cancer.

[0119] In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody are administered simultaneously. In some embodiments, the anti-TIGIT monoclonal and the anti-PD-Ll monoclonal antibody are coformulated. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody are administered separately.

[0120] In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody are mixed 24 hours or less prior to administration to the subject. In some embodiments of any of the above aspects, the anti- TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody are mixed 23 hours or less prior to administration to the subject. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody are mixed 22 hours or less prior to administration to the subject. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody are mixed 21 hours or less prior to administration to the subject. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody are mixed 20 hours or less prior to administration to the subject. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody and the anti- PD-Ll monoclonal antibody are mixed 19 hours or less prior to administration to the subject. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody are mixed 18 hours or less prior to administration to the subject. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody are mixed 17 hours or less prior to administration to the subject. In some embodiments of any of the above aspects, the anti- TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody are mixed 16 hours or less prior to administration to the subject. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody are mixed 15 hours or less prior to administration to the subject. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody are mixed 14 hours or less prior to administration to the subject. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody are mixed 13 hours or less prior to administration to the subject. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody and the anti- PD-Ll monoclonal antibody are mixed 12 hours or less prior to administration to the subject. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody are mixed 11 hours or less prior to administration to the subject. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody are mixed 10 hours or less prior to administration to the subject. In some embodiments of any of the above aspects, the anti- TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody are mixed 9 hours or less prior to administration to the subject. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody are mixed 8 hours or less prior to administration to the subject. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody are mixed 7 hours or less prior to administration to the subject. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody are mixed 6 hours or less prior to administration to the subject. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody and the anti- PD-Ll monoclonal antibody are mixed 5 hours or less prior to administration to the subject. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody are mixed 4 hours or less prior to administration to the subject. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody are mixed 3 hours or less prior to administration to the subject. In some embodiments of any of the above aspects, the anti- TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody are mixed 2 hours or less prior to administration to the subject. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody are mixed 1 hours or less prior to administration to the subject. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody are mixed 45 minutes or less prior to administration to the subject. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody are mixed 30 minutes or less prior to administration to the subject. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody and the anti- PD-Ll monoclonal antibody are mixed 15 minutes or less prior to administration to the subject. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody are mixed 10 minutes or less prior to administration to the subject. In some embodiments of any of the above aspects, the anti- TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody are mixed 5 minutes or less prior to administration to the subject. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody are mixed 4 minutes or less prior to administration to the subject. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody are mixed 3 minutes or less prior to administration to the subject. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody are mixed 2 minutes or less prior to administration to the subject. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody are mixed 1 minutes or less prior to administration to the subject.

[0121] In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody are mixed during administration to the subject.

[0122] In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody are administered parenterally. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody and the anti- PD-Ll monoclonal antibody are administered intravenously or subcutaneously. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody and the anti- PD-Ll monoclonal antibody are administered intravenously. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody are administered subcutaneously.

[0123] In some embodiments of any of the above aspects, the anti-PD-Ll monoclonal antibody is administered in a formulation comprising histidine acetate in a concentration of about 15 mM to about 25 mM, sucrose in a concentration of about 200 mM to about 280 mM, polysorbate in a concentration of about 0.04% (w/v) to about 0.08% (w/v), methionine in a concentration of about 5 mM to about 15 mM, and pH of about 5.3 to about 6.0. In some embodiments of any of the above aspects, the anti-PD-Ll monoclonal antibody is administered in a formulation comprising about 20 mM histidine acetate, about 240 mM sucrose, about 0.06% (w/v) polysorbate 20, about 10 mM methionine, and a pH of about 5.8. In some embodiments of any of the above aspects, the anti-PD-Ll monoclonal antibody is administered in a formulation comprising histidine acetate in a concentration of 15 mM to 25 mM, sucrose in a concentration of 200 mM to 280 mM, polysorbate in a concentration of 0.04% (w/v) to 0.08% (w/v), methionine in a concentration of 5 mM to 15 mM, and pH of 5.3 to 6.0. In some embodiments of any of the above aspects, the anti-PD-Ll monoclonal antibody is administered in a formulation comprising 20 mM histidine acetate, 240 mM sucrose, 0.06% (w/v) polysorbate 20, 10 mM methionine, and a pH of 5.8.

[0124] In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody is in a liquid pharmaceutical composition comprising 160 mg/mL tiragolumab and 2000 U/mL hyaluronidase in 20 mM histidine acetate, 240 mM sucrose, 10 mM methionine, 0.06% polysorbate 20, pH 5.5. In some embodiments, the medicament comprises 160 mg/mL tiragolumab and 2000 U/mL hyaluronidase in 20 mM histidine acetate, 240 mM sucrose, 10 mM methionine, 0.06% polysorbate 20, pH 5.5.

[0125] In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody and the anti-PD-Ll are in a liquid pharmaceutical formulation comprising 40 mg/ml tiragolumab, 80 mg/ml atezolizumab, 2000 U/ml hyaluronidase in 20 mM histidine acetate, 240 mM sucrose, 10 mM methionine, 0.06% polysorbate 20, pH 5.8. In some embodiments, medicament comprises 40 mg/ml tiragolumab, 80 mg/ml atezolizumab, 2000 U/ml hyaluronidase in 20 mM histidine acetate, 240 mM sucrose, 10 mM methionine, 0.06% polysorbate 20, pH 5.8.

[0126] Specific anti-TIGIT monoclonal antibody and anti-PD-Ll monoclonal antibody sequences are provided in Table 2.

Table 2: Amino acid sequences.

SEQ ID NO Antibody Ab Region Amino acid sequence

1 Anti-TIGIT HVR-H1 SNSAAWN

2 Anti-TIGIT HVR-H2 KTYYRFKWYSDYAVSVKG

3 Anti-TIGIT HVR-H3 ESTTYDLLAGPFDY

4 Anti-TIGIT HVR-L1 KSSQTVLYSSNNKKYLA

5 Anti-TIGIT HVR-L2 WASTRES

6 Anti-TIGIT HVR-L3 QQYYSTPFT SEQ ID NO Antibody Ab Region Amino acid sequence 7 Anti-TIGIT Heavy chain EVQLQQSGPGLVKPSQTLSLTCAISGDSV variable SSNSAAWNWIRQSPSRGLEWLGKTYYRF region (VH) KWYSD YAVS VKGRITINPDTSKNQF SLQL NSVTPEDTAVFYCTRESTTYDLLAGPFDY WGQGTLVTVSS

8 Anti-TIGIT VH QVQLQQSGPGLVKPSQTLSLTCAISGDSV SSNSAAWNWIRQSPSRGLEWLGKTYYRF KWYSD YAVS VKGRITINPDTSKNQF SLQL NSVTPEDTAVFYCTRESTTYDLLAGPFDY WGQGTLVTVSS

9 Anti-TIGIT Light chain DIVMTQ SPDSL AVSLGERATINCKS SQTV variable L YS SNNKKYL AWYQQKPGQPPNLLIYW region (VL) ASTRESGVPDRFSGSGSGTDFTLTISSLQA EDVAVYYCQQYYSTPFTFGPGTKVEIK

18 Anti-TIGIT Heavy chain EVQLQQSGPGLVKPSQTLSLTCAISGDSV

(no C- SSNSAAWNWIRQSPSRGLEWLGKTYYRF terminal KWYSD YAVS VKGRITINPDTSKNQF SLQL lysine) NSVTPEDTAVFYCTRESTTYDLLAGPFDY WGQGTLVTVSSASTKGPSVFPLAPSSKST SGGTAALGCLVKDYFPEPVTVSWNSGAL TSGVHTFPAVLQSSGLYSLSSVVTVPSSSL GTQTYICNVNHKPSNTKVDKKVEPKSCD KTHTCPPCPAPELLGGPSVFLFPPKPKDTL MISRTPEVTCVVVDVSHEDPEVKFNWYV DGVEVHNAKTKPREEQYNSTYRVVSVLT VLHQDWLNGI<EYI<CI<VSNI<ALPAPIEI<T ISKAKGQPREPQVYTLPPSREEMTKNQVS LTCLVKGFYPSDIAVEWESNGQPENNYK TTPPVLDSDGSFFLYSKLTVDKSRWQQG NVFSCSVMHEALHNHYTQKSLSLSPG

19 Anti-TIGIT Heavy chain EVQLQQSGPGLVKPSQTLSLTCAISGDSV (with C- SSNSAAWNWIRQSPSRGLEWLGKTYYRF terminal KWYSD YAVS VKGRITINPDTSKNQF SLQL lysine) NSVTPEDTAVFYCTRESTTYDLLAGPFDY WGQGTLVTVSSASTKGPSVFPLAPSSKST SGGTAALGCLVKDYFPEPVTVSWNSGAL TSGVHTFPAVLQSSGLYSLSSVVTVPSSSL GTQTYICNVNHKPSNTKVDKKVEPKSCD KTHTCPPCPAPELLGGPSVFLFPPKPKDTL MISRTPEVTCVVVDVSHEDPEVKFNWYV DGVEVHNAKTKPREEQYNSTYRVVSVLT VLHQDWLNGI<EYI<CI<VSNI<ALPAPIEI<T ISKAKGQPREPQVYTLPPSREEMTKNQVS LTCLVKGFYPSDIAVEWESNGQPENNYK TTPPVLDSDGSFFLYSKLTVDKSRWQQG NVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO Antibody Ab Region Amino acid sequence

24 Anti-TIGIT Heavy chain QVQLQQSGPGLVKPSQTLSLTCAISGDSV (EIQ; no C- SSNSAAWNWIRQSPSRGLEWLGKTYYRF terminal KWYSD YAVS VKGRITINPDTSKNQF SLQL lysine) NSVTPEDTAVFYCTRESTTYDLLAGPFDY WGQGTLVTVSSASTKGPSVFPLAPSSKST SGGTAALGCLVKDYFPEPVTVSWNSGAL TSGVHTFPAVLQSSGLYSLSSVVTVPSSSL GTQTYICNVNHKPSNTKVDKKVEPKSCD KTHTCPPCPAPELLGGPSVFLFPPKPKDTL MISRTPEVTCVVVDVSHEDPEVKFNWYV DGVEVHNAKTKPREEQYNSTYRVVSVLT VLHQDWLNGI<EYI<CI<VSNI<ALPAPIEI<T ISKAKGQPREPQVYTLPPSREEMTKNQVS LTCLVKGFYPSDIAVEWESNGQPENNYK TTPPVLDSDGSFFLYSKLTVDKSRWQQG NVFSCSVMHEALHNHYTQKSLSLSPG

Anti-TIGIT Heavy chain QVQLQQSGPGLVKPSQTLSLTCAISGDSV (EIQ; with C- SSNSAAWNWIRQSPSRGLEWLGKTYYRF terminal KWYSD YAVS VKGRITINPDTSKNQF SLQL lysine) NSVTPEDTAVFYCTRESTTYDLLAGPFDY WGQGTLVTVSSASTKGPSVFPLAPSSKST SGGTAALGCLVKDYFPEPVTVSWNSGAL TSGVHTFPAVLQSSGLYSLSSVVTVPSSSL GTQTYICNVNHKPSNTKVDKKVEPKSCD KTHTCPPCPAPELLGGPSVFLFPPKPKDTL MISRTPEVTCVVVDVSHEDPEVKFNWYV DGVEVHNAKTKPREEQYNSTYRVVSVLT VLHQDWLNGI<EYI<CI<VSNI<ALPAPIEI<T ISKAKGQPREPQVYTLPPSREEMTKNQVS LTCLVKGFYPSDIAVEWESNGQPENNYK TTPPVLDSDGSFFLYSKLTVDKSRWQQG NVFSCSVMHEALHNHYTQKSLSLSPGK

20 Anti-TIGIT Light chain DIVMTQ SPDSL AVSLGERATINCKS SQTV L YS SNNKKYL AWYQQKPGQPPNLLIYW ASTRESGVPDRFSGSGSGTDFTLTISSLQA EDVAVYYCQQYYSTPFTFGPGTKVEIKRT VAAPSVFIFPPSDEQLKSGTASVVCLLNN FYPREAKVQWKVDNALQSGNSQESVTE QDSKDSTYSLSSTLTLSKADYEKHKVYA CEVTHQGLSSPVTKSFNRGEC

10 Anti-PD-Ll HVR-H1 GFTFSDSWIH

11 Anti-PD-Ll HVR-H2 AWISPYGGSTYYADSVKG

12 Anti-PD-Ll HVR-H3 RHWPGGFDY

13 Anti-PD-Ll HVR-L1 RASQDVSTAVA

14 Anti-PD-Ll HVR-L2 SASFLYS

15 Anti-PD-Ll HVR-L3 QQYLYHPAT SEQ ID NO Antibody Ab Region Amino acid sequence

16 Anti-PD-Ll VH EVQLVESGGGLVQPGGSLRLSCAASGFTF SDSWMWVRQAPGKGLEWVAWISPYGG STYYADSVKGRFTISADTSKNTAYLQMN SLRAEDTAVYYCARRHWPGGFDYWGQG TLVTVSS

17 Anti-PD-Ll VL DIQMTQSPSSLSASVGDRVTITCRASQDV STAVAWYQQKPGKAPKLLIYSASFLYSG VPSRFSGSGSGTDFTLTISSLQPEDFATYY CQQYLYHPATFGQGTKVEIKR

21 Anti-PD-Ll Heavy chain EVQLVESGGGLVQPGGSLRLSCAASGFTF

(no C- SDSWMWVRQAPGKGLEWVAWISPYGG terminal STYYADSVKGRFTISADTSKNTAYLQMN lysine) SLRAEDTAVYYCARRHWPGGFDYWGQG TLVTVSSASTKGPSVFPLAPSSKSTSGGTA ALGCLVKDYFPEPVTVSWNSGALTSGVH TFP AVLQ S SGL YSLS S VVT VP S S SLGTQT Y ICNVNHKPSNTKVDKKVEPKSCDKTHTC PPCPAPELLGGPSVFLFPPKPKDTLMISRT PEVTCVVVDVSHEDPEVKFNWYVDGVE VHNAKTKPREEQYASTYRVVSVLTVLHQ DWLNGKEYKCKVSNKALPAPIEKTISKA KGQPREPQVYTLPPSREEMTKNQVSLTCL VKGFYPSDIAVEWESNGQPENNYKTTPP VLDSDGSFFLYSKLTVDKSRWQQGNVFS CSVMHEALHNHYTQKSLSLSPG

22 Anti-PD-Ll Heavy chain EVQLVESGGGLVQPGGSLRLSCAASGFTF (with C- SDSWMWVRQAPGKGLEWVAWISPYGG terminal STYYADSVKGRFTISADTSKNTAYLQMN lysine) SLRAEDTAVYYCARRHWPGGFDYWGQG TLVTVSSASTKGPSVFPLAPSSKSTSGGTA ALGCLVKDYFPEPVTVSWNSGALTSGVH TFP AVLQ S SGL YSLS SWT VP S S SLGTQT Y ICNVNHKPSNTKVDKKVEPKSCDKTHTC PPCPAPELLGGPSVFLFPPKPKDTLMISRT PEVTCVVVDVSHEDPEVKFNWYVDGVE VHNAKTKPREEQYASTYRVVSVLTVLHQ DWLNGKEYKCKVSNKALPAPIEKTISKA KGQPREPQVYTLPPSREEMTKNQVSLTCL VKGFYPSDIAVEWESNGQPENNYKTTPP VLDSDGSFFLYSKLTVDKSRWQQGNVFS CSVMHEALHNHYTQKSLSLSPGK SEQ ID NO Antibody Ab Region Amino acid sequence

23 Anti-PD-Ll Light chain DIQMTQSPSSLSASVGDRVTITCRASQDV

STAVAWYQQKPGKAPKLLIYSASFLYSG VPSRFSGSGSGTDFTLTISSLQPEDFATYY CQQYLYHPATFGQGTKVEIKRTVAAPSV FIFPPSDEQLKSGTASVVCLLNNFYPREA KVQWKVDNALQSGNSQESVTEQDSKDS TYSLSSTLTLSKADYEKHKVYACEVTHQ GLSSPVTKSFNRGEC

[0127] It is known in the art that, during the expression and processing of antibodies in a cell culture, C-terminal clipping by carboxypeptidases in the culture medium occurs. In some instances, only the C-terminal lysine residue of the heavy chain is clipped. In other instances, additional residues may be clipped. The sequences provided herein are also intended to encompass variants that occur, e.g., by C-terminal clipping, as a result of the production process.

[0128] It is also known in the art that the C-terminal cleavage process is imprecise and that additional C-terminal residues are cleaved. Accordingly, for each sequence disclosed herein that contains a C-terminal lysine, the corresponding sequence without the two C-terminal residues is also contemplated. In some embodiments, for each sequence disclosed herein that contains a C-terminal lysine, the corresponding sequence without the three C-terminal residues is also contemplated. In some embodiments, for each sequence disclosed herein that contains a C-terminal lysine, the corresponding sequence without the four C-terminal residues is also contemplated. In some embodiments, for each sequence disclosed herein that contains a C-terminal lysine, the corresponding sequence without the five C-terminal residues is also contemplated. In some embodiments, for each sequence disclosed herein that contains a C-terminal lysine, the corresponding sequence without the six C-terminal residues is also contemplated. In some embodiments, for each sequence disclosed herein that contains a C- terminal lysine, the corresponding sequence without the seven C-terminal residues is also contemplated. In some embodiments, for each sequence disclosed herein that contains a C- terminal lysine, the corresponding sequence without the eight C-terminal residues is also contemplated. In some embodiments, for each sequence disclosed herein that contains a C- terminal lysine, the corresponding sequence without the nine C-terminal residues is also contemplated. In some embodiments, for each sequence disclosed herein that contains a C- terminal lysine, the corresponding sequence without the ten C-terminal residues is also contemplated. In some embodiments, for each sequence disclosed herein that contains a C- terminal lysine, the corresponding sequence without the eleven C-terminal residues is also contemplated. In some embodiments, for each sequence disclosed herein that contains a C- terminal lysine, the corresponding sequence without the twelve C-terminal residues is also contemplated. In some embodiments, for each sequence disclosed herein that contains a C- terminal lysine, the corresponding sequence without the thirteen C-terminal residues is also contemplated. In some embodiments, for each sequence disclosed herein that contains a C- terminal lysine, the corresponding sequence without the fourteen C-terminal residues is also contemplated. In some embodiments, for each sequence disclosed herein that contains a C- terminal lysine, the corresponding sequence without the fifteen C-terminal residues is also contemplated.

[0129] In some embodiments, the anti-TIGIT monoclonal antibody is co-mixed with the anti- PD-L1 monoclonal antibody. In some embodiments, the anti-TIGIT monoclonal antibody is subcutaneously co-mixed with the anti-PD-Ll monoclonal antibody. In some embodiments, the anti-TIGIT monoclonal antibody is co-mixed with the anti-PD-Ll monoclonal antibody in the abdomen. In some embodiments, the anti-TIGIT monoclonal antibody is subcutaneously co-mixed with the anti-PD-Ll monoclonal antibody in the abdomen. In some embodiments, the anti-TIGIT monoclonal antibody is co-mixed with the anti-PD-Ll monoclonal antibody in the thigh. In some embodiments, the anti-TIGIT monoclonal antibody is subcutaneously comixed with the anti-PD-Ll monoclonal antibody in the thigh. In some embodiments, administration of the anti-PD-Ll monoclonal antibody is simultaneous with administration of the anti-TIGIT monoclonal antibody. In some embodiments, the anti-TIGIT monoclonal and the anti-PD-Ll monoclonal antibody are co-formulated. In some embodiments, intravenous administration of the anti-PD-Ll monoclonal antibody is sequential to the administration of the anti-TIGIT monoclonal antibody. In some embodiments, administration of the anti-PD-Ll monoclonal antibody is prior to administration of the anti-TIGIT monoclonal antibody. In some embodiments, administration of the anti-PD-Ll monoclonal antibody is subsequent to administration of the anti-TIGIT monoclonal antibody.

[0130] In some embodiments, the anti-TIGIT monoclonal antibody is administered at a frequency selected from the group consisting of Q1W, Q2W, Q3W, Q4W, Q5W and Q6W. In some embodiments, the anti-TIGIT monoclonal antibody is administered at a frequency of Q3W in one or more cycles. In some embodiments, the anti-PD-Ll monoclonal antibody is administered at a frequency of Q3W in one or more cycles. In some embodiments, the anti- PD-Ll monoclonal antibody and the anti-TIGIT monoclonal antibody are independently administered at a frequency of Q3W in one or more cycles. [0131] In some embodiments, 1,000 mg anti-TIGIT monoclonal antibody is co-mixed or coformulated with 1,875 mg or 2,000 mg anti-PD-Ll monoclonal antibody. In some embodiments, 1,000 mg anti-TIGIT monoclonal antibody is co-mixed with 2,000 mg anti-PD- Ll monoclonal antibody. In some embodiments, 1,000 mg anti-TIGIT monoclonal antibody is co-mixed with 1,875 mg anti-PD-Ll monoclonal antibody. In some embodiments, the comixture is administered subcutaneously. In some embodiments, the co-mixture is subcutaneously administered in the thigh. In some embodiments, the co-mixture is subcutaneously administered in the abdomen. In some embodiments, 1,000 mg anti-TIGIT monoclonal antibody is co-mixed with 2,000 mg anti-PD-Ll monoclonal antibody and subcutaneously administered in the abdomen of a subject in need thereof. In some embodiments, 1,000 mg anti-TIGIT monoclonal antibody is co-mixed with 1,875 mg anti-PD- Ll monoclonal antibody and subcutaneously administered in the thigh of a subject in need thereof.

[0132] In some embodiments, following the subcutaneous administration of the co-mixture, 1,200 mg anti-PD-Ll monoclonal antibody and 600 mg anti-TIGIT monoclonal antibody are intravenously administered Q3W. In some embodiments, the intravenous Q3W administration of 1,200 mg anti-PD-Ll monoclonal antibody and 600 mg anti-TIGIT monoclonal antibody begins in Cycle 2 (z.e. after one cycle of subcutaneous administration of the co-mixture). In some embodiments, the intravenous Q3W administration of 1,200 mg anti-PD-Ll monoclonal antibody and 600 mg anti-TIGIT monoclonal antibody begins in Cycle 4 (i.e. after three cycles of subcutaneous administration of the co-mixture). In some embodiments, 1,200 mg anti-PD- Ll monoclonal antibody and 600 mg anti-TIGIT monoclonal antibody are separately administered Q3W intravenously. In some embodiments, 2,000 mg anti-PD-Ll monoclonal antibody and 1,000 mg anti-TIGIT monoclonal antibody are administered Q3W, e.g., as a coformulation described herein. In some embodiments, 2,000 mg anti-PD-Ll monoclonal antibody and 1,000 mg anti-TIGIT monoclonal antibody are intravenously administered Q3W. In some embodiments, 2,000 mg anti-PD-Ll monoclonal antibody and 1,000 mg anti-TIGIT monoclonal antibody are separately administered Q3W intravenously.

[0133] In some embodiments, the liquid pharmaceutical formulation of this disclosure is administered every three weeks (Q3W). In some embodiments, the liquid pharmaceutical formulation of this disclosure is administered at a frequency of Q3W subcutaneously. In some embodiments, the liquid pharmaceutical formulation of this disclosure is administered at a frequency of Q3W intravenously. Articles of Manufacture

[0134] In another aspect, the present disclosure provides an article of manufacture comprising a formulation that comprises 1,000 mg of tiragolumab. In some embodiments, the article of manufacture comprises 1,000 mg of tiragolumab.

[0135] In some embodiments, the formulation further comprises 1,875 mg or 2,000 mg of atezolizumab. In some embodiments, the formulation further comprises 1,875 mg or 2,000 mg of atezolizumab. In some embodiments, the formulation further comprises 1,875 mg of atezolizumab. In some embodiments, the formulation further comprises 2,000 mg of atezolizumab. In some embodiments, the formulation further comprises 2,000 mg of atezolizumab.

[0136] In some embodiments, the formulation further comprises hyaluronidase. In some embodiments, the hyaluronidase is a recombinant human hyaluronidase. In some embodiments, the hyaluronidase is a human soluble PH20 hyaluronidase glycoprotein, such as rHuPH20. In some embodiments, the concentration of the hyaluronidase is 500 U/mL to 2600 U/mL. In some embodiments, the concentration of the hyaluronidase is 1400 U/mL to 2600 U/mL. In some embodiments, the concentration of the hyaluronidase is 2000 U/mL. [0137] In some embodiments, the formulation comprises 160 mg/mL of tiragolumab and 2000 U/mL hyaluronidase in 20 mM histidine acetate, 240 mM sucrose, 10 mM methionine, 0.06% polysorbate 20, pH 5.5. In some embodiments, the comprises 160 mg/mL of tiragolumab and 2000 U/mL hyaluronidase in 20 mM histidine acetate, 240 mM sucrose, 10 mM methionine, 0.06% polysorbate 20, pH 5.5. In some embodiments, the comprises 160 mg/mL of tiragolumab and 2000 U/mL of rHuPH20 in 20 mM histidine acetate, 240 mM sucrose, 10 mM methionine, 0.06% polysorbate 20, pH 5.5.

[0138] In another aspect, the present disclosure provides an article of manufacture comprising a formulation that comprises 1,000 mg of tiragolumab and 1,875 mg or 2,000 mg of atezolizumab. In some embodiments, the formulation comprises 1,000 mg of tiragolumab and 1,875 mg or 2,000 mg of atezolizumab. In some embodiments, the formulation comprises 1,000 mg of tiragolumab and 1,875 mg or 2,000 mg of atezolizumab. In some embodiments, the formulation comprises 1,000 mg of tiragolumab and 1,875 mg or 2,000 mg of atezolizumab.

[0139] In some embodiments, the formulation comprises 1,875 mg of atezolizumab. In some embodiments, the formulation comprises 1,875 mg of atezolizumab. [0140] In some embodiments, the formulation comprises 2,000 mg of atezolizumab. In some embodiments, the formulation comprises 2,000 mg of atezolizumab.

[0141] In some embodiments, the formulation further comprises hyaluronidase. In some embodiments, the concentration of the hyaluronidase is 2000 U/mL. In some embodiments, the hyaluronidase is a recombinant human hyaluronidase. In some embodiments, the recombinant hyaluronidase is a human soluble PH20 hyaluronidase glycoprotein, such as rHuPH20.

[0142] In some embodiments of any of the above aspects, the article of manufacture is a vial. In some embodiments of any of the above aspects, the vial is a single dosage vial. In some embodiments of any of the above aspects, the vial is a 10 cubic centimeter (“10-cc”) vial. In some embodiments of any of the above aspects, the vial is a 15-cc vial. In some embodiments of any of the above aspects, the vial is a 20-cc vial. In some embodiments of any of the above aspects, the vial is a 25-cc vial. In some embodiments of any of the above aspects, the vial is a 30-cc vial. In some embodiments of any of the above aspects, the vial is a 35-cc vial. In some embodiments of any of the above aspects, the vial is a 40-cc vial. In some embodiments of any of the above aspects, the vial is a 45-cc vial. In some embodiments of any of the above aspects, the vial is a 50-cc vial. In some embodiments of any of the above aspects, the vial is a glass vial. In some embodiments of any of the above aspects, the vial is a plastic vial.

[0143] In some embodiments of any of the above aspects, the vial is stoppered with a chlorobutyl elastomer stopper. In some embodiments of any of the above aspects, the stopper is a D21-7S stopper. Without being bound by theory, the D21-7S stopper leads to reduced particle formation in the liquid pharmaceutical formulation. In some embodiments of any of the above aspects, the D21-7S stopper has a thinner stopper septum.

[0144] In some embodiments of any of the above aspects, the article of manufacture is a pre-filled syringe. In some embodiments of any of the above aspects, the pre-filled syringe is a 10-cc pre-filled syringe. In some embodiments of any of the above aspects, the pre-filled syringe is a 15-cc pre-filled syringe. In some embodiments of any of the above aspects, the pre-filled syringe is a 20-cc pre-filled syringe. In some embodiments of any of the above aspects, the pre-filled syringe is a 25-cc pre-filled syringe. In some embodiments of any of the above aspects, the pre-filled syringe is a 30-cc pre-filled syringe. In some embodiments of any of the above aspects, the pre-filled syringe is a 35-cc pre-filled syringe. In some embodiments of any of the above aspects, the pre-filled syringe is a 40-cc pre-filled syringe. In some embodiments of any of the above aspects, the pre-filled syringe is a 45-cc pre-filled syringe. In some embodiments of any of the above aspects, the pre-filled syringe is a 50-cc pre-filled syringe.

[0145] In some embodiments of any of the above aspects, the article of manufacture is a syringe pump. In some embodiments of any of the above aspects, the article of manufacture is a subcutaneous administration device. In some embodiments of any of the above aspects, the subcutaneous administration device is selected from the group consisting of a syringe, a syringe pump, an injection device, an infusion pump, an injector pen, a needleless device, an autoinjector, and a subcutaneous patch delivery system. In some embodiments of any of the above aspects, the subcutaneous administration device is a syringe. In some embodiments of any of the above aspects, the subcutaneous administration device is a syringe pump. In some embodiments of any of the above aspects, the subcutaneous administration device is an injection device. In some embodiments of any of the above aspects, the subcutaneous administration device is an infusion pump. In some embodiments of any of the above aspects, the subcutaneous administration device is an injector pen. In some embodiments of any of the above aspects, the subcutaneous administration device is a needleless device. In some embodiments of any of the above aspects, the subcutaneous administration device is an autoinjector. In some embodiments of any of the above aspects, the subcutaneous administration device is a subcutaneous patch delivery system.

[0146] In another aspect, the present disclosure provides an article of manufacture comprising a subcutaneous administration device, which contains and delivers to a patient a 1,000 mg fixed dose of tiragolumab. In some embodiments, the subcutaneous administration device contains and delivers to a patient a 1,000 mg fixed dose of tiragolumab.

[0147] In some embodiments, the subcutaneous administration device further contains and delivers to the patient an 1,875 mg or 2,000 mg fixed dose of atezolizumab. In some embodiments, the subcutaneous administration device further contains and delivers to the patient an 1,875 mg or 2,000 mg fixed dose of atezolizumab. In some embodiments, the subcutaneous administration device further contains and delivers to the patient an 1,875 mg fixed dose of atezolizumab. In some embodiments, the subcutaneous administration device further contains and delivers to the patient an 1,875 mg fixed dose of atezolizumab. In some embodiments, the subcutaneous administration device further contains and delivers to the patient a 2,000 mg fixed dose of atezolizumab. In some embodiments, the subcutaneous administration device further contains and delivers to the patient a 2,000 mg fixed dose of atezolizumab. [0148] In some embodiments, the subcutaneous administration device further contains and delivers to the patient hyaluronidase. In some embodiments, the concentration of the hyaluronidase is 2000 U/mL. In some embodiments, the hyaluronidase is a recombinant human hyaluronidase. In some embodiments, the hyaluronidase is a human soluble PH20 hyaluronidase glycoprotein, such as rHuPH20.

[0149] In some embodiments, the subcutaneous administration device is selected from the group consisting of a syringe, a syringe pump, an injection device, an infusion pump, an injector pen, a needleless device, an autoinjector, and a subcutaneous patch delivery system. In some embodiments, the subcutaneous administration device is a syringe. In some embodiments, the subcutaneous administration device is a syringe pump. In some embodiments, the subcutaneous administration device is selected from the group consisting of an injection device. In some embodiments, the subcutaneous administration device is selected from the group consisting of an infusion pump. In some embodiments, the subcutaneous administration device is selected from the group consisting of an injector pen. In some embodiments, the subcutaneous administration device is selected from the group consisting of a needleless device. In some embodiments, the subcutaneous administration device is selected from the group consisting of an autoinjector. In some embodiments, the subcutaneous administration device is selected from the group consisting of a subcutaneous patch delivery system.

[0150] In some embodiments of any of the above aspects, the article of manufacture comprises about 3 mL to about 60 mL of tiragolumab, and one or more of hyaluronidase, a histidine buffer, sucrose, and polysorbate 20. In some embodiments of any of the above aspects, the article of manufacture comprises about 10 mL of tiragolumab, and one or more of hyaluronidase, a histidine buffer, sucrose, and polysorbate 20. In some embodiments of any of the above aspects, the article of manufacture comprises about 7 mL of tiragolumab, and one or more of hyaluronidase, a histidine buffer, sucrose, and polysorbate 20. In some embodiments of any of the above aspects, the article of manufacture comprises about 6.5 mL of tiragolumab, and one or more of hyaluronidase, a histidine buffer, sucrose, and polysorbate 20. In some embodiments of any of the above aspects, the article of manufacture comprises about 21 mL of tiragolumab, and one or more of hyaluronidase, a histidine buffer, sucrose, and polysorbate 20.

[0151] In some embodiments of any of the above aspects, the article of manufacture comprises about 3 mL to about 30 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 3 mL to about 25 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 3 mL to about 20 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 4 mL to about 25 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 4 mL to about 22 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 4 mL to about 20 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 4 mL to about 18 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 4 mL to about 16 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 4 mL to about 14 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 4 mL to about 12 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 4 mL to about 10 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 4 mL to about 8 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 5 mL to about 7 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 5 mL to about 8 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 5 mL to about 10 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 5 mL to about 21 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 5.5 mL to about 7.5 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 6 mL to about 8 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 6 mL to about 10 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 6 mL to about 12 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 8 mL to about 12 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 9 mL to about 11 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 15 mL to about 30 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 18 mL to about 30 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 18 mL to about 28 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 18 mL to about 26 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 18 mL to about 24 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 19 mL to about 23 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 20 mL to about 22 mL of the formulation.

[0152] In some embodiments of any of the above aspects, the article of manufacture comprises about 3 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 3.5 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 4 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 4.5 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 5 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 5.5 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 6 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 6.5 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 7 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 7.5 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 8 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 8.5 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 9 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 9.5 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 10 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 10.5 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 11 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 11.5 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 12 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 12.5 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 13 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 13.5 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 14 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about

14.5 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 15 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 15.5 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 16 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 16.5 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 17 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about

17.5 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 18 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 18.5 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 19 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 19.5 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 20 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 21 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 22 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 23 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 24 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 25 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 26 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 27 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 28 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 29 mL of the formulation. In some embodiments of any of the above aspects, the article of manufacture comprises about 30 mL of the formulation. [0153] In some embodiments of any of the above aspects, the article of manufacture comprises 3 mL to 30 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 3 mL to 25 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 3 mL to 20 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 4 mL to 25 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 4 mL to 22 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 4 mL to 20 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 4 mL to 18 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 4 mL to 16 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 4 mL to 14 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 4 mL to 12 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 4 mL to 10 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 4 mL to 8 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 5 mL to 7 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 5 mL to 8 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 5 mL to 10 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 5 mL to 21 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 5.5 mL to 7.5 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 6 mL to 8 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 6 mL to 10 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 6 mL to 12 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 8 mL to 12 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 9 mL to 11 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 15 mL to 30 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 18 mL to 30 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 18 mL to 28 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 18 mL to 26 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 18 mL to 24 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 19 mL to 23 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 20 mL to 22 mL of the formulation. [0154] In some embodiment of any of the above aspects, the article of manufacture comprises 3 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 3.5 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 4 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 4.5 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 5 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 5.5 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 6 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 6.5 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 7 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 7.5 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 8 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 8.5 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 9 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 9.5 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 10 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 10.5 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 11 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 11.5 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 12 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 12.5 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 13 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 13.5 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 14 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 14.5 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 15 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 15.5 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 16 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 16.5 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 17 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 17.5 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 18 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 18.5 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 19 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 19.5 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 20 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 21 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 22 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 23 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 24 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 25 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 26 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 27 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 28 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 29 mL of the formulation. In some embodiment of any of the above aspects, the article of manufacture comprises 30 mL of the formulation.

[0155] In another aspect, the present disclosure provides an article of manufacture comprising a formulation suitable for subcutaneous injection comprising: (a) 1000 mg of an anti-TIGIT monoclonal antibody, (b) 1875 mg or 2000 mg of an anti-PD-Ll monoclonal antibody, (c) 5 mM to 30 mM of a histidine buffer, (d) 180 mM to 320 mM of sucrose, (e) 0.03 % (w/v) to 0.08 % (w/v) polysorbate 20, (f) 500 U/mL to 2600 U/mL hyaluronidase, pH of about 5.2-6.1; wherein the anti-TIGIT monoclonal antibody comprises a heavy chain variable region comprising a HVR-H1 comprising the amino acid sequence of SEQ ID NO: 1; a HVR-H2 comprising the amino acid sequence of SEQ ID NO: 2; and a HVR-H3 comprising the amino acid sequence of SEQ ID NO: 3; and a light chain variable region comprising a HVR-L1 comprising the amino acid sequence of SEQ ID NO: 4; a HVR-L2 comprising the amino acid sequence of SEQ ID NO: 5; and a HVR-L3 comprising the amino acid sequence of SEQ ID NO: 6; and wherein the anti-PD-Ll monoclonal antibody comprises a heavy chain variable region comprising a HVR-H1 comprising the amino acid sequence of SEQ ID NO: 10; a HVR-H2 comprising the amino acid sequence of SEQ ID NO: 11; and a HVR-H3 comprising the amino acid sequence of SEQ ID NO: 12; and a light chain variable region comprising a HVR-L1 comprising the amino acid sequence of SEQ ID NO: 13; a HVR-L2 comprising the amino acid sequence of SEQ ID NO: 14; and a HVR-L3 comprising the amino acid sequence of SEQ ID NO: 15. In some embodiments, the article of manufacture comprises a formulation comprising: (a) 1000 mg of an anti-TIGIT monoclonal antibody, (b) 1875 mg or 2000 mg of an anti-PD-Ll monoclonal antibody, (c) 15 mM to 25 mM of a histidine buffer, (d) 200 mM to 280 mM of sucrose, (e) 0.04 % (w/v) to 0.08 % (w/v) polysorbate 20, (f) 1400 U/mL to 2600 U/mL hyaluronidase, pH of about 5.5-5.8. In some embodiments, the article of manufacture comprises a formulation suitable for subcutaneous injection comprising: (a) 1000 mg of an anti-TIGIT monoclonal antibody, (b) 1875 mg or 2000 mg of an anti-PD-Ll monoclonal antibody, (c) 15 mM to 25 mM of a histidine buffer, (d) 200 mM to 280 mM of sucrose, (e) 0.04 % (w/v) to 0.08 % (w/v) polysorbate 20, (f) 1400 U/mL to 2600 U/mL hyaluronidase, pH of about 5.5-5.8. In some embodiments, the article of manufacture comprises a formulation suitable for subcutaneous injection comprising: (a) 1000 mg of an anti-TIGIT monoclonal antibody, (b) 1875 mg of an anti-PD-Ll monoclonal antibody, (c) 15 mM to 25 mM of a histidine buffer, (d) 200 mM to 280 mM of sucrose, (e) 0.04 % (w/v) to 0.08 % (w/v) polysorbate 20, (f) 1400 U/mL to 2600 U/mL hyaluronidase, pH of about 5.5-5.8. In some embodiments, the article of manufacture comprises a formulation suitable for subcutaneous injection comprising: (a) 1000 mg of an anti-TIGIT monoclonal antibody, (b) 2000 mg of an anti-PD-Ll monoclonal antibody, (c) 15 mM to 25 mM of a histidine buffer, (d) 200 mM to 280 mM of sucrose, (e) 0.04 % (w/v) to 0.08 % (w/v) polysorbate 20, (f) 1400 U/mL to 2600 U/mL hyaluronidase, pH of about 5.5- 5.8.

[0156] In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 7. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 8. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody comprises a VL comprising the amino acid sequence of SEQ ID NO: 9. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 7 and a VL comprising the amino acid sequence of SEQ ID NO: 9. In some embodiments of any of the above aspects, the heavy chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 18. In some embodiments of any of the above aspects, the heavy chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 19. In some embodiments of any of the above aspects, the heavy chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 24. In some embodiments of any of the above aspects, the heavy chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 25. In some embodiments of any of the above aspects, the light chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 20. In some embodiments of any of the above aspects, the heavy chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 18 and the light chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 20. In some embodiments of any of the above aspects, the heavy chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 19 and the light chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 20. In some embodiments of any of the above aspects, the heavy chain of the anti- TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 24 and the light chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 20. In some embodiments of any of the above aspects, the heavy chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 25 and the light chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 20. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody is a full-length antibody. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody is a full-length IgG antibody. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody is a full- length IgGl antibody. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody is a full-length human IgGl antibody. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody is a full-length humanized IgGl antibody. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody retains one or more effector functions. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody retains all effector functions. In some embodiments of any of the above aspects, one or more effector functions of the anti-TIGIT monoclonal antibody may have been modified or eliminated. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody is tiragolumab. Tiragolumab is described in WHO Drug Information (International Nonproprietary Names for Pharmaceutical Substances), Proposed INN: List 117, Vol. 31, No. 2, published June 9, 2017 (see p. 343). In some embodiments, tiragolumab has the CAS Registry Number 1918185-84- 8. The anti-TIGIT monoclonal antibody may be an antibody fragment.

[0157] In some embodiments of any of the above aspects, the anti-PD-Ll monoclonal antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 16. In some embodiments of any of the above aspects, the anti-PD-Ll monoclonal antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 16. In some embodiments of any of the above aspects, the anti-PD-Ll monoclonal antibody comprises a VL comprising the amino acid sequence of SEQ ID NO: 17. In some embodiments of any of the above aspects, the anti-PD-Ll monoclonal antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 16 and a VL comprising the amino acid sequence of SEQ ID NO: 17. In some embodiments of any of the above aspects, the heavy chain of the anti-PD-Ll monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 21. In some embodiments of any of the above aspects, the heavy chain of the anti-PD-Ll monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 22. In some embodiments of any of the above aspects, the light chain of the anti-PD-Ll monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 23. In some embodiments of any of the above aspects, the heavy chain of the anti-PD-Ll monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 21, and the light chain of the anti-PD-Ll monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 23. In some embodiments of any of the above aspects, the heavy chain of the anti-PD-Ll monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 22, and the light chain of the anti-PD-Ll monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 23. In some embodiments of any of the above aspects, the anti-PD- Ll monoclonal antibody is a full-length antibody. In some embodiments, the anti-PD-Ll monoclonal antibody is a full-length IgG antibody. In some embodiments, the anti-PD-Ll monoclonal antibody is a full-length IgGl antibody. In some embodiments, the anti-PD-Ll monoclonal antibody is a full-length human IgGl antibody. In some embodiments, the anti- PD-Ll monoclonal antibody is a full-length humanized IgGl antibody. In some embodiments of any of the above aspects, the anti-PD-Ll monoclonal antibody retains one or more effector functions. In some embodiments of any of the above aspects, the anti-PD-Ll monoclonal antibody retains all effector functions. In some embodiments of any of the above aspects, one or more effector functions of the anti-PD-Ll monoclonal antibody may have been modified or eliminated. The anti-PD-Ll monoclonal antibody may be an antibody fragment. In some embodiments, the anti-PD-Ll monoclonal antibody is atezolizumab. In some embodiments, the anti-PD-Ll monoclonal antibody is atezolizumab, marketed as TECENTRIQ™. Atezolizumab is described in WHO Drug Information (International Nonproprietary Names for Pharmaceutical Substances), Proposed INN: List 112, Vol. 28, No. 4, 2014 (see page 488). In some embodiments, atezolizumab has the CAS Registry Number 1380723-44-3.

[0158] In another aspect, the present disclosure provides an article of manufacture comprising a formulation suitable for subcutaneous injection comprising: (a) about 1,000 mg of tiragolumab, (b) about 1875 mg or about 2000 mg of atezolizumab, (c) about 20 mM of histidine acetate, (d) about 240 mM of sucrose, (e) about 10 mM methionine, (f) about 0.06 % (w/v) polysorbate 20, and (g) about 2000 U/mL hyaluronidase, with a pH of about 5.8. In some embodiments, the article of manufacture comprises a formulation suitable for subcutaneous injection comprising: (a) about 1,000 mg of tiragolumab, (b) about 1875 mg or about 2000 mg of atezolizumab, (c) about 20 mM of histidine acetate, (d) about 240 mM of sucrose, (e) about 10 mM methionine, (f) about 0.06 % (w/v) polysorbate 20, and (g) about 2000 U/mL hyaluronidase, with a pH of about 5.8.

[0159] In some embodiments, the article of manufacture comprises a formulation suitable for subcutaneous injection comprising: (a) about 1,000 mg of tiragolumab, (b) about 1875 mg or about 2000 mg of atezolizumab, (c) about 20 mM of histidine acetate, (d) about 240 mM of sucrose, (e) about 10 mM methionine, (f) about 0.06 % (w/v) polysorbate 20, and (g) about 2000 U/mL hyaluronidase, with a pH of about 5.8.

[0160] In some embodiments, the article of manufacture comprises a formulation suitable for subcutaneous injection comprising: (a) about 1,000 mg of tiragolumab, (b) about 1875 mg of atezolizumab, (c) about 20 mM of histidine acetate, (d) about 240 mM of sucrose, (e) about 10 mM methionine, (f) about 0.06 % (w/v) polysorbate 20, and (g) about 2000 U/mL hyaluronidase, with a pH of about 5.8.

[0161] In some embodiments, the article of manufacture comprises a formulation suitable for subcutaneous injection comprising: (a) about 1,000 mg of tiragolumab, (b) about 2000 mg of atezolizumab, (c) about 20 mM of histidine acetate, (d) about 240 mM of sucrose, (e) about 10 mM methionine, (f) about 0.06 % (w/v) polysorbate 20, and (g) about 2000 U/mL hyaluronidase, with a pH of about 5.8.

[0162] In some embodiments, the article of manufacture comprises a formulation suitable for subcutaneous injection comprising: (a) 1,000 mg of tiragolumab, (b) 1875 mg or 2000 mg of atezolizumab, (c) 20 mM of histidine acetate, (d) 240 mM of sucrose, (e) 10 mM methionine, (f) 0.06 % (w/v) polysorbate 20, and (g) 2000 U/mL hyaluronidase, with a pH of 5.8.

[0163] In some embodiments, the article of manufacture comprises a formulation suitable for subcutaneous injection comprising: (a) 1,000 mg of tiragolumab, (b) 1875 mg of atezolizumab, (c) 20 mM of histidine acetate, (d) 240 mM of sucrose, (e) 10 mM methionine,

(f) 0.06 % (w/v) polysorbate 20, and (g) 2000 U/mL hyaluronidase, with a pH of 5.8.

[0164] In some embodiments, the article of manufacture comprises a formulation suitable for subcutaneous injection comprising: (a) 1,000 mg of tiragolumab, (b) 2000 mg of atezolizumab, (c) 20 mM of histidine acetate, (d) 240 mM of sucrose, (e) 10 mM methionine, (f) 0.06 % (w/v) polysorbate 20, and (g) 2000 U/mL hyaluronidase, with a pH of 5.8. [0165] In some embodiments of any of the above aspects, the article of manufacture comprises a subcutaneous administration device. In some embodiments, the subcutaneous administration device is selected from the group consisting of a syringe, a syringe pump, an injection device, an infusion pump, an injector pen, a needleless device, an autoinjector, and a subcutaneous patch delivery system. In some embodiments, the subcutaneous administration device is a syringe. In some embodiments, the subcutaneous administration device is a syringe pump. In some embodiments, the subcutaneous administration device is an injection device. In some embodiments, the subcutaneous administration device is an infusion pump. In some embodiments, the subcutaneous administration device is an injector pen. In some embodiments, the subcutaneous administration device is a needleless device. In some embodiments, the subcutaneous administration device is an autoinjector. In some embodiments, the subcutaneous administration device is a subcutaneous patch delivery system. In some embodiments, the subcutaneous administration device is a pre-filled syringe.

[0166] In some embodiments of any of the above aspects, the formulation contained in the article of manufacture is a formulation of this disclosure. In some embodiments of any of the above aspects, the article of manufacture contains a formulation of this disclosure. Pharmaceutical Formulations

[0167] In another aspect, the present disclosure provides a liquid pharmaceutical formulation comprising 160 mg/mL of tiragolumab and 2000 U/mL hyaluronidase in 20 mM histidine acetate, 240 mM sucrose, 10 mM methionine, 0.06% polysorbate 20, pH 5.5. In some embodiments, the comprises 160 mg/mL of tiragolumab and 2000 U/mL hyaluronidase in 20 mM histidine acetate, 240 mM sucrose, 10 mM methionine, 0.06% polysorbate 20, pH 5.5. In some embodiments, the comprises 160 mg/mL of tiragolumab and 2000 U/mL of rHuPH20 in 20 mM histidine acetate, 240 mM sucrose, 10 mM methionine, 0.06% polysorbate 20, pH 5.5.

[0168] In another aspect, the present disclosure provides a liquid pharmaceutical formulation comprising 40 mg/ml of tiragolumab, 80 mg/ml of atezolizumab, 2000 U/ml hyaluronidase in 20 mM histidine acetate, 240 mM sucrose, 10 mM methionine, 0.06% polysorbate 20, pH 5.8. In some embodiments, the formulation comprises 40 mg/ml of tiragolumab, 80 mg/ml of atezolizumab, 2000 U/ml hyaluronidase in 20 mM histidine acetate, 240 mM sucrose, 10 mM methionine, 0.06% polysorbate 20, pH 5.8.

[0169] In some embodiments, the formulation comprises 40 mg/ml of tiragolumab, 80 mg/ml of atezolizumab, 2000 U/ml rHuPH20 in 20 mM histidine acetate, 240 mM sucrose, 10 mM methionine, 0.06% polysorbate 20, pH 5.8.

EXEMPLARY EMBODIMENTS

[0170] Particular embodiments of the disclosure are set forth in the following numbered paragraphs:

1. A method of treating cancer in a subject in need thereof comprising subcutaneously administering to the subject a dose of an anti-TIGIT monoclonal antibody of about 1,000 mg; wherein the anti-TIGIT monoclonal antibody is a full-length antibody comprising a heavy chain variable region comprising a HVR-H1 comprising the amino acid sequence of SEQ ID NO: 1; a HVR-H2 comprising the amino acid sequence of SEQ ID NO: 2; and a HVR-H3 comprising the amino acid sequence of SEQ ID NO: 3; and a light chain variable region comprising a HVR-L1 comprising the amino acid sequence of SEQ ID NO: 4; a HVR-L2 comprising the amino acid sequence of SEQ ID NO: 5; and a HVR-L3 comprising the amino acid sequence of SEQ ID NO: 6.

2. Use of about 1,000 mg of an anti-TIGIT monoclonal antibody in the manufacture of a medicament for treating cancer in a subject in need thereof; wherein the medicament is formulated for subcutaneous administration, and wherein the anti-TIGIT monoclonal antibody is a full-length antibody comprising a heavy chain variable region comprising a HVR-H1 comprising the amino acid sequence of SEQ ID NO: 1; a HVR-H2 comprising the amino acid sequence of SEQ ID NO: 2; and a HVR-H3 comprising the amino acid sequence of SEQ ID NO: 3; and a light chain variable region comprising a HVR-L1 comprising the amino acid sequence of SEQ ID NO: 4; a HVR-L2 comprising the amino acid sequence of SEQ ID NO: 5; and a HVR-L3 comprising the amino acid sequence of SEQ ID NO: 6.

3. An anti-TIGIT monoclonal antibody for use in treating cancer in a subject in need thereof, wherein the anti-TIGIT monoclonal antibody is a full-length antibody comprising a heavy chain variable region comprising a HVR-H1 comprising the amino acid sequence of SEQ ID NO: 1; a HVR-H2 comprising the amino acid sequence of SEQ ID NO: 2; and a HVR-H3 comprising the amino acid sequence of SEQ ID NO: 3; and a light chain variable region comprising a HVR-L1 comprising the amino acid sequence of SEQ ID NO: 4; a HVR- L2 comprising the amino acid sequence of SEQ ID NO: 5; and a HVR-L3 comprising the amino acid sequence of SEQ ID NO: 6 and is subcutaneously administered at a dose of about 1,000 mg.

4. The method according to embodiment 1, the use according to embodiment 2, or anti- TIGIT monoclonal antibody according to embodiment 3, wherein the anti-TIGIT monoclonal antibody is administered in the thigh or the abdomen.

5. The method according to embodiment 1 or 4, the use according to embodiment 2 or 4, or the anti-TIGIT monoclonal antibody according to embodiment 3 or 4, wherein the anti- TIGIT monoclonal antibody is administered every three weeks (Q3W).

6. A method of treating cancer in a subject in need thereof comprising subcutaneously administering to the subject a dose of an anti-TIGIT monoclonal antibody of about 1,000 mg and administering to the subject about 1,875 mg to about 2,000 mg of an anti-PD-Ll monoclonal antibody; wherein the anti-TIGIT monoclonal antibody is a full-length antibody comprising a heavy chain variable region comprising a HVR-H1 comprising the amino acid sequence of SEQ ID NO: 1; a HVR-H2 comprising the amino acid sequence of SEQ ID NO: 2; and a HVR-H3 comprising the amino acid sequence of SEQ ID NO: 3; and a light chain variable region comprising a HVR-L1 comprising the amino acid sequence of SEQ ID NO: 4; a HVR-L2 comprising the amino acid sequence of SEQ ID NO: 5; and a HVR-L3 comprising the amino acid sequence of SEQ ID NO: 6; and wherein the anti-PD-Ll monoclonal antibody is a full-length antibody comprising a heavy chain variable region comprising a HVR-H1 comprising the amino acid sequence of SEQ ID NO: 10; a HVR-H2 comprising the amino acid sequence of SEQ ID NO: 11; and a HVR-H3 comprising the amino acid sequence of SEQ ID NO: 12; and a light chain variable region comprising a HVR-L1 comprising the amino acid sequence of SEQ ID NO: 13; a HVR-L2 comprising the amino acid sequence of SEQ ID NO: 14; and a HVR-L3 comprising the amino acid sequence of SEQ ID NO: 15.

7. Use of about 1,000 mg of an anti-TIGIT monoclonal antibody and about 1,875 mg to about 2,000 mg of an anti-PD-Ll monoclonal antibody in the manufacture of a medicament for treating cancer in a subject in need thereof; wherein the medicament is formulated for subcutaneous administration, and wherein the anti-TIGIT monoclonal antibody is a full- length antibody comprising a heavy chain variable region comprising a HVR-H1 comprising the amino acid sequence of SEQ ID NO: 1; a HVR-H2 comprising the amino acid sequence of SEQ ID NO: 2; and a HVR-H3 comprising the amino acid sequence of SEQ ID NO: 3; and a light chain variable region comprising a HVR-L1 comprising the amino acid sequence of SEQ ID NO: 4; a HVR-L2 comprising the amino acid sequence of SEQ ID NO: 5; and a HVR-L3 comprising the amino acid sequence of SEQ ID NO: 6; and wherein the anti-PD-Ll monoclonal antibody is a full-length antibody comprising a heavy chain variable region comprising a HVR-H1 comprising the amino acid sequence of SEQ ID NO: 10; a HVR-H2 comprising the amino acid sequence of SEQ ID NO: 11; and a HVR-H3 comprising the amino acid sequence of SEQ ID NO: 12; and a light chain variable region comprising a HVR-L1 comprising the amino acid sequence of SEQ ID NO: 13; a HVR-L2 comprising the amino acid sequence of SEQ ID NO: 14; and a HVR-L3 comprising the amino acid sequence of SEQ ID NO: 15.

8. An anti-TIGIT monoclonal antibody and an anti-PD-Ll monoclonal antibody for use in treating cancer in a subject in need thereof, wherein the anti-TIGIT monoclonal antibody is a full-length antibody comprising a heavy chain variable region comprising a HVR-H1 comprising the amino acid sequence of SEQ ID NO: 1; a HVR-H2 comprising the amino acid sequence of SEQ ID NO: 2; and a HVR-H3 comprising the amino acid sequence of SEQ ID NO: 3; and a light chain variable region comprising a HVR-L1 comprising the amino acid sequence of SEQ ID NO: 4; a HVR-L2 comprising the amino acid sequence of SEQ ID NO: 5; and a HVR-L3 comprising the amino acid sequence of SEQ ID NO: 6 and is subcutaneously administered at a dose of about 1,000 mg; and wherein the anti-PD-Ll monoclonal antibody is a full-length antibody comprising a heavy chain variable region comprising a HVR-H1 comprising the amino acid sequence of SEQ ID NO: 10; a HVR-H2 comprising the amino acid sequence of SEQ ID NO: 11; and a HVR-H3 comprising the amino acid sequence of SEQ ID NO: 12; and a light chain variable region comprising a HVR-L1 comprising the amino acid sequence of SEQ ID NO: 13; a HVR-L2 comprising the amino acid sequence of SEQ ID NO: 14; and a HVR-L3 comprising the amino acid sequence of SEQ ID NO: 15 and is administered at a dose of about 1,875 mg to about 2,000 mg.

9. The method according to embodiment 6, the use according to embodiment 7 or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to embodiment 8, wherein the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody, are administered simultaneously.

10. The method according to embodiment 6 or 9, the use according to embodiment 7 or 9, or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to embodiment 8 or 9, wherein the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody are co-formulated.

11. The method according to embodiment 6 or 9, the use according to embodiment 7 or 9, or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to embodiment 8 or 9, wherein the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody are mixed 24 hours or less prior to administration to the subject.

12. The method, the use or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to embodiment 11, wherein the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody are mixed during administration to the subject.

13. The method according to embodiment 6, the use according to embodiment 7 or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to embodiment 8, wherein the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody, are administered sequentially.

14. The method according to any one of any one of embodiments 6 and 9-13, the use according to any one of embodiments 7 and 9-13 or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to any one of embodiments 8-13, wherein the anti-PD-Ll monoclonal antibody is administered intravenously.

15. The method according to any one of any one of embodiments 6 and 9-13, the use according to any one of embodiments 7 and 9-13 or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to any one of embodiments 8-13, wherein the anti-PD-Ll monoclonal antibody is administered subcutaneously.

16. The method according to any one of embodiments 6 and 9-15, the use according to any one of embodiments 7 and 9-15 or the anti-TIGIT monoclonal antibody and the anti-PD- LI monoclonal antibody according to any one of embodiments 8-15, wherein the anti-TIGIT monoclonal antibody is administered every three weeks (Q3W).

17. The method according to any one of embodiments 1, 4-6 and 9-16, the use according to any one of embodiments 2, 4, 5, 7, and 9-16, the anti-TIGIT monoclonal antibody according to any one of embodiments 3-5 or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to any one of embodiments 8-16, wherein the cancer is selected from the group consisting of a lung cancer, a non-small cell lung cancer, a renal cell cancer, a urothelial cancer, a ureter cancer, a urethral cancer, a colorectal cancer, a colon cancer, a rectal cancer, a kidney cancer, a sarcoma, an ovarian cancer, a breast cancer, a cervical cancer, a fallopian tube cancer, an endometrial cancer, a uterine cancer, a pancreatic cancer, a gastric carcinoma, a bladder cancer, an esophageal cancer, a mesothelioma, a melanoma, a head and neck cancer, a thyroid cancer, a sarcoma, a prostate cancer, a penile cancer, a glioblastoma, a thymic carcinoma, an esophageal carcinoma, a nasopharyngeal cancer, a mesothelioma, a liver cancer, a biliary tract cancer, a HPV-positive cancer, a leukemia, a lymphoma, a brain cancer, a neuroendocrine cancer, a myeloma, a mycosis fungoides, a Merkel cell cancer, a hematologic malignancy, a deficient mismatch repair (dMMR) cancer, and a microsatellite instability-high (MSI-H) cancer.

18. The method according to any one of embodiments 1, 4-6 and 9-16, the use according to any one of embodiments 2, 4, 5, 7, and 9-16, the anti-TIGIT monoclonal antibody according to any one of embodiments 3-5 or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to any one of embodiments 8-16, wherein the cancer is selected from the group consisting of a bladder cancer, a muscle-invasive bladder cancer, a urothelial carcinoma, a ureter cancer, a urethral cancer, a ureter urothelial carcinoma, a urethral urothelial carcinoma, a renal cancer, a renal pelvis cancer, a renal cell carcinoma, a clear-cell renal carcinoma, a rectal cancer, a colon cancer, a colorectal cancer, a sarcoma, an osteosarcoma, a leiomyosarcoma, a pleomorphic sarcoma, a myxofibrosarcoma, a liposarcoma, a chondrosarcoma, a lung cancer, a non-small cell lung cancer, a fallopian tube cancer, a peritoneal carcinoma, an esophageal cancer, an esophageal squamous cell carcinoma, a mesothelioma, a pleural mesothelioma, a peritoneal mesothelioma, an ovarian cancer, a cervical cancer, a cervical adenosquamous carcinoma, a breast cancer, a triplenegative breast cancer, a HER2 -positive breast cancer, a HER2-negative breast cancer, an estrogen receptor-positive breast cancer, a progesterone receptor-positive breast cancer, a luminal B breast cancer, a lymphoma, a T-cell lymphoma, a B-cell lymphoma, a nasal -type lymphoma, non-Hodgkin’s lymphoma, a follicular lymphoma, a penile carcinoma, a prostate cancer, a castration-resistant prostate cancer, an endometrial cancer, a uterine cancer, a myeloma, a multiple myeloma, a head and neck cancer, a prostate cancer, a melanoma, a cutaneous melanoma, a Merkel cell carcinoma, a pancreatic cancer, hepatocellular carcinoma, gastric cancer, a gastroesophageal junction adenocarcinoma, a glioblastoma, a glioblastoma multiforme, a mycosis fungoides, an HPV-positive cancer, a HPV-related cervical carcinoma, a HPV-related anal squamous cell carcinoma, a HPV-related penile squamous cell carcinoma, a HPV-related vulvar squamous cell carcinoma, a vulvar cancer, a vaginal cancer, an anal cancer, an oropharyngeal cancer, an oropharyngeal squamous cell carcinoma, a leukemia, an acute myeloid leukemia, a bone cancer, a solitary bone plasmacytoma, a squamous cell carcinoma, a cutaneous squamous cell carcinoma, a thyroid cancer, a microsatellite stability/proficient mismatch repair (MSS/pMMR) metastatic colorectal cancer, a deficient mismatch repair (dMMR) cancer, a microsatellite instability-high (MSI-H) cancer, a nasaltype extranodal NK/T-Cell lymphoma, a neuroendocrine cancer, a biliary tract cancer, a cholangiocarcinoma, and an intrahepatic cholangiocarcinoma.

19. The method according to any one of embodiments 1, 4-6 and 9-16, the use according to any one of embodiments 2, 4, 5, 7, and 9-16, the anti-TIGIT monoclonal antibody according to any one of embodiments 3-5 or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to any one of embodiments 8-16, wherein the cancer is selected from the group consisting of a Merkel cell carcinoma, a urothelial carcinoma, a renal cell carcinoma, non-small cell lung cancer, a breast cancer, a triplenegative breast cancer, a hepatocellular carcinoma, a melanoma, a Hodgkin’s lymphoma, a head and neck cancer, a colorectal cancer, a gastric cancer, a cervical cancer, a primary mediastinal large B-cell lymphoma, a cutaneous squamous-cell carcinoma, a basal cell carcinoma, a bladder cancer, an endometrial cancer, an esophageal cancer, a malignant pleural mesothelioma, a tumor mutational burden (TMB)-high cancer, a deficient mismatch repair (dMMR) cancer, and a microsatellite instability -high (MSI-H) cancer.

20. The method according to any one of embodiments 1, 4-6 and 9-16, the use according to any one of embodiments 2, 4, 5, 7, and 9-16, the anti-TIGIT monoclonal antibody according to any one of embodiments 3-5 or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to any one of embodiments 8-16, wherein the cancer is selected from the group consisting of a lung cancer, a non-small cell lung cancer, a bronchogenic carcinoma, a breast cancer, a triple-negative breast cancer, an estrogen receptor-positive breast cancer, a HER2-positive breast cancer, a lobular metastatic breast cancer, a ductal breast carcinoma, a cervical cancer, a fallopian tube cancer, a fallopian tube serous adenocarcinoma, an ovarian cancer, an ovarian endometrioid tumor, an ovarian serous adenocarcinoma, an ovarian seromucinous carcinoma, a uterine cancer, an endometrial cancer, a skin cancer, a melanoma, a cutaneous melanoma, a Merkel cell carcinoma, a head and neck cancer, squamous cell carcinoma of head and neck, a hematologic malignancy, a leukemia, a myeloid leukemia, an acute myeloid leukemia, a chronic lymphocytic leukemia, a myelomonocytic leukemia, a thyroid cancer, thyroid gland carcinoma, a thymic carcinoma, a neuroendocrine cancer, a pheochromocytoma, a glioma, a glioblastoma multiforme, a paraganglioma, a lymphoma, a B-cell lymphoma, a Hodgkin lymphoma, a B-cell nonHodgkin lymphoma, a non-Hodgkin’s lymphoma, a cutaneous T-cell lymphoma, a diffuse large B-cell lymphoma, a follicular lymphoma, a marginal zone lymphoma, a pancreatic cancer, a pancreatic ductal adenocarcinoma, a rectal cancer, a colon cancer, a colorectal cancer, a urinary tract cancer, a genitourinary cancer, a mesothelioma, a pleural mesothelioma, a peritoneal mesothelioma, a sarcoma, a chondrosarcoma, a clear cell sarcoma, a liposarcoma, a myxoid/round cell liposarcoma, a synovial sarcoma, an alveolar soft part sarcoma, a gliosarcoma, a uterine carcinosarcoma, a kidney cancer, a non-clear cell kidney cancer, a renal cell carcinoma, a bladder cancer, a urothelial carcinoma, a muscle- invasive bladder cancer, a non-muscle invasive bladder cancer, a HER2-positive bladder cancer, a gallbladder carcinoma, a gastric cancer, an esophageal cancer, an esophageal squamous cell carcinoma, a gastrointestinal cancer, a gastroesophageal cancer, a gastroesophageal junction cancer, a HER2-positive gastric cancer, a primary peritoneal cancer, a cutaneous squamous cell carcinoma, a prostate cancer, a prostate adenocarcinoma, a castration-resistant prostate cancer, a urogenital cancer, a ureter urothelial carcinoma, a renal pelvis urothelial carcinoma, a urethral urothelial carcinoma, an appendix carcinoma, a penile cancer, an anal canal cancer, a hepatocellular carcinoma, a hepatobiliary cancer, an unresectable liver and intrahepatic bile duct carcinoma, a biliary tract cancer, a cholangiocarcinoma, an intrahepatic cholangiocarcinoma, an extrahepatic cholangiocarcinoma, an HPV-related cancer, an HPV-related anal squamous cell carcinoma, an HPV-related cervical squamous cell carcinoma, an HPV-related penile squamous cell carcinoma, an HPV-related vulvar squamous cell carcinoma, a nasopharynx carcinoma, a nasopharyngeal carcinoma, a laryngeal squamous cell carcinoma, a hypopharyngeal squamous cell carcinoma, an oral cavity squamous cell carcinoma, and a mycosis fungoides. 21. The method according to any one of embodiments 1, 4-6 and 9-16, the use according to any one of embodiments 2, 4, 5, 7, and 9-16, the anti-TIGIT monoclonal antibody according to any one of embodiments 3-5 or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to any one of embodiments 8-16, wherein the cancer is selected from the group consisting of urothelial carcinoma, non-small cell lung cancer (NSCLC), breast cancer, triple-negative breast cancer, hepatocellular carcinoma and melanoma.

22. The method according to any one of embodiments 1, 4-6 and 9-16, the use according to any one of embodiments 2, 4, 5, 7, and 9-16, the anti-TIGIT monoclonal antibody according to any one of embodiments 3-5 or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to any one of embodiments 8-16, wherein the cancer is selected from the group consisting of a multiple myeloma, a cervical cancer, an esophageal cancer, an esophageal squamous cell carcinoma, a lung cancer, a non-small cell lung cancer, a glioblastoma, an endometrial cancer, an ovarian cancer, a squamous cell cancer, a head and neck cancer.

23. The method according to any one of embodiments 1, 4-6 and 9-16, the use according to any one of embodiments 2, 4, 5, 7, and 9-16, the anti-TIGIT monoclonal antibody according to any one of embodiments 3-5 or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to any one of embodiments 8-16, wherein the cancer is selected from the group consisting of a cervical cancer, a squamous cell carcinoma of head and neck, a head and neck cancer, a non-small cell lung cancer, a non-squamous non- small cell lung cancer, an esophageal squamous cell carcinoma, an esophageal cancer, a breast cancer, a triple-negative breast cancer, a gastric cancer, a gastroesophageal junction adenocarcinoma, a multiple myeloma, a non-Hodgkin lymphoma, a B-cell lymphoma, a liver cancer, a bladder cancer, a urothelial carcinoma, a pancreatic cancer, and a pancreatic adenocarcinoma.

24. The method according to any one of embodiments 1, 4-6 and 9-16, the use according to any one of embodiments 2, 4, 5, 7, and 9-16, the anti-TIGIT monoclonal antibody according to any one of embodiments 3-5 or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to any one of embodiments 8-16, wherein the cancer is a solid tumor.

25. The method according to any one of embodiments 1, 4-6 and 9-16, the use according to any one of embodiments 2, 4, 5, 7, and 9-16, the anti-TIGIT monoclonal antibody according to any one of embodiments 3-5 or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to any one of embodiments 8-16, wherein the cancer is a hematological cancer. 26. The method according to any one of embodiments 6 and 9-25, the use according to any one of embodiments 7 and 9-25 or the anti-TIGIT monoclonal antibody and the anti-PD- L1 monoclonal antibody according to any one of embodiments 8-25, wherein the heavy chain variable region of the anti-PD-Ll monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 16.

27. The method according to any one of embodiments 6 and 9-26, the use according to any one of embodiments 7 and 9-26 or the anti-TIGIT monoclonal antibody and the anti-PD- Ll monoclonal antibody according to any one of embodiments 8-26, wherein the light chain variable region of the anti-PD-Ll monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 17.

28. The method according to any one of embodiments 6 and 9-27, the use according to any one of embodiments 7 and 9-27 or the anti-TIGIT monoclonal antibody and the anti-PD- Ll monoclonal antibody according to any one of embodiments 8-27, wherein the heavy chain variable region of the anti-PD-Ll monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 16 and the light chain variable region of the anti-PD-Ll monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 17.

29. The method according to any one of embodiments 6 and 9-28, the use according to any one of embodiments 7 and 9-28 or the anti-TIGIT monoclonal antibody and the anti-PD- Ll monoclonal antibody according to any one of embodiments 8-28, wherein the anti-PD-Ll monoclonal antibody is an IgG antibody.

30. The method, the use or the anti-TIGIT monoclonal antibody and the anti-PD-Ll antibody according to embodiment 29, wherein the anti-PD-Ll monoclonal antibody is an IgGl or an IgG4 antibody.

31. The method according to any one of embodiments 6 and 9-30, the use according to any one of embodiments 7 and 9-30 or the anti-TIGIT monoclonal antibody and the anti-PD- Ll monoclonal antibody according to any one of embodiments 8-30, wherein the anti-PD-Ll monoclonal antibody or anti-TIGIT monoclonal antibody is a human antibody.

32. The method according to any one of embodiments 6 and 9-30, the use according to any one of embodiments 7 and 9-30 or the anti-TIGIT monoclonal antibody and the anti-PD- Ll monoclonal antibody according to any one of embodiments 8-30, wherein the anti-PD-Ll monoclonal antibody or anti-TIGIT monoclonal antibody is a humanized antibody.

33. The method according to any one of embodiments 6 and 9-30, the use according to any one of embodiments 7 and 9-30 or the anti-TIGIT monoclonal antibody and the anti-PD- Ll monoclonal antibody according to any one of embodiments 8-30, wherein the anti-PD-Ll monoclonal antibody is selected from the group consisting of atezolizumab (MPDL3280A), durvalumab (MED 14736), avelumab, and MDX-1105.

34. The method according to any one of embodiments 1, 4-6 and 9-33, the use according to any one of embodiments 2, 4, 5, 7, and 9-33, the anti-TIGIT monoclonal antibody according to any one of embodiments 3-5 and 17-25 or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to any one of embodiments 8-33, wherein the heavy chain variable region of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 7 or SEQ ID NO: 8.

35. The method according to any one of embodiments 1, 4-6 and 9-34, the use according to any one of embodiments 2, 4, 5, 7, and 9-34, the anti-TIGIT monoclonal antibody according to any one of embodiments 3-5, 17-25, and 34 or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to any one of embodiments 8-

34, wherein the light chain variable region of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 9.

36. The method according to any one of embodiments 1, 4-6 and 9-35, the use according to any one of embodiments 2, 4, 5, 7, and 9-35, the anti-TIGIT monoclonal antibody according to any one of embodiments 3-5, 17-25, and 34-35 or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to any one of embodiments 8-

35, wherein the heavy chain variable region of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 7 or SEQ ID NO: 8 and the light chain variable region of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 9.

37. The method according to any one of embodiments 1, 4-6 and 9-36, the use according to any one of embodiments 2, 4, 5, 7, and 9-36, the anti-TIGIT monoclonal antibody according to any one of embodiments 3-5, 17-25, and 34-36 or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to any one of embodiments 8-

36, wherein the heavy chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 18 or SEQ ID NO: 24.

38. The method according to any one of embodiments 1, 4-6 and 9-37, the use according to any one of embodiments 2, 4, 5, 7, and 9-37, the anti-TIGIT monoclonal antibody according to any one of embodiments 3-5, 17-25, and 34-37 or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to any one of embodiments 8-

37, wherein the heavy chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 19 or SEQ ID NO: 25. 39. The method according to any one of embodiments 1, 4-6 and 9-38, the use according to any one of embodiments 2, 4, 5, 7, and 9-38, the anti-TIGIT monoclonal antibody according to any one of embodiments 3-5, 17-25, and 34-38 or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to any one of embodiments 8-

38, wherein the light chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 20.

40. The method according to any one of embodiments 1, 4-6 and 9-39, the use according to any one of embodiments 2, 4, 5, 7, and 9-39, the anti-TIGIT monoclonal antibody according to any one of embodiments 3-5, 17-25, and 34-39 or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to any one of embodiments 8-

39, wherein the heavy chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 18 or SEQ ID NO: 24, and the light chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 20.

41. The method according to any one of embodiments 1, 4-6 and 9-39, the use according to any one of embodiments 2, 4, 5, 7, and 9-39, the anti-TIGIT monoclonal antibody according to any one of embodiments 3-5, 17-25, and 34-39 or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to any one of embodiments 8- 39, wherein the heavy chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 19 or SEQ ID NO: 25, and the light chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 20.

42. The method according to any one of embodiments 1, 4-6 and 9-41, the use according to any one of embodiments 2, 4, 5, 7, and 9-41, the anti-TIGIT monoclonal antibody according to any one of embodiments 3-5, 17-25, and 34-41 or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to any one of embodiments 8- 41, wherein the anti-TIGIT monoclonal antibody is an IgG antibody.

43. The method, the use, the anti-TIGIT monoclonal antibody or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to embodiment 42, wherein the anti-TIGIT monoclonal antibody is an IgGl or an IgG4 antibody.

44. The method according to any one of embodiments 1, 4-6 and 9-43, the use according to any one of embodiments 2, 4, 5, 7, and 9-43, the anti-TIGIT monoclonal antibody according to any one of embodiments 3-5, 17-25, and 34-43 or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to any one of embodiments 8- 43, wherein the anti-TIGIT monoclonal antibody is a human antibody. 45. The method according to any one of embodiments 1, 4-6 and 9-43, the use according to any one of embodiments 2, 4, 5, 7, and 9-43, the anti-TIGIT monoclonal antibody according to any one of embodiments 3-5, 17-25, and 34-43 or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to any one of embodiments 8- 43, wherein the anti-TIGIT monoclonal antibody is a humanized antibody.

46. The method according to any one of embodiments 1, 4-6 and 9-43, the use according to any one of embodiments 2, 4, 5, 7, and 9-43, the anti-TIGIT monoclonal antibody according to any one of embodiments 3-5, 17-25, and 34-43 or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to any one of embodiments 8- 43, wherein the anti-TIGIT monoclonal antibody inhibits or blocks the interaction of CD226 with TIGIT.

47. The method according to any one of embodiments 1, 4-6 and 9-43, the use according to any one of embodiments 2, 4, 5, 7, and 9-43, the anti-TIGIT monoclonal antibody according to any one of embodiments 3-5, 17-25, and 34-43 or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to any one of embodiments 8- 43, wherein the anti-TIGIT monoclonal antibody is tiragolumab.

48. The method according to any one of embodiments 1, 4-6 and 9-47, the use according to any one of embodiments 2, 4, 5, 7, and 9-47, the anti-TIGIT monoclonal antibody according to any one of embodiments 3-5, 17-25, and 34-47 or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to any one of embodiments 8- 47, wherein the anti-TIGIT monoclonal antibody is in a liquid pharmaceutical composition comprising 160 mg/mL of tiragolumab and 2000 U/mL hyaluronidase in 20 mM histidine acetate, 240 mM sucrose, 10 mM methionine, 0.06% polysorbate 20, pH 5.5.

49. The method according to any one of embodiments 6 and 9-47, the use according to any one of embodiments 7 and 9-47, or the anti-TIGIT monoclonal antibody and the anti-PD- Ll monoclonal antibody according to any one of embodiments 8-47, wherein the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody are in a liquid pharmaceutical formulation comprising 40 mg/ml of tiragolumab, 80 mg/ml of atezolizumab, 2000 U/ml hyaluronidase in 20 mM histidine acetate, 240 mM sucrose, 10 mM methionine, 0.06% polysorbate 20, pH 5.8.

50. An article of manufacture comprising a formulation that comprises 1,000 mg of tiragolumab.

51. The article of manufacture according to embodiment 50, wherein the formulation further comprises 1,875 mg or 2,000 mg of atezolizumab. 52. The article of manufacture according to embodiment 50, wherein the formulation further comprises 1,875 mg of atezolizumab.

53. The article of manufacture according to embodiment 50, wherein the formulation further comprises 2,000 mg of atezolizumab.

54. The article of manufacture according to any one of embodiments 50-53, wherein the formulation further comprises hyaluronidase.

55. An article of manufacture comprising a formulation that comprises 1,000 mg of tiragolumab and 1,875 mg or 2,000 mg of atezolizumab.

56. The article of manufacture according to embodiment 55, wherein the formulation comprises 1,875 mg of atezolizumab.

57. The article of manufacture according to embodiment 55, wherein the formulation comprises 2,000 mg of atezolizumab.

58. The article of manufacture according to any one of embodiments 55-57, wherein the formulation further comprises hyaluronidase.

59. The article of manufacture according to embodiment 54 or 58, wherein the concentration of the hyaluronidase is 2000 U/mL.

60. The article of manufacture according to any one of embodiments 54 and 58-59, wherein the hyaluronidase is a recombinant human hyaluronidase.

61. The article of manufacture according to embodiment 60, wherein the recombinant hyaluronidase is a human soluble PH20 hyaluronidase glycoprotein, such as rHuPH20.

62. The article of manufacture according to any one of embodiments 50-61, wherein the article of manufacture is a vial.

63. The article of manufacture according to embodiment 62, wherein the vial is a single dosage vial.

64. The article of manufacture according to embodiment 62 or 63, wherein the vial is stoppered with a chlorobutyl elastomer stopper.

65. The article of manufacture according to any one of embodiments 50-61, wherein the article of manufacture is a pre-filled syringe.

66. The article of manufacture according to any one of embodiments 50-61, wherein the article of manufacture is a syringe pump.

67. The article of manufacture according to any one of embodiments 50-61, wherein the article of manufacture is a subcutaneous administration device.

68. The article of manufacture according to embodiment 67, wherein the subcutaneous administration device is selected from the group consisting of a syringe, a syringe pump, an injection device, an infusion pump, an injector pen, a needleless device, an autoinjector, and a subcutaneous patch delivery system.

69. An article of manufacture comprising a subcutaneous administration device, wherein the subcutaneous administration device contains and delivers to a patient a 1,000 mg fixed dose of tiragolumab.

70. The article of manufacture according to embodiment 69, wherein the subcutaneous administration device further contains and delivers to the patient a 1,875 mg or 2,000 mg fixed dose of atezolizumab.

71. The article of manufacture according to embodiment 70, wherein the subcutaneous administration device further contains and delivers to the patient a 1,875 mg fixed dose of atezolizumab.

72. The article of manufacture according to embodiment 70, wherein the subcutaneous administration device further contains and delivers to the patient a 2,000 mg fixed dose of atezolizumab.

73. The article of manufacture according to any one of embodiments 69-72, wherein the subcutaneous administration device further contains and delivers to the patient hyaluronidase.

74. The article of manufacture according to embodiment 73, wherein the hyaluronidase is a human soluble PH20 hyaluronidase glycoprotein, such as rHuPH20.

75. The article of manufacture according to any one of embodiments 69-74, wherein the subcutaneous administration device is selected from the group consisting of a syringe, a syringe pump, an injection device, an infusion pump, an injector pen, a needleless device, an autoinjector, and a subcutaneous patch delivery system.

76. The article of manufacture according to any one of embodiments 69-75, wherein the subcutaneous administration device is a syringe.

77. The article of manufacture according to embodiment 69-75, wherein the subcutaneous administration device is a syringe pump.

78. The article of manufacture according to any one of embodiments 50-77, wherein the article of manufacture comprises about 3 mL to about 60 mL of the anti-TIGIT full-length monoclonal antibody, and one or more of hyaluronidase, a histidine buffer, sucrose, and polysorbate 20.

79. The article of manufacture according to embodiment 78, wherein the article of manufacture comprises about 10 mL of tiragolumab, and one or more of hyaluronidase, a histidine buffer, sucrose, and polysorbate 20. 80. The article of manufacture according to embodiment 78, wherein the article of manufacture comprises about 7 mL of tiragolumab, and one or more of hyaluronidase, a histidine buffer, sucrose, and polysorbate 20.

81. The article of manufacture according to embodiment 78, wherein the article of manufacture comprises about 6.5 mL of tiragolumab, and one or more of hyaluronidase, a histidine buffer, sucrose, and polysorbate 20.

82. The article of manufacture according to embodiment 78, wherein the article of manufacture comprises about 21 mL of tiragolumab, and one or more of hyaluronidase, a histidine buffer, sucrose, and polysorbate 20.

EXAMPLES

Example 1. An Open-label, Multicenter Dose-Finding Study of Tiragolumab and Atezolizumab

[0171] A two to three single-arm, open-label, multicenter dose-finding study to determine the doses of subcutaneous (SC) administration of the anti-TIGIT monoclonal antibody tiragolumab in combination with subcutaneous administration of the anti-PD-Ll monoclonal antibody atezolizumab in comparison to sequential intravenous (IV) administration of atezolizumab followed by tiragolumab was initiated and is ongoing conducted in subjects with locally advanced or metastatic solid tumors on the basis of pharmacokinetic (PK) analysis of serum tiragolumab and atezolizumab (ie., Ctrough at Cycle 1 (pre-dose Cycle 2)).

[0172] The study consists of three cohorts, as follows:

• Cohort 1 : Cycle 1 : Subjects received either (1) 880 mg tiragolumab SC co-mixed with 2000 mg atezolizumab SC in the abdomen, or (2) 880 mg tiragolumab SC co-mixed with 1875 mg atezolizumab SC in the thigh, at Day 1 of the first cycle (21 days). Cycle 2 onwards: Subjects will receive 1200 mg atezolizumab IV followed by 600 mg tiragolumab IV every 3 weeks (Q3W) (Day 1 of each cycle) from Cycle 2 onwards until disease progression, loss of clinical benefit, unacceptable toxicity, or withdrawal of consent.

• Cohort 2: Cycle 1 to 3 : Subjects will receive 1,000 mg tiragolumab SC co-mixed with 1,875 mg atezolizumab SC in the thigh Q3W at Day 1 of each cycle for 3 cycles (21 days each). Cycle 4 onwards: Subjects will receive 1200 mg atezolizumab IV followed by 600 mg tiragolumab IV Q3W (Day 1 of each cycle) starting from Cycle 4 onwards until disease progression, loss of clinical benefit, unacceptable toxicity, or withdrawal of consent. • Cohort 3 : Cycle 1 to 3 : Subjects will receive tiragolumab 1,000 mg SC co-mixed with 1,875 mg atezolizumab SC in the abdomen Q3W at Day 1 of each cycle for 3 cycles (21 days each). Cycle 4 onwards: Subjects will receive 1200 mg atezolizumab IV followed by 600 mg tiragolumab IV Q3W (Day 1 of each cycle) starting from Cycle 4 onwards until disease progression, loss of clinical benefit, unacceptable toxicity, or withdrawal of consent.

[0173] Cohort 1 enrolled 30 eligible subjects (15 subjects for injection in the abdomen (Cohort 1A) and 15 subjects for injection in the thigh (Cohort IB)), and Cohorts 2 and 3 will enroll approximately 25 to 30 eligible subjects each to achieve at least 15 evaluable subjects in each cohort, for a total of approximately 74 to 100 eligible subjects. Cohort 3 may not be started or may enroll fewer subjects if the data from Cohort 2 are considered sufficient. Based on the known PK profile of tiragolumab IV and atezolizumab IV, the sample size will allow for estimation of the PK parameters to enable Phase III dose selection.

[0174] Pharmacokinetic model parameter estimates were obtained after 15 subj ects in Cohort 1 A were subcutaneously administered a single dose of 880 mg tiragolumab in the abdomen, followed by intravenous administration of 600 mg tiragolumab. See, Table 3. Data from two representative subjects from Cohort 1A and two representative subjects from Cohort IB were used to generate a pharmacokinetic model fit over time (days). See, Fig. 2A and Fig. 2B, respectively.

Table 3. Population Pharmacokinetic Model Parameter Estimates

[0175] Two-hundred simulated clinical trials based on the population pharmacokinetic model were conducted using patient characteristics from 326 subjects. Table 4, below, depicts a summary statistics table of simulated serum tiragolumab concentrations after the simulated subjects were administered the indicated regimen and dose number. [0176] As shown in Table 4, statistical analysis of the predictive pharmacokinetic profiles indicates that subcutaneous administration of 1000 mg tiragolumab Q3W is non-inferior to intravenous administration of 600 mg tiragolumab Q3W, as shown in the predicted Cycle 1 AUC and Cmin values, following either abdomen or thigh as administration sites for the subcutaneous dose. Therefore, 1000 mg subcutaneous dose will be as efficacious as the 600 mg tiragolumab Q3W IV dose. Accordingly, subcutaneous administration of 1000 mg tiragolumab was selected as the dose for Cohorts 2 and 3.

Table 4. Summary Statistics Table of Serum Tiragolumab Concentration

[0177] Subjects who discontinue study treatment prematurely, defined as discontinuation prior to completion of 2 cycles in Cohort 1, or 4 cycles in Cohorts 2 and 3, for reasons other than toxicity, may be replaced if they are not considered evaluable. [0178] All subjects will be required to report any symptoms and adverse events as soon as possible, particularly during the first 72 hours after the first injection. The first two patients each in the thigh and abdomen injection group of Cohort 1 (subjects in the thigh and abdomen injection group may be enrolled concurrently) and the first 2 subjects each in Cohorts 2 and 3 (subjects in Cohorts 2 and 3 may be enrolled concurrently) will be observed for 1 week before dosing the next subj ect. There will be no staggering of subj ect enrollment after the third subj ect in the thigh and abdomen groups in Cohorts 2 and 3. The cohort review of all safety data begins 7 days after the last subject of the respective cohort receives the second cycle dose.

[0179] After initiation of study treatment, all adverse events will be reported until 30 days after the final dose of study treatment or until initiation of a new systemic anti-cancer therapy, whichever occurs first, and serious adverse events will continue to be reported until 90 days after the final dose of study treatment or until initiation of a new systemic anti-cancer therapy, whichever occurs first. In addition, adverse events of special interest will continue to be reported until 90 days after the final dose of study treatment, regardless of initiation of subsequent anti-cancer therapy. After this period, any deaths or serious adverse events that are believed to be related to prior treatment with study drug(s) will be reported. Each adverse event will be followed until the event has resolved to baseline grade or better, the event is assessed as stable, the subject is lost to follow-up, or the subject withdraws consent. Every effort should be made to follow all serious adverse events considered to be related to study treatment or protocol -related procedures until a final outcome can be reported.

[0180] Tumor assessments were performed every 6 weeks (Q6W) (± 7 days) for the first 48 weeks and every 9 weeks (Q9W) (± 7 days) subsequently until radiographic progressive disease (PD) or loss of clinical benefit. Subjects continue to be followed for overall survival (OS) until death, lost-to-follow-up, withdrawal from the study, or study termination, whichever occurs first.

[0181] Fig. 1 provides an overview of the study design.

Rationale

[0182] The study will determine the dose and site of administration by comparing a SC comix administration of tiragolumab and atezolizumab with their IV routes of administration, and assess safety, tolerability, and PK. In previous studies, for both tiragolumab and atezolizumab, only IV administration method was tested in combination. Bioavailability of tiragolumab and atezolizumab in combination following SC administration, safety, immunogenicity, and preliminary efficacy data will facilitate further development of SC routes of administration. In addition, safety, PK, and immunogenicity for rHuPH20 will also be assessed. A co-mix with 2000 U/mL rHuPH20 will be generated from the atezolizumab SC and tiragolumab SC drug products. Objectives and Endpoints

[0183] This study was designed to evaluate the pharmacokinetics (PK), safety, tolerability, and exploratory efficacy of various doses of tiragolumab and atezolizumab administered as a single SC injection (z.e., a tiragolumab and atezolizumab SC co-mix with rHuPH20) and of the sequential administration of tiragolumab and atezolizumab IV in subjects with locally advanced or metastatic solid tumors. Objectives and corresponding endpoints are described in Table 5 infra.

Table 5. Objectives and Endpoints

[0184] Cohort 1 subjects underwent tumor assessments at baseline and Q6W (± 7 days) for 48 weeks following Day 1 of Cycle 1. After the completion of the Week 48 tumor assessment, tumor assessments were performed every 9 weeks (± 7 days), until radiographic disease progression per RECIST vl. l, withdrawal of consent, death, or study termination, whichever occurs first. Subjects who are treated beyond disease progression per RECIST vl.l will undergo tumor assessments Q6W (± 2 weeks) after initial documentation of progression, or more frequently if clinically indicated, regardless of time in study, until treatment is discontinued. Scans may be performed at any time if progressive disease or loss of clinical benefit is suspected.

[0185] Response was assessed on the imaging modalities described above (e.g., CT scan and MRI), with use of RECIST vl. l. The assessment of overall tumor response at all timepoints will be based on RECIST vl.l. Results were reviewed before dosing at the next cycle. Study treatment with tiragolumab and atezolizumab will be continued as long as subjects are experiencing clinical benefit in the absence of unacceptable toxicity or symptomatic deterioration attributed to disease progression after an integrated assessment of radiographic data, biopsy results, and clinical status. Subjects who meet criteria for disease progression per RECIST vl. l will be permitted to continue study treatment if they meet all of the criteria and provide written consent.

Response Evaluation and Biomarkers and Biological Samples

[0186] An objective response will be assessed according to RECIST vl.l and determined by repeat assessment at > 4 weeks after initial documentation of CR and PR.

Laboratory tests that will be performed include:

1. Serology: HIV serology, HBV serology (e.g., HBsAg, HBsAb, and total HBcAb); HBV DNA for subjects with negative HBsAg and HBsAb tests and a positive total HBcAb; HCV serology (e.g., HCV antibody and (if HCV antibody test is positive) HCV RNA); EBV serology (e.g., EBV viral capsid antigen (VCA) IgM; EBV VCA IgG or EBV nuclear antigen (EBNA) IgG; and EBV PCR);

2. Hematology: white blood cell (WBC) count with differential (neutrophils, eosinophils, basophils, monocytes, lymphocytes), red blood cell (RBC) count, hemoglobin, hematocrit, platelet count, and differential count;

3. Chemistry panel (serum or plasma): bicarbonate or total carbon dioxide (if considered the standard of care for the region), sodium, magnesium, potassium, calcium, chloride, glucose, blood urea nitrogen (BUN) or urea, creatinine, total protein, albumin, phosphate, total bilirubin, ALP, ALT, AST, and lactate dehydrogenase (LDH);

4. Serum C-reactive protein (CRP)

5. Urinalysis, including dipstick (pH, specific gravity, glucose, protein, ketones, blood;

6. Pregnancy test: All women of childbearing potential will have a serum pregnancy test during screening 14 days prior to the initiation of study drug. During the study, urine pregnancy tests will be performed within 96 hours of dosing on Day 1 of every cycle, and after study treatment is discontinued;

7. Coagulation (INR and aPTT) or prothrombin time (PTT); and

8. Thyroid-stimulating hormone (TSH), free T3 (or total T3 at sites where free T3 is not performed), and free T4.

[0187] Samples for the following laboratory tests will be sent for analysis:

1. Serum and plasma samples for PK analysis (tiragolumab and atezolizumab with use of a validated assay). PK/ADA samples may be used for PK/ADA related assessments interchangeably;

2. Serum and plasma samples for ADA analysis (tiragolumab, atezolizumab, and rHuPH20) with use of a validated assay;

3. Plasma samples for rHuPH20 concentration with use of a validated assay;

4. Blood, plasma, serum and peripheral blood mononuclear cells (PBMC) for exploratory research on biomarkers; and

5. Archival tissue sample (if available) obtained at baseline for exploratory biomarkers including but not limited to PD-L1 and TIGIT. a. A representative FFPE tumor specimen in a paraffin block or 10 to 15 slides containing unstained, freshly cut, serial sections on slides from an FFPE tumor specimen will be submitted along with an associated pathology report prior to study enrollment. b. Tumor tissue will be of good quality based on total and viable tumor content. Priority will be given to the most recent tissue biopsy with the highest tumor content and lowest necrotic area. Samples collected via resection, coreneedle biopsy (at least 3 cores, embedded in a single paraffin block), or excisional, incisional, punch, forceps biopsy, or EBUS-TBNA are acceptable. Fine-needle aspiration (defined as samples that do not preserve tissue architecture and yield cell suspension and/or smears), brushing, cell pellets from pleural effusion, and lavage samples are not acceptable. Tumor tissue from bone metastases that have been decalcified is not acceptable. c. If archival tumor tissue is unavailable or is determined to be unsuitable for required testing, a fresh pretreatment tumor biopsy may be required.

[0188] Exploratory biomarker research may include, but will not be limited to, analysis of genes or gene signatures associated with tumor immunobiology (e.g., PD-L1 and TIGIT), lymphocyte subpopulations, T-cell receptor repertoire, or cytokines associated with T cell activation. Research may involve extraction of DNA, cell-free DNA, or RNA; analysis of mutations, single nucleotide polymorphisms, and other genomic variants; and genomic profiling through the use of next-generation sequencing (NGS) of a comprehensive panel of genes. DNA extracted from blood may be compared with DNA extracted from tissue to identify somatic variants by distinguishing germline variants from somatic variants. NGS methods may include whole genome sequencing (WGS) or whole exome sequencing (WES) of blood samples but only at participating sites and will be optional.

[0189] Safety assessments performed in this study included monitoring and recording adverse events (e.g., serious adverse events and adverse events of special interest), performing safety laboratory assessments, measuring vital signs (e.g., pulse rate, respiratory rate, blood pressure, and temperature), and conducting other tests that are deemed critical to the safety evaluation of the study.

PK Analysis

[0190] PK analysis for the Cohort 1 subjects provided sufficient data to enable estimation of key parameters (e.g., area under the concentration-time curve [AUC], time to maximum concentration [tmax], maximum concentration [Cmax], half-life, Ctrough), with subjects grouped by treatment. Estimates for these parameters tabulated and summarized (mean, standard deviation, coefficient of variation, median, minimum, and maximum). See, Table 4. Intersubject variability and drug accumulation was evaluated. Additional PK analyses will be conducted as appropriate.

Subcutaneous Administration

[0191] The atezolizumab SC and tiragolumab SC co-mix was generated from the atezolizumab SC and tiragolumab SC drug products, which each contain rHuPH20 at a concentration of 2000 U/mL. The drug product was administered subcutaneously in the anterior thigh region or in the lower part of the abdomen. Cohort 1 subjects received one dose of atezolizumab SC and tiragolumab SC co-mix via the SC route. Cohort 2 and 3 subjects will receive three doses of atezolizumab SC and tiragolumab SC co-mix via the SC route. Atezolizumab SC and tiragolumab SC co-mix were administered per the instructions outlined in Table 6.

Table 6. Administration of First and Subsequent Atezolizumab SC and Tiragolumab SC CoMix injections

[0192] The SC injection was administered via either a B. Braun Perfusor® Space Infusion Pump or a Smiths Medical Medfusion Syringe Pump at a rate of 1.0 mL/min to 2.0 mL/min. Disposable Becton-Dickenson plastic syringes and KORU HigH-Flo 24G SC injection sets were used with the syringe pump(s) to administer the SC doses.

[0193] When applicable, the injection site is alternated between the left and right thigh.

New injections will be given at least 2.5 cm from the old site and never into areas where the skin is red, bruised, tender, or hard. If administered in the abdomen, injection will be given in either of the two lower quadrants around the umbilicus; it will not be administered above the umbilicus. In all cases (abdomen or thigh), start and stop times of the SC injection will be captured.

[0194] No premedication will be allowed for the first dose of atezolizumab SC and tiragolumab SC co-mix. Premedication may be administered for Cycles > 2 at the discretion of the treating physician. Injection sites will be digitally photographed after a SC injection if a severe adverse reaction at the injection site is observed. Patients will remain in the unit for 8 hours postdose after the first dose. They will return for safety assessments on specified days afterwards. [0195] The subject’s vital signs (e.g., pulse rate, respiratory rate, blood pressure, and temperature) will be determined within 60 minutes before and 30 (± 10) minutes after the injection, and as clinically indicated.

Intravenous Administration [0196] Administration of atezolizumab and tiragolumab IV beginning in Cycle 2 of Cohort

1 was performed in a monitored setting where there is immediate access to trained personnel and adequate equipment and medicine to manage potentially serious reactions. No dose modification for atezolizumab or tiragolumab was allowed.

[0197] Atezolizumab IV infusions were administered per the instructions outlined in Table 7. Following the administration of atezolizumab and an observation period (see Table 7), subjects received 600 mg tiragolumab administered by IV infusion on Day 1 of each 21 -day cycle.

Table 7. Administration of First and Subsequent Atezolizumab IV Infusions

[0198] Tiragolumab infusions were administered per the instructions outlined in Table 8.

Table 8. Administration of First and Subsequent IV Infusions of Tiragolumab

[0199] The following rules apply as long as neither atezolizumab nor tiragolumab has been permanently discontinued: • Treatment cycles will begin with dosing of atezolizumab and tiragolumab on Day 1 of each

21 -day cycle. If either study drug is delayed due to a drug related toxicity, it is recommended that the other study drug is also delayed because the safety profiles for atezolizumab and tiragolumab are similar; however, a cycle may begin with the administration of the other study drug if considered appropriate.

• In case of delays in dosing of one study drug for drug related toxicity while the other study drug is given as planned, it is recommended that the study drug being delayed will be administered at the next scheduled infusion (i.e., at the next scheduled 21 day cycle).

Claims

CLAIMS What is claimed is:

4. The method according to claim 1, the use according to claim 2, or anti-TIGIT monoclonal antibody according to claim 3, wherein the anti-TIGIT monoclonal antibody is administered in the thigh or the abdomen.

5. The method according to claim 1 or 4, the use according to claim 2 or 4, or the anti- TIGIT monoclonal antibody according to claim 3 or 4, wherein the anti-TIGIT monoclonal antibody is administered every three weeks (Q3W).

9. The method according to claim 6, the use according to claim 7 or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to claim 8, wherein the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody are administered simultaneously.

10. The method according to claim 6 or 9, the use according to claim 7 or 9, or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to claim 8 or 9, wherein the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody are co-formulated.

11. The method according to claim 6 or 9, the use according to claim 7 or 9, or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to claim 8 or 9, wherein the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody are mixed 24 hours or less prior to administration to the subject.

12. The method, the use or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to claim 11, wherein the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody are mixed during administration to the subject.

13. The method according to claim 6, the use according to claim 7 or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to claim 8, wherein the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody, are administered sequentially.

14. The method according to any one of any one of claims 6 and 9-13, the use according to any one of claims 7 and 9-13 or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to any one of claims 8-13, wherein the anti-PD-Ll monoclonal antibody is administered intravenously.

15. The method according to any one of any one of claims 6 and 9-13, the use according to any one of claims 7 and 9-13 or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to any one of claims 8-13, wherein the anti-PD-Ll monoclonal antibody is administered subcutaneously.

16. The method according to any one of claims 6 and 9-15, the use according to any one of claims 7 and 9-15 or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to any one of claims 8-15, wherein the anti-TIGIT monoclonal antibody is administered every three weeks (Q3W).

17. The method according to any one of claims 1, 4-6 and 9-16, the use according to any one of claims 2, 4, 5, 7, and 9-16, the anti-TIGIT monoclonal antibody according to any one of claims 3-5 or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to any one of claims 8-16, wherein the cancer is selected from the group consisting of a lung cancer, a non-small cell lung cancer, a renal cell cancer, a urothelial cancer, a ureter cancer, a urethral cancer, a colorectal cancer, a colon cancer, a rectal cancer, a kidney cancer, a sarcoma, an ovarian cancer, a breast cancer, a cervical cancer, a fallopian tube cancer, an endometrial cancer, a uterine cancer, a pancreatic cancer, a gastric carcinoma, a bladder cancer, an esophageal cancer, a mesothelioma, a melanoma, a head and neck cancer, a thyroid cancer, a sarcoma, a prostate cancer, a penile cancer, a glioblastoma, a thymic carcinoma, an esophageal carcinoma, a nasopharyngeal cancer, a mesothelioma, a liver cancer, a biliary tract cancer, a HPV-positive cancer, a leukemia, a lymphoma, a brain cancer, a neuroendocrine cancer, a myeloma, a mycosis fungoides, a Merkel cell cancer, a hematologic malignancy, a deficient mismatch repair (dMMR) cancer, and a microsatellite instability-high (MSI-H) cancer.

18. The method according to any one of claims 1, 4-6 and 9-16, the use according to any one of claims 2, 4, 5, 7, and 9-16, the anti-TIGIT monoclonal antibody according to any one of claims 3-5 or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to any one of claims 8-16, wherein the cancer is selected from the group consisting of a bladder cancer, a muscle-invasive bladder cancer, a urothelial carcinoma, a ureter cancer, a urethral cancer, a ureter urothelial carcinoma, a urethral urothelial carcinoma, a renal cancer, a renal pelvis cancer, a renal cell carcinoma, a clear-cell renal carcinoma, a rectal cancer, a colon cancer, a colorectal cancer, a sarcoma, an osteosarcoma, a leiomyosarcoma, a pleomorphic sarcoma, a myxofibrosarcoma, a liposarcoma, a chondrosarcoma, a lung cancer, a non-small cell lung cancer, a fallopian tube cancer, a peritoneal carcinoma, an esophageal cancer, an esophageal squamous cell carcinoma, a mesothelioma, a pleural mesothelioma, a peritoneal mesothelioma, an ovarian cancer, a cervical cancer, a cervical adenosquamous carcinoma, a breast cancer, a triple-negative breast cancer, a HER2 -positive breast cancer, a HER2 -negative breast cancer, an estrogen receptorpositive breast cancer, a progesterone receptor-positive breast cancer, a luminal B breast cancer, a lymphoma, a T-cell lymphoma, a B-cell lymphoma, a nasal-type lymphoma, nonHodgkin’s lymphoma, a follicular lymphoma, a penile carcinoma, a prostate cancer, a castration-resistant prostate cancer, an endometrial cancer, a uterine cancer, a myeloma, a multiple myeloma, a head and neck cancer, a prostate cancer, a melanoma, a cutaneous melanoma, a Merkel cell carcinoma, a pancreatic cancer, hepatocellular carcinoma, gastric cancer, a gastroesophageal junction adenocarcinoma, a glioblastoma, a glioblastoma multiforme, a mycosis fungoides, an HPV-positive cancer, a HPV-related cervical carcinoma, a HPV-related anal squamous cell carcinoma, a HPV-related penile squamous cell carcinoma, a HPV-related vulvar squamous cell carcinoma, a vulvar cancer, a vaginal cancer, an anal cancer, an oropharyngeal cancer, an oropharyngeal squamous cell carcinoma, a leukemia, an acute myeloid leukemia, a bone cancer, a solitary bone plasmacytoma, a squamous cell carcinoma, a cutaneous squamous cell carcinoma, a thyroid cancer, a microsatellite stability/proficient mismatch repair (MSS/pMMR) metastatic colorectal cancer, a deficient mismatch repair (dMMR) cancer, a microsatellite instability-high (MSI-H) cancer, a nasaltype extranodal NK/T-Cell lymphoma, a neuroendocrine cancer, a biliary tract cancer, a cholangiocarcinoma, and an intrahepatic cholangiocarcinoma.

19. The method according to any one of claims 1, 4-6 and 9-16, the use according to any one of claims 2, 4, 5, 7, and 9-16, the anti-TIGIT monoclonal antibody according to any one of claims 3-5 or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to any one of claims 8-16, wherein the cancer is selected from the group consisting of a Merkel cell carcinoma, a urothelial carcinoma, a renal cell carcinoma, non- small cell lung cancer, a breast cancer, a triple-negative breast cancer, a hepatocellular carcinoma, a melanoma, a Hodgkin’s lymphoma, a head and neck cancer, a colorectal cancer, a gastric cancer, a cervical cancer, a primary mediastinal large B-cell lymphoma, a cutaneous squamous-cell carcinoma, a basal cell carcinoma, a bladder cancer, an endometrial cancer, an esophageal cancer, a malignant pleural mesothelioma, a tumor mutational burden (TMB)- high cancer, a deficient mismatch repair (dMMR) cancer, and a microsatellite instability-high (MSI-H) cancer.

20. The method according to any one of claims 1, 4-6 and 9-16, the use according to any one of claims 2, 4, 5, 7, and 9-16, the anti-TIGIT monoclonal antibody according to any one of claims 3-5 or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to any one of claims 8-16, wherein the cancer is selected from the group consisting of a lung cancer, a non-small cell lung cancer, a bronchogenic carcinoma, a breast cancer, a triple-negative breast cancer, an estrogen receptor-positive breast cancer, a HER2- positive breast cancer, a lobular metastatic breast cancer, a ductal breast carcinoma, a cervical cancer, a fallopian tube cancer, a fallopian tube serous adenocarcinoma, an ovarian cancer, an ovarian endometrioid tumor, an ovarian serous adenocarcinoma, an ovarian seromucinous carcinoma, a uterine cancer, an endometrial cancer, a skin cancer, a melanoma, a cutaneous melanoma, a Merkel cell carcinoma, a head and neck cancer, squamous cell carcinoma of head and neck, a hematologic malignancy, a leukemia, a myeloid leukemia, an acute myeloid leukemia, a chronic lymphocytic leukemia, a myelomonocytic leukemia, a thyroid cancer, thyroid gland carcinoma, a thymic carcinoma, a neuroendocrine cancer, a pheochromocytoma, a glioma, a glioblastoma multiforme, a paraganglioma, a lymphoma, a B-cell lymphoma, a Hodgkin lymphoma, a B-cell non-Hodgkin lymphoma, a non-Hodgkin’s lymphoma, a cutaneous T-cell lymphoma, a diffuse large B-cell lymphoma, a follicular lymphoma, a marginal zone lymphoma, a pancreatic cancer, a pancreatic ductal adenocarcinoma, a rectal cancer, a colon cancer, a colorectal cancer, a urinary tract cancer, a genitourinary cancer, a mesothelioma, a pleural mesothelioma, a peritoneal mesothelioma, a sarcoma, a chondrosarcoma, a clear cell sarcoma, a liposarcoma, a myxoid/round cell liposarcoma, a synovial sarcoma, an alveolar soft part sarcoma, a gliosarcoma, a uterine carcinosarcoma, a kidney cancer, a non-clear cell kidney cancer, a renal cell carcinoma, a bladder cancer, a urothelial carcinoma, a muscle-invasive bladder cancer, a non-muscle invasive bladder cancer, a HER2-positive bladder cancer, a gallbladder carcinoma, a gastric cancer, an esophageal cancer, an esophageal squamous cell carcinoma, a gastrointestinal cancer, a gastroesophageal cancer, a gastroesophageal junction cancer, a HER2-positive gastric cancer, a primary peritoneal cancer, a cutaneous squamous cell carcinoma, a prostate cancer, a prostate adenocarcinoma, a castration-resistant prostate cancer, a urogenital cancer, a ureter urothelial carcinoma, a renal pelvis urothelial carcinoma, a urethral urothelial carcinoma, an appendix carcinoma, a penile cancer, an anal canal cancer, a hepatocellular carcinoma, a hepatobiliary cancer, an unresectable liver and intrahepatic bile duct carcinoma, a biliary tract cancer, a cholangiocarcinoma, an intrahepatic cholangiocarcinoma, an extrahepatic cholangiocarcinoma, an HPV-related cancer, an HPV-related anal squamous cell carcinoma, an HPV-related cervical squamous cell carcinoma, an HPV-related penile squamous cell carcinoma, an HPV-related vulvar squamous cell carcinoma, a nasopharynx carcinoma, a nasopharyngeal carcinoma, a laryngeal squamous cell carcinoma, a hypopharyngeal squamous cell carcinoma, an oral cavity squamous cell carcinoma, and a mycosis fungoides.

21. The method according to any one of claims 1, 4-6 and 9-16, the use according to any one of claims 2, 4, 5, 7, and 9-16, the anti-TIGIT monoclonal antibody according to any one of claims 3-5 or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to any one of claims 8-16, wherein the cancer is selected from the group consisting of urothelial carcinoma, non-small cell lung cancer (NSCLC), breast cancer, triplenegative breast cancer, hepatocellular carcinoma and melanoma.

22. The method according to any one of claims 1, 4-6 and 9-16, the use according to any one of claims 2, 4, 5, 7, and 9-16, the anti-TIGIT monoclonal antibody according to any one of claims 3-5 or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to any one of claims 8-16, wherein the cancer is selected from the group consisting of a multiple myeloma, a cervical cancer, an esophageal cancer, an esophageal squamous cell carcinoma, a lung cancer, a non-small cell lung cancer, a glioblastoma, an endometrial cancer, an ovarian cancer, a squamous cell cancer, a head and neck cancer.

23. The method according to any one of claims 1, 4-6 and 9-16, the use according to any one of claims 2, 4, 5, 7, and 9-16, the anti-TIGIT monoclonal antibody according to any one of claims 3-5 or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to any one of claims 8-16, wherein the cancer is selected from the group consisting of a cervical cancer, a squamous cell carcinoma of head and neck, a head and neck cancer, a non-small cell lung cancer, a non-squamous non-small cell lung cancer, an esophageal squamous cell carcinoma, an esophageal cancer, a breast cancer, a triple-negative breast cancer, a gastric cancer, a gastroesophageal junction adenocarcinoma, a multiple myeloma, a non-Hodgkin lymphoma, a B-cell lymphoma, a liver cancer, a bladder cancer, a urothelial carcinoma, a pancreatic cancer, and a pancreatic adenocarcinoma.

24. The method according to any one of claims 1, 4-6 and 9-16, the use according to any one of claims 2, 4, 5, 7, and 9-16, the anti-TIGIT monoclonal antibody according to any one of claims 3-5 or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to any one of claims 8-16, wherein the cancer is a solid tumor.

25. The method according to any one of claims 1, 4-6 and 9-16, the use according to any one of claims 2, 4, 5, 7, and 9-16, the anti-TIGIT monoclonal antibody according to any one of claims 3-5 or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to any one of claims 8-16, wherein the cancer is a hematological cancer.

26. The method according to any one of claims 6 and 9-25, the use according to any one of claims 7 and 9-25 or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to any one of claims 8-25, wherein the heavy chain variable region of the anti-PD-Ll monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 16.

27. The method according to any one of claims 6 and 9-26, the use according to any one of claims 7 and 9-26 or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to any one of claims 8-26, wherein the light chain variable region of the anti-PD-Ll monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 17.

28. The method according to any one of claims 6 and 9-27, the use according to any one of claims 7 and 9-27 or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to any one of claims 8-27, wherein the heavy chain variable region of the anti-PD-Ll monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 16 and the light chain variable region of the anti-PD-Ll monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 17.

29. The method according to any one of claims 6 and 9-28, the use according to any one of claims 7 and 9-28 or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to any one of claims 8-28, wherein the anti-PD-Ll monoclonal antibody is an IgG antibody.

30. The method, the use or the anti-TIGIT monoclonal antibody and the anti-PD-Ll antibody according to claim 29, wherein the anti-PD-Ll monoclonal antibody is an IgGl or an IgG4 antibody.

31. The method according to any one of claims 6 and 9-30, the use according to any one of claims 7 and 9-30 or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to any one of claims 8-30, wherein the anti-PD-Ll monoclonal antibody or the anti-TIGIT monoclonal antibody is a human antibody.

32. The method according to any one of claims 6 and 9-30, the use according to any one of claims 7 and 9-30 or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to any one of claims 8-30, wherein the anti-PD-Ll monoclonal antibody or the anti-TIGIT monoclonal antibody is a humanized antibody.

33. The method according to any one of claims 6 and 9-30, the use according to any one of claims 7 and 9-30 or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to any one of claims 8-30, wherein the anti-PD-Ll monoclonal antibody is selected from the group consisting of atezolizumab (MPDL3280A), durvalumab (MEDI4736), avelumab, and MDX-1105.

34. The method according to any one of claims 1, 4-6 and 9-33, the use according to any one of claims 2, 4, 5, 7, and 9-33, the anti-TIGIT monoclonal antibody according to any one of claims 3-5 and 17-25 or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to any one of claims 8-33, wherein the heavy chain variable region of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 7 or SEQ ID NO: 8.

35. The method according to any one of claims 1, 4-6 and 9-34, the use according to any one of claims 2, 4, 5, 7, and 9-34, the anti-TIGIT monoclonal antibody according to any one of claims 3-5, 17-25, and 34 or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to any one of claims 8-34, wherein the light chain variable region of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 9.

36. The method according to any one of claims 1, 4-6 and 9-35, the use according to any one of claims 2, 4, 5, 7, and 9-35, the anti-TIGIT monoclonal antibody according to any one of claims 3-5, 17-25, and 34-35 or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to any one of claims 8-35, wherein the heavy chain variable region of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 7 or SEQ ID NO: 8 and the light chain variable region of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 9.

37. The method according to any one of claims 1, 4-6 and 9-36, the use according to any one of claims 2, 4, 5, 7, and 9-36, the anti-TIGIT monoclonal antibody according to any one of claims 3-5, 17-25, and 34-36 or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to any one of claims 8-36, wherein the heavy chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 18 or SEQ ID NO: 24.

38. The method according to any one of claims 1, 4-6 and 9-37, the use according to any one of claims 2, 4, 5, 7, and 9-37, the anti-TIGIT monoclonal antibody according to any one of claims 3-5, 17-25, and 34-37 or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to any one of claims 8-37, wherein the heavy chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 19 or SEQ ID NO: 25.

39. The method according to any one of claims 1, 4-6 and 9-38, the use according to any one of claims 2, 4, 5, 7, and 9-38, the anti-TIGIT monoclonal antibody according to any one of claims 3-5, 17-25, and 34-38 or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to any one of claims 8-38, wherein the light chain of the anti- TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 20.

40. The method according to any one of claims 1, 4-6 and 9-39, the use according to any one of claims 2, 4, 5, 7, and 9-39, the anti-TIGIT monoclonal antibody according to any one of claims 3-5, 17-25, and 34-39 or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to any one of claims 8-39, wherein the heavy chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 18 or SEQ ID NO: 24, and the light chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 20.

41. The method according to any one of claims 1, 4-6 and 9-39, the use according to any one of claims 2, 4, 5, 7, and 9-39, the anti-TIGIT monoclonal antibody according to any one of claims 3-5, 17-25, and 34-39 or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to any one of claims 8-39, wherein the heavy chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 19 or SEQ ID NO: 25, and the light chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 20.

42. The method according to any one of claims 1, 4-6 and 9-41, the use according to any one of claims 2, 4, 5, 7, and 9-41, the anti-TIGIT monoclonal antibody according to any one of claims 3-5, 17-25, and 34-41 or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to any one of claims 8-41, wherein the anti-TIGIT monoclonal antibody is an IgG antibody.

43. The method, the use, the anti-TIGIT monoclonal antibody or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to claim 42, wherein the anti-TIGIT monoclonal antibody is an IgGl or an IgG4 antibody.

44. The method according to any one of claims 1, 4-6 and 9-43, the use according to any one of claims 2, 4, 5, 7, and 9-43, the anti-TIGIT monoclonal antibody according to any one of claims 3-5, 17-25, and 34-43 or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to any one of claims 8-43, wherein the anti-TIGIT monoclonal antibody is a human antibody.

45. The method according to any one of claims 1, 4-6 and 9-43, the use according to any one of claims 2, 4, 5, 7, and 9-43, the anti-TIGIT monoclonal antibody according to any one of claims 3-5, 17-25, and 34-43 or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to any one of claims 8-43, wherein the anti-TIGIT monoclonal antibody is a humanized antibody.

46. The method according to any one of claims 1, 4-6 and 9-43, the use according to any one of claims 2, 4, 5, 7, and 9-43, the anti-TIGIT monoclonal antibody according to any one of claims 3-5, 17-25, and 34-43 or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to any one of claims 8-43, wherein the anti-TIGIT monoclonal antibody inhibits or blocks the interaction of CD226 with TIGIT.

47. The method according to any one of claims 1, 4-6 and 9-43, the use according to any one of claims 2, 4, 5, 7, and 9-43, the anti-TIGIT monoclonal antibody according to any one of claims 3-5, 17-25, and 34-43 or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to any one of claims 8-43, wherein the anti-TIGIT monoclonal antibody is tiragolumab.

48. The method according to any one of claims 1, 4-6 and 9-47, the use according to any one of claims 2, 4, 5, 7, and 9-47, the anti-TIGIT monoclonal antibody according to any one of claims 3-5, 17-25, and 34-47 or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to any one of claims 8-47, wherein the anti-TIGIT monoclonal antibody is in a liquid pharmaceutical composition comprising 160 mg/mL of tiragolumab and 2000 U/mL hyaluronidase in 20 mM histidine acetate, 240 mM sucrose, 10 mM methionine, 0.06% polysorbate 20, pH 5.5.

49. The method according to any one of claims 6 and 9-47, the use according to any one of claims 7 and 9-47, or the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody according to any one of claims 8-47, wherein the anti-TIGIT monoclonal antibody and the anti-PD-Ll monoclonal antibody are in a liquid pharmaceutical formulation comprising 40 mg/ml of tiragolumab, 80 mg/ml of atezolizumab, 2000 U/ml hyaluronidase in 20 mM histidine acetate, 240 mM sucrose, 10 mM methionine, 0.06% polysorbate 20, pH 5.8.

51. The article of manufacture according to claim 50, wherein the formulation further comprises 1,875 mg or 2,000 mg of atezolizumab.

52. The article of manufacture according to claim 50, wherein the formulation further comprises 1,875 mg of atezolizumab.

53. The article of manufacture according to claim 50, wherein the formulation further comprises 2,000 mg of atezolizumab.

54. The article of manufacture according to any one of claims 50-53, wherein the formulation further comprises hyaluronidase.

56. The article of manufacture according to claim 55, wherein the formulation comprises 1,875 mg of atezolizumab.

57. The article of manufacture according to claim 55, wherein the formulation comprises 2,000 mg of atezolizumab.

58. The article of manufacture according to any one of claims 55-57, wherein the formulation further comprises hyaluronidase.

59. The article of manufacture according to claim 54 or 58, wherein the concentration of the hyaluronidase is 2000 U/mL.

60. The article of manufacture according to any one of claims 54 and 58-59, wherein the hyaluronidase is a recombinant human hyaluronidase.

61. The article of manufacture according to claim 60, wherein the recombinant hyaluronidase is a human soluble PH20 hyaluronidase glycoprotein, such as rHuPH20.

62. The article of manufacture according to any one of claims 50-61, wherein the article of manufacture is a vial.

63. The article of manufacture according to claim 62, wherein the vial is a single dosage vial.

64. The article of manufacture according to claim 62 or 63, wherein the vial is stoppered with a chlorobutyl elastomer stopper.

65. The article of manufacture according to any one of claims 50-61, wherein the article of manufacture is a pre-filled syringe.

66. The article of manufacture according to any one of claims 50-61, wherein the article of manufacture is a syringe pump.

67. The article of manufacture according to any one of claims 50-61, wherein the article of manufacture is a subcutaneous administration device.

68. The article of manufacture according to claim 67, wherein the subcutaneous administration device is selected from the group consisting of a syringe, a syringe pump, an injection device, an infusion pump, an injector pen, a needleless device, an autoinjector, and a subcutaneous patch delivery system.

70. The article of manufacture according to claim 69, wherein the subcutaneous administration device further contains and delivers to the patient a 1,875 mg or 2,000 mg fixed dose of atezolizumab.

71. The article of manufacture according to claim 70, wherein the subcutaneous administration device further contains and delivers to the patient a 1,875 mg fixed dose of atezolizumab.

72. The article of manufacture according to claim 70, wherein the subcutaneous administration device further contains and delivers to the patient a 2,000 mg fixed dose of atezolizumab.

73. The article of manufacture according to any one of claims 69-72, wherein the subcutaneous administration device further contains and delivers to the patient hyaluronidase.

74. The article of manufacture according to claim 73, wherein the hyaluronidase is a human soluble PH20 hyaluronidase glycoprotein, such as rHuPH20.

75. The article of manufacture according to any one of claims 69-74, wherein the subcutaneous administration device is selected from the group consisting of a syringe, a syringe pump, an injection device, an infusion pump, an injector pen, a needleless device, an autoinjector, and a subcutaneous patch delivery system.

76. The article of manufacture according to any one of claims 69-75, wherein the subcutaneous administration device is a syringe.

77. The article of manufacture according to claim 69-75, wherein the subcutaneous administration device is a syringe pump.

78. The article of manufacture according to any one of claims 50-77, wherein the article of manufacture comprises about 3 mL to about 60 mL of the anti-TIGIT full-length monoclonal antibody, and one or more of hyaluronidase, a histidine buffer, sucrose, and polysorbate 20.

79. The article of manufacture according to claim 78, wherein the article of manufacture comprises about 10 mL of tiragolumab, and one or more of hyaluronidase, a histidine buffer, sucrose, and polysorbate 20.

80. The article of manufacture according to claim 78, wherein the article of manufacture comprises about 7 mL of tiragolumab, and one or more of hyaluronidase, a histidine buffer, sucrose, and polysorbate 20.

81. The article of manufacture according to claim 78, wherein the article of manufacture comprises about 6.5 mL of tiragolumab, and one or more of hyaluronidase, a histidine buffer, sucrose, and polysorbate 20.

82. The article of manufacture according to claim 78, wherein the article of manufacture comprises about 21 mL of tiragolumab, and one or more of hyaluronidase, a histidine buffer, sucrose, and polysorbate 20.