WO2025252203A1 - 抗Nectin-4抗体药物偶联物治疗肿瘤的用途 - Google Patents

抗Nectin-4抗体药物偶联物治疗肿瘤的用途

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Publication number
WO2025252203A1
WO2025252203A1 PCT/CN2025/099583 CN2025099583W WO2025252203A1 WO 2025252203 A1 WO2025252203 A1 WO 2025252203A1 CN 2025099583 W CN2025099583 W CN 2025099583W WO 2025252203 A1 WO2025252203 A1 WO 2025252203A1
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Prior art keywords
approximately
antibody
weeks
once
nectin
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PCT/CN2025/099583
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English (en)
French (fr)
Inventor
施薇
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Jiangsu Hengrui Pharmaceutical Co Ltd
Shanghai Shengdi Pharmaceutical Co Ltd
Original Assignee
Jiangsu Hengrui Pharmaceutical Co Ltd
Shanghai Shengdi Pharmaceutical Co Ltd
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Application filed by Jiangsu Hengrui Pharmaceutical Co Ltd, Shanghai Shengdi Pharmaceutical Co Ltd filed Critical Jiangsu Hengrui Pharmaceutical Co Ltd
Publication of WO2025252203A1 publication Critical patent/WO2025252203A1/zh
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/04—Antineoplastic agents specific for metastasis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/22—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors ; against growth regulators
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants

Definitions

  • This disclosure pertains to the pharmaceutical field and relates to methods for treating tumors with anti-Nectin-4 antibody-drug conjugates and their combination with other therapeutic agents, as well as their pharmaceutical uses.
  • Nectin-4 (gene name PVRL4, poliovirus receptor 4) is a protein belonging to the Nectin family of the immunoglobulin superfamily. The Nectin family works in conjunction with cadherins to significantly influence the generation and maintenance of adhesive junctions (AJs) and tight junctions (TJs), regulating various cellular behaviors, including cell adhesion, growth, differentiation, migration, and apoptosis. Unlike Nectin 1-3, which are widely expressed in normal adult tissues, Nectin-4 is specifically expressed in the embryo and placenta, expressed in a few normal adult tissues (including skin), and overexpressed in tumor tissues (distributed not only in AJs but also at cell apex and released into plasma).
  • AJs adhesive junctions
  • TJs tight junctions
  • Nectin-4 exhibits specific high expression in tumor tissues and is closely related to tumor prognosis.
  • the potential mechanisms by which Nectin-4 promotes tumor development and metastasis include: 1) promoting tumor angiogenesis: by activating the PI3K/AKT signaling pathway; 2) promoting tumor cell growth, proliferation, and migration: by activating the Ras-associated C3 botulinum toxin substrate 1 (Rac1) signaling pathway; and 3) promoting epithelial-mesenchymal transition (EMT):
  • Nectin-4 can regulate cell adhesion, remodel the actin cytoskeleton, and enhance the driving force for pseudopodia to extend in tumor cells, ultimately leading to tumor development and spread.
  • ADCs Antibody-drug conjugates
  • ADCs are small molecule drugs with cytotoxic properties covalently linked to an antibody via a chemical link. Using the antibody as a carrier, the drug is delivered directly to target cells. ADCs combine the high targeting specificity of antibodies with the potent cytotoxic effects of cytotoxic drugs, and are considered a next-generation antibody-targeted therapy.
  • Nectin-4 ADCs the antibody specifically recognizes and binds to the Nectin-4 receptor on the surface of target cells. It then enters the target cell via endocytosis, where it is broken down and released into the cell to release the cytotoxic drug. Finally, the cytotoxic drug exerts its anti-tumor effect by damaging DNA or acting on microtubules, preventing cell division, and inducing apoptosis.
  • This disclosure provides a method for treating tumors with anti-Nectin-4 antibody-drug conjugates and their pharmaceutical uses.
  • this disclosure provides for any of the following uses:
  • Anti-Nectin-4 antibody-drug conjugate which is used to treat tumors
  • An anti-Nectin-4 antibody-drug conjugate is used to treat tumors, wherein the anti-Nectin-4 antibody-drug conjugate is administered to a subject in combination with an immunotherapy agent;
  • An immunotherapy agent is used to treat tumors, wherein the immunotherapy agent is administered to a subject in combination with an anti-Nectin-4 antibody-drug conjugate;
  • the anti-Nectin-4 antibody-drug conjugate is used to treat tumors, wherein the anti-Nectin-4 antibody-drug conjugate is administered to the subject in combination with an immunotherapy agent and a VEGF signaling pathway inhibitor;
  • An immunotherapy agent is used to treat tumors, wherein the immunotherapy agent is administered to a subject in combination with an anti-Nectin-4 antibody-drug conjugate and a VEGF signaling pathway inhibitor;
  • VEGF signaling pathway inhibitor wherein the VEGF signaling pathway inhibitor is administered to the subject in combination with an immunotherapy agent and an anti-Nectin-4 antibody-drug conjugate;
  • the anti-Nectin-4 antibody-drug conjugate is used to treat tumors, wherein the anti-Nectin-4 antibody-drug conjugate is administered to the subject in combination with an immunotherapy agent and a platinum-based drug;
  • An immunotherapy agent is used to treat tumors, wherein the immunotherapy agent is administered to a subject in combination with an anti-Nectin-4 antibody-drug conjugate and a platinum-based drug;
  • Platinum-based drugs wherein the platinum-based drugs are administered to the subject in combination with an immunotherapy agent and an anti-Nectin-4 antibody-drug conjugate;
  • a pharmaceutical composition, kit or article for treating tumors wherein the pharmaceutical composition, kit or article comprises an anti-Nectin-4 antibody-drug conjugate;
  • a pharmaceutical composition, kit or article for treating tumors wherein the pharmaceutical composition, kit or article comprises an anti-Nectin-4 antibody-drug conjugate and an immunotherapeutic agent;
  • a pharmaceutical composition, kit or article for treating tumors wherein the pharmaceutical composition, kit or article comprises an anti-Nectin-4 antibody-drug conjugate, an immunotherapeutic agent and a VEGF signaling pathway inhibitor;
  • a pharmaceutical composition, kit or article for treating tumors wherein the pharmaceutical composition, kit or article comprises an anti-Nectin-4 antibody-drug conjugate, an immunotherapy agent and a platinum-based drug;
  • compositions, kit or article in the preparation of a medicament for treating tumors, wherein the pharmaceutical composition, kit or article comprises an anti-Nectin-4 antibody-drug conjugate, an immunotherapeutic agent and a VEGF signaling pathway inhibitor.
  • this disclosure provides a method as shown in any of the following:
  • Methods of treating tumors including administering a therapeutically effective amount of anti-Nectin-4 antibody-drug conjugate to subjects in need;
  • a method of treating tumors including administering a pharmaceutical composition, kit, or article to a subject in need; wherein the pharmaceutical composition, kit, or article comprises an anti-Nectin-4 antibody-drug conjugate;
  • a method of treating tumors comprising administering a pharmaceutical composition, kit, or article to a subject in need; wherein the pharmaceutical composition, kit, or article comprises an anti-Nectin-4 antibody-drug conjugate and an immunotherapeutic agent;
  • a method of treating tumors including administering a pharmaceutical composition, kit, or article to a subject in need; wherein the pharmaceutical composition, kit, or article comprises an anti-Nectin-4 antibody-drug conjugate and an immunotherapeutic agent and a VEGF signaling pathway inhibitor;
  • a method of treating tumors including administering a pharmaceutical composition, kit, or article to a subject in need; wherein the pharmaceutical composition, kit, or article comprises an anti-Nectin-4 antibody-drug conjugate and immunotherapeutic agents and platinum-based drugs.
  • this disclosure provides a product as shown in any of the following:
  • a pharmaceutical composition comprising an anti-Nectin-4 antibody-drug conjugate
  • a pharmaceutical composition comprising an anti-Nectin-4 antibody-drug conjugate and an immunotherapeutic agent
  • a pharmaceutical composition comprising an anti-Nectin-4 antibody-drug conjugate, an immunotherapeutic agent and a VEGF signaling pathway inhibitor;
  • a pharmaceutical composition comprising an anti-Nectin-4 antibody-drug conjugate, an immunotherapeutic agent, and a platinum-based drug;
  • a kit comprising an anti-Nectin-4 antibody-drug conjugate, an immunotherapy agent and a platinum-based drug;
  • Products including anti-Nectin-4 antibody-drug conjugates, immunotherapeutic agents and platinum-based drugs.
  • the kit or article of manufacture further comprises one or more containers, each independently containing an anti-Nectin-4 antibody-drug conjugate. In some embodiments, the kit or article of manufacture further comprises one or more containers, each independently containing an anti-Nectin-4 antibody-drug conjugate and an immunotherapeutic agent. In some embodiments, the kit or article of manufacture further comprises one or more containers, each independently containing an anti-Nectin-4 antibody-drug conjugate, an immunotherapeutic agent, and a VEGF signaling pathway inhibitor. In some embodiments, the kit or article of manufacture further comprises one or more containers, each independently containing an anti-Nectin-4 antibody-drug conjugate, an immunotherapeutic agent, and a platinum-based drug.
  • the anti-Nectin-4 antibody-drug conjugate is present in an individually packaged form in the pharmaceutical composition. In some embodiments, the anti-Nectin-4 antibody-drug conjugate and an immunotherapeutic agent are present in an individually packaged form in the pharmaceutical composition. In some embodiments, the anti-Nectin-4 antibody-drug conjugate, an immunotherapeutic agent, and a VEGF signaling pathway inhibitor are present in an individually packaged form in the pharmaceutical composition. In some embodiments, the anti-Nectin-4 antibody-drug conjugate, an immunotherapeutic agent, and a platinum-based drug are present in an individually packaged form in the pharmaceutical composition.
  • the tumor is a solid tumor. In some embodiments, the tumor is an advanced solid tumor.
  • the tumor is non-small cell lung cancer. In some embodiments, the tumor is advanced non-small cell lung cancer. In some embodiments, the tumor is locally advanced or metastatic non-small cell lung cancer. In some embodiments, the tumor is locally advanced unresectable or metastatic non-small cell lung cancer.
  • the tumor is squamous or non-squamous non-small cell lung cancer.
  • the tumor is squamous non-small cell lung cancer. In some embodiments, the tumor is advanced squamous non-small cell lung cancer. In some embodiments, the tumor is locally advanced or metastatic squamous non-small cell lung cancer. In some embodiments, the tumor is locally advanced unresectable or metastatic squamous non-small cell lung cancer.
  • the tumor is non-squamous non-small cell lung cancer. In some embodiments, the tumor is advanced non-squamous non-small cell lung cancer. In some embodiments, the tumor is locally advanced or metastatic non-squamous non-small cell lung cancer. In some embodiments, the tumor is locally advanced unresectable or metastatic non-squamous non-small cell lung cancer.
  • the tumor is driver gene-positive non-small cell lung cancer. In some embodiments, the tumor is driver gene-positive advanced non-small cell lung cancer. In some embodiments, the tumor is driver gene-positive locally advanced or metastatic non-small cell lung cancer. In some embodiments, the tumor is driver gene-positive locally advanced unresectable or metastatic non-small cell lung cancer.
  • the tumor is EGFR-mutant non-small cell lung cancer. In some embodiments, the tumor is EGFR-mutant advanced non-small cell lung cancer. In some embodiments, the tumor is EGFR-mutant locally advanced or metastatic non-small cell lung cancer. In some embodiments, the tumor is EGFR-mutant locally advanced unresectable or metastatic non-small cell lung cancer.
  • the tumor is a driver gene-positive non-squamous non-small cell lung cancer. In some embodiments, the tumor is a driver gene-positive advanced non-squamous non-small cell lung cancer. In some embodiments, the tumor is a driver gene-positive locally advanced or metastatic non-squamous non-small cell lung cancer. In some embodiments, the tumor is a driver gene-positive locally advanced unresectable or metastatic non-squamous non-small cell lung cancer.
  • the tumor is EGFR-mutant non-squamous non-small cell lung cancer. In some embodiments, the tumor is EGFR-mutant advanced non-squamous non-small cell lung cancer. In some embodiments, the tumor is EGFR-mutant locally advanced or metastatic non-squamous non-small cell lung cancer. In some embodiments, the tumor is EGFR-mutant locally advanced unresectable or metastatic non-squamous non-small cell lung cancer.
  • the tumor is EGFR driver gene negative (also known as "EGFR wild-type,” including driver gene negative and positive for other driver genes besides EGFR) non-squamous non-small cell lung cancer.
  • the tumor is EGFR driver gene negative (EGFR wild-type) advanced non-squamous non-small cell lung cancer.
  • the tumor is EGFR driver gene negative (EGFR wild-type) locally advanced or metastatic non-squamous non-small cell lung cancer.
  • the tumor is EGFR driver gene negative (EGFR wild-type) locally advanced unresectable or metastatic non-squamous non-small cell lung cancer.
  • the tumor is driver gene-negative non-small cell lung cancer. In some embodiments, the tumor is driver gene-negative advanced non-small cell lung cancer. In some embodiments, the tumor is driver gene-negative locally advanced or metastatic non-small cell lung cancer. In some embodiments, the tumor is driver gene-negative locally advanced unresectable or metastatic non-small cell lung cancer.
  • the tumor is driver gene-negative non-squamous non-small cell lung cancer. In some embodiments, the tumor is driver gene-negative advanced non-squamous non-small cell lung cancer. In some embodiments, the tumor is driver gene-negative locally advanced or metastatic non-squamous non-small cell lung cancer. In some embodiments, the tumor is driver gene-negative locally advanced unresectable or metastatic non-squamous non-small cell lung cancer.
  • the tumor is non-squamous non-small cell lung cancer that is positive for other driver genes (driver genes other than EGFR mutations). In some embodiments, the tumor is locally advanced or metastatic non-squamous non-small cell lung cancer that is positive for other driver genes. In some embodiments, the tumor is locally advanced, unresectable, or metastatic non-squamous non-small cell lung cancer that is positive for other driver genes.
  • the tumor is Nectin-4 positive non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 positive advanced non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 positive locally advanced or metastatic non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 positive locally advanced unresectable or metastatic non-small cell lung cancer.
  • the tumor is Nectin-4 negative non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 negative advanced non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 negative locally advanced or metastatic non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 negative locally advanced unresectable or metastatic non-small cell lung cancer.
  • the tumor is esophageal cancer. In some embodiments, the tumor is advanced esophageal cancer. In some embodiments, the tumor is locally advanced or metastatic esophageal cancer. In some embodiments, the tumor is locally advanced unresectable or metastatic esophageal cancer. In some embodiments, the tumor is esophageal squamous cell carcinoma. In some embodiments, the tumor is advanced esophageal squamous cell carcinoma. In some embodiments, the tumor is locally advanced or metastatic esophageal squamous cell carcinoma. In some embodiments, the tumor is locally advanced unresectable or metastatic esophageal squamous cell carcinoma.
  • subjects with any of the aforementioned non-small cell lung cancer or esophageal cancer have previously received standard anti-tumor treatment selected from chemotherapy, immunotherapy, and/or targeted therapy, wherein the chemotherapy includes platinum-based chemotherapy.
  • the subject with driver gene-negative non-small cell lung cancer as described above has previously received standard anti-tumor therapy, which includes immunotherapy and platinum-based chemotherapy.
  • the immunotherapy is PD-1/PD-L1 inhibitor therapy.
  • the subject has previously received ⁇ 2 lines of chemotherapy.
  • the subject has previously received ⁇ 2 lines of anti-tumor therapy.
  • subjects with driver gene-positive non-small cell lung cancer as described above who have previously received standard anti-tumor therapy, and whose standard anti-tumor therapy is the same as that for driver gene-negative subjects if no approved targeted therapy is available for the driver gene, are included in some implementations.
  • the standard anti-tumor therapy includes immunotherapy and platinum-based chemotherapy, wherein the immunotherapy is a PD-1/PD-L1 inhibitor.
  • the subject has received ⁇ 2 lines of chemotherapy.
  • the subject has received ⁇ 2 lines of anti-tumor therapy.
  • a subject with driver gene-positive non-small cell lung cancer as described above has previously received standard anti-tumor therapy, and if an approved targeted therapy is available for the driver gene, their standard anti-tumor therapy includes at least one targeted drug therapy.
  • the standard anti-tumor therapy includes at least one targeted drug therapy and platinum-based chemotherapy.
  • the subject has received ⁇ 2 lines of chemotherapy. In some embodiments, the subject has received ⁇ 2 lines of anti-tumor therapy.
  • the subject with any of the foregoing descriptions of esophageal cancer has previously received standard anti-tumor therapy, which includes immunotherapy and platinum-based chemotherapy.
  • the immunotherapy is PD-1/PD-L1 inhibitor therapy.
  • the subject has previously received ⁇ 2 lines of chemotherapy.
  • the subject has previously received ⁇ 2 lines of anti-tumor therapy.
  • subjects with any of the aforementioned non-small cell lung cancer or esophageal cancer who have previously failed or are intolerant of standard anti-tumor therapy have no standard therapy available, or refuse standard therapy, wherein the standard anti-tumor therapy is selected from chemotherapy, immunotherapy, and/or targeted drug therapy, wherein the chemotherapy includes platinum-based chemotherapy.
  • subjects with driver gene-negative non-small cell lung cancer as described in any of the preceding embodiments have previously failed or are intolerant of standard anti-tumor therapy, have no standard therapy available, or refuse standard therapy, wherein the standard anti-tumor therapy includes immunotherapy and platinum-based chemotherapy.
  • the immunotherapy is PD-1/PD-L1 inhibitor therapy.
  • the subject has previously received ⁇ 2 lines of chemotherapy.
  • the subject has previously received ⁇ 2 lines of anti-tumor therapy.
  • the standard anti-tumor therapy includes immunotherapy and platinum-based chemotherapy, wherein the immunotherapy is a PD-1/PD-L1 inhibitor.
  • the subject has received ⁇ 2 lines of chemotherapy.
  • the subject has received ⁇ 2 lines of anti-tumor therapy.
  • the standard anti-tumor therapy comprises at least one targeted drug therapy and platinum-based chemotherapy.
  • the subject has previously received ⁇ 2 lines of chemotherapy. In some embodiments, the subject has previously received ⁇ 2 lines of anti-tumor therapy.
  • the subject with any of the foregoing descriptions of esophageal cancer has previously failed or is intolerant of standard anti-tumor therapy, has no standard therapy available, or refuses standard therapy, which includes immunotherapy and platinum-based chemotherapy.
  • the immunotherapy is a PD-1/PD-L1 inhibitor.
  • the subject has previously received ⁇ 2 lines of chemotherapy.
  • the subject has previously received ⁇ 2 lines of anti-tumor therapy.
  • the subject with any of the aforementioned non-small cell lung cancer or esophageal cancer is previously untreated (has not received systemic anti-tumor therapy).
  • the subject with any of the aforementioned driver gene-positive non-small cell lung cancer is previously untreated (has not received systemic anti-tumor therapy), and there is no approved targeted therapy for the driver gene.
  • subjects with any of the aforementioned non-small cell lung cancers are previously untreated (have not received systemic antitumor therapy) and have a single STK11 mutation, a single KEAP1 mutation, or a STK11/KEAP1 co-mutation.
  • the positive driver gene includes, but is not limited to, EGFR mutations, ALK fusions, ROS1 fusions, BRAF V600E mutations, NTRK fusions, MET14 exon skipping mutations, RET fusions, KRAS G12C mutations, HER-2 mutations, EGFR T790M mutations, and/or EGFR exon 20 insertions.
  • the positive driver gene is an EGFR mutation or other driver gene positivity.
  • the tumor is driver gene-negative squamous non-small cell lung cancer. In some embodiments, the tumor is driver gene-negative locally advanced or metastatic squamous non-small cell lung cancer. In some embodiments, the tumor is driver gene-negative locally advanced unresectable or metastatic squamous non-small cell lung cancer. In some embodiments, the tumor is driver gene-positive squamous non-small cell lung cancer. In some embodiments, the tumor is driver gene-positive locally advanced or metastatic squamous non-small cell lung cancer. In some embodiments, the tumor is driver gene-positive locally advanced unresectable or metastatic squamous non-small cell lung cancer.
  • the tumor is driver gene-negative non-squamous non-small cell lung cancer. In some embodiments, the tumor is driver gene-negative locally advanced or metastatic non-squamous non-small cell lung cancer. In some embodiments, the tumor is driver gene-negative locally advanced unresectable or metastatic non-squamous non-small cell lung cancer.
  • the tumor is Nectin-4 positive squamous or non-squamous non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 positive squamous non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 positive locally advanced or metastatic squamous non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 positive locally advanced unresectable or metastatic squamous non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 positive non-squamous non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 positive locally advanced or metastatic non-squamous non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 positive locally advanced unresectable or metastatic non-squamous non-small cell lung cancer.
  • the tumor is Nectin-4 negative squamous or non-squamous non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 negative squamous non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 negative locally advanced or metastatic squamous non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 negative locally advanced unresectable or metastatic squamous non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 negative non-squamous non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 negative locally advanced or metastatic non-squamous non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 negative locally advanced unresectable or metastatic non-squamous non-small cell lung cancer.
  • the tumor is Nectin-4 positive and driver gene positive non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 positive and driver gene positive locally advanced or metastatic non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 positive and driver gene positive locally advanced unresectable or metastatic non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 positive and driver gene negative non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 positive and driver gene negative locally advanced or metastatic non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 positive and driver gene negative locally advanced or metastatic non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 positive and driver gene negative locally advanced or metastatic non-small cell lung cancer.
  • the tumor is Nectin-4 positive and EGFR driver gene negative (EGFR wild-type) non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 positive and EGFR driver gene negative locally advanced or metastatic non-small cell lung cancer. In some embodiments, the tumor is locally advanced, unresectable, or metastatic non-small cell lung cancer that is Nectin-4 positive and EGFR driver gene negative. In some embodiments, the tumor is Nectin-4 negative and driver gene positive non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 negative and driver gene positive locally advanced or metastatic non-small cell lung cancer.
  • the tumor is Nectin-4 negative and driver gene positive locally advanced or metastatic non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 negative and driver gene negative non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 negative and driver gene negative locally advanced or metastatic non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 negative and driver gene negative locally advanced or metastatic non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 negative and driver gene negative locally advanced or metastatic non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 negative and EGFR driver gene negative locally advanced or metastatic non-small cell lung cancer. In some embodiments, the tumor is locally advanced, unresectable, or metastatic non-small cell lung cancer that is Nectin-4 negative and EGFR driver gene negative.
  • the tumor is Nectin-4 positive and driver gene positive squamous non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 positive and driver gene positive locally advanced or metastatic squamous non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 positive and driver gene positive locally advanced unresectable or metastatic squamous non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 positive and driver gene negative squamous non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 positive and driver gene negative locally advanced or metastatic squamous non-small cell lung cancer.
  • the tumor is Nectin-4 positive and driver gene negative locally advanced or metastatic squamous non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 negative and driver gene positive squamous non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 negative and driver gene positive locally advanced or metastatic squamous non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 negative and driver gene positive locally advanced unresectable or metastatic squamous non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 negative and driver gene negative squamous non-small cell lung cancer.
  • the tumor is Nectin-4 negative and driver gene negative locally advanced or metastatic squamous non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 negative and driver gene negative locally advanced unresectable or metastatic squamous non-small cell lung cancer.
  • the tumor is Nectin-4 positive and driver gene positive non-squamous non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 positive and driver gene positive locally advanced or metastatic non-squamous non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 positive and driver gene positive locally advanced unresectable or metastatic non-squamous non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 positive and driver gene negative non-squamous non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 positive and driver gene negative locally advanced or metastatic non-squamous non-small cell lung cancer.
  • the tumor is Nectin-4 positive and driver gene negative locally advanced or metastatic non-squamous non-small cell lung cancer.
  • the tumor is Nectin-4 positive and EGFR driver gene negative (EGFR wild-type) non-squamous non-small cell lung cancer.
  • the tumor is Nectin-4 positive and EGFR driver gene negative locally advanced or metastatic non-squamous non-small cell lung cancer.
  • the tumor is locally advanced, unresectable, or metastatic non-squamous non-small cell lung cancer that is Nectin-4 positive and EGFR driver gene negative.
  • the tumor is Nectin-4 negative and driver gene positive non-squamous non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 negative and driver gene positive locally advanced or metastatic non-squamous non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 negative and driver gene positive locally advanced or metastatic non-squamous non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 negative and driver gene negative non-squamous non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 negative and driver gene negative locally advanced or metastatic non-squamous non-small cell lung cancer.
  • the tumor is Nectin-4 negative and EGFR driver gene negative non-squamous non-small cell lung cancer. In some embodiments, the tumor is locally advanced or metastatic non-squamous non-small cell lung cancer that is Nectin-4 negative and EGFR driver gene negative. In some embodiments, the tumor is locally advanced unresectable or metastatic non-squamous non-small cell lung cancer that is Nectin-4 negative and EGFR driver gene negative.
  • the tumor is EGFR-mutant squamous non-small cell lung cancer. In some embodiments, the tumor is EGFR-mutant advanced squamous non-small cell lung cancer. In some embodiments, the tumor is EGFR-mutant locally advanced or metastatic squamous non-small cell lung cancer. In some embodiments, the tumor is EGFR-mutant locally advanced unresectable or metastatic squamous non-small cell lung cancer.
  • the tumor is Nectin-4 positive and EGFR mutation-positive non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 positive and EGFR mutation-positive locally advanced or metastatic non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 positive and EGFR mutation-positive locally advanced unresectable or metastatic non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 negative and EGFR mutation-positive non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 negative and EGFR mutation-positive locally advanced or metastatic non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 negative and EGFR mutation-positive locally advanced unresectable or metastatic non-small cell lung cancer.
  • the tumor is Nectin-4 positive and EGFR mutation-positive squamous non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 positive and EGFR mutation-positive locally advanced or metastatic squamous non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 positive and EGFR mutation-positive locally advanced unresectable or metastatic squamous non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 positive and EGFR mutation-positive non-squamous non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 positive and EGFR mutation-positive locally advanced or metastatic non-squamous non-small cell lung cancer.
  • the tumor is Nectin-4 positive and EGFR mutation-positive locally advanced unresectable or metastatic non-squamous non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 negative and EGFR mutation-positive squamous non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 negative and EGFR mutation-positive locally advanced or metastatic squamous non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 negative and EGFR mutation positive locally advanced unresectable or metastatic squamous non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 negative and EGFR mutation positive non-squamous non-small cell lung cancer.
  • the tumor is Nectin-4 negative and EGFR mutation positive locally advanced or metastatic non-squamous non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 negative and EGFR mutation positive locally advanced unresectable or metastatic non-squamous non-small cell lung cancer.
  • the tumor is non-small cell lung cancer that is positive for other driver genes (driver genes other than EGFR mutations). In some embodiments, the tumor is advanced non-small cell lung cancer that is positive for other driver genes. In some embodiments, the tumor is locally advanced or metastatic non-small cell lung cancer that is positive for other driver genes. In some embodiments, the tumor is locally advanced, unresectable, or metastatic non-small cell lung cancer that is positive for other driver genes.
  • the tumor is squamous non-small cell lung cancer that is positive for other driver genes (driver genes other than EGFR mutations). In some embodiments, the tumor is locally advanced or metastatic squamous non-small cell lung cancer that is positive for other driver genes. In some embodiments, the tumor is locally advanced unresectable or metastatic squamous non-small cell lung cancer that is positive for other driver genes. In some embodiments, the tumor is Nectin-4 positive and other driver gene positive non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 positive and other driver gene positive locally advanced or metastatic non-small cell lung cancer.
  • the tumor is Nectin-4 positive and other driver gene positive locally advanced unresectable or metastatic non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 negative and other driver gene positive non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 negative and other driver gene positive locally advanced or metastatic non-small cell lung cancer. In some implementations, the tumor is locally advanced, unresectable, or metastatic non-small cell lung cancer that is Nectin-4 negative and positive for other driver genes.
  • the tumor is Nectin-4 positive and other driver gene positive squamous non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 positive and other driver gene positive locally advanced or metastatic squamous non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 positive and other driver gene positive locally advanced unresectable or metastatic squamous non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 positive and other driver gene positive non-squamous non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 positive and other driver gene positive locally advanced or metastatic non-squamous non-small cell lung cancer.
  • the tumor is Nectin-4 positive and other driver gene positive locally advanced unresectable or metastatic non-squamous non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 negative and other driver gene positive squamous non-small cell lung cancer. In some embodiments, the tumor is Nectin-4 negative and other driver gene positive locally advanced or metastatic squamous non-small cell lung cancer. In some embodiments, the tumor is locally advanced, unresectable, or metastatic squamous non-small cell lung cancer that is Nectin-4 negative and positive for other driver genes. In some embodiments, the tumor is non-squamous non-small cell lung cancer that is Nectin-4 negative and positive for other driver genes.
  • the tumor is locally advanced or metastatic non-squamous non-small cell lung cancer that is Nectin-4 negative and positive for other driver genes. In some embodiments, the tumor is locally advanced, unresectable, or metastatic non-squamous non-small cell lung cancer that is Nectin-4 negative and positive for other driver genes.
  • the tumor is in a subject who has failed or is intolerant of standard treatment, has no standard treatment, or refuses standard treatment, which includes: for driver gene-negative subjects, receiving immunotherapy and platinum-based chemotherapy; for driver gene-positive subjects, receiving targeted therapy and platinum-based chemotherapy.
  • the tumor is driver gene-negative non-small cell lung cancer that has failed immunotherapy and platinum-based chemotherapy. In some embodiments, the tumor is driver gene-negative locally advanced or metastatic non-small cell lung cancer that has failed immunotherapy and platinum-based chemotherapy. In some embodiments, the tumor is driver gene-negative locally advanced unresectable or metastatic non-small cell lung cancer that has failed immunotherapy and platinum-based chemotherapy.
  • the tumor is driver gene-negative squamous non-small cell lung cancer that has failed immunotherapy and platinum-based chemotherapy. In some embodiments, the tumor is driver gene-negative locally advanced or metastatic squamous non-small cell lung cancer that has failed immunotherapy and platinum-based chemotherapy. In some embodiments, the tumor is driver gene-negative locally advanced unresectable or metastatic squamous non-small cell lung cancer that has failed immunotherapy and platinum-based chemotherapy. In some embodiments, the tumor is driver gene-negative non-squamous non-small cell lung cancer that has failed immunotherapy and platinum-based chemotherapy. In some embodiments, the tumor is driver gene-negative locally advanced or metastatic non-squamous non-small cell lung cancer that has failed immunotherapy and platinum-based chemotherapy. In some embodiments, the tumor is driver gene-negative locally advanced unresectable or metastatic non-squamous non-small cell lung cancer that has failed immunotherapy and platinum-based chemotherapy.
  • the tumor is Nectin-4 negative and driver gene negative non-small cell lung cancer that has failed immunotherapy and platinum-based chemotherapy. In some embodiments, the tumor is Nectin-4 negative and driver gene negative locally advanced or metastatic non-small cell lung cancer that has failed immunotherapy and platinum-based chemotherapy. In some embodiments, the tumor is Nectin-4 negative and driver gene negative locally advanced unresectable or metastatic non-small cell lung cancer that has failed immunotherapy and platinum-based chemotherapy. In some embodiments, the tumor is Nectin-4 positive and driver gene negative non-small cell lung cancer that has failed immunotherapy and platinum-based chemotherapy.
  • the tumor is Nectin-4 positive and driver gene negative locally advanced or metastatic non-small cell lung cancer that has failed immunotherapy and platinum-based chemotherapy. In some embodiments, the tumor is Nectin-4 positive and driver gene negative locally advanced unresectable or metastatic non-small cell lung cancer that has failed immunotherapy and platinum-based chemotherapy.
  • the tumor is Nectin-4 negative and driver gene negative squamous non-small cell lung cancer that has failed immunotherapy and platinum-based chemotherapy. In some embodiments, the tumor is Nectin-4 negative and driver gene negative locally advanced or metastatic squamous non-small cell lung cancer that has failed immunotherapy and platinum-based chemotherapy. In some embodiments, the tumor is Nectin-4 negative and driver gene negative locally advanced unresectable or metastatic squamous non-small cell lung cancer that has failed immunotherapy and platinum-based chemotherapy. In some embodiments, the tumor is Nectin-4 positive and driver gene negative squamous non-small cell lung cancer that has failed immunotherapy and platinum-based chemotherapy.
  • the tumor is Nectin-4 positive and driver gene negative locally advanced or metastatic squamous non-small cell lung cancer that has failed immunotherapy and platinum-based chemotherapy. In some embodiments, the tumor is Nectin-4 positive and driver gene negative locally advanced unresectable or metastatic squamous non-small cell lung cancer that has failed immunotherapy and platinum-based chemotherapy.
  • the tumor is Nectin-4 negative and driver gene negative, and is a non-squamous non-small cell lung cancer that has failed immunotherapy and platinum-based chemotherapy.
  • the tumor is Nectin-4 negative and driver gene negative, and is a locally advanced or metastatic non-squamous non-small cell lung cancer that has failed immunotherapy and platinum-based chemotherapy.
  • the tumor is Nectin-4 negative and driver gene negative, and is a locally advanced unresectable or metastatic non-squamous non-small cell lung cancer that has failed immunotherapy and platinum-based chemotherapy.
  • the tumor is Nectin-4 positive and driver gene negative, and is a non-squamous non-small cell lung cancer that has failed immunotherapy and platinum-based chemotherapy.
  • the tumor is Nectin-4 positive and driver gene negative, and is a locally advanced or metastatic non-squamous non-small cell lung cancer that has failed immunotherapy and platinum-based chemotherapy.
  • the tumor is Nectin-4 positive and driver gene negative, and is a locally advanced unresectable or metastatic non-squamous non-small cell lung cancer that has failed immunotherapy and platinum-based chemotherapy.
  • the tumor is driver gene-positive non-small cell lung cancer that has failed at least one targeted therapy and platinum-based chemotherapy. In some embodiments, the tumor is driver gene-positive locally advanced or metastatic non-small cell lung cancer that has failed at least one targeted therapy and platinum-based chemotherapy. In some embodiments, the tumor is driver gene-positive locally advanced unresectable or metastatic non-small cell lung cancer that has failed at least one targeted therapy and platinum-based chemotherapy.
  • the tumor is a driver gene-positive squamous non-small cell lung cancer that has failed at least one targeted therapy and platinum-based chemotherapy. In some embodiments, the tumor is a driver gene-positive locally advanced or metastatic squamous non-small cell lung cancer that has failed at least one targeted therapy and platinum-based chemotherapy. In some embodiments, the tumor is a driver gene-positive locally advanced unresectable or metastatic squamous non-small cell lung cancer that has failed at least one targeted therapy and platinum-based chemotherapy. In some embodiments, the tumor is a driver gene-positive non-squamous non-small cell lung cancer that has failed at least one targeted therapy and platinum-based chemotherapy.
  • the tumor is a driver gene-positive locally advanced or metastatic non-squamous non-small cell lung cancer that has failed at least one targeted therapy and platinum-based chemotherapy. In some embodiments, the tumor is a driver gene-positive locally advanced unresectable or metastatic non-squamous non-small cell lung cancer that has failed at least one targeted therapy and platinum-based chemotherapy.
  • the tumor is Nectin-4 negative and driver gene positive, and is a non-small cell lung cancer that has failed at least one targeted therapy and platinum-based chemotherapy.
  • the tumor is Nectin-4 negative and driver gene positive, and is a locally advanced or metastatic non-small cell lung cancer that has failed at least one targeted therapy and platinum-based chemotherapy.
  • the tumor is Nectin-4 negative and driver gene positive, and is a locally advanced, unresectable or metastatic non-small cell lung cancer that has failed at least one targeted therapy and platinum-based chemotherapy.
  • the tumor is Nectin-4 positive and driver gene positive, and is a non-small cell lung cancer that has failed at least one targeted therapy and platinum-based chemotherapy.
  • the tumor is Nectin-4 positive and driver gene positive, and is a locally advanced or metastatic non-small cell lung cancer that has failed at least one targeted therapy and platinum-based chemotherapy. In some embodiments, the tumor is Nectin-4 positive and driver gene positive, and is a locally advanced, unresectable or metastatic non-small cell lung cancer that has failed at least one targeted therapy and platinum-based chemotherapy.
  • the tumor is Nectin-4 negative and driver gene positive squamous non-small cell lung cancer that has failed at least one targeted therapy and platinum-based chemotherapy. In some embodiments, the tumor is Nectin-4 negative and driver gene positive locally advanced or metastatic squamous non-small cell lung cancer that has failed at least one targeted therapy and platinum-based chemotherapy. In some embodiments, the tumor is Nectin-4 negative and driver gene positive locally advanced unresectable or metastatic squamous non-small cell lung cancer that has failed at least one targeted therapy and platinum-based chemotherapy. In some embodiments, the tumor is Nectin-4 positive and driver gene positive squamous non-small cell lung cancer that has failed at least one targeted therapy and platinum-based chemotherapy.
  • the tumor is Nectin-4 positive and driver gene positive locally advanced or metastatic squamous non-small cell lung cancer that has failed at least one targeted therapy and platinum-based chemotherapy.
  • the tumor is a locally advanced, unresectable or metastatic squamous non-small cell lung cancer that is Nectin-4 positive and driver gene positive and has failed at least one targeted therapy and platinum-based chemotherapy.
  • the tumor is Nectin-4 negative and driver gene positive, and is a non-squamous non-small cell lung cancer that has failed at least one targeted therapy and platinum-based chemotherapy.
  • the tumor is Nectin-4 negative and driver gene positive, and is a locally advanced or metastatic non-squamous non-small cell lung cancer that has failed at least one targeted therapy and platinum-based chemotherapy.
  • the tumor is Nectin-4 negative and driver gene positive, and is a locally advanced unresectable or metastatic non-squamous non-small cell lung cancer that has failed at least one targeted therapy and platinum-based chemotherapy.
  • the tumor is Nectin-4 positive and driver gene positive, and is a non-squamous non-small cell lung cancer that has failed at least one targeted therapy and platinum-based chemotherapy.
  • the tumor is Nectin-4 positive and driver gene positive, and is a locally advanced or metastatic non-squamous non-small cell lung cancer that has failed at least one targeted therapy and platinum-based chemotherapy.
  • the tumor is locally advanced, unresectable or metastatic non-squamous non-small cell lung cancer that is Nectin-4 positive and driver gene positive and has failed at least one targeted therapy and platinum-based chemotherapy.
  • the tumor is EGFR mutation-positive non-small cell lung cancer that has failed at least one targeted therapy and platinum-based chemotherapy. In some embodiments, the tumor is EGFR mutation-positive locally advanced or metastatic non-small cell lung cancer that has failed at least one targeted therapy and platinum-based chemotherapy. In some embodiments, the tumor is EGFR mutation-positive locally advanced unresectable or metastatic non-small cell lung cancer that has failed at least one targeted therapy and platinum-based chemotherapy.
  • the tumor is EGFR mutation-positive squamous non-small cell lung cancer that has failed at least one targeted therapy and platinum-based chemotherapy. In some embodiments, the tumor is EGFR mutation-positive locally advanced or metastatic squamous non-small cell lung cancer that has failed at least one targeted therapy and platinum-based chemotherapy. In some embodiments, the tumor is EGFR mutation-positive locally advanced unresectable or metastatic squamous non-small cell lung cancer that has failed at least one targeted therapy and platinum-based chemotherapy. In some embodiments, the tumor is EGFR mutation-positive non-squamous non-small cell lung cancer that has failed at least one targeted therapy and platinum-based chemotherapy.
  • the tumor is EGFR mutation-positive locally advanced or metastatic non-squamous non-small cell lung cancer that has failed at least one targeted therapy and platinum-based chemotherapy. In some embodiments, the tumor is EGFR mutation-positive locally advanced unresectable or metastatic non-squamous non-small cell lung cancer that has failed at least one targeted therapy and platinum-based chemotherapy.
  • the tumor is Nectin-4 negative and EGFR mutation positive non-small cell lung cancer that has failed at least one targeted therapy and platinum-based chemotherapy. In some embodiments, the tumor is Nectin-4 negative and EGFR mutation positive locally advanced or metastatic non-small cell lung cancer that has failed at least one targeted therapy and platinum-based chemotherapy. In some embodiments, the tumor is Nectin-4 negative and EGFR mutation positive locally advanced unresectable or metastatic non-small cell lung cancer that has failed at least one targeted therapy and platinum-based chemotherapy. In some embodiments, the tumor is Nectin-4 positive and EGFR mutation positive non-small cell lung cancer that has failed at least one targeted therapy and platinum-based chemotherapy.
  • the tumor is Nectin-4 positive and EGFR mutation positive locally advanced or metastatic non-small cell lung cancer that has failed at least one targeted therapy and platinum-based chemotherapy. In some embodiments, the tumor is Nectin-4 positive and EGFR mutation positive locally advanced unresectable or metastatic non-small cell lung cancer that has failed at least one targeted therapy and platinum-based chemotherapy.
  • the tumor is Nectin-4 positive and EGFR mutation positive squamous non-small cell lung cancer that has failed at least one targeted therapy and platinum-based chemotherapy.
  • the tumor is Nectin-4 positive and EGFR mutation positive locally advanced or metastatic squamous non-small cell lung cancer that has failed at least one targeted therapy and platinum-based chemotherapy.
  • the tumor is locally advanced, unresectable or metastatic squamous non-small cell lung cancer that is Nectin-4 positive and EGFR mutation positive and has failed at least one targeted therapy and platinum-based chemotherapy.
  • the tumor is Nectin-4 negative and EGFR mutation positive, and is a non-squamous non-small cell lung cancer that has failed at least one targeted therapy and platinum-based chemotherapy.
  • the tumor is Nectin-4 negative and EGFR mutation positive, and is a locally advanced or metastatic non-squamous non-small cell lung cancer that has failed at least one targeted therapy and platinum-based chemotherapy.
  • the tumor is Nectin-4 negative and EGFR mutation positive, and is a locally advanced unresectable or metastatic non-squamous non-small cell lung cancer that has failed at least one targeted therapy and platinum-based chemotherapy.
  • the tumor is Nectin-4 positive and EGFR mutation positive, and is a non-squamous non-small cell lung cancer that has failed at least one targeted therapy and platinum-based chemotherapy.
  • the tumor is Nectin-4 positive and EGFR mutation positive, and is a locally advanced or metastatic non-squamous non-small cell lung cancer that has failed at least one targeted therapy and platinum-based chemotherapy.
  • the tumor is locally advanced, unresectable or metastatic non-squamous non-small cell lung cancer that is Nectin-4 positive and EGFR mutation positive and has failed at least one targeted therapy and platinum-based chemotherapy.
  • the tumor is non-small cell lung cancer that is positive for other driver genes (excluding EGFR mutation-positive) and has failed at least one targeted therapy and platinum-based chemotherapy.
  • the tumor is locally advanced or metastatic non-small cell lung cancer that is positive for other driver genes (excluding EGFR mutation-positive) and has failed at least one targeted therapy and platinum-based chemotherapy.
  • the tumor is locally advanced, unresectable, or metastatic non-small cell lung cancer that is positive for other driver genes (excluding EGFR mutation-positive) and has failed at least one targeted therapy and platinum-based chemotherapy.
  • the tumor is squamous non-small cell lung cancer that is positive for other driver genes (excluding EGFR mutation-positive) and has failed at least one targeted therapy and platinum-based chemotherapy.
  • the tumor is locally advanced or metastatic squamous non-small cell lung cancer that is positive for other driver genes (excluding EGFR mutation-positive) and has failed at least one targeted therapy and platinum-based chemotherapy.
  • the tumor is locally advanced unresectable or metastatic squamous non-small cell lung cancer that is positive for other driver genes (excluding EGFR mutation-positive) and has failed at least one targeted therapy and platinum-based chemotherapy.
  • the tumor is non-squamous non-small cell lung cancer that is positive for other driver genes and has failed at least one targeted therapy and platinum-based chemotherapy.
  • the tumor is locally advanced or metastatic non-squamous non-small cell lung cancer that is positive for other driver genes (excluding EGFR mutation-positive) and has failed at least one targeted therapy and platinum-based chemotherapy.
  • the tumor is locally advanced, unresectable or metastatic non-squamous non-small cell lung cancer that is positive for other driver genes (excluding EGFR mutation-positive driver genes) and has failed at least one targeted therapy and platinum-based chemotherapy.
  • the tumor is Nectin-4 negative and other driver gene positive (excluding EGFR mutation positive), and is a non-small cell lung cancer that has failed at least one targeted therapy and platinum-based chemotherapy.
  • the tumor is Nectin-4 negative and other driver gene positive (excluding EGFR mutation positive), and is a locally advanced or metastatic non-small cell lung cancer that has failed at least one targeted therapy and platinum-based chemotherapy.
  • the tumor is Nectin-4 negative and other driver gene positive (excluding EGFR mutation positive), and is a locally advanced, unresectable, or metastatic non-small cell lung cancer that has failed at least one targeted therapy and platinum-based chemotherapy.
  • the tumor is Nectin-4 positive and other driver gene positive (excluding EGFR mutation positive), and is a non-small cell lung cancer that has failed at least one targeted therapy and platinum-based chemotherapy.
  • the tumor is Nectin-4 positive and other driver gene positive (excluding EGFR mutation positive), and is a locally advanced or metastatic non-small cell lung cancer that has failed at least one targeted therapy and platinum-based chemotherapy.
  • the tumor is locally advanced unresectable or metastatic non-small cell lung cancer that is Nectin-4 positive and other driver gene positive (except for EGFR mutation positive), and has failed at least one targeted therapy and platinum-based chemotherapy.
  • the tumor is Nectin-4 negative and other driver gene positive (excluding EGFR mutation positive), and is a squamous non-small cell lung cancer that has failed at least one targeted therapy and platinum-based chemotherapy.
  • the tumor is Nectin-4 negative and other driver gene positive (excluding EGFR mutation positive), and is a locally advanced or metastatic squamous non-small cell lung cancer that has failed at least one targeted therapy and platinum-based chemotherapy.
  • the tumor is Nectin-4 negative and other driver gene positive (excluding EGFR mutation positive), and is a locally advanced unresectable or metastatic squamous non-small cell lung cancer that has failed at least one targeted therapy and platinum-based chemotherapy.
  • the tumor is Nectin-4 positive and other driver gene positive (excluding EGFR mutation positive), and is a squamous non-small cell lung cancer that has failed at least one targeted therapy and platinum-based chemotherapy.
  • the tumor is locally advanced or metastatic squamous non-small cell lung cancer that is Nectin-4 positive and positive for other driver genes (excluding EGFR mutation-positive), and has failed at least one targeted therapy and platinum-based chemotherapy.
  • the tumor is locally advanced, unresectable, or metastatic squamous non-small cell lung cancer that is Nectin-4 positive and positive for other driver genes (excluding EGFR mutation-positive), and has failed at least one targeted therapy and platinum-based chemotherapy.
  • the tumor is Nectin-4 negative and other driver gene positive (excluding EGFR mutation positive), and is a non-squamous non-small cell lung cancer that has failed at least one targeted therapy and platinum-based chemotherapy.
  • the tumor is Nectin-4 negative and other driver gene positive (excluding EGFR mutation positive), and is a locally advanced or metastatic non-squamous non-small cell lung cancer that has failed at least one targeted therapy and platinum-based chemotherapy.
  • the tumor is Nectin-4 negative and other driver gene positive (excluding EGFR mutation positive), and is a locally advanced unresectable or metastatic non-squamous non-small cell lung cancer that has failed at least one targeted therapy and platinum-based chemotherapy.
  • the tumor is Nectin-4 positive and other driver gene positive (excluding EGFR mutation positive), and is a non-squamous non-small cell lung cancer that has failed at least one targeted therapy and platinum-based chemotherapy.
  • the tumor is locally advanced or metastatic non-squamous non-small cell lung cancer that is Nectin-4 positive and positive for other driver genes (excluding EGFR mutation-positive driver genes), and has failed at least one targeted therapy and platinum-based chemotherapy.
  • the tumor is locally advanced unresectable or metastatic non-squamous non-small cell lung cancer that is Nectin-4 positive and positive for other driver genes (excluding EGFR mutation-positive driver genes), and has failed at least one targeted therapy and platinum-based chemotherapy.
  • the tumor is non-small cell lung cancer (NSCLC) in a subject who has failed or is intolerant of standard treatment.
  • the tumor is NSCLC in a subject who has received ⁇ 2 lines of systemic anti-tumor therapy.
  • the tumor is driver gene-negative non-squamous NSCLC in a subject.
  • the tumor is non-squamous NSCLC in a subject who is driver gene-negative and has progressed after prior platinum-based chemotherapy and PD-(L)1 therapy.
  • the tumor is non-squamous NSCLC in a subject who has a driver gene mutation and has progressed after receiving at least one targeted therapy for that driver gene mutation and after platinum-based chemotherapy.
  • the tumor is in a subject who has not previously received systemic antitumor therapy for non-small cell lung cancer. In some embodiments, the tumor is in a subject who has not previously received systemic antitumor therapy for locally advanced or metastatic non-small cell lung cancer. In some embodiments, the tumor is in a subject who has not previously received systemic antitumor therapy for locally advanced unresectable or metastatic non-small cell lung cancer.
  • the tumor is non-small cell lung cancer in the subject who does not have a positive driver gene. In some embodiments, the tumor is locally advanced or metastatic non-small cell lung cancer in the subject who does not have a positive driver gene. In some embodiments, the tumor is non-squamous non-small cell lung cancer in the subject who does not have a positive driver gene. In some embodiments, the tumor is locally advanced or metastatic non-squamous non-small cell lung cancer in the subject who does not have a positive driver gene. In some embodiments, the tumor is locally advanced unresectable or metastatic non-squamous non-small cell lung cancer in the subject who does not have a positive driver gene.
  • the positive driver gene includes, but is not limited to, EGFR mutation, ALK fusion, ROS1 fusion, BRAF V600E mutation, NTRK fusion, MET14 exon skipping mutation, RET fusion, KRAS G12C mutation, HER-2 mutation, EGFR T790M mutation, and/or EGFR exon 20 insertion.
  • the positive driver gene is EGFR mutation positive or other driver gene positive.
  • the tumor is Nectin-4 positive non-small cell lung cancer with PD-L1 TPS ⁇ 50%. In some embodiments, the tumor is locally advanced or metastatic non-small cell lung cancer that is Nectin-4 positive and has PD-L1 TPS ⁇ 50%.
  • the tumor is Nectin-4 positive squamous non-small cell lung cancer with PD-L1 TPS ⁇ 50%. In some embodiments, the tumor is Nectin-4 positive non-squamous non-small cell lung cancer with PD-L1 TPS ⁇ 50%.
  • the tumor is Nectin-4 positive, locally advanced or metastatic squamous non-small cell lung cancer with PD-L1 TPS ⁇ 50%. In some embodiments, the tumor is Nectin-4 positive, locally advanced or metastatic non-squamous non-small cell lung cancer with PD-L1 TPS ⁇ 50%.
  • the tumor is Nectin-4 positive and driver gene negative non-small cell lung cancer with PD-L1 TPS ⁇ 50%. In some embodiments, the tumor is Nectin-4 positive and driver gene negative locally advanced or metastatic non-small cell lung cancer with PD-L1 TPS ⁇ 50%.
  • the tumor is a squamous non-small cell lung cancer that is Nectin-4 positive and driver gene negative, with PD-L1 TPS ⁇ 50%. In some embodiments, the tumor is a non-squamous non-small cell lung cancer that is Nectin-4 positive and driver gene negative, with PD-L1 TPS ⁇ 50%.
  • the tumor is locally advanced or metastatic squamous non-small cell lung cancer that is Nectin-4 positive and driver gene negative, with PD-L1 TPS ⁇ 50%. In some embodiments, the tumor is locally advanced or metastatic non-squamous non-small cell lung cancer that is Nectin-4 positive and driver gene negative, with PD-L1 TPS ⁇ 50%.
  • the tumor is in subjects who have failed PD-1/PD-L1 inhibitor and platinum-based chemotherapy and have received ⁇ 2 lines of prior therapy. In some embodiments, the tumor is in subjects who have not previously received systemic antitumor therapy for locally advanced unresectable or metastatic esophageal cancer.
  • the tumor is a Nectin-4 positive tumor. In some embodiments, the tumor is a Nectin-4 positive advanced solid tumor. In some embodiments, the tumor is Nectin-4 positive esophageal cancer. In some embodiments, the tumor is Nectin-4 positive locally advanced or metastatic esophageal cancer. In some embodiments, the tumor is Nectin-4 positive esophageal squamous cell carcinoma. In some embodiments, the tumor is Nectin-4 positive locally advanced or metastatic esophageal squamous cell carcinoma.
  • standard treatment and systemic anti-tumor therapy are treatment regimens well-known to those skilled in the art for non-small cell lung cancer (advanced non-small cell lung cancer) or esophageal cancer (advanced esophageal cancer), such as treatment regimens disclosed in treatment guidelines approved by regulatory authorities; and systemic therapy with investigational drugs for solid tumors.
  • treatments include, but are not limited to, detailed and up-to-date information on standard treatment regimens and systemic anti-tumor therapy regimens (including first-line, second-line, third-line, and fourth-line treatment) for various cancers provided in the NCCN and CSCO guidelines.
  • the anti-Nectin-4 antibody-drug conjugates provided in this disclosure are used to treat patients with non-small cell lung cancer who have failed standard therapy ( ⁇ 2 lines of prior chemotherapy), significantly improving the objective response rate and progression-free survival (ORR of 30.4% and DCR of 89.1%). Specifically, for squamous non-small cell lung cancer patients, the ORR is 25%, the DCR is 100%, and the median progression-free survival (mPFS) at an 8 mg/kg dose is 6.0 months; for non-squamous non-small cell lung cancer patients, the ORR is 36.7% and the DCR is 83.3%.
  • mPFS median progression-free survival
  • an ORR of 48.6% and an mPFS of 8.5 months can be achieved at a 6 mg/kg dose, and an ORR of 43.8% and an mPFS of 8.5 months can be achieved at an 8 mg/kg dose; for EGFR-mutant non-squamous non-small cell lung cancer patients...
  • the ORR was 25%, the DCR was 72.7%, and the mPFS at an 8 mg/kg dose was 5.7 months.
  • the ORR at an 8 mg/kg dose was 21.1%
  • the DCR was 68.4%
  • the mPFS was 5.7 months.
  • it has significant therapeutic advantages and provides a positive and effective clinical treatment option for non-small cell lung cancer patients who have failed previous treatment.
  • the anti-Nectin-4 antibody-drug conjugate provided in this disclosure was administered as a monotherapy to subjects with solid tumors, and ⁇ grade 3 TRAEs occurred in 35.2% of all subjects, demonstrating a tolerable and manageable clinical safety profile.
  • the anti-Nectin-4 antibody-drug conjugates provided in this disclosure are used to treat patients with non-small cell lung cancer who have failed standard therapy ( ⁇ 2 lines of prior systemic antitumor therapy), and can significantly improve the objective response rate (ORR).
  • ORR objective response rate
  • the ORR is 30% and the DCR is 80%.
  • the ORR is 29.7% and the DCR is 91.9%, demonstrating significant therapeutic advantages compared to other ADC drugs targeting the same target and other standard treatment regimens, providing a positive and effective clinical treatment option for patients with non-small cell lung cancer who have failed treatment.
  • the anti-Nectin-4 antibody-drug conjugate provided in this disclosure can significantly improve the objective response rate (ORR) in treatment-na ⁇ ve patients with non-small cell lung cancer (NSCLC) who have not previously received systemic antitumor therapy.
  • ORR objective response rate
  • NSCLC non-small cell lung cancer
  • ADC-4 8 mg/kg, Q3W
  • anti-PD-L1 antibody 1200 mg, Q3W
  • DCR disease control rate
  • the anti-Nectin-4 antibody-drug conjugate provided in this disclosure in combination with an immunotherapy agent, was administered to subjects.
  • 38% experienced ⁇ grade 3 TRAEs
  • 26.3% experienced ⁇ grade 3 TRAEs.
  • the combination therapy did not significantly increase drug toxicity, and this combination regimen demonstrated a tolerable and manageable safety advantage.
  • the anti-Nectin-4 antibody-drug conjugate disclosed herein, used as monotherapy is employed to treat esophageal cancer patients who have failed standard therapy ( ⁇ 2 lines of prior chemotherapy).
  • ORR objective response rate
  • PFS progression-free survival
  • DCR disease control rate
  • mPFS median progression-free survival
  • mOS median overall survival
  • the anti-Nectin-4 antibody-drug conjugate provided in this disclosure in combination with an immunotherapy agent, can significantly improve the objective response rate of esophageal cancer patients who have failed standard therapy ( ⁇ 2 lines of prior treatment).
  • dose level 1 ADC-4, 6 mg/kg Q3W + anti-PD-L1 antibody, 1200 mg Q3W
  • the ORR was 23.5% and the DCR was 82.4%.
  • dose level 2 ADC-4, 8 mg/kg Q3W + anti-PD-L1 antibody, 1200 mg Q3W
  • the ORR was 40.5% and the DCR was 89.2%.
  • the anti-Nectin-4 antibody-drug conjugates provided in this disclosure can significantly improve the objective response rate (ORR) in treatment-na ⁇ ve esophageal cancer patients (who have not previously received systemic antitumor therapy).
  • ORR objective response rate
  • the ORR was 64.7% and the DCR was 91.2%.
  • the anti-Nectin-4 antibody-drug conjugate provided in this disclosure administered in combination with an immunotherapy agent, has demonstrated a tolerable and manageable clinical safety profile in esophageal cancer patients, with only 18.8% of treatment-na ⁇ ve esophageal cancer patients experiencing a grade ⁇ 3 TRAE.
  • the combination therapy did not significantly increase drug toxicity, demonstrating a tolerable and manageable safety advantage.
  • the anti-Nectin-4 antibody-drug conjugate is derived from antibody-drug conjugates of any structure in WO2022228406A and WO2023221971A.
  • the structure, preparation method and other related contents of the immunoconjugates in the above patents are incorporated herein by reference.
  • the anti-Nectin-4 antibody-drug conjugate has the structure shown in the following formula:
  • n is 1 to 10
  • n is a decimal or an integer.
  • n is 1 to 8.
  • n is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or any decimal or integer between any two of the aforementioned values.
  • n is an integer or decimal of 3 to 5, for example, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 4.0, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 5.0.
  • n is 3.5 to 4.7.
  • the anti-Nectin-4 antibody is derived from any type of anti-Nectin-4 antibody or its antigen-binding fragment as described in WO2022228406A. This disclosure incorporates the antibody sequences, preparation methods, and other related contents of the aforementioned patent by reference.
  • the anti-Nectin-4 antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3 as shown in SEQ ID NO:1-3, and the light chain variable region comprises LCDR1, LCDR2 and LCDR3 as shown in SEQ ID NO:4-6.
  • VH heavy chain variable region
  • VL light chain variable region
  • the anti-Nectin-4 antibody comprises any one of the aforementioned HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, or any combination of two, three, four, five, or six of them.
  • the anti-Nectin-4 antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL): wherein the VH comprises HCDR1, HCDR2, and HCDR3 of the amino acid sequence shown in SEQ ID NO: 7, and the VL comprises LCDR1, LCDR2, and LCDR3 of the amino acid sequence shown in SEQ ID NO: 8.
  • VH heavy chain variable region
  • VL light chain variable region
  • the aforementioned CDRs are defined according to the Kabat, IMGT, Chothia, AbM, or Contact definition schemes. In some specific embodiments, the CDRs are defined according to the Kabat definition scheme.
  • the anti-Nectin-4 antibody is a chimeric, humanized, fully human antibody or its antigen-binding fragment.
  • the anti-Nectin-4 antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises an amino acid sequence as shown in or having at least 80% or 90% identity with SEQ ID NO: 7, and the VL comprises an amino acid sequence as shown in or having at least 80% or 90% identity with SEQ ID NO: 8.
  • the anti-Nectin-4 antibody comprises any one or both of the aforementioned VH and VL.
  • the anti-Nectin-4 antibody further comprises a heavy chain constant region and/or a light chain constant region.
  • the heavy chain constant region of the antibody may be selected from the constant regions of human IgG1, IgG2, IgG3, IgG4, and their variants.
  • the light chain constant region may be selected from the light chain constant region of human ⁇ , ⁇ chains, or their variants.
  • the anti-Nectin-4 antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises an amino acid sequence as shown in SEQ ID NO:9 or having at least 80% or at least 90% sequence identity with it; and/or, the light chain comprises an amino acid sequence as shown in SEQ ID NO:10 or having at least 80% or at least 90% sequence identity with it.
  • the anti-Nectin-4 antibody comprises a heavy chain with an amino acid sequence as shown in SEQ ID NO:9 and a light chain with an amino acid sequence as shown in SEQ ID NO:10.
  • the underlined portion is the variable region sequence of the antibody heavy or light chain
  • the ununderlined portion is the constant region sequence of the antibody.
  • At least 80% or 90% encompasses 80% and above, such as at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, and any numerical range between the two.
  • antibody is used in the broadest sense, encompassing a wide variety of antibody structures, including but not limited to monoclonal antibodies, polyclonal antibodies, multispecific antibodies (e.g., bispecific antibodies), full-length antibodies, or antigen-binding fragments thereof (also referred to as “antigen-binding portions"), provided they exhibit the desired antigen-binding activity.
  • the antibody is a full-length antibody or an antigen-binding fragment thereof.
  • the anti-Nectin-4 antibody-drug conjugate was prepared as in Example 1.
  • the dosage of the anti-Nectin-4 antibody-drug conjugate may be selected from about 0.1 mg/kg to about 50 mg/kg, about 0.1 mg/kg to about 40 mg/kg, about 0.1 mg/kg to about 30 mg/kg, about 0.1 mg/kg to about 20 mg/kg, about 1.0 mg/kg to about 20 mg/kg, about 1.0 mg/kg to about 19 mg/kg, about 1.0 mg/kg to about 18 mg/kg, about 1.0 mg/kg to about 17 mg/kg, about 1.0 mg/kg to about 16 mg/kg, about 1.0 mg/kg to about 15 mg/kg, about 1.0 mg/kg to about 14 mg/kg, about 1.0 mg/kg to about 13 mg/kg, about 1.0 mg/kg to about 12 mg/kg, about 1.0 mg/kg to about 11 mg/kg, about 1.0 mg/kg to about 10.5 mg/kg, or about 1.0 mg/kg.
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is selected from about 1.0 mg/kg, about 1.1 mg/kg, about 1.2 mg/kg, about 1.3 mg/kg, about 1.4 mg/kg, about 1.5 mg/kg, about 1.6 mg/kg, about 1.7 mg/kg, about 1.8 mg/kg, about 1.9 mg/kg, about 2.0 mg/kg, about 2.1 mg/kg, about 2.2 mg/kg, about 2.3 mg/kg, about 2.4 mg/kg, about 2.5 mg/kg, about 2.6 mg/kg, about 2.7 mg/kg, about 2.8 mg/kg, about 2.9 mg/kg, about 3.0 mg/kg, about 3.1 mg/kg, about 3.2 mg/kg, and about 3.4 mg/kg.
  • mg/kg approximately 3.5 mg/kg, approximately 3.6 mg/kg, approximately 3.7 mg/kg, approximately 3.8 mg/kg, approximately 3.9 mg/kg, approximately 4.0 mg/kg, approximately 4.1 mg/kg, approximately 4.2 mg/kg, approximately 4.3 mg/kg, approximately 4.4 mg/kg, approximately 4.5 mg/kg, approximately 4.6 mg/kg, approximately 4.7 mg/kg, approximately 4.8 mg/kg, approximately 4.9 mg/kg, approximately 5.0 mg/kg, approximately 5.1 mg/kg, approximately 5.2 mg/kg, approximately 5.3 mg/kg, approximately 5.4 mg/kg, approximately 5.5 mg/kg, approximately 5.6 mg/kg, approximately 5.7 mg/kg, approximately 5.8 mg/kg, approximately 5.9 mg/kg, approximately 6.0 mg/kg, approximately 6 0.1 mg/kg, approximately 6.2 mg/kg, approximately 6.3 mg/kg, approximately 6.4 mg/kg, approximately 6.5 mg/kg, approximately 6.6 mg/kg, approximately 6.7 mg/kg, approximately 6.8 mg/kg, approximately 6.9 mg/kg, approximately 7.0 mg/
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is selected from 1.0 mg/kg, 1.1 mg/kg, 1.2 mg/kg, 1.3 mg/kg, 1.4 mg/kg, 1.5 mg/kg, 1.6 mg/kg, 1.7 mg/kg, 1.8 mg/kg, 1.9 mg/kg, 2.0 mg/kg, 2.1 mg/kg, 2.2 mg/kg, 2.3 mg/kg, 2.4 mg/kg, 2.5 mg/kg, 2.6 mg/kg, 2.7 mg/kg, 2.8 mg/kg, 2.9 mg/kg, 3.0 mg/kg, 3.1 mg/kg, 3.2 mg/kg, 3...
  • .4mg/kg 3.5mg/kg, 3.6mg/kg, 3.7mg/kg, 3.8mg/kg, 3.9mg/kg, 4.0mg/kg, 4.1mg/kg, 4.2mg/kg, 4.3mg/kg, 4.4mg/kg, 4.5mg/kg, 4.6mg/kg, 4.7mg /kg, 4.8mg/kg, 4.9mg/kg, 5.0mg/kg, 5.1mg/kg, 5.2mg/kg, 5.3mg/kg, 5.4mg/kg, 5.5mg/kg, 5.6mg/kg, 5.7mg/kg, 5.8mg/kg, 5.9mg/kg, 6.0mg/kg, 6 .1mg/kg, 6.2mg/kg, 6.3mg/kg, 6.4mg/kg, 6.5mg/kg, 6.6mg/kg, 6.7mg/kg, 6.8mg/kg, 6.9mg/kg
  • the anti-Nectin-4 antibody-drug conjugate is administered at least once every 2 weeks, at least once every 3 weeks, at least once every 4 weeks, at least once every 6 weeks, or at least once every 8 weeks. In some embodiments, the anti-Nectin-4 antibody-drug conjugate is administered once every 2 weeks, once every 3 weeks, twice every 3 weeks, once every 4 weeks, once every 6 weeks, or once every 8 weeks. In some embodiments, the anti-Nectin-4 antibody-drug conjugate is administered once every 3 weeks or twice every 3 weeks.
  • the anti-Nectin-4 antibody-drug conjugate is administered at a dose of about 5 mg/kg, about 6 mg/kg, about 7 mg/kg, about 8 mg/kg, about 9 mg/kg, or about 10 mg/kg, at a frequency of once every 3 weeks. In some embodiments, the anti-Nectin-4 antibody-drug conjugate is administered at a dose of about 1 mg/kg, about 2 mg/kg, about 3 mg/kg, or about 4 mg/kg, at a frequency of twice every 3 weeks. In some embodiments, the anti-Nectin-4 antibody-drug conjugate is administered at a dose of about 4 mg/kg, at a frequency of twice every 3 weeks.
  • the anti-Nectin-4 antibody-drug conjugate is administered at a dose of about 1 mg/kg, about 2 mg/kg, about 3 mg/kg, or about 4 mg/kg, at a frequency of twice every 3 weeks, with administration on days D1 and D8 of each cycle. In some embodiments, the anti-Nectin-4 antibody-drug conjugate is administered at a dose of about 4 mg/kg, twice every 3 weeks, on days D1 and D8 of each cycle. In some embodiments, the anti-Nectin-4 antibody-drug conjugate is administered at a dose of about 6 mg/kg or about 8 mg/kg, once every 3 weeks.
  • the anti-Nectin-4 antibody-drug conjugate is administered via oral, parenteral, or transdermal routes; the parenteral administration includes, but is not limited to, intravenous, subcutaneous, and intramuscular injection. In some specific embodiments, the anti-Nectin-4 antibody-drug conjugate is administered via intravenous injection.
  • the anti-Nectin-4 antibody-drug conjugate is formulated in an injectable form.
  • the injectable form of the anti-Nectin-4 antibody-drug conjugate is a solution or lyophilized powder for injection, comprising the anti-Nectin-4 antibody-drug conjugate and one or more pharmaceutically acceptable excipients.
  • the anti-Nectin-4 antibody-drug conjugate is formulated as any composition selected from WO2023221971A.
  • the immunotherapeutic agent comprises any one or a combination of two of anti-PD-L1 antibodies and anti-CTLA-4 antibodies.
  • the immunotherapeutic agent includes any one of the following: an anti-PD-L1 antibody, an anti-CTLA-4 antibody, or a combination of an anti-PD-L1 antibody and an anti-CTLA-4 antibody.
  • the anti-PD-L1 antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3 as shown in SEQ ID NO:11-13, and the light chain variable region comprises LCDR1, LCDR2 and LCDR3 as shown in SEQ ID NO:14-16.
  • VH heavy chain variable region
  • VL light chain variable region
  • the anti-PD-L1 antibody comprises any one of the aforementioned HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, or any combination of two, three, four, five, or six of them.
  • the anti-PD-L1 antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL): wherein the VH comprises HCDR1, HCDR2, and HCDR3 of the amino acid sequence shown in SEQ ID NO: 17, and the VL comprises LCDR1, LCDR2, and LCDR3 of the amino acid sequence shown in SEQ ID NO: 18.
  • VH heavy chain variable region
  • VL light chain variable region
  • the aforementioned CDRs are defined according to the Kabat, IMGT, Chothia, AbM, or Contact definition schemes. In some specific embodiments, the CDRs are defined according to the Kabat definition scheme.
  • the anti-PD-L1 antibody is a chimeric, humanized, fully human antibody or its antigen-binding fragment.
  • the anti-PD-L1 antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises an amino acid sequence as shown in or having at least 80% or 90% identity with SEQ ID NO: 17, and the VL comprises an amino acid sequence as shown in or having at least 80% or 90% identity with SEQ ID NO: 18.
  • VH heavy chain variable region
  • VL light chain variable region
  • the underlined part is the CDR area determined according to the Kabat numbering rules.
  • the anti-PD-L1 antibody comprises any one or both of the aforementioned VH and VL.
  • the anti-PD-L1 antibody further comprises a heavy chain constant region and/or a light chain constant region.
  • the heavy chain constant region of the antibody may be selected from the constant regions of human IgG1, IgG2, IgG3, IgG4, and their variants.
  • the anti-PD-L1 antibody comprises a human IgG2 or IgG4 heavy chain constant region.
  • the anti-PD-L1 antibody comprises an IgG4 heavy chain constant region incorporating F234A and L235A mutations.
  • the light chain constant region may be selected from the light chain constant region of human ⁇ , ⁇ chains, or their variants.
  • the anti-PD-L1 antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises an amino acid sequence as shown in SEQ ID NO:19 or having at least 80% or at least 90% sequence identity therewith; and/or, the light chain comprises an amino acid sequence as shown in SEQ ID NO:20 or having at least 80% or at least 90% sequence identity therewith.
  • the anti-PD-L1 antibody comprises a heavy chain with an amino acid sequence as shown in SEQ ID NO:19 and a light chain with an amino acid sequence as shown in SEQ ID NO:20.
  • the underlined portion is the variable region sequence of the antibody heavy or light chain
  • the ununderlined portion is the constant region sequence of the antibody.
  • the preparation of the above-mentioned anti-PD-L1 antibody or its antigen-binding fragment can refer to WO2017084495A1 and WO2018210230A1.
  • the relevant contents of antibody sequences, preparation methods and compositions in WO2017084495A1 and WO2018210230A1 are incorporated herein by reference.
  • At least 80% or 90% encompasses 80% and above, such as at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, and any numerical range between the two.
  • the dosage of the anti-PD-L1 antibody may be selected from about 5 mg to about 5000 mg, about 50 mg to about 5000 mg, about 100 mg to about 5000 mg, about 100 mg to about 4500 mg, about 100 mg to about 4000 mg, about 100 mg to about 3500 mg, about 100 mg to about 3000 mg, about 100 mg to about 2500 mg, about 100 mg to about 2000 mg, about 100 mg to about 1500 mg, about 500 mg to about 100 mg.
  • mg to about 3500 mg about 500 mg to about 3000 mg, about 500 mg to about 2500 mg, about 500 mg to about 2000 mg, about 500 mg to about 1500 mg, about 800 mg to about 3500 mg, about 800 mg to about 3000 mg, about 800 mg to about 2500 mg, about 800 mg to about 2000 mg, about 800 mg to about 1500 mg, or about 1000 mg to about 1500 mg; and numerical ranges between any two.
  • the dosage of the anti-PD-L1 antibody is approximately 5 mg, approximately 25 mg, approximately 50 mg, approximately 60 mg, approximately 70 mg, approximately 75 mg, approximately 100 mg, approximately 125 mg, approximately 150 mg, approximately 175 mg, approximately 200 mg, 225 mg, approximately 250 mg, approximately 375 mg, approximately 400 mg, approximately 425 mg, approximately 450 mg, approximately 475 mg, approximately 500 mg, approximately 550 mg, approximately 600 mg, 650 mg, approximately 700 mg, and approximately 750 mg.
  • the dosage of the anti-PD-L1 antibody is 5 mg, 25 mg, 50 mg, 60 mg, 70 mg, 75 mg, 100 mg, 125 mg, 150 mg, 175 mg, 200 mg, 225 mg, 250 mg, 375 mg, 400 mg, 425 mg, 450 mg, 475 mg, 500 mg, 550 mg, 600 mg, 650 mg, 700 mg, 750 mg, etc.
  • the dosage of the anti-PD-L1 antibody is approximately 1200 mg.
  • the anti-PD-L1 antibody is administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks. In some specific embodiments, the anti-PD-L1 antibody is administered once every 3 weeks.
  • the dose of the anti-PD-L1 antibody is about 1200 mg, administered once every 3 weeks.
  • the anti-PD-L1 antibody is administered via oral, parenteral, or transdermal routes; the parenteral administration includes, but is not limited to, intravenous, subcutaneous, and intramuscular injection. In some embodiments, the anti-PD-L1 antibody is administered via intravenous injection.
  • the anti-CTLA-4 antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3 as shown in SEQ ID NO:21-23, and the light chain variable region comprises LCDR1, LCDR2 and LCDR3 as shown in SEQ ID NO:24-26.
  • VH heavy chain variable region
  • VL light chain variable region
  • the anti-CTLA-4 antibody comprises any one of the aforementioned HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, or any combination of two, three, four, five, or six of them.
  • the anti-CTLA-4 antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL): wherein the VH comprises HCDR1, HCDR2, and HCDR3 of the amino acid sequence shown in SEQ ID NO: 27, and the VL comprises LCDR1, LCDR2, and LCDR3 of the amino acid sequence shown in SEQ ID NO: 28.
  • VH heavy chain variable region
  • VL light chain variable region
  • the aforementioned CDRs are defined according to the Kabat, IMGT, Chothia, AbM, or Contact definition schemes. In some specific embodiments, the CDRs are defined according to the Kabat definition scheme.
  • the anti-CTLA-4 antibody is a chimeric, humanized, fully human antibody or its antigen-binding fragment.
  • the anti-CTLA-4 antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises an amino acid sequence as shown in or having at least 80% or 90% identity with SEQ ID NO: 27, and the VL comprises an amino acid sequence as shown in or having at least 80% or 90% identity with SEQ ID NO: 28.
  • VH heavy chain variable region
  • VL light chain variable region
  • the anti-CTLA-4 antibody comprises any one or both of the aforementioned VH and VL.
  • the anti-CTLA-4 antibody further comprises a heavy chain constant region and/or a light chain constant region.
  • the heavy chain constant region of the antibody may be selected from the constant regions of human IgG1, IgG2, IgG3, IgG4, and their variants.
  • the light chain constant region may be selected from the light chain constant region of human ⁇ , ⁇ chains, or their variants.
  • the anti-CTLA-4 antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises an amino acid sequence as shown in SEQ ID NO:29 or having at least 80% or at least 90% sequence identity therewith; and/or, the light chain comprises an amino acid sequence as shown in SEQ ID NO:30 or having at least 80% or at least 90% sequence identity therewith.
  • the anti-CTLA-4 antibody comprises a heavy chain with an amino acid sequence as shown in SEQ ID NO:29 and a light chain with an amino acid sequence as shown in SEQ ID NO:30.
  • the underlined portion is the variable region sequence of the antibody heavy or light chain
  • the ununderlined portion is the constant region sequence of the antibody.
  • At least 80% or 90% encompasses 80% and above, such as at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, and any numerical range between the two.
  • the dosage of the anti-CTLA-4 antibody may be selected from about 0.1 mg/kg to about 100 mg/kg, 0.1 mg/kg to about 50 mg/kg, 0.1 mg/kg to about 20 mg/kg, about 0.1 mg/kg to about 10 mg/kg, about 0.1 mg/kg to about 9 mg/kg, about 0.1 mg/kg to about 8 mg/kg, about 0.1 mg/kg to about 7 mg/kg, about 0.1 mg/kg to about 6 mg/kg, about 0.1 mg/kg to about 5 mg/kg, about 0.5 mg/kg to about 50 mg/kg, about 0.5 mg/kg to about 20 mg/kg, about 0.5 mg/kg to about 10 mg/kg, about 0.5 mg/kg to about 9 mg/kg, about 0.5 mg/kg to about 8 mg/kg, about 0.5 mg/kg to about 7 mg/kg, about 0.5 mg/kg to about 6 mg/kg, and about 0.5 mg/kg to about 5 mg/kg.
  • the dosage of the anti-CTLA-4 antibody is approximately 0.1 mg/kg, approximately 0.2 mg/kg, approximately 0.3 mg/kg, approximately 0.4 mg/kg, approximately 0.5 mg/kg, approximately 0.6 mg/kg, approximately 0.7 mg/kg, approximately 0.8 mg/kg, approximately 0.9 mg/kg, approximately 1.0 mg/kg, approximately 1.1 mg/kg, approximately 1.2 mg/kg, approximately 1.3 mg/kg, and approximately 1.4 mg/kg.
  • mg/kg approximately 4.9 mg/kg, approximately 5.0 mg/kg, approximately 5.1 mg/kg, approximately 5.2 mg/kg, approximately 5.3 mg/kg, approximately 5.4 mg/kg, approximately 5.5 mg/kg, approximately 5.6 mg/kg, approximately 5.7 mg/kg, approximately 5.8 mg/kg, approximately 5.9 mg/kg, approximately 6.0 mg/kg, approximately 6.1 mg/kg, approximately 6.2 mg/kg, approximately 6.3 mg/kg, approximately 6.4 mg/kg, approximately 6.5 mg/kg, approximately 6.6 mg/kg, approximately 6.7 mg/kg, approximately 6.8 mg/kg, approximately 6.9 mg/kg, approximately 7.0 mg/kg, approximately 7.1 mg/kg, approximately 7.2 mg/kg, approximately 7.3 mg/kg, approximately 7.4 mg/kg, approximately 7.5 mg/kg, approximately 7.6 mg/kg, approximately 7.7 mg/kg, approximately 7.8 mg/kg, approximately 7.9 mg/kg, approximately 8.0 mg/kg, approximately 8.1 mg/kg kg, approximately 8.2 mg/kg, approximately 8.3 mg/kg, approximately 8.4 mg/
  • mg/kg approximately 9.9 mg/kg, approximately 10.0 mg/kg, approximately 10.5 mg/kg, approximately 11 mg/kg, approximately 11.5 mg/kg, approximately 12 mg/kg, approximately 12.5 mg/kg, approximately 13 mg/kg, approximately 13.5 mg/kg, approximately 14 mg/kg, approximately 14.5 mg/kg, approximately 15 mg/kg, approximately 15 mg/kg, approximately 16 mg/kg, approximately 17 mg/kg, approximately 18 mg/kg, approximately 19 mg/kg g/kg, approximately 20 mg/kg, approximately 21 mg/kg, approximately 22 mg/kg, approximately 23 mg/kg, approximately 24 mg/kg, approximately 25 mg/kg, approximately 26 mg/kg, approximately 27 mg/kg, approximately 28 mg/kg, approximately 29 mg/kg, approximately 30 mg/kg, approximately 35 mg/kg, approximately 40 mg/kg, approximately 45 mg/kg, approximately 50 mg/kg, approximately 100 mg/kg, or any range of values between these points.
  • the dosage of the anti-CTLA-4 antibody is 0.1 mg/kg, 0.2 mg/kg, 0.3 mg/kg, 0.4 mg/kg, 0.5 mg/kg, 0.6 mg/kg, 0.7 mg/kg, 0.8 mg/kg, 0.9 mg/kg, 1.0 mg/kg, 1.1 mg/kg, 1.2 mg/kg, 1.3 mg/kg, 1.4 mg/kg, 1.5 mg/kg, 1.6 mg/kg, 1.7 mg/kg, 1.8 mg/kg, 1.9 mg/kg, 2.0 mg/kg, 2.1 mg/kg, 2.2 mg/kg, 2.3 mg/kg, 2.4 mg/kg, 2.5 mg/kg, 2.6 mg/kg, 2.7 mg/kg, 2.8 mg/kg, 2.9 mg/kg, 3.0 mg/kg, 3.1 mg/kg, 3.1 mg/kg, 0.2 mg/kg, 0.3 mg/kg, 0.4 mg/kg, 0.5 mg/kg, 0.6 mg/kg, 0.7 mg/kg, 0.8 mg/kg, 0.9 mg/kg, 1.0 mg/kg,
  • the dosage of the anti-CTLA-4 antibody is approximately 4.0 mg/kg.
  • the dosage of the anti-CTLA-4 antibody may be selected as approximately 1-1000 mg, approximately 1-800 mg, approximately 1-700 mg, approximately 1-600 mg, approximately 1-500 mg, approximately 5-500 mg, approximately 10-500 mg, approximately 20-500 mg, approximately 30-500 mg, approximately 40-500 mg, approximately 50-500 mg, approximately 60-500 mg, approximately 10-400 mg, approximately 20-400 mg, approximately 30-400 mg, approximately 40-400 mg, approximately 50-400 mg, approximately 60-400 mg, approximately 10-350 mg, approximately 20-350 mg, approximately 30-350 mg, approximately 40-3 50 mg, approximately 50-350 mg, approximately 60-350 mg, approximately 10-300 mg, approximately 20-300 mg, approximately 30-300 mg, approximately 40-300 mg, approximately 50-300 mg, approximately 60-300 mg, approximately 10-150 mg, approximately 20-150 mg, approximately 30-150 mg, approximately 40-150 mg, approximately 50-150 mg, approximately 60-150 mg, approximately 10-100 mg, approximately 20-100 mg, approximately 30-100 mg, approximately 40-100 mg, approximately 50-150 mg, approximately 60-150 mg, approximately 10-100 mg, approximately
  • the dosage of the anti-CTLA-4 antibody is about 1 mg, about 5 mg, about 10 mg, about 15 mg, about 20 mg, about 25 mg, about 30 mg, about 31 mg, about 32 mg, about 33 mg, about 34 mg, about 35 mg, about 36 mg, about 37 mg, about 38 mg, about 39 mg, about 40 mg, about 41 mg, about 42 mg, about 43 mg, about 44 mg, about 45 mg, about 46 mg, about 47 mg, about 48 mg, about 49 mg, about 50 mg, or about [other dosages not specified].
  • the dosage of the anti-CTLA-4 antibody is 1 mg, 5 mg, 10 mg, 15 mg, 20 mg, 25 mg, 30 mg, 31 mg, 32 mg, 33 mg, 34 mg, 35 mg, 36 mg, 37 mg, 38 mg, 39 mg, 40 mg, 41 mg, 42 mg, 43 mg, 44 mg, 45 mg, 46 mg, 47 mg, 48 mg, 49 mg, or 50 mg.
  • the dosage of the anti-CTLA-4 antibody is approximately 70 mg.
  • the dosage of the anti-CTLA-4 antibody is about 280 mg or 210 mg.
  • the anti-CTLA-4 antibody is administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 6 weeks, once every 8 weeks, once every 10 weeks, once every 12 weeks, once every 14 weeks, once every 16 weeks, or as a single dose. In some embodiments, the anti-CTLA-4 antibody is administered once every 12 weeks.
  • the anti-CTLA-4 antibody is administered once every 6 weeks or as a single dose. In some embodiments, the anti-CTLA-4 antibody is administered as a single dose of about 280 mg in week 1, with no administration from weeks 2 to 12, and from week 13 onwards, the dose is about 70 mg, administered once every 6 weeks.
  • a 21-day cycle is used. On the first day of the first cycle, a single dose of 280 mg or 210 mg is administered. No dose is administered in cycles 2-4. Starting from the first day of the fifth cycle, 70 mg is administered every 6 weeks (C1D1 280 mg or 210 mg once, C2-C4 no dose, C5 and subsequent cycles 70 mg Q6W).
  • the anti-CTLA-4 antibody is administered via oral, parenteral, or transdermal routes; the parenteral administration includes, but is not limited to, intravenous, subcutaneous, and intramuscular injection. In some embodiments, the anti-CTLA-4 antibody is administered via intravenous injection.
  • the VEGF signaling pathway inhibitor is an anti-VEGF antibody.
  • the anti-VEGF antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3 as shown in SEQ ID NO:31-33, and the light chain variable region comprises LCDR1, LCDR2 and LCDR3 as shown in SEQ ID NO:34-36.
  • VH heavy chain variable region
  • VL light chain variable region
  • the anti-VEGF antibody as described in any of the preceding embodiments comprises a heavy chain variable region and a light chain variable region, wherein the amino acid sequence of the heavy chain variable region HCDR1 is shown in SEQ ID NO: 31, the amino acid sequence of HCDR2 is shown in SEQ ID NO: 32, and the amino acid sequence of HCDR3 is shown in SEQ ID NO: 33, and the amino acid sequence of the light chain variable region LCDR1 is shown in SEQ ID NO: 34, the amino acid sequence of LCDR2 is shown in SEQ ID NO: 35, and the amino acid sequence of LCDR3 is shown in SEQ ID NO: 36.
  • the CDR sequences described above are shown in Table 4 below:
  • the CDR mentioned above is defined according to the Kabat definition scheme.
  • the anti-VEGF antibody as described in any of the preceding embodiments comprises any one of the aforementioned HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, or any combination of two, three, four, five or six of them.
  • the anti-VEGF antibody as described in any of the preceding embodiments comprises a heavy chain variable region and a light chain variable region, the heavy chain variable region comprising HCDR1, HCDR2 and HCDR3 of the amino acid sequence shown in SEQ ID NO: 37, and the light chain variable region comprising LCDR1, LCDR2 and LCDR3 of the amino acid sequence shown in SEQ ID NO: 38.
  • the heavy chain variable regions HCDR1, HCDR2, and HCDR3 and the light chain variable regions LCDR1, LCDR2, and LCDR3 are defined according to a numbering rule selected from Kabat, IMGT, Chothia, AbM, and Contact.
  • the anti-VEGF antibody or its antigen-binding fragment is a chimeric, humanized, or fully human antibody or its antigen-binding fragment.
  • the anti-VEGF antibody or its antigen-binding fragment wherein the heavy chain variable region comprises an amino acid sequence as shown in SEQ ID NO: 37, or an amino acid sequence having at least 80% or 90% sequence identity with it; and the light chain variable region comprises an amino acid sequence as shown in SEQ ID NO: 38, or an amino acid sequence having at least 80% or 90% sequence identity with it.
  • Anti-VEGF antibody heavy chain variable region
  • Anti-VEGF antibody light chain variable region
  • the heavy chain variable region of the anti-VEGF antibody contains an amino acid sequence as shown in or having at least 80% identity with SEQ ID NO: 37, and the light chain variable region contains an amino acid sequence as shown in or having at least 80% identity with SEQ ID NO: 38.
  • the anti-VEGF antibody further comprises a heavy chain constant region and/or a light chain constant region.
  • the heavy chain constant region of the antibody constant region is selected from the human IgG1, IgG2, IgG3 and IgG4 constant regions and their variants;
  • the light chain constant region of the antibody constant region is selected from the human antibody ⁇ and ⁇ chain constant regions and their variants.
  • the anti-VEGF antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises an amino acid sequence as shown in or having at least 80% sequence identity with SEQ ID NO:19; and/or, the light chain comprises an amino acid sequence as shown in or having at least 80% sequence identity with SEQ ID NO:20.
  • the anti-VEGF antibody comprises a heavy chain with an amino acid sequence as shown in SEQ ID NO:39 and a light chain with an amino acid sequence as shown in SEQ ID NO:40.
  • the underlined portion is the variable region sequence of the antibody heavy or light chain
  • the ununderlined portion is the constant region sequence of the antibody.
  • the dosage of the anti-VEGF antibody may be selected from about 1.0 mg/kg to about 30 mg/kg, about 1 mg/kg to about 25 mg/kg; about 1.0 mg/kg to about 20 mg/kg, about 1.0 mg/kg to about 19 mg/kg, about 1.0 mg/kg to about 18 mg/kg, about 1.0 mg/kg to about 17 mg/kg, about 1.0 mg/kg to about 16 mg/kg, about 1.0 mg/kg to about 15 mg/kg, about 1.0 mg/kg to about 14 mg/kg, about 1.0 mg/kg to about 13 mg/kg, about 1.0 mg/kg to about 12 mg/kg, about 1.0 mg/kg to about 11 mg/kg, about 1.0 mg/kg to about 10 mg/kg, about 2 mg/kg to about 25 mg/kg; about 2.0 mg/kg to about 20 mg/kg, about 2.0 mg/kg to about 19 mg/kg, about 2.0 mg/kg to about 18 mg/kg, about 2.0 mg/kg to about 17 mg/kg, about 2.0 mg/kg to about 16 mg
  • the dosage of the anti-VEGF antibody is about 2.0 mg/kg, about 3.0 mg/kg, about 4.0 mg/kg, about 5.0 mg/kg, about 6.0 mg/kg, about 6.5 mg/kg, about 7.0 mg/kg, about 7.5 mg/kg, 8.0 mg/kg, 8.5 mg/kg, about 9.0 mg/kg, about 9.5 mg/kg, about 10.0 mg/kg, about 10.5 mg/kg, about 11.0 mg/kg, about 11.5 mg/kg, about 12.0 mg/kg, about 12.5 mg/kg, about 1 3.0 mg/kg, approximately 13.5 mg/kg, approximately 14.0 mg/kg, approximately 14.5 mg/kg, approximately 15.0 mg/kg, approximately 15.5 mg/kg, approximately 16.0 mg/kg, approximately 16.5 mg/kg, approximately 17.0 mg/kg, approximately 18.0 mg/kg, approximately 19.0 mg/kg, approximately 20.0 mg/kg, approximately 21.0 mg/kg, approximately 22.0 mg/kg, approximately 23.0 mg/kg, approximately 24.0 mg/kg, approximately 25.0 mg/kg,
  • the dosage of the anti-VEGF antibody is 2.0 mg/kg, 3.0 mg/kg, 4.0 mg/kg, 5.0 mg/kg, 6.0 mg/kg, 6.5 mg/kg, 7.0 mg/kg, 7.5 mg/kg, 8.0 mg/kg, 8.5 mg/kg, 9.0 mg/kg, 9.5 mg/kg, 10.0 mg/kg, 10.5 mg/kg, 11.0 mg/kg, 11.5 mg/kg, 12.0 mg/kg, 12.5 mg/kg, 1 3.0 mg/kg, 13.5 mg/kg, 14.0 mg/kg, 14.5 mg/kg, 15.0 mg/kg, 15.5 mg/kg, 16.0 mg/kg, 16.5 mg/kg, 17.0 mg/kg, 18.0 mg/kg, 19.0 mg/kg, 20.0 mg/kg, 21.0 mg/kg, 22.0 mg/kg, 23.0 mg/kg, 24.0 mg/kg, 25.0 mg/kg, 30.0 mg/kg, or any range between these values.
  • the anti-VEGF antibody is administered once every 1 week, once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 6 weeks, once every 8 weeks, once every 10 weeks, or once every 12 weeks. In some specific embodiments, the anti-VEGF antibody is administered once every 3 weeks.
  • the dosing regimen for the anti-VEGF antibody is selected from any of the following:
  • the dosage of the anti-VEGF antibody is from about 1.0 mg/kg to about 30 mg/kg, and the dosing frequency is once every 1 week, once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 6 weeks, once every 8 weeks, once every 10 weeks, or once every 12 weeks.
  • the dosage of the anti-VEGF antibody is from about 1.0 mg/kg to about 25 mg/kg, and the dosing frequency is once every 1 week, once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 6 weeks, once every 8 weeks, once every 10 weeks, or once every 12 weeks.
  • the dosage of the anti-VEGF antibody is from about 2.0 mg/kg to about 25 mg/kg, and the dosing frequency is once every 1 week, once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 6 weeks, once every 8 weeks, once every 10 weeks, or once every 12 weeks.
  • the dosage of the anti-VEGF antibody is from about 7.0 mg/kg to about 23 mg/kg, and the dosing frequency is once every 1 week, once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 6 weeks, once every 8 weeks, once every 10 weeks, or once every 12 weeks.
  • the dosage of the anti-VEGF antibody is from about 2.0 mg/kg to about 20 mg/kg, and the dosing frequency is once every 1 week, once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 6 weeks, once every 8 weeks, once every 10 weeks, or once every 12 weeks.
  • the dosage of the anti-VEGF antibody is from about 5.0 mg/kg to about 20 mg/kg, and the dosing frequency is once every 1 week, once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 6 weeks, once every 8 weeks, once every 10 weeks, or once every 12 weeks.
  • the dosage of the anti-VEGF antibody is from about 7.0 mg/kg to about 20 mg/kg, and the dosing frequency is once every 1 week, once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 6 weeks, once every 8 weeks, once every 10 weeks, or once every 12 weeks.
  • the dosage of the anti-VEGF antibody is from about 8.0 mg/kg to about 20 mg/kg, and the dosing frequency is once every 1 week, once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 6 weeks, once every 8 weeks, once every 10 weeks, or once every 12 weeks.
  • the dosage of the anti-VEGF antibody is from about 9.0 mg/kg to about 20 mg/kg, and the dosing frequency is once every 1 week, once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 6 weeks, once every 8 weeks, once every 10 weeks, or once every 12 weeks.
  • the dosage of the anti-VEGF antibody is about 10 mg/kg to about 20 mg/kg, and the dosing frequency is once every 1 week, once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 6 weeks, once every 8 weeks, once every 10 weeks, or once every 12 weeks.
  • the dosage of the anti-VEGF antibody is from about 11 mg/kg to about 19 mg/kg, and the dosing frequency is once every 1 week, once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 6 weeks, once every 8 weeks, once every 10 weeks, or once every 12 weeks.
  • the dosage of the anti-VEGF antibody is about 12 mg/kg to about 18 mg/kg, and the dosing frequency is once every 1 week, once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 6 weeks, once every 8 weeks, once every 10 weeks, or once every 12 weeks.
  • the dosage of the anti-VEGF antibody is from about 13 mg/kg to about 17 mg/kg, and the dosing frequency is once every 1 week, once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 6 weeks, once every 8 weeks, once every 10 weeks, or once every 12 weeks.
  • the dosage of the anti-VEGF antibody is about 14 mg/kg to about 16 mg/kg, and the dosing frequency is once every 1 week, once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 6 weeks, once every 8 weeks, once every 10 weeks, or once every 12 weeks.
  • the dosage of the anti-VEGF antibody is about 14 mg/kg to about 16 mg/kg, and the dosing frequency is once every 1 week, once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 6 weeks, once every 8 weeks, once every 10 weeks, or once every 12 weeks.
  • the dosage of the anti-VEGF antibody is from about 1 mg/kg to about 15 mg/kg, and the dosing frequency is once every 1 week, once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 6 weeks, once every 8 weeks, once every 10 weeks, or once every 12 weeks.
  • the dosage of the anti-VEGF antibody is from about 2 mg/kg to about 14 mg/kg, and the dosing frequency is once every 1 week, once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 6 weeks, once every 8 weeks, once every 10 weeks, or once every 12 weeks.
  • the dosage of the anti-VEGF antibody is from about 2 mg/kg to about 13 mg/kg, and the dosing frequency is once every 1 week, once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 6 weeks, once every 8 weeks, once every 10 weeks, or once every 12 weeks.
  • the dosage of the anti-VEGF antibody is from about 3 mg/kg to about 12 mg/kg, and the dosing frequency is once every 1 week, once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 6 weeks, once every 8 weeks, once every 10 weeks, or once every 12 weeks.
  • the dosage of the anti-VEGF antibody is from about 4 mg/kg to about 11 mg/kg, and the dosing frequency is once every 1 week, once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 6 weeks, once every 8 weeks, once every 10 weeks, or once every 12 weeks.
  • the dosage of the anti-VEGF antibody is from about 5 mg/kg to about 10 mg/kg, and the dosing frequency is once every 1 week, once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 6 weeks, once every 8 weeks, once every 10 weeks, or once every 12 weeks.
  • the dosage of the anti-VEGF antibody is from about 6 mg/kg to about 9 mg/kg, and the dosing frequency is once every 1 week, once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 6 weeks, once every 8 weeks, once every 10 weeks, or once every 12 weeks.
  • the dosage of the anti-VEGF antibody is about 7 mg/kg to about 8 mg/kg, and the dosing frequency is once every 1 week, once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 6 weeks, once every 8 weeks, once every 10 weeks, or once every 12 weeks.
  • the dosage of the anti-VEGF antibody is approximately 2.0 mg/kg, approximately 3.0 mg/kg, approximately 4.0 mg/kg, approximately 5.0 mg/kg, approximately 6.0 mg/kg, approximately 6.5 mg/kg, approximately 7.0 mg/kg, approximately 7.5 mg/kg, 8.0 mg/kg, 8.5 mg/kg, approximately 9.0 mg/kg, approximately 9.5 mg/kg, approximately 10.0 mg/kg, approximately 10.5 mg/kg, approximately 11.0 mg/kg, approximately 11.5 mg/kg, approximately 12.0 mg/kg, approximately 12.5 mg/kg, approximately 13.0 mg/kg, approximately 13.5 mg/kg, and approximately 14.0 mg/kg.
  • the dosages are approximately 14.5 mg/kg, 15.0 mg/kg, 16.0 mg/kg, 16.5 mg/kg, 17.0 mg/kg, 18.0 mg/kg, 19.0 mg/kg, 20.0 mg/kg, 21.0 mg/kg, 22.0 mg/kg, 23.0 mg/kg, 24.0 mg/kg, 25.0 mg/kg, and 30.0 mg/kg.
  • the dosing frequency is once every week, once every two weeks, once every three weeks, once every four weeks, once every six weeks, once every eight weeks, once every ten weeks, or once every twelve weeks.
  • the dosage of the anti-VEGF antibody is approximately 5.0 mg/kg, and the dosing frequency is once every 3 weeks;
  • the dosage of the anti-VEGF antibody is approximately 5.5 mg/kg, and the dosing frequency is once every 3 weeks;
  • the dosage of the anti-VEGF antibody is approximately 6.0 mg/kg, and the dosing frequency is once every 3 weeks;
  • the dosage of the anti-VEGF antibody is approximately 6.5 mg/kg, and the dosing frequency is once every 3 weeks;
  • the dosage of the anti-VEGF antibody is approximately 7.0 mg/kg, and the dosing frequency is once every 3 weeks;
  • the dosage of the anti-VEGF antibody is approximately 7.5 mg/kg, and the dosing frequency is once every 3 weeks;
  • the dosage of the anti-VEGF antibody is approximately 8.0 mg/kg, and the dosing frequency is once every 3 weeks;
  • the dosage of the anti-VEGF antibody is approximately 8.5 mg/kg, and the dosing frequency is once every 3 weeks;
  • the dosage of the anti-VEGF antibody is approximately 9.0 mg/kg, and the dosing frequency is once every 3 weeks;
  • the dosage of the anti-VEGF antibody is approximately 9.5 mg/kg, and the dosing frequency is once every 3 weeks;
  • the dosage of the anti-VEGF antibody is approximately 10.0 mg/kg, and the dosing frequency is once every 3 weeks;
  • the dosage of the anti-VEGF antibody is approximately 10.5 mg/kg, and the dosing frequency is once every 3 weeks;
  • the dosage of the anti-VEGF antibody is approximately 11.0 mg/kg, and the dosing frequency is once every 3 weeks;
  • the dosage of the anti-VEGF antibody is approximately 11.5 mg/kg, and the dosing frequency is once every 3 weeks;
  • the dosage of the anti-VEGF antibody is approximately 12.0 mg/kg, and the dosing frequency is once every 3 weeks;
  • the dosage of the anti-VEGF antibody is approximately 12.5 mg/kg, and the dosing frequency is once every 3 weeks;
  • the dosage of the anti-VEGF antibody is approximately 13.0 mg/kg, and the dosing frequency is once every 3 weeks;
  • the dosage of the anti-VEGF antibody is approximately 13.5 mg/kg, and the dosing frequency is once every 3 weeks;
  • the dosage of the anti-VEGF antibody is approximately 14.0 mg/kg, and the dosing frequency is once every 3 weeks;
  • the dosage of the anti-VEGF antibody is approximately 14.5 mg/kg, and the dosing frequency is once every 3 weeks;
  • the dosage of the anti-VEGF antibody is approximately 15.0 mg/kg, and the dosing frequency is once every 3 weeks;
  • the dosage of the anti-VEGF antibody is approximately 15.5 mg/kg, and the dosing frequency is once every 3 weeks;
  • the dosage of the anti-VEGF antibody is approximately 16.0 mg/kg, and the dosing frequency is once every 3 weeks;
  • the dosage of the anti-VEGF antibody is approximately 16.5 mg/kg, and the dosing frequency is once every 3 weeks;
  • the dosage of the anti-VEGF antibody is approximately 17.0 mg/kg, and the dosing frequency is once every 3 weeks;
  • the dosage of the anti-VEGF antibody is approximately 17.5 mg/kg, and the dosing frequency is once every 3 weeks;
  • the dosage of the anti-VEGF antibody is approximately 18.0 mg/kg, and the dosing frequency is once every 3 weeks;
  • the dosage of the anti-VEGF antibody is approximately 18.5 mg/kg, and the dosing frequency is once every 3 weeks;
  • the dosage of the anti-VEGF antibody is approximately 19.0 mg/kg, and the dosing frequency is once every 3 weeks;
  • the dosage of the anti-VEGF antibody is approximately 19.5 mg/kg, and the dosing frequency is once every 3 weeks;
  • the dosage of the anti-VEGF antibody is approximately 20.0 mg/kg, and the dosing frequency is once every 3 weeks;
  • the dosage of the anti-VEGF antibody is approximately 21.5 mg/kg, and the dosing frequency is once every 3 weeks;
  • the dosage of the anti-VEGF antibody is approximately 22.0 mg/kg, and the dosing frequency is once every 3 weeks;
  • the dosage of the anti-VEGF antibody is approximately 22.5 mg/kg, and the dosing frequency is once every 3 weeks;
  • the dosage of the anti-VEGF antibody is approximately 23.0 mg/kg, and the dosing frequency is once every 3 weeks;
  • the dosage of the anti-VEGF antibody is approximately 23.5 mg/kg, and the dosing frequency is once every 3 weeks;
  • the dosage of the anti-VEGF antibody is approximately 24.0 mg/kg, and the dosing frequency is once every 3 weeks;
  • the dosage of the anti-VEGF antibody is approximately 24.5 mg/kg, and the dosing frequency is once every 3 weeks;
  • the dosage of the anti-VEGF antibody is approximately 25.0 mg/kg, and the dosing frequency is once every 3 weeks.
  • the anti-VEGF antibody is administered once every 3 weeks.
  • the anti-VEGF antibody in any of the above-described dosing regimens, can be administered orally, parenterally, or transdermally, with parenterally administration including but not limited to intravenous injection, subcutaneous injection, and intramuscular injection. In some embodiments, the anti-VEGF antibody is administered via intravenous infusion.
  • the anti-VEGF antibody is configured in an injectable form.
  • the injectable form of the anti-VEGF antibody is a solution or lyophilized powder for injection, comprising the anti-VEGF antibody and one or more pharmaceutically acceptable excipients.
  • the platinum-based drug is carboplatin or cisplatin.
  • the platinum-based drug is cisplatin
  • the dosage of cisplatin is about 1 mg/ m2 to about 500 mg/ m2 , or about 50 mg/ m2 to about 150 mg/ m2 ; for example, about 1 mg/ m2 to about 200 mg/ m2 , about 1 mg/ m2 to about 150 mg/ m2 , about 1 mg/ m2 to about 100 mg/ m2 , about 15 mg/ m2 to about 150 mg/ m2 , about 20 mg/ m2 to about 150 mg/ m2 , about 30 mg/m2 to about 150 mg/ m2 , about 30 mg/ m2 to about 100 mg/ m2 , about 30 mg/ m2 to about 85 mg/ m2 , about 45 mg/ m2 to about 85 mg/ m2 , or about 50 mg/ m2 to about 150 mg/ m2 .
  • the dosage of cisplatin is approximately 1 mg/ m2 , approximately 5 mg/ m2 , approximately 15 mg/ m2 , approximately 20 mg/ m2 , approximately 25 mg/ m2 , approximately 30 mg/m2, approximately 35 mg/ m2 , approximately 40 mg/ m2 , approximately 45 mg/ m2 , approximately 50 mg/ m2 , approximately 51 mg/ m2 , approximately 52 mg/ m2 , approximately 53 mg/ m2 , approximately 55 mg/ m2 , approximately 57 mg/ m2 , approximately 58 mg/ m2 , approximately 60 mg/ m2 , approximately 61 mg/ m2 , approximately 62 mg/ m2 , approximately 63 mg/ m2 , approximately 64 mg/ m2 , approximately 65 mg/ m2 , approximately 66 mg/ m2 , and approximately 67 mg/m2.
  • the cisplatin is administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks. In some specific embodiments, the cisplatin is administered once every 3 weeks.
  • the cisplatin is administered at a dose of about 1 mg/ m2 to about 500 mg/ m2 , and at a frequency of once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks. In some specific embodiments, the cisplatin is administered at a dose of about 1 mg/ m2 to about 500 mg/ m2 , and at a frequency of once every 3 weeks.
  • the cisplatin is administered at a dose of about 1 mg/ m2 to about 200 mg/ m2 , and at a frequency of once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks. In some specific embodiments, the cisplatin is administered at a dose of about 1 mg/ m2 to about 200 mg/ m2 , and at a frequency of once every 3 weeks.
  • the cisplatin is administered at a dose of about 5 mg/ m2 to about 100 mg/ m2 , and at a frequency of once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks. In some specific embodiments, the cisplatin is administered at a dose of about 5 mg/ m2 to about 100 mg/ m2 , and at a frequency of once every 3 weeks.
  • the cisplatin is administered at a dose of about 50 mg/ m2 to about 100 mg/ m2 , and at a frequency of once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks. In some specific embodiments, the cisplatin is administered at a dose of about 50 mg/ m2 to about 100 mg/ m2 , and at a frequency of once every 3 weeks.
  • the cisplatin is administered at a dose of about 60 mg/ m2 to about 85 mg/ m2 , and at a frequency of once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks. In some specific embodiments, the cisplatin is administered at a dose of about 60 mg/ m2 to about 85 mg/ m2 , and at a frequency of once every 3 weeks.
  • the cisplatin is administered at a dose of about 70 mg/ m2 , once every 3 weeks.
  • the cisplatin is administered at a dose of approximately 71 mg/ m2 , once every 3 weeks.
  • the cisplatin is administered at a dose of approximately 72 mg/ m2 , once every 3 weeks.
  • the cisplatin is administered at a dose of approximately 73 mg/ m2 , once every 3 weeks.
  • the cisplatin is administered at a dose of approximately 74 mg/ m2 , once every 3 weeks.
  • the cisplatin is administered at a dose of about 75 mg/ m2 , once every 3 weeks.
  • the cisplatin is administered at a dose of approximately 76 mg/ m2 , once every 3 weeks.
  • the cisplatin is administered at a dose of approximately 77 mg/ m2 , once every 3 weeks.
  • the cisplatin is administered at a dose of approximately 78 mg/ m2 , once every 3 weeks.
  • the cisplatin is administered at a dose of approximately 79 mg/ m2 , once every 3 weeks.
  • the cisplatin is administered at a dose of about 80 mg/ m2 , once every 3 weeks.
  • the cisplatin is administered at a dose of approximately 81 mg/ m2 , once every 3 weeks.
  • the cisplatin is administered at a dose of approximately 82 mg/ m2 , once every 3 weeks.
  • the cisplatin is administered at a dose of approximately 83 mg/ m2 , once every 3 weeks.
  • the cisplatin is administered at a dose of approximately 84 mg/ m2 , once every 3 weeks.
  • the cisplatin is administered at a dose of about 85 mg/ m2 , once every 3 weeks.
  • cisplatin can be administered orally, parenterally, or transdermally, with parenterial administration including but not limited to intravenous injection, subcutaneous injection, and intramuscular injection. In some specific embodiments, cisplatin is administered via intravenous injection. In some specific embodiments, cisplatin is administered via intravenous infusion.
  • the platinum-based drug is carboplatin
  • the dosage of carboplatin is from about 0.1 mg/mL/min to about 50 mg/mL/min, for example, from about 1 mg/mL/min to 20 mg/mL/min, from about 1 mg/mL/min to 10 mg/mL/min, from about 1 mg/mL/min to 8 mg/mL/min, from about 1 mg/mL/min to 6 mg/mL/min, from about 2 mg/mL/min to 10 mg/mL/min, from about 2 mg/mL/min to about 8 mg/mL/min, from about 2 mg/mL/min to about 6 mg/mL/min, from about 3 mg/mL/min to about 8 mg/mL/min, from about 3 mg/mL/min to 6 mg/mL/min, and from about 4 mg/mL/min to 6 mg/mL/min.
  • the dosage of carboplatin (based on AUC) is about 0.1 mg/mL/min, about 0.5 mg/mL/min, about 0.6 mg/mL/min, about 0.7 mg/mL/min, about 0.8 mg/mL/min, about 0.9 mg/mL/min, about 1.0 mg/mL/min, about 1.1 mg/mL/min, about 1.2 mg/mL/min, about 1.3 mg/mL/min, and about 1.4 mg/mL/min. approx. 1.5 mg/mL/min, approx. 1.6 mg/mL/min, approx. 1.7 mg/mL/min, approx. 1.8 mg/mL/min, approx. 1.9 mg/mL/min, approx.
  • the carboplatin is administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks. In some specific embodiments, the carboplatin is administered once every 3 weeks.
  • the dosage (based on AUC) of carboplatin is from about 0.1 mg/mL/min to about 50 mg/mL/min, and the dosing frequency is once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks. In some embodiments, the dosage (based on AUC) of carboplatin is from about 0.1 mg/mL/min to about 50 mg/mL/min, and the dosing frequency is once every 3 weeks.
  • the dosage (based on AUC) of carboplatin is from about 1 mg/mL/min to about 20 mg/mL/min, and the dosing frequency is once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks. In some embodiments, the dosage (based on AUC) of carboplatin is from about 1 mg/mL/min to about 20 mg/mL/min, and the dosing frequency is once every 3 weeks.
  • the dosage (based on AUC) of carboplatin is from about 1 mg/mL/min to about 10 mg/mL/min, and the dosing frequency is once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks. In some embodiments, the dosage (based on AUC) of carboplatin is from about 1 mg/mL/min to about 10 mg/mL/min, and the dosing frequency is once every 3 weeks.
  • the dosage (based on AUC) of carboplatin is from about 1 mg/mL/min to about 8 mg/mL/min, and the dosing frequency is once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks. In some embodiments, the dosage (based on AUC) of carboplatin is from about 1 mg/mL/min to about 8 mg/mL/min, and the dosing frequency is once every 3 weeks.
  • the dosage (based on AUC) of carboplatin is from about 2 mg/mL/min to about 10 mg/mL/min, and the dosing frequency is once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks. In some embodiments, the dosage (based on AUC) of carboplatin is from about 2 mg/mL/min to about 10 mg/mL/min, and the dosing frequency is once every 3 weeks.
  • the dosage (based on AUC) of carboplatin is from about 2 mg/mL/min to about 8 mg/mL/min, and the dosing frequency is once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks. In some embodiments, the dosage (based on AUC) of carboplatin is from about 2 mg/mL/min to about 8 mg/mL/min, and the dosing frequency is once every 3 weeks.
  • the dosage of carboplatin (based on AUC) is from about 3 mg/mL/min to about 8 mg/mL/min, and the dosing frequency is once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks. In some specific embodiments, the dosage of carboplatin (based on AUC) is from about 3 mg/mL/min to about 8 mg/mL/min, and the dosing frequency is once every 3 weeks.
  • the dosage of carboplatin in AUC is about 1 mg/mL/min to about 6 mg/mL/min, and the dosing frequency is once every 3 weeks.
  • the dosage of carboplatin in AUC is about 2 mg/mL/min to about 6 mg/mL/min, and the dosing frequency is once every 3 weeks.
  • the dosage of carboplatin in AUC is about 3 mg/mL/min to about 6 mg/mL/min, and the dosing frequency is once every 3 weeks.
  • the dosage of carboplatin in AUC is about 4 mg/mL/min to about 6 mg/mL/min, and the dosing frequency is once every 3 weeks.
  • the dosage of carboplatin in AUC is about 5 mg/mL/min to about 6 mg/mL/min, and the dosing frequency is once every 3 weeks.
  • the dosage of carboplatin in AUC is about 2 mg/mL/min, and the dosing frequency is once every 3 weeks.
  • the dosage of carboplatin in AUC is about 3 mg/mL/min, and the dosing frequency is once every 3 weeks.
  • the dosage of carboplatin in AUC is about 4 mg/mL/min, and the dosing frequency is once every 3 weeks.
  • the dosage of carboplatin in AUC is about 5 mg/mL/min, and the dosing frequency is once every 3 weeks.
  • the dosage of carboplatin in AUC is about 6 mg/mL/min, and the dosing frequency is once every 3 weeks.
  • the dosage of carboplatin in AUC is about 7 mg/mL/min, and the dosing frequency is once every 3 weeks.
  • the dosage of carboplatin in AUC is about 8 mg/mL/min, and the dosing frequency is once every 3 weeks.
  • carboplatin can be administered orally, parenterally, or transdermally, with parenterial administration including but not limited to intravenous injection, subcutaneous injection, and intramuscular injection. In some specific embodiments, carboplatin is administered via intravenous injection. In some specific embodiments, carboplatin is administered via intravenous infusion.
  • any of the foregoing uses, methods, or compositions are selected from the pharmaceutical administration shown in any of the following:
  • the dosing regimen for anti-Nectin-4 antibody-drug conjugate monotherapy is as follows:
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is 0.1-50 mg/kg, and the frequency of administration is at least once every 2 weeks, at least once every 3 weeks, at least once every 4 weeks, at least once every 6 weeks, or at least once every 8 weeks.
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is 0.1-20 mg/kg, and the frequency of administration is at least once every 2 weeks, at least once every 3 weeks, at least once every 4 weeks, at least once every 6 weeks, or at least once every 8 weeks.
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is 1-15 mg/kg, and the dosing frequency is once every 2 weeks, once every 3 weeks, twice every 3 weeks, once every 4 weeks, once every 6 weeks, or once every 8 weeks.
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is 1-10 mg/kg, and the dosing frequency is once every 2 weeks, once every 3 weeks, twice every 3 weeks, once every 4 weeks, once every 6 weeks, or once every 8 weeks.
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 1 mg/kg, approximately 2 mg/kg, approximately 3 mg/kg, approximately 4 mg/kg, approximately 5 mg/kg, approximately 6 mg/kg, approximately 7 mg/kg, approximately 8 mg/kg or approximately 10 mg/kg, and the dosing frequency is once every 2 weeks, once every 3 weeks, twice every 3 weeks, once every 4 weeks, once every 6 weeks or once every 8 weeks;
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 1 mg/kg, approximately 2 mg/kg, approximately 3 mg/kg, approximately 4 mg/kg, approximately 5 mg/kg, approximately 6 mg/kg, approximately 7 mg/kg, approximately 8 mg/kg or approximately 10 mg/kg, and the dosing frequency is once every 3 weeks or twice every 3 weeks;
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 5 mg/kg, 6 mg/kg, 7 mg/kg, 8 mg/kg, 9 mg/kg, or 10 mg/kg, administered once every 3 weeks; or
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 1 mg/kg, approximately 2 mg/kg, approximately 3 mg/kg, and approximately 4 mg/kg, administered twice every 3 weeks.
  • the dosing regimen of the anti-Nectin-4 antibody-drug conjugate combined with the anti-PD-L1 antibody is as follows:
  • the dosage of anti-Nectin-4 antibody-drug conjugate is 0.1-50 mg/kg, and the frequency of administration is at least once every 2 weeks, at least once every 3 weeks, at least once every 4 weeks, at least once every 6 weeks, or at least once every 8 weeks;
  • the dosage of anti-PD-L1 antibody is 5-5000 mg, and the frequency of administration is once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks;
  • the dosage of anti-Nectin-4 antibody-drug conjugate is 0.1-20 mg/kg, and the dosing frequency is once every 2 weeks, once every 3 weeks, twice every 3 weeks, once every 4 weeks, once every 6 weeks, or once every 8 weeks;
  • the dosage of anti-PD-L1 antibody is 5-5000 mg, and the dosing frequency is once every 3 weeks;
  • the dosage of anti-Nectin-4 antibody-drug conjugate is 1-10 mg/kg, and the frequency of administration is twice or once every 3 weeks;
  • the dosage of anti-PD-L1 antibody is 5-5000 mg, and the frequency of administration is once every 3 weeks.
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 1 mg/kg, approximately 2 mg/kg, approximately 3 mg/kg, approximately 4 mg/kg, approximately 5 mg/kg, approximately 6 mg/kg, approximately 7 mg/kg, approximately 8 mg/kg, or approximately 10 mg/kg; the dosing frequency is twice every 3 weeks or once every 3 weeks; b ) The dosage of the anti-PD-L1 antibody is 5-5000 mg, and the dosing frequency is once every 3 weeks;
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 5 mg/kg, approximately 6 mg/kg, approximately 7 mg/kg, approximately 8 mg/kg, approximately 9 mg/kg, or approximately 10 mg/kg; the dosing frequency is once every 3 weeks; b ) The dosage of the anti-PD-L1 antibody is 5-5000 mg, and the dosing frequency is once every 3 weeks;
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is 1 mg/kg, approximately 2 mg/kg, approximately 3 mg/kg, or approximately 4 mg/kg; the dosing frequency is twice every 3 weeks; b ) The dosage of the anti-PD-L1 antibody is 5-5000 mg, and the dosing frequency is once every 3 weeks;
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is 1-10 mg/kg, administered twice or once every 3 weeks;
  • the dosage of the anti-PD-L1 antibody is approximately 100 mg, 500 mg, 800 mg, 900 mg, 1000 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, 1500 mg, 1600 mg, 1800 mg, 2000 mg, 2200 mg, 2500 mg, or 3000 mg, administered once every 3 weeks.
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 1 mg/kg, approximately 2 mg/kg, approximately 3 mg/kg, approximately 4 mg/kg, approximately 5 mg/kg, approximately 6 mg/kg, approximately 7 mg/kg, approximately 8 mg/kg, approximately 9 mg/kg, or approximately 10 mg/kg, administered twice or once every 3 weeks;
  • the dosage of the anti-PD-L1 antibody is approximately 100 mg, approximately 500 mg, approximately 800 mg, approximately 900 mg, approximately 1000 mg, approximately 1100 mg, approximately 1200 mg, approximately 1300 mg, approximately 1400 mg, approximately 1500 mg, approximately 1600 mg, approximately 1800 mg, approximately 2000 mg, approximately 2200 mg, approximately 2500 mg, or approximately 3000 mg, administered once every 3 weeks;
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 3 mg/kg or approximately 4 mg/kg, administered twice every 3 weeks;
  • the dosage of the anti-PD-L1 antibody is approximately 100 mg, approximately 500 mg, approximately 800 mg, approximately 900 mg, approximately 1000 mg, approximately 1100 mg, approximately 1200 mg, approximately 1300 mg, approximately 1400 mg, approximately 1500 mg, approximately 1600 mg, approximately 1800 mg, approximately 2000 mg, approximately 2200 mg, approximately 2500 mg, or approximately 3000 mg, administered once every 3 weeks;
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 3 mg/kg or approximately 4 mg/kg, administered twice every 3 weeks; b ) The dosage of the anti-PD-L1 antibody is approximately 1200 mg, administered once every 3 weeks.
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 5 mg/kg, approximately 6 mg/kg, approximately 7 mg/kg, approximately 8 mg/kg, approximately 9 mg/kg, or approximately 10 mg/kg, administered once every 3 weeks;
  • the dosage of the anti-PD-L1 antibody is approximately 100 mg, approximately 500 mg, approximately 800 mg, approximately 900 mg, approximately 1000 mg, approximately 1100 mg, approximately 1200 mg, approximately 1300 mg, approximately 1400 mg, approximately 1500 mg, approximately 1600 mg, approximately 1800 mg, approximately 2000 mg, approximately 2200 mg, approximately 2500 mg, or approximately 3000 mg, administered once every 3 weeks;
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 5 mg/kg, approximately 6 mg/kg, approximately 7 mg/kg, approximately 8 mg/kg, approximately 9 mg/kg, or approximately 10 mg/kg, administered once every 3 weeks;
  • the dosage of the anti-PD-L1 antibody is approximately 1200 mg, administered once every 3 weeks.
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 4 mg/kg, administered twice every 3 weeks, on days 1 and 8 of each cycle; b ) The dosage of the anti-PD-L1 antibody is approximately 1200 mg, administered once every 3 weeks.
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 6 mg/kg, administered once every 3 weeks; b ) The dosage of the anti-PD-L1 antibody is approximately 1200 mg, administered once every 3 weeks; or,
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 8 mg/kg, administered once every 3 weeks; b ) The dosage of the anti-PD-L1 antibody is approximately 1200 mg, administered once every 3 weeks.
  • the dosing regimen of the anti-Nectin-4 antibody-drug conjugate combined with the anti-CTLA-4 antibody is as follows:
  • the dosage of anti-Nectin-4 antibody-drug conjugate is 0.1-50 mg/kg, and the dosing frequency is at least once every 2 weeks, at least once every 3 weeks, at least once every 4 weeks, at least once every 6 weeks, or at least once every 8 weeks;
  • the dosage of anti-CTLA-4 antibody is 1-1000 mg, and the dosing frequency is once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 6 weeks, once every 8 weeks, once every 10 weeks, once every 12 weeks, once every 14 weeks, once every 16 weeks, or a single dose;
  • the dosage of anti-Nectin-4 antibody-drug conjugate is 1-20 mg/kg, administered once every 2 weeks, once every 3 weeks, twice every 3 weeks, once every 4 weeks, once every 6 weeks, or once every 8 weeks;
  • the dosage of anti-CTLA-4 antibody is 1-1000 mg, administered once every 6 weeks or as a single dose;
  • the dosage of anti-Nectin-4 antibody-drug conjugate is 1-10 mg/kg, and the frequency of administration is twice every 3 weeks or once every 3 weeks;
  • the dosage of anti-CTLA-4 antibody is 1-1000 mg, and the frequency of administration is once every 6 weeks or a single dose.
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 1 mg/kg, approximately 2 mg/kg, approximately 3 mg/kg, approximately 4 mg/kg, approximately 5 mg/kg, approximately 6 mg/kg, approximately 7 mg/kg, approximately 8 mg/kg, or approximately 10 mg/kg; the dosing frequency is twice every 3 weeks or once every 3 weeks; b ) The dosage of the anti-CTLA-4 antibody is 1-1000 mg, the dosing frequency is once every 6 weeks or a single dose;
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 5 mg/kg, approximately 6 mg/kg, approximately 7 mg/kg, approximately 8 mg/kg, approximately 9 mg/kg, or approximately 10 mg/kg; the dosing frequency is once every 3 weeks; b ) The dosage of the anti-CTLA-4 antibody is 1-1000 mg, the dosing frequency is once every 6 weeks or a single dose;
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is 1 mg/kg, approximately 2 mg/kg, approximately 3 mg/kg, or approximately 4 mg/kg; the dosing frequency is twice every 3 weeks; b ) The dosage of the anti-CTLA-4 antibody is 1-1000 mg, the dosing frequency is once every 6 weeks or a single dose;
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is 1-10 mg/kg, administered twice or once every 3 weeks;
  • the dosage of the anti-CTLA-4 antibody is approximately 10 mg, approximately 20 mg, approximately 30 mg, approximately 40 mg, approximately 50 mg, approximately 60 mg, approximately 70 mg, approximately 80 mg, approximately 90 mg, approximately 100 mg, approximately 150 mg, approximately 200 mg, approximately 210 mg, approximately 220 mg, approximately 230 mg, approximately 240 mg, approximately 250 mg, approximately 260 mg, approximately 270 mg, approximately 280 mg, approximately 290 mg, approximately 300 mg, approximately 350 mg, approximately 500 mg, or approximately 700 mg, administered once every 6 weeks or as a single dose;
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 1 mg/kg, approximately 2 mg/kg, approximately 3 mg/kg, approximately 4 mg/kg, approximately 5 mg/kg, approximately 6 mg/kg, approximately 7 mg/kg, approximately 8 mg/kg, approximately 9 mg/kg, or approximately 10 mg/kg, administered twice or once every 3 weeks;
  • the dosage of anti-CTLA-4 antibody is approximately 10 mg, approximately 20 mg, approximately 30 mg, approximately 40 mg, approximately 50 mg, approximately 60 mg, approximately 70 mg, approximately 80 mg, approximately 90 mg, approximately 100 mg, approximately 150 mg, approximately 200 mg, approximately 210 mg, approximately 220 mg, approximately 230 mg, approximately 240 mg, approximately 250 mg, approximately 260 mg, approximately 270 mg, approximately 280 mg, approximately 290 mg, approximately 300 mg, approximately 350 mg, approximately 500 mg, or approximately 700 mg, and the dosing frequency is once every 6 weeks or a single dose.
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 3 mg/kg or approximately 4 mg/kg, administered twice every 3 weeks;
  • the dosage of the anti-CTLA-4 antibody is approximately 10 mg, approximately 20 mg, approximately 30 mg, approximately 40 mg, approximately 50 mg, approximately 60 mg, approximately 70 mg, approximately 80 mg, approximately 90 mg, approximately 100 mg, approximately 150 mg, approximately 200 mg, approximately 210 mg, approximately 220 mg, approximately 230 mg, approximately 240 mg, approximately 250 mg, approximately 260 mg, approximately 270 mg, approximately 280 mg, approximately 290 mg, approximately 300 mg, approximately 350 mg, approximately 500 mg, or approximately 700 mg, administered once every 6 weeks or as a single dose;
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 5 mg/kg, approximately 6 mg/kg, approximately 7 mg/kg, approximately 8 mg/kg, approximately 9 mg/kg, or approximately 10 mg/kg, administered once every 3 weeks;
  • the dosage of the anti-CTLA-4 antibody is approximately 10 mg, approximately 20 mg, approximately 30 mg, approximately 40 mg, approximately 50 mg, approximately 60 mg, approximately 70 mg, approximately 80 mg, approximately 90 mg, approximately 100 mg, approximately 150 mg, approximately 200 mg, approximately 210 mg, approximately 220 mg, approximately 230 mg, approximately 240 mg, approximately 250 mg, approximately 260 mg, approximately 270 mg, approximately 280 mg, approximately 290 mg, approximately 300 mg, approximately 350 mg, approximately 500 mg, or approximately 700 mg, administered once every 6 weeks or as a single dose;
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 4 mg/kg, administered twice every 3 weeks, on days 1 and 8 of each cycle; b ) The anti-CTLA-4 antibody is administered once in week 1 at a dose of approximately 280 mg or 210 mg, with no administration from week 2 to week 12. From week 13 onwards, the dosage is approximately 70 mg, administered once every 6 weeks.
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 6 mg/kg, administered once every 3 weeks; b ) The anti-CTLA-4 antibody is administered as a single dose of approximately 280 mg or 210 mg in week 1, with no administration from weeks 2 to 12. From week 13 onwards, the dosage is approximately 70 mg, administered once every 6 weeks; or,
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 8 mg/kg, administered once every 3 weeks; b ) The anti-CTLA-4 antibody is administered once in week 1 at a dose of approximately 280 mg or 210 mg, with no administration from week 2 to week 12. From week 13 onwards, the dosage is approximately 70 mg, administered once every 6 weeks.
  • the dosing regimen of the anti-Nectin-4 antibody-drug conjugate in combination with the anti-PD-L1 antibody and the anti-CTLA-4 antibody is as follows:
  • the dosage of anti-Nectin-4 antibody-drug conjugate is 0.1-50 mg/kg, administered at least once every 2 weeks, 3 weeks, 4 weeks, 6 weeks, or 8 weeks; b1 ) The dosage of anti-PD-L1 antibody is 5-5000 mg, administered at least once every 2 weeks, 3 weeks, 4 weeks, 5 weeks, or 6 weeks; b2 ) The dosage of anti-CTLA-4 antibody is 1-1000 mg, administered at the following frequencies: once every 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, 10 weeks, 12 weeks, 14 weeks, 16 weeks, or as a single dose.
  • the dosage of anti-Nectin-4 antibody-drug conjugate is 1-20 mg/kg, administered once every 2 weeks, once every 3 weeks, twice every 3 weeks, once every 4 weeks, once every 6 weeks, or once every 8 weeks; b1 ) The dosage of anti-PD-L1 antibody is 5-5000 mg, administered once every 3 weeks; b2 ) The dosage of anti-CTLA-4 antibody is 1-1000 mg, administered once every 6 weeks or as a single dose.
  • the dosage of anti-Nectin-4 antibody-drug conjugate is 1-10 mg/kg, administered twice or once every 3 weeks; b1 ) The dosage of anti-PD-L1 antibody is 5-5000 mg, administered once every 3 weeks; b2 ) The dosage of anti-CTLA-4 antibody is 1-1000 mg, administered once every 6 weeks or as a single dose.
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 1 mg/kg, approximately 2 mg/kg, approximately 3 mg/kg, approximately 4 mg/kg, approximately 5 mg/kg, approximately 6 mg/kg, approximately 7 mg/kg, approximately 8 mg/kg, or approximately 10 mg/kg; the dosing frequency is twice every 3 weeks or once every 3 weeks; b1 ) The dosage of the anti-PD-L1 antibody is 5-5000 mg, and the dosing frequency is once every 3 weeks; b2 ) The dosage of the anti-CTLA-4 antibody is 1-1000 mg, and the dosing frequency is once every 6 weeks or a single dose;
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 5 mg/kg, 6 mg/kg, 7 mg/kg, 8 mg/kg, 9 mg/kg, or 10 mg/kg; the dosing frequency is once every 3 weeks; b1 ) The dosage of the anti-PD-L1 antibody is 5-5000 mg, and the dosing frequency is once every 3 weeks; b2 ) The dosage of the anti-CTLA-4 antibody is 1-1000 mg, and the dosing frequency is once every 6 weeks or a single dose;
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is 1 mg/kg, approximately 2 mg/kg, approximately 3 mg/kg, or approximately 4 mg/kg; the dosing frequency is twice every 3 weeks; b1 ) The dosage of the anti-PD-L1 antibody is 5-5000 mg, and the dosing frequency is once every 3 weeks; b2 ) The dosage of the anti-CTLA-4 antibody is 1-1000 mg, and the dosing frequency is once every 6 weeks or a single dose;
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is 1-10 mg/kg, administered twice or once every 3 weeks;
  • the dosage of the anti-PD-L1 antibody is approximately 100 mg, 500 mg, 800 mg, 900 mg, 1000 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, 1500 mg, 1600 mg, 1800 mg, 2000 mg, 2200 mg, 2500 mg, or 3000 mg, administered once every 3 weeks;
  • the dosage of anti-CTLA-4 antibody is approximately 10 mg, approximately 20 mg, approximately 30 mg, approximately 40 mg, approximately 50 mg, approximately 60 mg, approximately 70 mg, approximately 80 mg, approximately 90 mg, approximately 100 mg, approximately 150 mg, approximately 200 mg, approximately 210 mg, approximately 220 mg, approximately 230 mg, approximately 240 mg, approximately 250 mg, approximately 260 mg, approximately 270 mg, approximately 280 mg, approximately 290 mg, approximately 300 mg, approximately 350 mg, approximately 500 mg, or approximately 700 mg, and the dosing frequency is once every 6 weeks or a
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 1 mg/kg, approximately 2 mg/kg, approximately 3 mg/kg, approximately 4 mg/kg, approximately 5 mg/kg, approximately 6 mg/kg, approximately 7 mg/kg, approximately 8 mg/kg, approximately 9 mg/kg, or approximately 10 mg/kg, administered twice or once every 3 weeks;
  • the dosage of the anti-PD-L1 antibody is approximately 100 mg, approximately 500 mg, approximately 800 mg, approximately 900 mg, approximately 1000 mg, approximately 1100 mg, approximately 1200 mg, approximately 1300 mg, approximately 1400 mg, approximately 1500 mg, approximately 1600 mg, approximately 1800 mg, approximately 2000 mg, approximately 2200 mg, approximately 2500 mg, or approximately 3000 mg, administered once every 3 weeks;
  • the dosage of anti-CTLA-4 antibody is approximately 10 mg, approximately 20 mg, approximately 30 mg, approximately 40 mg, approximately 50 mg, approximately 60 mg, approximately 70 mg, approximately 80 mg, approximately 90 mg, approximately 100 mg, approximately 150 mg, approximately 200 mg, approximately 210 mg, approximately 2
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 3 mg/kg or approximately 4 mg/kg, administered twice every 3 weeks; b1 )
  • the dosage of the anti-PD-L1 antibody is approximately 100 mg, approximately 500 mg, approximately 800 mg, approximately 900 mg, approximately 1000 mg, approximately 1100 mg, approximately 1200 mg, approximately 1300 mg, approximately 1400 mg, approximately 1500 mg, approximately 1600 mg, approximately 1800 mg, approximately 2000 mg, approximately 2200 mg, approximately 2500 mg, or approximately 3000 mg, administered once every 3 weeks;
  • the dosage of anti-CTLA-4 antibody is approximately 10 mg, approximately 20 mg, approximately 30 mg, approximately 40 mg, approximately 50 mg, approximately 60 mg, approximately 70 mg, approximately 80 mg, approximately 90 mg, approximately 100 mg, approximately 150 mg, approximately 200 mg, approximately 210 mg, approximately 220 mg, approximately 230 mg, approximately 240 mg, approximately 250 mg, approximately 260 mg, approximately 270 mg, approximately 280 mg, approximately 290 mg, approximately 300 mg, approximately 350 mg, approximately 500 mg,
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 5 mg/kg, 6 mg/kg, 7 mg/kg, 8 mg/kg, 9 mg/kg, or 10 mg/kg, administered once every 3 weeks;
  • the dosage of the anti-PD-L1 antibody is approximately 100 mg, 500 mg, 800 mg, 900 mg, 1000 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, 1500 mg, 1600 mg, 1800 mg, 2000 mg, 2200 mg, 2500 mg, or 3000 mg, administered once every 3 weeks;
  • the dosage of anti-CTLA-4 antibody is approximately 10 mg, approximately 20 mg, approximately 30 mg, approximately 40 mg, approximately 50 mg, approximately 60 mg, approximately 70 mg, approximately 80 mg, approximately 90 mg, approximately 100 mg, approximately 150 mg, approximately 200 mg, approximately 210 mg, approximately 220 mg, approximately 230 mg, approximately 240 mg, approximately 250 mg, approximately 260 mg, approximately 270 mg, approximately 280 mg, approximately 290 mg, approximately 300 mg, approximately 350 mg, approximately
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 4 mg/kg, administered twice every 3 weeks, on days 1 and 8 of each cycle; b1 ) The dosage of the anti-PD-L1 antibody is approximately 1200 mg, administered once every 3 weeks; b2 ) The anti-CTLA-4 antibody is administered as a single dose of approximately 280 mg or 210 mg in week 1, with no administration from week 2 to week 12. From week 13 onwards, the dosage is approximately 70 mg, administered once every 6 weeks.
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 6 mg/kg, administered once every 3 weeks; b1 ) The dosage of the anti-PD-L1 antibody is approximately 1200 mg, administered once every 3 weeks; b2 ) The anti-CTLA-4 antibody is administered as a single dose of approximately 280 mg or 210 mg in week 1, with no administration from weeks 2 to 12, and from week 13 onwards, the dosage is approximately 70 mg, administered once every 6 weeks; or,
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 8 mg/kg, administered once every 3 weeks; b1 ) The dosage of the anti-PD-L1 antibody is approximately 1200 mg, administered once every 3 weeks; b2 ) The anti-CTLA-4 antibody is administered as a single dose of approximately 280 mg or 210 mg in week 1, with no administration from week 2 to week 12. From week 13 onwards, the dosage is approximately 70 mg, administered once every 6 weeks.
  • the dosing regimen of the anti-Nectin-4 antibody-drug conjugate combined with the anti-PD-L1 antibody and the anti-VEGF antibody is as follows:
  • the dosage of anti-Nectin-4 antibody-drug conjugate is 0.1-50 mg/kg, and the frequency of administration is at least once every 2 weeks, at least once every 3 weeks, at least once every 4 weeks, at least once every 6 weeks, or at least once every 8 weeks;
  • the dosage of anti-PD-L1 antibody is 5-5000 mg, and the frequency of administration is once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks;
  • the dosage of anti-VEGF antibody is 1 mg/kg-30 mg/kg, and the frequency of administration is once every 1 week, once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 6 weeks, once every 8 weeks, once every 10 weeks, or once every 12 weeks.
  • the dosage of anti-Nectin-4 antibody-drug conjugate is 0.1-20 mg/kg, administered once every 2 weeks, once every 3 weeks, twice every 3 weeks, once every 4 weeks, once every 6 weeks, or once every 8 weeks; b1 ) The dosage of anti-PD-L1 antibody is 5-5000 mg, administered once every 3 weeks; b2 ) The dosage of anti-VEGF antibody is 1 mg/kg-30 mg/kg, administered once every 3 weeks.
  • the dosage of anti-Nectin-4 antibody-drug conjugate is 1-10 mg/kg, administered twice or once every 3 weeks; b1 ) The dosage of anti-PD-L1 antibody is 5-5000 mg, administered once every 3 weeks; b2 ) The dosage of anti-VEGF antibody is 1 mg/kg-30 mg/kg, administered once every 3 weeks.
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 1 mg/kg, approximately 2 mg/kg, approximately 3 mg/kg, approximately 4 mg/kg, approximately 5 mg/kg, approximately 6 mg/kg, approximately 7 mg/kg, approximately 8 mg/kg, or approximately 10 mg/kg; the dosing frequency is twice every 3 weeks or once every 3 weeks; b1 ) The dosage of the anti-PD-L1 antibody is 5-5000 mg, and the dosing frequency is once every 3 weeks; b2 ) The dosage of the anti-VEGF antibody is 1 mg/kg-30 mg/kg, and the dosing frequency is once every 3 weeks;
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 5 mg/kg, 6 mg/kg, 7 mg/kg, 8 mg/kg, 9 mg/kg, or 10 mg/kg; the dosing frequency is once every 3 weeks; b1 ) The dosage of the anti-PD-L1 antibody is 5-5000 mg, and the dosing frequency is once every 3 weeks; b2 ) The dosage of the anti-VEGF antibody is 1 mg/kg-30 mg/kg, and the dosing frequency is once every 3 weeks;
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is 1 mg/kg, approximately 2 mg/kg, approximately 3 mg/kg, or approximately 4 mg/kg; the dosing frequency is twice every 3 weeks; b1 ) The dosage of the anti-PD-L1 antibody is 5-5000 mg, and the dosing frequency is once every 3 weeks; b2 ) The dosage of the anti-VEGF antibody is 1 mg/kg-30 mg/kg, and the dosing frequency is once every 3 weeks;
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is 1-10 mg/kg, administered twice or once every 3 weeks;
  • the dosage of the anti-PD-L1 antibody is approximately 100 mg, 500 mg, 800 mg, 900 mg, 1000 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, 1500 mg, 1600 mg, 1800 mg, 2000 mg, 2200 mg, 2500 mg, or 3000 mg, administered once every 3 weeks;
  • the dosage of anti-VEGF antibody is approximately 2.0 mg/kg, approximately 3.0 mg/kg, approximately 4.0 mg/kg, approximately 5 mg/kg, approximately 6.0 mg/kg, approximately 7.5 mg/kg, approximately 8.0 mg/kg, approximately 9.0 mg/kg, approximately 10 mg/kg, approximately 11 mg/kg, approximately 12 mg/kg, approximately 13 mg/kg, approximately 14 mg/kg, approximately 15 mg/kg, approximately 16 mg/kg, approximately 17 mg/kg, approximately 18 mg/kg, approximately 19 mg/kg, approximately 20 mg/kg, approximately 21.0 mg
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 1 mg/kg, approximately 2 mg/kg, approximately 3 mg/kg, approximately 4 mg/kg, approximately 5 mg/kg, approximately 6 mg/kg, approximately 7 mg/kg, approximately 8 mg/kg, approximately 9 mg/kg, or approximately 10 mg/kg, administered twice or once every 3 weeks;
  • the dosage of the anti-PD-L1 antibody is approximately 100 mg, approximately 500 mg, approximately 800 mg, approximately 900 mg, approximately 1000 mg, approximately 1100 mg, approximately 1200 mg, approximately 1300 mg, approximately 1400 mg, approximately 1500 mg, approximately 1600 mg, approximately 1800 mg, approximately 2000 mg, approximately 2200 mg, approximately 2500 mg, or approximately 3000 mg, administered once every 3 weeks;
  • the dosage of anti-VEGF antibody is approximately 2.0 mg/kg, approximately 3.0 mg/kg, approximately 4.0 mg/kg, approximately 5 mg/kg, approximately 6.0 mg/kg, approximately 7.5 mg/kg, approximately 8.0 mg/kg, approximately 9.0 mg/kg, approximately 10
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 3 mg/kg or approximately 4 mg/kg, administered twice every 3 weeks; b1 )
  • the dosage of the anti-PD-L1 antibody is approximately 100 mg, approximately 500 mg, approximately 800 mg, approximately 900 mg, approximately 1000 mg, approximately 1100 mg, approximately 1200 mg, approximately 1300 mg, approximately 1400 mg, approximately 1500 mg, approximately 1600 mg, approximately 1800 mg, approximately 2000 mg, approximately 2200 mg, approximately 2500 mg, or approximately 3000 mg, administered once every 3 weeks;
  • the dosage of anti-VEGF antibody is approximately 2.0 mg/kg, approximately 3.0 mg/kg, approximately 4.0 mg/kg, approximately 5 mg/kg, approximately 6.0 mg/kg, approximately 7.5 mg/kg, approximately 8.0 mg/kg, approximately 9.0 mg/kg, approximately 10 mg/kg, approximately 11 mg/kg, approximately 12 mg/kg, approximately 13 mg/kg, approximately 14 mg/kg, approximately 15 mg/kg, approximately 16 mg/kg, approximately 17 mg/kg, approximately 18 mg
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 3 mg/kg or approximately 4 mg/kg, administered twice every 3 weeks; b1 ) The dosage of the anti-PD-L1 antibody is approximately 1200 mg, administered once every 3 weeks; b2 ) The dosage of the anti-VEGF antibody is approximately 7.5 mg/kg or approximately 15 mg/kg, administered once every 3 weeks.
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 5 mg/kg, 6 mg/kg, 7 mg/kg, 8 mg/kg, 9 mg/kg, or 10 mg/kg, administered once every 3 weeks;
  • the dosage of the anti-PD-L1 antibody is approximately 100 mg, 500 mg, 800 mg, 900 mg, 1000 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, 1500 mg, 1600 mg, 1800 mg, 2000 mg, 2200 mg, 2500 mg, or 3000 mg, administered once every 3 weeks;
  • the dosage of anti-VEGF antibody is approximately 2.0 mg/kg, approximately 3.0 mg/kg, approximately 4.0 mg/kg, approximately 5 mg/kg, approximately 6.0 mg/kg, approximately 7.5 mg/kg, approximately 8.0 mg/kg, approximately 9.0 mg/kg, approximately 10 mg/kg, approximately 11 mg/kg, approximately 12 mg/kg, approximately 13 mg/kg, approximately 14 mg/kg, approximately 15 mg/kg, approximately 16 mg/kg, approximately 17 mg/kg,
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 5 mg/kg, 6 mg/kg, 7 mg/kg, 8 mg/kg, 9 mg/kg, or 10 mg/kg, administered once every 3 weeks; b1 ) The dosage of the anti-PD-L1 antibody is approximately 1200 mg, administered once every 3 weeks; b2 ) The dosage of the anti-VEGF antibody is approximately 7.5 mg/kg, administered once every 3 weeks.
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 5 mg/kg, 6 mg/kg, 7 mg/kg, 8 mg/kg, 9 mg/kg, or 10 mg/kg, administered once every 3 weeks; b1 ) The dosage of the anti-PD-L1 antibody is approximately 1200 mg, administered once every 3 weeks; b2 ) The dosage of the anti-VEGF antibody is approximately 15 mg/kg, administered once every 3 weeks.
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 4 mg/kg, administered twice every 3 weeks, on days 1 and 8 of each cycle; b1 ) The dosage of the anti-PD-L1 antibody is approximately 1200 mg, administered once every 3 weeks; b2 ) The dosage of the anti-VEGF antibody is approximately 7.5 mg/kg, administered once every 3 weeks.
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 4 mg/kg, administered twice every 3 weeks, on days 1 and 8 of each cycle; b1 ) The dosage of the anti-PD-L1 antibody is approximately 1200 mg, administered once every 3 weeks; b2 ) The dosage of the anti-VEGF antibody is approximately 15 mg/kg, administered once every 3 weeks.
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 6 mg/kg, administered once every 3 weeks; b1 ) The dosage of the anti-PD-L1 antibody is approximately 1200 mg, administered once every 3 weeks; b2 ) The dosage of the anti-VEGF antibody is approximately 7.5 mg/kg, administered once every 3 weeks.
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 6 mg/kg, administered once every 3 weeks; b1 ) The dosage of the anti-PD-L1 antibody is approximately 1200 mg, administered once every 3 weeks; b2 ) The dosage of the anti-VEGF antibody is approximately 15 mg/kg, administered once every 3 weeks.
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 8 mg/kg, administered once every 3 weeks; b1 ) The dosage of the anti-PD-L1 antibody is approximately 1200 mg, administered once every 3 weeks; b2 ) The dosage of the anti-VEGF antibody is approximately 7.5 mg/kg, administered once every 3 weeks.
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 8 mg/kg, administered once every 3 weeks; b1 ) The dosage of the anti-PD-L1 antibody is approximately 1200 mg, administered once every 3 weeks; b2 ) The dosage of the anti-VEGF antibody is approximately 15 mg/kg, administered once every 3 weeks.
  • the dosing regimen of the anti-Nectin-4 antibody-drug conjugate in combination with anti-PD-L1 antibody, anti-CTLA-4 antibody, and anti-VEGF antibody is as follows:
  • the dosage of anti-Nectin-4 antibody-drug conjugate is 0.1-50 mg/kg, administered at least once every 2 weeks, 3 weeks, 4 weeks, 6 weeks, or 8 weeks; b1 ) The dosage of anti-PD-L1 antibody is 5-5000 mg, administered at least once every 2 weeks, 3 weeks, 4 weeks, 5 weeks, or 6 weeks; b2 ) The dosage of anti-CTLA-4 antibody is 1-1000 mg, administered at least once every 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, 10 weeks, 12 weeks, 14 weeks, 16 weeks, or as a single dose; b3 ) The dosage of anti-VEGF antibody is 1 mg/kg-30 mg/kg, and the dosing frequency is once every 1 week, once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 6 weeks, once every 8 weeks, once every 10 weeks, or once every 12 weeks.
  • the dosage of anti-Nectin-4 antibody-drug conjugate is 1-20 mg/kg, administered once every 2 weeks, once every 3 weeks, twice every 3 weeks, once every 4 weeks, once every 6 weeks, or once every 8 weeks; b1 ) The dosage of anti-PD-L1 antibody is 5-5000 mg, administered once every 3 weeks; b2 ) The dosage of anti-CTLA-4 antibody is 1-1000 mg, administered once every 6 weeks or as a single dose; b3 ) The dosage of anti-VEGF antibody is 1 mg/kg-30 mg/kg, administered once every 3 weeks.
  • the dosage of anti-Nectin-4 antibody-drug conjugate is 1-10 mg/kg, administered twice or once every 3 weeks; b1 ) The dosage of anti-PD-L1 antibody is 5-5000 mg, administered once every 3 weeks; b2 ) The dosage of anti-CTLA-4 antibody is 1-1000 mg, administered once every 6 weeks or as a single dose; b3 ) The dosage of anti-VEGF antibody is 1 mg/kg-30 mg/kg, administered once every 3 weeks.
  • the dosage of anti-Nectin-4 antibody-drug conjugate is approximately 1 mg/kg, approximately 2 mg/kg, approximately 3 mg/kg, approximately 4 mg/kg, approximately 5 mg/kg, approximately 6 mg/kg, approximately 7 mg/kg, approximately 8 mg/kg, or approximately 10 mg/kg; the dosing frequency is twice every 3 weeks or once every 3 weeks; b1 ) The dosage of anti-PD-L1 antibody is 5-5000 mg, and the dosing frequency is once every 3 weeks; b2 ) The dosage of anti-CTLA-4 antibody is 1-1000 mg, and the dosing frequency is once every 6 weeks or a single dose; b3 ) The dosage of anti-VEGF antibody is 1 mg/kg-30 mg/kg, and the dosing frequency is once every 3 weeks;
  • the dosage of anti-Nectin-4 antibody-drug conjugate is approximately 5 mg/kg, 6 mg/kg, 7 mg/kg, 8 mg/kg, 9 mg/kg, or 10 mg/kg; the dosing frequency is once every 3 weeks; b1 ) The dosage of anti-PD-L1 antibody is 5-5000 mg, and the dosing frequency is once every 3 weeks; b2 ) The dosage of anti-CTLA-4 antibody is 1-1000 mg, and the dosing frequency is once every 6 weeks or a single dose; b3 ) The dosage of anti-VEGF antibody is 1 mg/kg-30 mg/kg, and the dosing frequency is once every 3 weeks;
  • the dosage of anti-Nectin-4 antibody-drug conjugate is 1 mg/kg, approximately 2 mg/kg, approximately 3 mg/kg, or approximately 4 mg/kg; the dosing frequency is twice every 3 weeks; b1 ) The dosage of anti-PD-L1 antibody is 5-5000 mg, and the dosing frequency is once every 3 weeks; b2 ) The dosage of anti-CTLA-4 antibody is 1-1000 mg, and the dosing frequency is once every 6 weeks or a single dose; b3 ) The dosage of anti-VEGF antibody is 1 mg/kg-30 mg/kg, and the dosing frequency is once every 3 weeks;
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is 1-10 mg/kg, administered twice or once every 3 weeks;
  • the dosage of the anti-PD-L1 antibody is approximately 100 mg, 500 mg, 800 mg, 900 mg, 1000 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, 1500 mg, 1600 mg, 1800 mg, 2000 mg, 2200 mg, 2500 mg, or 3000 mg, administered once every 3 weeks;
  • the dosage of anti-CTLA-4 antibody is approximately 10 mg, approximately 20 mg, approximately 30 mg, approximately 40 mg, approximately 50 mg, approximately 60 mg, approximately 70 mg, approximately 80 mg, approximately 90 mg, approximately 100 mg, approximately 150 mg, approximately 200 mg, approximately 210 mg, approximately 220 mg, approximately 230 mg, approximately 240 mg, approximately 250 mg, approximately 260 mg, approximately 270 mg, approximately 280 mg, approximately 290 mg, approximately 300 mg, approximately 350 mg, approximately 500 mg, or approximately 700 mg, administered once every 6 weeks or as a single dose
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 1 mg/kg, approximately 2 mg/kg, approximately 3 mg/kg, approximately 4 mg/kg, approximately 5 mg/kg, approximately 6 mg/kg, approximately 7 mg/kg, approximately 8 mg/kg, approximately 9 mg/kg, or approximately 10 mg/kg, administered twice or once every 3 weeks;
  • the dosage of the anti-PD-L1 antibody is approximately 100 mg, approximately 500 mg, approximately 800 mg, approximately 900 mg, approximately 1000 mg, approximately 1100 mg, approximately 1200 mg, approximately 1300 mg, approximately 1400 mg, approximately 1500 mg, approximately 1600 mg, approximately 1800 mg, approximately 2000 mg, approximately 2200 mg, approximately 2500 mg, or approximately 3000 mg, administered once every 3 weeks;
  • the dosage of anti-CTLA-4 antibody is approximately 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 150 mg, 200 mg, 210 mg, 220 mg, 230 mg, 240 mg, 250 mg
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 3 mg/kg or approximately 4 mg/kg, administered twice every 3 weeks; b1 )
  • the dosage of the anti-PD-L1 antibody is approximately 100 mg, approximately 500 mg, approximately 800 mg, approximately 900 mg, approximately 1000 mg, approximately 1100 mg, approximately 1200 mg, approximately 1300 mg, approximately 1400 mg, approximately 1500 mg, approximately 1600 mg, approximately 1800 mg, approximately 2000 mg, approximately 2200 mg, approximately 2500 mg, or approximately 3000 mg, administered once every 3 weeks;
  • the dosage of anti-CTLA-4 antibody is approximately 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 150 mg, 200 mg, 210 mg, 220 mg, 230 mg, 240 mg, 250 mg, 260 mg, 270 mg, 280 mg, 290 mg, 300 mg, 350 mg, 500 mg, or 700 mg, administered once every 6 weeks or as a single dose; b 3
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 5 mg/kg, 6 mg/kg, 7 mg/kg, 8 mg/kg, 9 mg/kg, or 10 mg/kg, administered once every 3 weeks;
  • the dosage of the anti-PD-L1 antibody is approximately 100 mg, 500 mg, 800 mg, 900 mg, 1000 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, 1500 mg, 1600 mg, 1800 mg, 2000 mg, 2200 mg, 2500 mg, or 3000 mg, administered once every 3 weeks;
  • the dosage of anti-CTLA-4 antibody is approximately 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 150 mg, 200 mg, 210 mg, 220 mg, 230 mg, 240 mg, 250 mg, 260 mg, 270 mg, 280 mg, 290 mg, 300 mg, 350 mg, 500 mg, or 700 mg, administered once every 6 weeks or as a single dose; b 3
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 4 mg/kg, administered twice every 3 weeks, on days 1 and 8 of each cycle; b1 ) The dosage of the anti-PD-L1 antibody is approximately 1200 mg, administered once every 3 weeks; b2 ) The anti-CTLA-4 antibody is administered as a single dose of approximately 280 mg or 210 mg in week 1, with no administration from week 2 to week 12. From week 13 onwards, the dosage is approximately 70 mg, administered once every 6 weeks; b3 ) The dosage of the anti-VEGF antibody is approximately 7.5 mg/kg, administered once every 3 weeks.
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 4 mg/kg, administered twice every 3 weeks, on days 1 and 8 of each cycle; b1 ) The dosage of the anti-PD-L1 antibody is approximately 1200 mg, administered once every 3 weeks; b2 ) The anti-CTLA-4 antibody is administered as a single dose of approximately 280 mg or 210 mg in week 1, with no administration from week 2 to week 12. From week 13 onwards, the dosage is approximately 70 mg, administered once every 6 weeks; b3 ) The dosage of the anti-VEGF antibody is approximately 15 mg/kg, administered once every 3 weeks.
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 6 mg/kg, administered once every 3 weeks; b1 ) The dosage of the anti-PD-L1 antibody is approximately 1200 mg, administered once every 3 weeks; b2 ) The anti-CTLA-4 antibody is administered as a single dose of approximately 280 mg or 210 mg in week 1, with no administration from week 2 to week 12, and from week 13 onwards, the dosage is approximately 70 mg, administered once every 6 weeks; b3 ) The dosage of the anti-VEGF antibody is approximately 7.5 mg/kg, administered once every 3 weeks.
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 6 mg/kg, administered once every 3 weeks; b1 ) The dosage of the anti-PD-L1 antibody is approximately 1200 mg, administered once every 3 weeks; b2 ) The anti-CTLA-4 antibody is administered as a single dose of approximately 280 mg or 210 mg in week 1, with no administration from week 2 to week 12. From week 13 onwards, the dosage is approximately 70 mg, administered once every 6 weeks; b3 ) The dosage of the anti-VEGF antibody is approximately 15 mg/kg, administered once every 3 weeks.
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 8 mg/kg, administered once every 3 weeks; b1 ) The dosage of the anti-PD-L1 antibody is approximately 1200 mg, administered once every 3 weeks; b2 ) The anti-CTLA-4 antibody is administered as a single dose of approximately 280 mg or 210 mg in week 1, with no administration from weeks 2 to 12, and from week 13 onwards, the dosage is approximately 70 mg, administered once every 6 weeks; b3 ) The dosage of the anti-VEGF antibody is approximately 7.5 mg/kg, administered once every 3 weeks; or
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 8 mg/kg, administered once every 3 weeks; b1 ) The dosage of the anti-PD-L1 antibody is approximately 1200 mg, administered once every 3 weeks; b2 ) The anti-CTLA-4 antibody is administered as a single dose of approximately 280 mg or 210 mg in week 1, with no administration from week 2 to week 12. From week 13 onwards, the dosage is approximately 70 mg, administered once every 6 weeks; b3 ) The dosage of the anti-VEGF antibody is approximately 15 mg/kg, administered once every 3 weeks.
  • the dosing regimen of the anti-Nectin-4 antibody-drug conjugate combined with the anti-PD-L1 antibody and carboplatin is as follows:
  • the dosage of anti-Nectin-4 antibody-drug conjugate is 0.1-50 mg/kg, administered at least once every 2 weeks, 3 weeks, 4 weeks, 6 weeks, or 8 weeks; b1 ) The dosage of anti-PD-L1 antibody is 5-5000 mg, administered at least once every 2 weeks, 3 weeks, 4 weeks, 5 weeks, or 6 weeks; b2 ) The dosage (based on AUC) of carboplatin is approximately 0.1 mg/mL/min to approximately 50 mg/mL/min, administered once every 3 weeks.
  • the dosage of anti-Nectin-4 antibody-drug conjugate is 0.1-20 mg/kg, administered once every 2 weeks, once every 3 weeks, twice every 3 weeks, once every 4 weeks, once every 6 weeks, or once every 8 weeks; b1 ) The dosage of anti-PD-L1 antibody is 5-5000 mg, administered once every 3 weeks; b2 ) The dosage of carboplatin (based on AUC) is approximately 0.1 mg/mL/min to approximately 50 mg/mL/min, administered once every 3 weeks.
  • the dosage of anti-Nectin-4 antibody-drug conjugate is 1-10 mg/kg, administered twice or once every 3 weeks; b1 ) The dosage of anti-PD-L1 antibody is 5-5000 mg, administered once every 3 weeks; b2 ) The dosage of carboplatin (based on AUC) is approximately 0.1 mg/mL/min to approximately 50 mg/mL/min, administered once every 3 weeks.
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 1 mg/kg, approximately 2 mg/kg, approximately 3 mg/kg, approximately 4 mg/kg, approximately 5 mg/kg, approximately 6 mg/kg, approximately 7 mg/kg, approximately 8 mg/kg, or approximately 10 mg/kg; the dosing frequency is twice every 3 weeks or once every 3 weeks; b1 ) The dosage of the anti-PD-L1 antibody is 5-5000 mg, and the dosing frequency is once every 3 weeks; b2 ) The dosage of carboplatin (based on AUC) is approximately 0.1 mg/mL/min to approximately 50 mg/mL/min, and the dosing frequency is once every 3 weeks;
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 5 mg/kg, 6 mg/kg, 7 mg/kg, 8 mg/kg, 9 mg/kg, or 10 mg/kg; the frequency of administration is once every 3 weeks; b1 ) The dosage of the anti-PD-L1 antibody is 5-5000 mg, and the frequency of administration is once every 3 weeks; b2 ) The dosage of carboplatin (based on AUC) is approximately 0.1 mg/mL/min to approximately 50 mg/mL/min, and the frequency of administration is once every 3 weeks;
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is 1 mg/kg, approximately 2 mg/kg, approximately 3 mg/kg, or approximately 4 mg/kg; the dosing frequency is twice every 3 weeks; b1 ) The dosage of the anti-PD-L1 antibody is 5-5000 mg, and the dosing frequency is once every 3 weeks; b2 ) The dosage of carboplatin (based on AUC) is approximately 0.1 mg/mL/min to approximately 50 mg/mL/min, and the dosing frequency is once every 3 weeks;
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is 1-10 mg/kg, administered twice or once every 3 weeks;
  • the dosage of the anti-PD-L1 antibody is approximately 100 mg, 500 mg, 800 mg, 900 mg, 1000 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, 1500 mg, 1600 mg, 1800 mg, 2000 mg, 2200 mg, 2500 mg, or 3000 mg, administered once every 3 weeks;
  • the dosage of carboplatin (based on AUC) is approximately 1 mg/mL/min, approximately 2 mg/mL/min, approximately 3 mg/mL/min, approximately 4 mg/mL/min, approximately 5 mg/mL/min, approximately 6 mg/mL/min, approximately 7 mg/mL/min, approximately 8 mg/mL/min, approximately 9 mg/mL/min, and approximately 10 mg/mL/min, with a dosing frequency of once every 3 weeks.
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 1 mg/kg, approximately 2 mg/kg, approximately 3 mg/kg, approximately 4 mg/kg, approximately 5 mg/kg, approximately 6 mg/kg, approximately 7 mg/kg, approximately 8 mg/kg, approximately 9 mg/kg, or approximately 10 mg/kg, administered twice or once every 3 weeks;
  • the dosage of the anti-PD-L1 antibody is approximately 100 mg, approximately 500 mg, approximately 800 mg, approximately 900 mg, approximately 1000 mg, approximately 1100 mg, approximately 1200 mg, approximately 1300 mg, approximately 1400 mg, approximately 1500 mg, approximately 1600 mg, approximately 1800 mg, approximately 2000 mg, approximately 2200 mg, approximately 2500 mg, or approximately 3000 mg, administered once every 3 weeks;
  • the dosage of carboplatin (based on AUC) is approximately 1 mg/mL/min, approximately 2 mg/mL/min, approximately 3 mg/mL/min, approximately 4 mg/mL/min, approximately 5 mg/mL/min, approximately 6 mg/mL
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 3 mg/kg or approximately 4 mg/kg, administered twice every 3 weeks; b1 )
  • the dosage of the anti-PD-L1 antibody is approximately 100 mg, approximately 500 mg, approximately 800 mg, approximately 900 mg, approximately 1000 mg, approximately 1100 mg, approximately 1200 mg, approximately 1300 mg, approximately 1400 mg, approximately 1500 mg, approximately 1600 mg, approximately 1800 mg, approximately 2000 mg, approximately 2200 mg, approximately 2500 mg, or approximately 3000 mg, administered once every 3 weeks;
  • the dosage of carboplatin (based on AUC) is approximately 1 mg/mL/min, approximately 2 mg/mL/min, approximately 3 mg/mL/min, approximately 4 mg/mL/min, approximately 5 mg/mL/min, approximately 6 mg/mL/min, approximately 7 mg/mL/min, approximately 8 mg/mL/min, approximately 9 mg/mL/min, and approximately 10 mg/mL/min, with a dosing frequency of once
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 3 mg/kg or approximately 4 mg/kg, administered twice every 3 weeks; b1 ) The dosage of the anti-PD-L1 antibody is approximately 1200 mg, administered once every 3 weeks; b2 ) The dosage of carboplatin (based on AUC) is approximately 4 mg/mL/min or 5 mg/mL/min, administered once every 3 weeks.
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 5 mg/kg, 6 mg/kg, 7 mg/kg, 8 mg/kg, 9 mg/kg, or 10 mg/kg, administered once every 3 weeks;
  • the dosage of the anti-PD-L1 antibody is approximately 100 mg, 500 mg, 800 mg, 900 mg, 1000 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, 1500 mg, 1600 mg, 1800 mg, 2000 mg, 2200 mg, 2500 mg, or 3000 mg, administered once every 3 weeks;
  • the dosage of carboplatin (based on AUC) is approximately 1 mg/mL/min, approximately 2 mg/mL/min, approximately 3 mg/mL/min, approximately 4 mg/mL/min, approximately 5 mg/mL/min, approximately 6 mg/mL/min, approximately 7 mg/mL/min, approximately 8 mg/mL/min, approximately 9 mg/mL/min, and approximately 10 mg/mL/min, with a dosing
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 5 mg/kg, 6 mg/kg, 7 mg/kg, 8 mg/kg, 9 mg/kg, or 10 mg/kg, administered once every 3 weeks; b1 ) The dosage of the anti-PD-L1 antibody is approximately 1200 mg/kg, administered once every 3 weeks; b2 ) The dosage of carboplatin (based on AUC) is approximately 4 mg/mL/min or 5 mg/mL/min, administered once every 3 weeks.
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 4 mg/kg, administered twice every 3 weeks, on days 1 and 8 of each cycle; b1 ) The dosage of the anti-PD-L1 antibody is approximately 1200 mg, administered once every 3 weeks; b2 ) The dosage of carboplatin (based on AUC) is approximately 4 mg/mL/min, administered once every 3 weeks.
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 4 mg/kg, administered twice every 3 weeks, on days 1 and 8 of each cycle; b1 ) The dosage of the anti-PD-L1 antibody is approximately 1200 mg, administered once every 3 weeks; b2 ) The dosage of carboplatin (based on AUC) is approximately 5 mg/mL/min, administered once every 3 weeks.
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 6 mg/kg, administered once every 3 weeks; b1 ) The dosage of the anti-PD-L1 antibody is approximately 1200 mg, administered once every 3 weeks; b2 ) The dosage of carboplatin (based on AUC) is approximately 4 mg/mL/min, administered once every 3 weeks.
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 6 mg/kg, administered once every 3 weeks; b1 ) The dosage of the anti-PD-L1 antibody is approximately 1200 mg, administered once every 3 weeks; b2 ) The dosage of carboplatin (based on AUC) is approximately 5 mg/mL/min, administered once every 3 weeks.
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 8 mg/kg, administered once every 3 weeks; b1 ) The dosage of the anti-PD-L1 antibody is approximately 1200 mg, administered once every 3 weeks; b2 ) The dosage of carboplatin (based on AUC) is approximately 4 mg/mL/min, administered once every 3 weeks; or,
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 8 mg/kg, administered once every 3 weeks; b1 ) The dosage of the anti-PD-L1 antibody is approximately 1200 mg, administered once every 3 weeks; b2 ) The dosage of carboplatin (based on AUC) is approximately 5 mg/mL/min, administered once every 3 weeks.
  • the dosing regimen of the anti-Nectin-4 antibody-drug conjugate combined with the anti-PD-L1 antibody and cisplatin is as follows:
  • the dosage of anti-Nectin-4 antibody-drug conjugate is 0.1-50 mg/kg, administered at least once every 2 weeks, 3 weeks, 4 weeks, 6 weeks, or 8 weeks; b1 ) The dosage of anti-PD-L1 antibody is 5-5000 mg, administered at least once every 2 weeks, 3 weeks, 4 weeks, 5 weeks, or 6 weeks; b2 ) The dosage of cisplatin is approximately 1 mg/ m2 to approximately 500 mg/ m2 , administered once every 3 weeks.
  • the dosage of anti-Nectin-4 antibody-drug conjugate is 0.1-20 mg/kg, administered once every 2 weeks, once every 3 weeks, twice every 3 weeks, once every 4 weeks, once every 6 weeks, or once every 8 weeks; b1 ) The dosage of anti-PD-L1 antibody is 5-5000 mg, administered once every 3 weeks; b2 ) The dosage of cisplatin is approximately 1 mg/ m2 to approximately 500 mg/ m2 , administered once every 3 weeks.
  • the dosage of anti-Nectin-4 antibody-drug conjugate is 1-10 mg/kg, administered twice or once every 3 weeks; b1 ) The dosage of anti-PD-L1 antibody is 5-5000 mg, administered once every 3 weeks; b2 ) The dosage of cisplatin is approximately 1 mg/ m2 to approximately 500 mg/ m2 , administered once every 3 weeks.
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 1 mg/kg, approximately 2 mg/kg, approximately 3 mg/kg, approximately 4 mg/kg, approximately 5 mg/kg, approximately 6 mg/kg, approximately 7 mg/kg, approximately 8 mg/kg, or approximately 10 mg/kg; the dosing frequency is twice every 3 weeks or once every 3 weeks; b1 ) The dosage of the anti-PD-L1 antibody is 5-5000 mg, and the dosing frequency is once every 3 weeks; b2 ) The dosage of cisplatin is approximately 1 mg/ m2 to approximately 500 mg/ m2 , and the dosing frequency is once every 3 weeks;
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 5 mg/kg, approximately 6 mg/kg, approximately 7 mg/kg, approximately 8 mg/kg, approximately 9 mg/kg, or approximately 10 mg/kg; the dosing frequency is once every 3 weeks; b1 ) The dosage of the anti-PD-L1 antibody is 5-5000 mg, and the dosing frequency is once every 3 weeks; b2 ) The dosage of cisplatin is approximately 1 mg/ m2 to approximately 500 mg/ m2 , and the dosing frequency is once every 3 weeks;
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is 1 mg/kg, approximately 2 mg/kg, approximately 3 mg/kg, or approximately 4 mg/kg; the dosing frequency is twice every 3 weeks; b1 ) The dosage of the anti-PD-L1 antibody is 5-5000 mg, and the dosing frequency is once every 3 weeks; b2 ) The dosage of cisplatin is approximately 1 mg/ m2 to approximately 500 mg/ m2 , and the dosing frequency is once every 3 weeks;
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is 1-10 mg/kg, administered twice or once every 3 weeks;
  • the dosage of the anti-PD-L1 antibody is approximately 100 mg, 500 mg, 800 mg, 900 mg, 1000 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, 1500 mg, 1600 mg, 1800 mg, 2000 mg, 2200 mg, 2500 mg, or 3000 mg, administered once every 3 weeks;
  • the dosage of cisplatin is approximately 50 mg/ m2 , 51 mg/ m2 , 52 mg/ m2 , 53 mg/ m2 , 55 mg/ m2 , or 57 mg/ m2.
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 1 mg/kg, approximately 2 mg/kg, approximately 3 mg/kg, approximately 4 mg/kg, approximately 5 mg/kg, approximately 6 mg/kg, approximately 7 mg/kg, approximately 8 mg/kg, approximately 9 mg/kg, or approximately 10 mg/kg, administered twice or once every 3 weeks;
  • the dosage of the anti-PD-L1 antibody is approximately 100 mg, approximately 500 mg, approximately 800 mg, approximately 900 mg, approximately 1000 mg, approximately 1100 mg, approximately 1200 mg, approximately 1300 mg, approximately 1400 mg, approximately 1500 mg, approximately 1600 mg, approximately 1800 mg, approximately 2000 mg, approximately 2200 mg, approximately 2500 mg, or approximately 3000 mg, administered once every 3 weeks;
  • the dosage of cisplatin is approximately 50 mg/m2 .
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 3 mg/kg or approximately 4 mg/kg, administered twice every 3 weeks; b1 )
  • the dosage of the anti-PD-L1 antibody is approximately 100 mg, approximately 500 mg, approximately 800 mg, approximately 900 mg, approximately 1000 mg, approximately 1100 mg, approximately 1200 mg, approximately 1300 mg, approximately 1400 mg, approximately 1500 mg, approximately 1600 mg, approximately 1800 mg, approximately 2000 mg, approximately 2200 mg, approximately 2500 mg, or approximately 3000 mg, administered once every 3 weeks;
  • the dosage of cisplatin is approximately 50 mg/ m2 , approximately 51 mg/ m2 , approximately 52 mg/ m2 , approximately 53 mg/ m2 , approximately 55 mg/ m2 , or approximately 57 mg/ m2.
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 3 mg/kg or approximately 4 mg/kg, administered twice every 3 weeks; b1 ) The dosage of the anti-PD-L1 antibody is approximately 1200 mg, administered once every 3 weeks; b2 ) The dosage of cisplatin is approximately 75 mg/ m2 , administered once every 3 weeks.
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 5 mg/kg, 6 mg/kg, 7 mg/kg, 8 mg/kg, 9 mg/kg, or 10 mg/kg, administered once every 3 weeks;
  • the dosage of the anti-PD-L1 antibody is approximately 100 mg, 500 mg, 800 mg, 900 mg, 1000 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, 1500 mg, 1600 mg, 1800 mg, 2000 mg, 2200 mg, 2500 mg, or 3000 mg, administered once every 3 weeks;
  • the dosage of cisplatin is approximately 50 mg/ m2 , 51 mg/ m2 , 52 mg/ m2 , or 53 mg/ m2.
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 5 mg/kg, 6 mg/kg, 7 mg/kg, 8 mg/kg, 9 mg/kg, or 10 mg/kg, administered once every 3 weeks; b1 ) The dosage of the anti-PD-L1 antibody is approximately 1200 mg/m2, administered once every 3 weeks; b2 ) The dosage of cisplatin is approximately 75 mg/ m2 , administered once every 3 weeks.
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 4 mg/kg, administered twice every 3 weeks, on days 1 and 8 of each cycle; b1 ) The dosage of the anti-PD-L1 antibody is approximately 1200 mg, administered once every 3 weeks; b2 ) The dosage of cisplatin is approximately 75 mg/ m2 , administered once every 3 weeks.
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 6 mg/kg, administered once every 3 weeks; b1 ) The dosage of the anti-PD-L1 antibody is approximately 1200 mg, administered once every 3 weeks; b2 ) The dosage of cisplatin is approximately 75 mg/ m2 , administered once every 3 weeks; or,
  • the dosage of the anti-Nectin-4 antibody-drug conjugate is approximately 8 mg/kg, administered once every 3 weeks; b1 ) The dosage of the anti-PD-L1 antibody is approximately 1200 mg, administered once every 3 weeks; b2 ) The dosage of cisplatin is approximately 75 mg/ m2 , administered once every 3 weeks.
  • the recommended dosing sequence for the anti-Nectin-4 antibody-drug conjugate combined with the anti-PD-L1 antibody is as follows: administer the anti-Nectin-4 antibody-drug conjugate first, followed by the anti-PD-L1 antibody.
  • the interval between the two drug administrations should be >30 minutes, and administration should ideally be completed on the same day.
  • the recommended dosing order for the anti-Nectin-4 antibody-drug conjugate combined with the anti-PD-L1 antibody and anti-VEGF antibody is as follows: administer the anti-Nectin-4 antibody-drug conjugate first, then the anti-PD-L1 antibody, and finally the anti-VEGF antibody.
  • the interval between the two drug administrations should be >30 minutes, and administration should ideally be completed on the same day.
  • the recommended dosing order for the anti-Nectin-4 antibody-drug conjugate combined with the anti-PD-L1 antibody and platinum-based drug is as follows: administer the anti-Nectin-4 antibody-drug conjugate first, followed by the anti-PD-L1 antibody, and finally the platinum-based drug.
  • the time interval between the two drug administrations should be greater than 30 minutes, and the administration should ideally be completed on the same day.
  • the recommended dosing order for the anti-Nectin-4 antibody-drug conjugate combined with the anti-PD-L1 antibody and anti-CTLA-4 antibody is as follows: administer the anti-Nectin-4 antibody-drug conjugate first, then the anti-PD-L1 antibody, and finally the anti-CTLA-4 antibody.
  • the interval between the two drug administrations should be >30 minutes, and administration should ideally be completed on the same day.
  • the recommended dosing order for the anti-Nectin-4 antibody-drug conjugate combined with anti-PD-L1 antibody, anti-CTLA-4 antibody, and anti-VEGF antibody is as follows: first administer the anti-Nectin-4 antibody-drug conjugate, then the anti-PD-L1 antibody, then the anti-CTLA-4 antibody, and finally the anti-VEGF antibody.
  • the interval between the two drug administrations should be >30 minutes, and the administration should ideally be completed on the same day.
  • Anti-Nectin-4 antibody-drug conjugates and their combination with other therapeutic agents have shown certain clinical benefits in targeted therapy for non-small cell lung cancer and esophageal cancer, bringing patients clinical benefits superior to existing treatments, and controlling or alleviating their condition.
  • this disclosure defines the following:
  • Antibody-drug conjugates are drugs that link antibodies or antibody fragments to biologically active cytotoxic drugs or small molecule drugs with cytotoxic activity via stable chemical linker compounds. They fully utilize the specificity of antibodies in binding to tumor cell-specific or highly expressed antigens and the high efficiency of cytotoxic agents, while avoiding toxic side effects on normal cells. Compared to traditional chemotherapy drugs, antibody-drug conjugates can precisely bind to tumor cells and reduce the impact on normal cells.
  • an antibody-drug conjugate does not exhibit significant chemical changes, then the antibody "retains its chemical stability" in the drug formulation.
  • Chemical stability can be assessed by detecting and quantifying the chemically altered form of the protein.
  • Degradation processes that frequently alter the chemical structure of proteins include hydrolysis or truncation (evaluated by methods such as size exclusion chromatography and CE-SDS), oxidation (evaluated by methods such as peptide mapping combined with mass spectrometry or MALDI/TOF/MS), deamidation (evaluated by methods such as ion exchange chromatography, capillary isoelectric focusing, peptide mapping, and isofpartate measurement), and isomerization (evaluated by measuring isofpartate content, peptide mapping, etc.).
  • the antibody-drug conjugate "retains its biological activity" in the drug formulation.
  • antibody is used in the broadest sense to encompass various antibody structures, including but not limited to monoclonal antibodies, polyclonal antibodies; monospecific antibodies, multispecific antibodies (e.g., bispecific antibodies), full-length antibodies, and antibody fragments (or antigen-binding fragments, or antigen-binding portions), as long as they exhibit the desired antigen-binding activity.
  • Antibodies can refer to immunoglobulins, which are tetrapeptide chains composed of two identical heavy chains and two identical light chains linked by interchain disulfide bonds. The amino acid composition and sequence of the constant region of the immunoglobulin heavy chain differ, thus their antigenicity also differs.
  • immunoglobulins can be divided into five classes, or isotypes of immunoglobulins: IgM, IgD, IgG, IgA, and IgE, with their corresponding heavy chains being ⁇ , ⁇ , ⁇ , ⁇ , and ⁇ chains, respectively.
  • IgM immunoglobulins
  • IgD immunoglobulins
  • IgG immunoglobulins
  • IgA immunoglobulins
  • IgE immunoglobulins
  • different subclasses can be distinguished; for example, IgG can be divided into IgG1, IgG2, IgG3, and IgG4.
  • Light chains are classified as ⁇ chains or ⁇ chains based on differences in their constant regions.
  • Each of the five classes of Ig can have either a ⁇ chain or a ⁇ chain.
  • variable region The sequence of approximately 110 amino acids near the N-terminus of the antibody heavy and light chains varies considerably, forming the variable region (V region); the remaining amino acid sequences near the C-terminus are relatively stable, forming the constant region (C region).
  • the variable region includes three hypervariable regions (CDRs) and four relatively conserved backbone regions (FRs). The three hypervariable regions determine the antibody's specificity and are also known as complementarity-determining regions (CDRs).
  • Each light chain variable region (VL) and heavy chain variable region (VH) consists of three CDRs and four FRs, arranged from the amino terminus to the carboxyl terminus in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4.
  • the three CDRs of the light chain refer to LCDR1, LCDR2, and LCDR3; the three CDRs of the heavy chain refer to HCDR1, HCDR2, and HCDR3.
  • CDR contact ligand
  • the amino acid sequence boundaries of CDRs can be determined using various well-known schemes, such as the "Kabat” numbering rule (see Kabat et al. (1991), “Sequences of Proteins of Immunological Interest", 5th edition, Public Health Service, National Institutes of Health, Bethesda, MD), the "Chothia” numbering rule, the “ABM” numbering rule, the "contact” numbering rule (see Martin, ACR. Protein Sequence and Structure Analysis of Antibody Variable Domains[J]. 2001), and the ImMunoGenTics (IMGT) numbering rule (Lefranc, M.P. et al., Dev. Comp. Immunol., 27, 55-77 (2003); Front Immunol. 2018 Oct 16; 9:2278), etc.
  • IMGT ImMunoGenTics
  • antigen-binding fragment or “functional fragment” or “antigen-binding portion” refer to one or more fragments of an intact antibody that retain the ability to specifically bind to an antigen. It has been shown that fragments of full-length antibodies can be used for antigen-binding function.
  • binding fragments encompassed in the term “antigen-binding fragment” include: (i) a Fab fragment, a monovalent fragment consisting of VL, VH, CL, and CH1 domains; (ii) an F(ab') 2 fragment, a bivalent fragment comprising two Fab fragments connected by disulfide bridges on their hinge regions; (iii) an Fd fragment consisting of VH and CH1 domains; (iv) an Fv fragment consisting of the VH and VL domains of a single arm of the antibody; (v) dsFv, a stable antigen-binding fragment formed by interchain disulfide bonds between VH and VL; (vi) scFv; and (vii) bispecific, bispecific, and multispecific antibodies comprising fragments such as scFv, dsFv, and Fab.
  • binding refers to the binding of an antibody to an epitope on a pre-defined antigen.
  • antibodies bind with an affinity (KD) of approximately less than 10 ⁇ 8 M, such as approximately less than 10 ⁇ 9 M, 10 ⁇ 10 M, 10 ⁇ 11 M, or even smaller.
  • KD refers to the dissociation equilibrium constant of a specific antibody-antigen interaction.
  • the antibodies of this disclosure bind IL-5 with a dissociation equilibrium constant (KD) of less than about 10 ⁇ 7 M, such as less than about 10 ⁇ 8 M, 10 ⁇ 9 M, or 10 ⁇ 10 M or smaller, for example, as determined in a BIACORE instrument using surface plasmon resonance (SPR) technology.
  • SPR surface plasmon resonance
  • Homology refers to the sequence similarity between two polynucleotide sequences or two polypeptides. Two compared sequences are homologous at positions occupied by the same bases or amino acid monomer subunits; for example, if every position in two DNA molecules is occupied by adenine. The percentage of homology between two sequences is a function of the number of matching or homologous positions shared by the two sequences divided by the number of positions compared multiplied by 100. For example, in optimal sequence alignment, if 6 out of 10 positions in two sequences match or are homologous, then the two sequences are 60% homologous; if 95 out of 100 positions in two sequences match or are homologous, then the two sequences are 95% homologous.
  • comparisons are made when aligning two sequences to give the maximum percentage of homology.
  • comparisons can be performed using the BLAST algorithm, where the algorithm's parameters are chosen to give the maximum match between the sequences over the entire length of each reference sequence.
  • the following references relate to the BLAST algorithm frequently used in sequence analysis: BLAST Algorithms: Altschul, S.F. et al., (1990) J. Mol. Biol. 215: 403-410; Gish, W. et al., (1993) Nature Genet. 3: 266-272; Madden, T.L. et al., (1996) Meth. Enzymol. 266: 131-141; Altschul, S.F.
  • “giving” and “treatment” refer to the contact of an exogenous drug, therapeutic agent, diagnostic agent, or composition with the animal, human, subject, cell, tissue, organ, or biological fluid.
  • “Giving” and “treatment” can refer to, for example, therapeutic, pharmacokinetic, diagnostic, research, and experimental methods.
  • Cellular treatment includes contact between a reagent and cells, as well as contact between a reagent and a fluid, wherein the fluid is in contact with the cells.
  • “Giving” and “treatment” also mean the treatment of, for example, cells, by means of a reagent, diagnostic agent, conjugate composition, or by means of another cell in vitro and ex vivo.
  • “treatment” refers to therapeutic treatment, preventative or prophylactic measures, research, and diagnostic applications.
  • Treatment means administering an oral or topical therapeutic agent, such as a composition comprising any of the compounds disclosed herein, to a patient who has symptoms of one or more diseases, and the therapeutic agent is known to have a therapeutic effect on these symptoms.
  • a therapeutic agent is administered in a treated patient or population in an amount that effectively relieves symptoms of one or more diseases to induce the regression of such symptoms or inhibit their progression to any clinically measurable extent.
  • the amount of a therapeutic agent that effectively relieves any specific disease symptom can vary depending on a variety of factors, such as the patient's disease state, age, and weight, and the drug's ability to produce the desired therapeutic effect in the patient.
  • Whether the disease symptoms have been relieved can be evaluated using any clinical testing methods commonly used by a physician or other healthcare professional to assess the severity or progression of the symptoms.
  • the embodiments of this disclosure e.g., treatment methods or products
  • may be ineffective in alleviating symptoms of each target disease they should reduce symptoms of the target disease in a statistically significant number of patients, as determined by any statistical test known in the art, such as the Student t-test, chi-square test, U-test according to Mann and Whitney, Kruskal-Wallis test (H-test), Jonckheere-Terpstra test, and Wilcoxon test.
  • an "effective amount” includes the amount sufficient to improve or prevent the symptoms or condition of a medically diagnosed disease.
  • An effective amount also means the amount sufficient to allow or facilitate diagnosis.
  • the effective amount for a particular patient or veterinary subject can vary depending on factors such as the condition to be treated, the patient's overall health, the route and dosage of administration, and the severity of side effects.
  • An effective amount can be the maximum dose or administration regimen that avoids significant side effects or toxicity.
  • subject and “patient” refer to mammals, especially primates, and particularly humans.
  • Nectin-4 positive refers to the expression of nectin-4 in the cell membrane or cytoplasm detected by immunohistochemistry. If the expression value is ⁇ 1, then nectin-4 is positive.
  • driver gene in this disclosure includes, but is not limited to, EGFR mutations, ALK fusions, ROS1 fusions, BRAF V600E mutations, NTRK fusions, MET14 exon skipping mutations, RET fusions, KRAS G12C mutations, HER-2 mutations, EGFR-sensitive mutations, EGFR T790M mutations, and EGFR exon 20 insertions.
  • Driver gene positive in this disclosure refers to the detection of specific gene mutations in non-small cell lung cancer by gene detection or immunohistochemistry.
  • driver gene positive includes, but is not limited to, EGFR mutations, EGFR-sensitive mutations, EGFR T790M mutations, EGFR exon 20 insertions, ALK fusions, ROS1 fusions, BRAF V600E mutations, NTRK fusions, MET14 exon skipping mutations, RET fusions, KRAS G12C mutations, and HER-2 mutations.
  • “Driver gene positive” in this disclosure also includes other non-small cell lung cancer-specific gene mutations to be discovered.
  • driver gene negative means that the driver gene for non-small cell lung cancer is not detected by methods such as gene testing or immunohistochemistry. Patients who are “driver gene positive but for whom there is no approved targeted therapy” will be treated in accordance with the treatment guidelines for "driver gene negative” patients.
  • immunotherapy refers to tumor immunotherapy represented by immune checkpoint inhibitors (ICIs), including but not limited to programmed cell death receptor 1 (PD-1), programmed cell death ligand 1 (PD-L1), and cytotoxic T lymphocyte associated antigen 4 (CTLA-4).
  • ICIs immune checkpoint inhibitors
  • PD-1 programmed cell death receptor 1
  • PD-L1 programmed cell death ligand 1
  • CTLA-4 cytotoxic T lymphocyte associated antigen 4
  • platinum-based chemotherapy including treatment with platinum-based drugs such as cisplatin and carboplatin.
  • targeted drug therapy refers to approved or future newly approved targeted drug therapies for "driver gene positive” mutations, including but not limited to approved targeted drug therapies for EGFR mutations, KRAS G12C mutations, HER-2 mutations, EGFR sensitive mutations, EGFR T790M mutations, EGFR exon 20 insertions, ALK fusions, ROS1 fusions, NTRK fusions, BRAF V600E mutations, MET exon 14 skipping mutations, RET fusions, etc.
  • n refers to the average amount of cytotoxic drug loaded onto each antibody or its antigen-binding fragment in the antibody-drug conjugate molecule. It can also be expressed as the ratio of drug amount to antibody amount, which is the average amount of drug in each ADC molecule after the conjugation reaction is identified by hydrophobic chromatography (HIC) mass spectrometry.
  • HIC hydrophobic chromatography
  • “Pharmaceutical composition” means a mixture containing one or more of the compounds described herein or their physiologically/pharmacologically acceptable salts or prodrugs, along with other chemical components, such as physiologically/pharmacologically acceptable carriers and excipients.
  • the purpose of a pharmaceutical composition is to facilitate administration to a living organism, thereby promoting the absorption of the active ingredient and its biological activity.
  • the anti-Nectin-4 antibody-drug conjugate is the ADC-4 prepared in Examples 3-4 of WO2023221971A (incorporated in its entirety by reference), with the following structure:
  • the anti-Nectin-4 antibody is derived from antibody NEC49, whose CDR sequence is shown in Table 1.
  • the full-length heavy chain of antibody NEC49 is shown in SEQ ID NO: 9, and the full-length light chain is shown in SEQ ID NO: 10.
  • Example 2 An open-label, single-arm, multicenter phase I clinical study of the safety, tolerability, efficacy, and pharmacokinetics of ADC-4 in patients with advanced solid tumors.
  • the ADC-4 prepared in Example 1 was in the form of an injection (sterile powder for injection).
  • the Eastern Cooperative Oncology Group (ECOG) performance status score is 0-1.
  • Cohort A Pathologically confirmed unresectable locally advanced/metastatic non-small cell lung cancer: including i) NSCLC subjects with driver gene-negative disease who have received PD-(L)1 and platinum-based chemotherapy, unless they are unsuitable for or refuse such treatment; ii) NSCLC subjects with known driver gene-positive disease who have received at least one targeted therapy for the driver gene-positive mutation if an approved targeted therapy has been approved; iii) If receiving chemotherapy, the number of previous lines of chemotherapy is ⁇ 2.
  • Cohort D Pathologically confirmed unresectable locally advanced/metastatic esophageal squamous cell carcinoma; For locally advanced/metastatic disease, subjects must have received PD-(L)1 and platinum-based chemotherapy and have ⁇ 2 lines of prior chemotherapy.
  • NSCLC non-squamous non-small cell lung cancer
  • Cohort A5 included Nectin-4 negative non-small cell lung cancer patients.
  • Non-squamous non-small cell lung cancer in cohorts A1, A2, and A3 must undergo driver gene mutation testing, including but not limited to EGFR gene testing and other driver gene (referring to driver genes other than EGFR gene) testing and/or immunohistochemical testing, and will be enrolled in different cohorts based on the test results.
  • driver gene mutation testing including but not limited to EGFR gene testing and other driver gene (referring to driver genes other than EGFR gene) testing and/or immunohistochemical testing, and will be enrolled in different cohorts based on the test results.
  • the starting dose of ADC-4 is 1 mg/kg, administered by intravenous infusion, once every 3 weeks (Q3W), with a treatment cycle of 21 days.
  • a Bayesian optimal interval (BOIN) design was employed, with a dose escalation study starting at a dose of 1 mg/kg.
  • the BOIN design phase included five pre-defined dose groups (2 mg/kg, 4 mg/kg, 6 mg/kg, 8 mg/kg, and 10 mg/kg).
  • Subjects were enrolled starting at the initial dose, with 3-6 subjects per cohort receiving treatment.
  • the dose for the next cohort was determined according to the BOIN design dose escalation decision table, up to the maximum single-dose group size (12 subjects) or the maximum total sample size (36 subjects) specified in the protocol, or the dose escalation was terminated early by the Safety Monitoring Committee (SMC).
  • SMC Safety Monitoring Committee
  • the principal investigator and the sponsor would jointly discuss and decide whether to add other dose groups (higher, intermediate, or lower doses) and/or adjust the dosing frequency (e.g., once weekly, QW) based on the obtained safety, tolerability, pharmacokinetic, immunogenicity, and efficacy information.
  • PK pharmacokinetic
  • the therapeutic expansion phase will be divided into six main cohorts based on tumor type:
  • Cohort A1 Subjects with EGFR-mutant non-squamous non-small cell lung cancer (NSCLC) treated with 6 mg/kg or 8 mg/kg Q3W ADC-4;
  • NSCLC non-squamous non-small cell lung cancer
  • Cohort A2 Subjects with non-squamous non-small cell lung cancer (NSCLC) who received 6 mg/kg or 8 mg/kg Q3W ADC-4 dosing;
  • NSCLC non-squamous non-small cell lung cancer
  • Cohort A3 Subjects with non-squamous non-small cell lung cancer (NSCLC) who received 6 mg/kg or 8 mg/kg Q3W ADC-4 therapy for other driver gene-positive (driver gene-positive other than EGFR gene) disease.
  • NSCLC non-squamous non-small cell lung cancer
  • Cohort A4 Subjects with squamous non-small cell lung cancer treated with 6 mg/kg or 8 mg/kg Q3W ADC-4;
  • Cohort A5 Subjects with Nectin-4 negative non-small cell lung cancer (squamous non-small cell lung cancer and non-squamous non-small cell lung cancer) who received 6 mg/kg or 8 mg/kg Q3W ADC-4 administration.
  • ADC-4 Intravenous infusion, 2 mg/kg, 4 mg/kg, 6 mg/kg, 8 mg/kg, 10 mg/kg, Q3W or other explored/determined doses.
  • Tumor assessment was performed using the RECIST v1.1 criteria, and all subjects underwent baseline tumor imaging assessment during the screening period. Efficacy was evaluated using the RECIST v1.1 criteria, and the efficacy endpoints included investigator-assessed ORR, DCR, DoR, PFS, and OS.
  • the baseline characteristics of some enrolled subjects are shown in Table 5: Among the 165 enrolled subjects (including 83 non-small cell lung cancer patients), the median age of all enrolled subjects was 60 years, 86.1% had an ECOG score of 1, and 65.5% of patients had received ⁇ 2 lines of prior systemic anti-tumor therapy; for the non-small cell lung cancer patients, the median age was 61 years, 95.2% had an ECOG score of 1, and 78.3% of patients had received ⁇ 2 lines of prior systemic anti-tumor therapy.
  • the ORR was 30.4% (36.7% for non-squamous cell carcinoma and 18.8% for squamous cell carcinoma)
  • the DCR was 89.1% (83.3% for non-squamous cell carcinoma and 100% for squamous cell carcinoma)
  • 14 patients achieved PR (30.4%)
  • 27 patients achieved SD (58.7%)
  • 4 patients achieved PD (8.7%): among the non-squamous cell carcinoma patients, 11 patients achieved PR (36.7%), 14 patients achieved SD (46.7%), and 4 patients achieved PD (13.3%); and among the squamous cell carcinoma patients, 3 patients achieved PR (18.8%), 13 patients achieved SD (81.3%), and 0 patients achieved PD.
  • the ORR was 43.5%, the DCR was 84.1%, and the mPFS was 5.7 months (as of December 20, 2024, the mPFS was 8.5 months at a dose of 6 mg/kg and 5.7 months at a dose of 8 mg/kg).
  • the ORR was 25.0%, the DCR was 72.7%, and one patient achieved complete remission (CR) (2.3%).
  • the mPFS was 4.3 months (as of December 20, 2024, the mPFS was 2.6 months at a dose of 6 mg/kg and 4.3 months at a dose of 8 mg/kg; as of May 2025, the mPFS was 5.7 months at a dose of 8 mg/kg).
  • the ORR was 25%
  • the DCR was 100%
  • the mPFS was 4.5 months (as of December 20, 2024, the mPFS was 4.4 months at the 6 mg/kg dose and 6.0 months at the 8 mg/kg dose).
  • the ORR for EGFR-mutant NSCLC subjects at a dose of 6 mg/kg was 48.6%, the DCR was 80%, and the mPFS was 8.5 months (data as of May 2025); the ORR at a dose of 8 mg/kg was 43.8%, the DCR was 90.6%, and the mPFS was 8.5 months (data as of May 2025).
  • the ORR at a dose of 8 mg/kg was 21.1%
  • the DCR was 68.4%
  • Safety assessments will be conducted for all subjects after enrollment in the study at each treatment cycle. These assessments will include the incidence and severity of adverse events (AEs) and serious adverse events (SAEs) (as determined according to the NCI-CTCAEv5.0 criteria), changes in vital signs, abnormal laboratory test results, and the incidence of dose suspension, dose reduction, and dose termination due to study drug-related toxicity during the trial.
  • AEs adverse events
  • SAEs serious adverse events
  • Safety evaluation results for a subset of subjects are shown in Table 9. 35.2% (58/165) of these patients experienced grade ⁇ 3 TRAEs. The most common TRAEs ( ⁇ 10%) included decreased neutrophil count (16.4%) and decreased white blood cell count (13.3%). Safety evaluation results for all enrolled subjects (395 cases) showed that the ADC-4 antibody-drug conjugate was well-tolerated, with extremely low incidences of interstitial lung disease (ILD) and grade ⁇ 3 skin toxicities (both 0.3%), and no new safety issues were identified.
  • ILD interstitial lung disease
  • ADC-4 antibody-drug conjugates exhibit a tolerable and manageable safety profile and show promising antitumor activity in non-small cell lung cancer.
  • Example 3 A multicenter, open-label phase IB/II clinical study of the safety, tolerability, and efficacy of ADC-4 combined with immunotherapy agents, with or without other antitumor therapies, in subjects with locally advanced or metastatic non-small cell lung cancer.
  • ADC-4 prepared in Example 1 The dosage form is an injection (lyophilized powder).
  • Anti-PD-L1 antibody the heavy chain of which is shown in SEQ ID NO: 19 and the light chain of which is shown in SEQ ID NO: 20.
  • the dosage form is an injection.
  • Anti-VEGF antibody the heavy chain of which is shown in SEQ ID NO: 39 and the light chain of which is shown in SEQ ID NO: 40.
  • the dosage form is an injection.
  • the Eastern Cooperative Oncology Group (ECOG) performance status score is 0-1.
  • subjects who have failed, are intolerant of, or refuse standard treatment must meet the following criteria: For subjects with negative driver genes, they must have received immunotherapy and platinum-based chemotherapy, and have had ⁇ 2 lines of prior systemic anti-tumor therapy; For subjects with positive driver genes, they must have received targeted therapy and platinum-based chemotherapy, and have had ⁇ 2 lines of prior systemic anti-tumor therapy.
  • Phase II cohorts A and C enrolled subjects with squamous cell carcinoma (squamous non-small cell lung cancer), while cohorts B and D enrolled subjects with non-squamous cell carcinoma (non-squamous non-small cell lung cancer). All subjects must not have received prior systemic anti-tumor therapy for locally advanced unresectable or metastatic non-small cell lung cancer, including systemic therapy with investigational drugs indicated for solid tumors.
  • Subjects who have previously received neoadjuvant/adjuvant chemotherapy, radical surgery with radiotherapy, or chemoradiotherapy for non-metastatic tumors with a cure-oriented approach are eligible for enrollment, provided they meet the following criteria: at least 6 months have passed since the end of the last cycle of chemotherapy, radical surgery, radiotherapy, or chemoradiotherapy before the first dose of medication; and at least 12 months have passed since the end of the last cycle of immunotherapy before the first dose of medication.
  • Subjects with non-squamous non-small cell lung cancer (NSCLC) in cohorts B and D must undergo EGFR gene testing and ALK gene and/or immunohistochemical testing.
  • Subjects with EGFR mutation-positive or ALK fusion-positive results are ineligible for enrollment.
  • subjects with other driver gene mutations (other than EGFR or ALK genes) and for whom approved targeted therapies are available are also ineligible for enrollment.
  • Subjects must be able to provide archived or fresh tumor tissue with positive Nectin-4 expression and a PD-L1 TPS ⁇ 1% for Phase II patients (based on immunohistochemical [IHC] testing at a central laboratory). For subjects unable to provide tumor tissue samples meeting the above requirements, enrollment will be determined in consultation with the sponsor.
  • Dosage level 1 ADC-4 6 mg/kg Q3W + anti-PD-L1 antibody 1200 mg Q3W
  • Dosage level 2 ADC-4 8 mg/kg Q3W + anti-PD-L1 antibody 1200 mg Q3W.
  • ADC-4 4mg/kg Q3W + anti-PD-L1 antibody 1200mg Q3W + cisplatin 75mg/ m2 Q3W; or
  • Dosage level 1 ADC-4 8 mg/kg Q3W + anti-PD-L1 antibody 1200 mg Q3W + anti-VEGF antibody 7.5 mg/kg Q3W;
  • Dosage level 2 ADC-4 8 mg/kg Q3W + anti-PD-L1 antibody 1200 mg Q3W + anti-VEGF antibody 15 mg/kg Q3W.
  • Cohort A Subjects receiving ADC-4 (selected dose, Q3W) + anti-PD-L1 antibody (1200 mg, Q3W) for squamous cell carcinoma (squamous non-small cell lung cancer);
  • Cohort B Subjects receiving ADC-4 (selected dose, Q3W) + anti-PD-L1 antibody (1200 mg, Q3W) for non-squamous carcinoma (non-squamous non-small cell lung cancer);
  • Cohort C Subjects treated with squamous cell carcinoma (squamous non-small cell lung cancer) receiving ADC-4 (selected dose, Q3W) + anti-PD-L1 antibody (1200 mg, Q3W) + carboplatin (AUC4 or AUC5, Q3W); or
  • Cohort D Subjects receiving ADC-4 (selected dose, Q3W) + anti-PD-L1 antibody (1200 mg, Q3W) + carboplatin (AUC4 or AUC5, Q3W) for non-squamous cell carcinoma (non-squamous non-small cell lung cancer); or
  • Cohort E Subjects with non-small cell lung cancer who received ADC-4 (8 mg/kg, Q3W) + anti-PD-L1 antibody (1200 mg, Q3W) + anti-VEGF antibody (selected dose, Q3W).
  • ADC-4 Intravenous infusion, 4 mg/kg, 6 mg/kg, 8 mg/kg, Q3W or other explored/determined doses.
  • Anti-PD-L1 antibody Intravenous infusion, 1200 mg, once every 3 weeks, each infusion time is 30-60 minutes, 21 days as one cycle (Q3W).
  • Carboplatin administered according to the Calvert formula: Intravenous infusion, dose calculated based on AUC4 or AUC5, every 3 weeks. Specific medication administration can be based on prescription information or the research center's standard operating procedure.
  • Calvert formula: Carboplatin dose (mg) set AUC (mg/mL ⁇ min) ⁇ [endogenous creatinine clearance (mL/min) + 25]. Endogenous creatinine clearance is calculated using the Cockcroft-Gault formula:
  • Serum creatinine concentration mg/dL
  • Serum creatinine concentration ⁇ mol/L
  • Age is expressed in years, and weight is expressed in kilograms (kg).
  • Cisplatin Intravenous infusion, 75 mg/ m2 , once every 3 weeks, with each infusion recommended to last 1-2 hours.
  • Anti-VEGF antibody intravenous infusion, 7.5 mg/kg, 15 mg/kg, with each dosing cycle lasting 3 weeks.
  • Administration sequence 1) For two-drug combination therapy, it is recommended to administer ADC-4 first, followed by anti-PD-L1 antibody; 2) For three-drug combination therapy, it is recommended to administer ADC-4 first, followed by anti-PD-L1 antibody, and finally carboplatin or cisplatin or anti-VEGF antibody.
  • the time interval between two drug administrations should be >30 minutes. Administration should be completed on the same day if possible. Separate infusion bags and filters should be used for different drug infusions.
  • Treatment with anti-PD-L1 antibodies must be discontinued after a cumulative total of 35 doses. Carboplatin/cisplatin should be used for 2-4 cycles. If a study drug is discontinued prematurely due to intolerance, other study drugs may be considered for continued use.
  • Tumor assessment was performed using the RECIST v1.1 criteria, and all subjects underwent baseline tumor imaging assessment during the screening period. Efficacy endpoints included investigator-assessed ORR, DCR, DoR, PFS, and OS.
  • the clinical trial is still ongoing.
  • the subjects enrolled in Phase IB (including non-squamous cell carcinoma and squamous cell carcinoma subjects) had an ORR of 30% and a DCR of 80% at IB-Part 1 dose level 1, and an ORR of 29.7% and a DCR of 91.9% at IB-Part 1 dose level 2.
  • the subjects enrolled in Phase II had an ORR of 69.6% and a DCR of 96.4% at the ADC-4 (8 mg/kg, Q3W) + anti-PD-L1 antibody (1200 mg, Q3W) dose level (as shown in Table 2).
  • Safety assessments will be conducted for all subjects after enrollment in the study at each treatment cycle. These assessments will include the incidence and severity of adverse events (AEs) and serious adverse events (SAEs) (as determined according to the NCI-CTCAEv5.0 criteria), changes in vital signs, abnormal laboratory test results, and the incidence of dose suspension, dose reduction, and dose termination due to study drug-related toxicity during the trial.
  • AEs adverse events
  • SAEs serious adverse events
  • ADC-4 antibody-drug conjugates combined with other therapeutic agents have demonstrated tolerable and manageable safety profiles and show promising antitumor activity in both second-line and first-line treatment of non-small cell lung cancer.
  • Example 4 A multicenter, open-label phase IB/II clinical study of the safety, tolerability, and efficacy of ADC-4 combined with immunotherapy agents, with or without other antitumor therapies, in subjects with advanced solid tumors.
  • ADC-4 prepared in Example 1 The dosage form is an injection (lyophilized powder).
  • Anti-PD-L1 antibody the heavy chain of which is shown in SEQ ID NO: 19 and the light chain of which is shown in SEQ ID NO: 20.
  • the dosage form is an injection.
  • Anti-CTLA-4 antibody the heavy chain of which is shown in SEQ ID NO: 29 and the light chain of which is shown in SEQ ID NO: 30.
  • the dosage form is an injection.
  • Anti-VEGF antibody the heavy chain of which is shown in SEQ ID NO: 39 and the light chain of which is shown in SEQ ID NO: 40.
  • the dosage form is an injection.
  • the Eastern Cooperative Oncology Group (ECOG) performance status score is 0-1.
  • Phase Ib participants must be patients with locally advanced or metastatic non-small cell lung cancer who have failed, are intolerant of, or refuse standard therapy; and have received no more than two lines of prior systemic anti-tumor therapy. For non-squamous cell carcinoma participants, genetic testing results are required.
  • Cohort A included squamous cell carcinoma subjects
  • Cohort B included non-squamous cell carcinoma subjects
  • Cohort C included non-small cell lung cancer subjects with STK11 single mutation, KEAP1 single mutation, or STK11/KEAP1 co-mutation
  • Cohort D included non-small cell lung cancer subjects.
  • Non-squamous cell carcinoma (NSCLC) patients must undergo EGFR gene testing and ALK gene and/or immunohistochemical testing; patients with EGFR mutations or ALK positivity are ineligible for enrollment. Additionally, patients with other driver gene mutations (besides EGFR or ALK gene positive mutations) and for whom approved targeted therapies are available are also ineligible for enrollment.
  • NSCLC Non-squamous cell carcinoma
  • Subjects must be able to provide archived or fresh tumor tissue for testing Nectin-4 and PD-L1 TPS expression levels. For subjects unable to provide tumor tissue samples meeting the above requirements, enrollment will be determined in consultation with the sponsor.
  • Dosage group 1 ADC-4 (6 mg/kg, Q3W) + anti-PD-L1 antibody (1200 mg, Q3W) + anti-CTLA-4 antibody (C1D1 280 mg once, C2-C4 no administration, C5 and subsequent cycles 70 mg Q6W)
  • Dosage group 2 ADC-4 (8 mg/kg, Q3W) + anti-PD-L1 antibody (1200 mg, Q3W) + anti-CTLA-4 antibody (C1D1 280 mg once, C2-C4 no administration, C5 and subsequent cycles 70 mg Q6W).
  • ADC-4 (8 mg/kg, Q3W) + anti-PD-L1 antibody (1200 mg, Q3W) + anti-CTLA-4 antibody (C1D1 280 mg once, C2-C4 no administration, C5 and subsequent cycles 70 mg Q6W) + anti-VEGF antibody (15 mg/kg, Q3W).
  • SMC will decide whether to explore combination therapy with ADC-4 or anti-VEGF antibody or anti-CTLA-4 antibody down-dose groups, or to proceed with Phase II therapy based on the safety and efficacy data obtained.
  • Cohort A Subjects with squamous cell carcinoma (squamous non-small cell lung cancer) treated with ADC-4 (selected dose, Q3W) + anti-PD-L1 antibody (1200 mg, Q3W) + anti-CTLA-4 antibody (C1D1 280 mg once, C2-C4 without administration, C5 and subsequent cycles 70 mg Q6W);
  • Cohort B Subjects with non-squamous non-small cell lung cancer who received ADC-4 (selected dose, Q3W) + anti-PD-L1 antibody (1200 mg, Q3W) + anti-CTLA-4 antibody (C1D1 280 mg once, C2-C4 without administration, C5 and subsequent cycles 70 mg Q6W);
  • Cohort C Non-small cell lung cancer patients with STK11 single mutation, KEAP1 single mutation, or STK11/KEAP1 co-mutation who received ADC-4 (selected dose, Q3W) + anti-PD-L1 antibody (1200 mg, Q3W) + anti-CTLA-4 antibody (C1D1 280 mg once, C2-C4 without administration, C5 and subsequent cycles 70 mg Q6W);
  • Cohort D Received ADC-4 (selected dose, Q3W) + anti-PD-L1 antibody (1200 mg, Q3W) + anti-CTLA-4 antibody (C1D1 280 mg once, C2-C4 without administration, C5 and subsequent cycles 70 mg Q6W) + bevacizumab 15 mg/kg Q3W for non-small cell lung cancer subjects.
  • the administration method of the anti-CTLA-4 antibody means "with a 21-day cycle, a single 280mg dose on the first day of the first cycle, no administration in the second to fourth cycles, and from the first day of the fifth cycle onwards, administration at a frequency of 70mg every 6 weeks (also known as "every other cycle”)”.
  • ADC-4 Intravenous infusion, 6 mg/kg, 8 mg/kg, Q3W; or other exploratory/determined doses.
  • the first intravenous infusion should last 90 ⁇ 10 min. If no infusion-related reaction occurs after the first administration, subsequent infusions may be shortened to approximately 30 min (not less than 20 min and not more than 60 min, including the flushing phase).
  • Anti-PD-L1 antibody Intravenous infusion, 1200 mg, once every 3 weeks, each infusion lasting 30-60 minutes, for a 21-day cycle (Q3W). The total number of doses should not exceed 35.
  • Anti-CTLA-4 antibody Intravenous infusion. Administer a single dose of 280 mg for C1D1, no doses for C2-C4, and 70 mg every 6 weeks for C5 and subsequent cycles (a single 280 mg dose on day 1 of the first cycle, no doses for cycles 2-4, and starting from day 1 of the fifth cycle, administer 70 mg every 6 weeks). Each intravenous infusion lasts 30 ⁇ 10 minutes, with each cycle lasting 21 days. The cumulative treatment period should not exceed 2 years.
  • Anti-VEGF antibody Intravenous infusion, 15 mg/kg or other exploratory/determined dose, in a 3-week cycle, with the first day of each cycle.
  • Administration order It is recommended to administer ADC-4 first, followed by anti-PD-L1 antibody, then anti-CTLA-4 antibody, and finally anti-VEGF antibody (if necessary).
  • the interval between administration of the two drugs should be >30 minutes.
  • Anti-PD-L1 antibody treatment must be discontinued after a cumulative total of 35 doses.
  • Anti-CTLA-4 antibody treatment should not exceed 2 years in total. If a study drug is discontinued prematurely due to intolerance, the use of other study drugs may be considered.
  • Efficacy endpoints included investigator-assessed objective response rate (ORR), disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), and overall survival (OS).
  • ORR objective response rate
  • DCR disease control rate
  • DoR duration of response
  • PFS progression-free survival
  • OS overall survival
  • Safety assessments will be conducted for all subjects after enrollment in the study at each treatment cycle. These assessments will include the incidence and severity of adverse events (AEs) and serious adverse events (SAEs) (as determined according to the NCI-CTCAEv5.0 criteria), changes in vital signs, abnormal laboratory test results, and the incidence of dose suspension, dose reduction, and dose termination due to study drug-related toxicity during the trial.
  • AEs adverse events
  • SAEs serious adverse events
  • ADC-4 antibody-drug conjugates combined with other therapeutic agents have demonstrated tolerable and manageable safety profiles and show promising antitumor activity in both second-line and first-line treatment of non-small cell lung cancer.
  • Example 5 A multicenter, open-label phase IB/II clinical study of the safety, tolerability, and efficacy of ADC-4 in patients with locally advanced or metastatic esophageal cancer, with or without other antitumor therapies.
  • ADC-4 prepared in Example 1 The dosage form is an injection (lyophilized powder).
  • Anti-PD-L1 antibody the heavy chain of which is shown in SEQ ID NO: 19 and the light chain of which is shown in SEQ ID NO: 20.
  • the dosage form is an injection.
  • Anti-CTLA-4 antibody the heavy chain of which is shown in SEQ ID NO: 29 and the light chain of which is shown in SEQ ID NO: 30.
  • the dosage form is an injection.
  • Cisplatin injection for injection is a marketed drug.
  • the Eastern Cooperative Oncology Group (ECOG) performance status score is 0-1.
  • stage Ib Patients with pathologically confirmed locally advanced unresectable or metastatic esophageal squamous cell carcinoma, stage Ib, who have failed, are intolerant of, or refuse standard treatment, must have received PD-(L)1 and platinum-based chemotherapy and have ⁇ 2 lines of prior treatment.
  • PD-(L)1 and platinum-based chemotherapy For subjects who have previously received neoadjuvant/adjuvant chemotherapy or radical chemoradiotherapy for non-metastatic tumors, if disease recurrence or metastasis occurs within ⁇ 6 months after treatment completion, this treatment can be considered as first-line therapy.
  • Phase II participants were those who had not received systemic anti-tumor therapy for locally advanced unresectable or metastatic esophageal cancer, including systemic therapy with investigational drugs indicated for solid tumors; if they had previously received neoadjuvant/adjuvant chemotherapy, immunotherapy, radical surgery, radiotherapy, or chemoradiotherapy for non-metastatic tumors with a cure-oriented approach, at least 6 months had passed since the end of the last cycle of chemotherapy, radical surgery, radiotherapy, or chemoradiotherapy before the first dose of medication; or at least 12 months had passed since the end of the last cycle of immunotherapy before the first dose of medication.
  • Dosage Level 2 ADC-4 8mg/kg Q3W + anti-PD-L1 antibody 1200mg Q3W.
  • Dosage Level 2 ADC-4 6mg/kg Q3W + Anti-PD-L1 antibody 1200mg Q3W + Cisplatin 75mg/ m2 Q3W.
  • Dosage Level 1 ADC-4 (6 mg/kg, Q3W) + anti-PD-L1 antibody (1200 mg, Q3W) + anti-CTLA-4 antibody (C1D1 280 mg once, C2-C4 no administration, C5 and subsequent cycles 70 mg Q6W).
  • Dosage Level 2 ADC-4 (8 mg/kg, Q3W) + anti-PD-L1 antibody (1200 mg, Q3W) + anti-CTLA-4 antibody (C1D1 280 mg once, C2-C4 no administration, C5 and subsequent cycles 70 mg Q6W).
  • the administration method of the anti-CTLA-4 antibody means "with a 21-day cycle, a single 280mg dose on the first day of the first cycle, no administration in the second to fourth cycles, and from the first day of the fifth cycle onwards, administration at a frequency of 70mg every 6 weeks (also known as "every other cycle”)”.
  • Cohort A Patients receiving ADC-4 (selected dose, Q3W) + anti-PD-L1 antibody (1200 mg, Q3W) for esophageal squamous cell carcinoma;
  • Cohort B Patients with esophageal squamous cell carcinoma treated with ADC-4 (selected dose, Q3W) + anti-PD-L1 antibody (1200 mg, Q3W) + cisplatin (75 mg/ m2 , Q3W).
  • Cohort C Patients with esophageal squamous cell carcinoma received ADC-4 (selected dose, Q3W) + anti-PD-L1 antibody (1200 mg, Q3W) + anti-CTLA-4 antibody (C1D1 280 mg once, C2-C4 without administration, C5 and subsequent cycles 70 mg Q6W).
  • ADC-4 Intravenous infusion, 4 mg/kg, 6 mg/kg, 8 mg/kg, Q3W or other explored/determined doses.
  • Anti-PD-L1 antibody Intravenous infusion, 1200 mg, once every 3 weeks, each infusion time is 30-60 minutes, 21 days as one cycle (Q3W).
  • Cisplatin Intravenous infusion, 75 mg/ m2 , once every 3 weeks, each infusion lasting about 60 minutes, with a maximum of 4 cycles of chemotherapy.
  • Anti-CTLA-4 antibody Intravenous infusion. Administer a single dose of 280 mg for C1D1, no doses for C2-C4, and 70 mg every 6 weeks for C5 and subsequent cycles (a single 280 mg dose on day 1 of the first cycle, no doses for cycles 2-4, and starting from day 1 of the fifth cycle, administer 70 mg every 6 weeks). Each intravenous infusion lasts 30 ⁇ 10 minutes, with each cycle lasting 21 days. The total duration of treatment should not exceed 2 years.
  • Administration sequence 1) For two-drug combination therapy, it is recommended to administer ADC-4 first, followed by anti-PD-L1 antibody; 2) For three-drug combination therapy, it is recommended to administer ADC-4 first, followed by anti-PD-L1 antibody, and finally cisplatin or anti-CTLA-4 antibody.
  • the time interval between two drug administrations should be >30 minutes. Administration should ideally be completed on the same day. Separate infusion bags and filters should be used for different drug infusions.
  • Anti-PD-L1 antibody treatment requires a cumulative total of 35 doses; anti-CTLA-4 antibody treatment requires two years from the start of the first dose. If a study drug is discontinued early due to intolerance, other study drugs may be considered for continued use.
  • Tumor assessment was performed using the RECIST v1.1 criteria, and all subjects underwent baseline tumor imaging assessment during the screening period. Efficacy endpoints included investigator-assessed ORR, DCR, DoR, PFS, and OS.
  • the ORR was 30% and the DCR was 90% at Part 1 dose level 1 (part1-1), and the ORR was 46.4% and the DCR was 92.9% at Part 1 dose level 2 (part1-2).
  • the ORR was 64.7% and the DCR was 91.2% at cohort A (II-A, where the ADC-4 dose was 8 mg/kg), and the ORR was 61.9% and the DCR was 95.2% at cohort C (II-C, where the ADC-4 dose was 8 mg/kg).
  • IB-part3 completed at least one tumor assessment.
  • 4 subjects were at part3 dose level 1, including 3 with SD (stable disease) and 1 with PD (progressive disease); and 4 subjects were at part3 dose level 2, including 2 with PR (partial response) and 2 with SD (stable disease).
  • Safety assessments will be conducted for all subjects after enrollment in the study at each treatment cycle. These assessments will include the incidence and severity of adverse events (AEs) and serious adverse events (SAEs) (as determined according to the NCI-CTCAEv5.0 criteria), changes in vital signs, abnormal laboratory test results, and the incidence of dose suspension, dose reduction, and dose termination due to study drug-related toxicity during the trial.
  • AEs adverse events
  • SAEs serious adverse events
  • ADC-4 antibody-drug conjugates combined with immunotherapeutic agents demonstrate a tolerable and manageable safety profile and show promising antitumor activity in both second-line and first-line treatment of esophageal squamous cell carcinoma.

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Abstract

抗Nectin-4抗体药物偶联物治疗肿瘤的方法及医药用途、抗Nectin-4抗体药物偶联物联合其它治疗剂治疗肿瘤的方法及医药用途。

Description

抗Nectin-4抗体药物偶联物治疗肿瘤的用途
本公开要求如下专利申请的优先权：于2024年06月06日提交，申请号为202410730228.X的中国专利申请；于2024年06月14日提交，申请号为202410769468.0的中国专利申请；于2024年08月24日提交，申请号为202411169353.4的中国专利申请；于2024年09月08日提交，申请号为202411251599.6的中国专利申请；于2024年09月08日提交，申请号为202411251596.2的中国专利申请；于2024年09月08日提交，申请号为202411251591.X的中国专利申请；于2024年04月23日提交，申请号为202510515473.3的中国专利申请；于2024年05月30日提交，申请号为202510718264.9的中国专利申请；。前述专利申请的全部内容通过引用结合至本公开中。
技术领域
本公开属于医药领域，涉及抗Nectin-4抗体药物偶联物及其联用其它治疗剂治疗肿瘤的方法及医药用途。
背景技术
Nectin-4(基因名称PVRL4，脊髓灰质炎病毒受体4)蛋白是属于免疫球蛋白超家族的Nectin家族。Nectin家族与钙黏着蛋白共同作用，对粘着连接(AJs)和紧密连接(TJs)的产生和维持具有显着影响，它们调节多种细胞行为，包括细胞粘附、生长、分化、迁移和凋亡。与Nectin1-3在正常成年组织中广泛表达不同，Nectin-4蛋白在胚胎和胎盘中特异性表达，在少数正常成年组织(包括皮肤)中表达，以及在肿瘤组织中过表达(除AJ外，也分布在细胞顶端及游离到血浆中)。Nectin-4在肿瘤组织中都具有特异性高表达，并且与肿瘤的预后密切相关。Nectin-4促进肿瘤的发生和转移的潜在机制包括：1)促进肿瘤血管新生：通过激活PI3K/AKT信号通路促进肿瘤血管生成；2)促进肿瘤细胞生长、增殖和迁移：通过激活Ras相关的C3肉毒杆菌毒素底物1(Rac1)信号通路；3)促进上皮细胞-间充质转化(EMT)：Nectin-4可调节细胞间粘附，重塑肌动蛋白细胞骨架，增强伪足在肿瘤细胞中延伸的驱动力，最终导致肿瘤发展和扩散。
抗体药物偶联物(ADC)是通过一个化学链接将具有细胞毒性的小分子药物共价连接到抗体上，以抗体作为载体将小分子药物靶向运输到目标细胞中，其兼具了抗体的高度靶向性以及细胞毒药物对靶细胞的强大杀伤力，被认为是新一代抗体靶向治疗药物。Nectin-4 ADC中的抗体特异性识别并结合靶细胞表面的Nectin-4受体，随后通过内吞作用进入靶细胞，在胞内经分解释放出细胞毒药物，最后细胞毒药物通过破坏DNA或者作用于微管，阻止细胞分裂、引起细胞的凋亡，从而发挥抗肿瘤作用。
目前，针对Nectin-4靶点，本领域需要开发安全、有效的药物治疗方案。
发明内容
本公开提供抗Nectin-4抗体药物偶联物治疗肿瘤的方法及医药用途。
在一些实施方案中，本公开提供如下任一项所示的用途：
(1)抗Nectin-4抗体药物偶联物在制备治疗肿瘤的药物中的用途；
(2)抗Nectin-4抗体药物偶联物联合免疫治疗剂在制备治疗肿瘤的药物中的用途；
(3)抗Nectin-4抗体药物偶联物联合免疫治疗剂和VEGF信号通路抑制剂在制备治疗肿瘤的药物中的用途；
(4)抗Nectin-4抗体药物偶联物联合免疫治疗剂和铂类药物在制备治疗肿瘤的药物中的用途；(5)抗Nectin-4抗体药物偶联物和免疫治疗剂的组合在制备治疗肿瘤的药物中的用途；
(5)抗Nectin-4抗体药物偶联物、免疫治疗剂和VEGF信号通路抑制剂的组合在制备治疗肿瘤的药物中的用途；
(6)抗Nectin-4抗体药物偶联物联合免疫治疗剂和铂类药物在制备治疗肿瘤的药物中的用途；
(7)抗Nectin-4抗体药物偶联物，其用于治疗肿瘤；
(8)抗Nectin-4抗体药物偶联物联合免疫治疗剂，用于治疗肿瘤；
(9)抗Nectin-4抗体药物偶联物联合免疫治疗剂和VEGF信号通路抑制剂，用于治疗肿瘤；
(10)抗Nectin-4抗体药物偶联物联合免疫治疗剂和铂类药物在制备治疗肿瘤的药物中的用途；
(11)抗Nectin-4抗体药物偶联物用于治疗肿瘤，其中，所述抗Nectin-4抗体药物偶联物联合免疫治疗剂施用于受试者；
(12)免疫治疗剂用于治疗肿瘤，其中，所述免疫治疗剂联合抗Nectin-4抗体药物偶联物施用于受试者；
(13)抗Nectin-4抗体药物偶联物用于治疗肿瘤，其中，所述抗Nectin-4抗体药物偶联物联合免疫治疗剂和VEGF信号通路抑制剂施用于受试者；
(14)免疫治疗剂用于治疗肿瘤，其中，所述免疫治疗剂联合抗Nectin-4抗体药物偶联物和VEGF信号通路抑制剂施用于受试者；
(15)VEGF信号通路抑制剂，其中，所述VEGF信号通路抑制剂联合免疫治疗剂和抗Nectin-4抗体药物偶联物施用于受试者；
(16)抗Nectin-4抗体药物偶联物用于治疗肿瘤，其中，所述抗Nectin-4抗体药物偶联物联合免疫治疗剂和铂类药物施用于受试者；
(17)免疫治疗剂用于治疗肿瘤，其中，所述免疫治疗剂联合抗Nectin-4抗体药物偶联物和铂类药物施用于受试者；
(18)铂类药物，其中，所述铂类药物联合免疫治疗剂和抗Nectin-4抗体药物偶联物施用于受试者；
(19)用于治疗肿瘤的抗Nectin-4抗体药物偶联物，其中，所述抗Nectin-4抗体药物偶联物施用于受试者；
(20)用于治疗肿瘤的药物组合物、药剂盒或制品，其中，所述药物组合物、药剂盒或制品包括抗Nectin-4抗体药物偶联物；
(21)用于治疗肿瘤的药物组合物、药剂盒或制品，其中，所述药物组合物、药剂盒或制品包括抗Nectin-4抗体药物偶联物和免疫治疗剂；
(22)用于治疗肿瘤的药物组合物、药剂盒或制品，其中，所述药物组合物、药剂盒或制品包括抗Nectin-4抗体药物偶联物、免疫治疗剂和VEGF信号通路抑制剂；
(23)用于治疗肿瘤的药物组合物、药剂盒或制品，其中，所述药物组合物、药剂盒或制品包括抗Nectin-4抗体药物偶联物、免疫治疗剂和铂类药物；
(24)药物组合物、药剂盒或制品在制备治疗肿瘤的药物中的用途，其中，所述药物组合物、药剂盒或制品包括抗Nectin-4抗体药物偶联物；
(25)药物组合物、药剂盒或制品在制备治疗肿瘤的药物中的用途，其中，所述药物组合物、药剂盒或制品包括抗Nectin-4抗体药物偶联物和免疫治疗剂；
(26)药物组合物、药剂盒或制品在制备治疗肿瘤的药物中的用途，其中，所述药物组合物、药剂盒或制品包括抗Nectin-4抗体药物偶联物、免疫治疗剂和VEGF信号通路抑制剂；
(27)药物组合物、药剂盒或制品在制备治疗肿瘤的药物中的用途，其中，所述药物组合物、药剂盒或制品包括抗Nectin-4抗体药物偶联物、免疫治疗剂和铂类药物。
在一些实施方案中，本公开提供如下任一项所示的方法：
(1)治疗肿瘤的方法，包括向有需要的受试者施用治疗有效量的抗Nectin-4抗体药物偶联物；
(2)治疗肿瘤的方法，包括向有需要的受试者施用治疗有效量的抗Nectin-4抗体药物偶联物和免疫治疗剂；
(3)治疗肿瘤的方法，包括向有需要的受试者施用治疗有效量的抗Nectin-4抗体药物偶联物、免疫治疗剂和VEGF信号通路抑制剂；
(4)治疗肿瘤的方法，包括向有需要的受试者施用治疗有效量的抗Nectin-4抗体药物偶联物、免疫治疗剂和铂类药物；
(5)治疗肿瘤的方法，包括向有需要的受试者施用药物组合物、药剂盒或制品；其中，所述药物组合物、药剂盒或制品包括抗Nectin-4抗体药物偶联物；
(6)治疗肿瘤的方法，包括向有需要的受试者施用药物组合物、药剂盒或制品；其中，所述药物组合物、药剂盒或制品包括抗Nectin-4抗体药物偶联物和和免疫治疗剂；
(7)治疗肿瘤的方法，包括向有需要的受试者施用药物组合物、药剂盒或制品；其中，所述药物组合物、药剂盒或制品包括抗Nectin-4抗体药物偶联物和和免疫治疗剂和VEGF信号通路抑制剂；
(8)治疗肿瘤的方法，包括向有需要的受试者施用药物组合物、药剂盒或制品；其中，所述药物组合物、药剂盒或制品包括抗Nectin-4抗体药物偶联物和和免疫治疗剂和铂类药物。
在一些实施方案中，本公开提供如下任一项所示的产品：
(1)药物组合物，其包括抗Nectin-4抗体药物偶联物；
(2)药剂盒，其包括抗Nectin-4抗体药物偶联物；
(3)制品，其包括抗Nectin-4抗体药物偶联物；
(4)药物组合物，其包括抗Nectin-4抗体药物偶联物和免疫治疗剂；
(5)药剂盒，其包括抗Nectin-4抗体药物偶联物和免疫治疗剂；
(6)制品，其包括抗Nectin-4抗体药物偶联物和免疫治疗剂；
(7)药物组合物，其包括抗Nectin-4抗体药物偶联物、免疫治疗剂和VEGF信号通路抑制剂；
(8)药剂盒，其包括抗Nectin-4抗体药物偶联物、免疫治疗剂和VEGF信号通路抑制剂；
(9)制品，其包括抗Nectin-4抗体药物偶联物、免疫治疗剂和铂类药物；
(10)药物组合物，其包括抗Nectin-4抗体药物偶联物、免疫治疗剂和铂类药物；
(11)药剂盒，其包括抗Nectin-4抗体药物偶联物、免疫治疗剂和铂类药物；
(12)制品，其包括抗Nectin-4抗体药物偶联物、免疫治疗剂和铂类药物。
在一些实施方案中，药剂盒或制品还包含一个或多个容器，其独立的包含抗Nectin-4抗体药物偶联物。在一些实施方案中，药剂盒或制品还包含一个或多个容器，其各自独立的包含抗Nectin-4抗体药物偶联物和免疫治疗剂。在一些实施方案中，药剂盒或制品还包含一个或多个容器，其各自独立的包含抗Nectin-4抗体药物偶联物、免疫治疗剂和VEGF信号通路抑制剂。在一些实施方案中，药剂盒或制品还包含一个或多个容器，其各自独立的包含抗Nectin-4抗体药物偶联物、免疫治疗剂和铂类药物。
在一些实施方案中，所述药物组合物中，抗Nectin-4抗体药物偶联物以独立包装地形式存在。在一些实施方案中，所述药物组合物中，抗Nectin-4抗体药物偶联物和免疫治疗剂以独立包装地形式存在。在一些实施方案中，所述药物组合物中，抗Nectin-4抗体药物偶联物、免疫治疗剂和VEGF信号通路抑制剂以独立包装地形式存在。在一些实施方案中，所述药物组合物中，抗Nectin-4抗体药物偶联物、免疫治疗剂和铂类药物以独立包装地形式存在。
在一些实施方案中，所述肿瘤是实体瘤。在一些实施方案中，所述肿瘤是晚期实体瘤。
在一些实施方案中，所述肿瘤是非小细胞肺癌。在一些实施方案中，所述肿瘤是晚期非小细胞肺癌。在一些实施方案中，所述肿瘤是局部晚期或转移性非小细胞肺癌。在一些实施方案中，所述肿瘤是局部晚期不可切除或转移性非小细胞肺癌。
在一些实施方案中，所述肿瘤是鳞状或非鳞状非小细胞肺癌。
在一些实施方案中，所述肿瘤是鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是晚期鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是局部晚期或转移性鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是局部晚期不可切除或转移性鳞状非小细胞肺癌。
在一些实施方案中，所述肿瘤是非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是晚期非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是局部晚期或转移性非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是局部晚期不可切除或转移性非鳞状非小细胞肺癌。
在一些实施方案中，所述肿瘤为驱动基因阳性的非小细胞肺癌。在一些实施方案中，所述肿瘤为驱动基因阳性的晚期非小细胞肺癌。在一些实施方案中，所述肿瘤为驱动基因阳性的局部晚期或转移性非小细胞肺癌。在一些实施方案中，所述肿瘤为驱动基因阳性的局部晚期不可切除或转移性非小细胞肺癌。
在一些实施方案中，所述肿瘤是EGFR突变型非小细胞肺癌。在一些实施方案中，所述肿瘤是EGFR突变型晚期非小细胞肺癌。在一些实施方案中，所述肿瘤是EGFR突变型局部晚期或转移性非小细胞肺癌。在一些实施方案中，所述肿瘤是EGFR突变型局部晚期不可切除或转移性非小细胞肺癌。
在一些实施方案中，所述肿瘤是驱动基因阳性的非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是驱动基因阳性的晚期非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是驱动基因阳性的局部晚期或转移性非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是驱动基因阳性的局部晚期不可切除或转移性非鳞状非小细胞肺癌。
在一些实施方案中，所述肿瘤是EGFR突变型非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是EGFR突变型晚期非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是EGFR突变型局部晚期或转移性非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是EGFR突变型局部晚期不可切除或转移性非鳞状非小细胞肺癌。
在一些实施方案中，所述肿瘤是EGFR驱动基因阴性(又称“EGFR野生型”，包括驱动基因阴性和除EGFR之外的其它驱动基因阳性)非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是EGFR驱动基因阴性(EGFR野生型)晚期非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是EGFR驱动基因阴性(EGFR野生型)局部晚期或转移性非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是EGFR驱动基因阴性(EGFR野生型)局部晚期不可切除或转移性非鳞状非小细胞肺癌。
在一些实施方案中，所述肿瘤为驱动基因阴性的非小细胞肺癌。在一些实施方案中，所述肿瘤为驱动基因阴性的晚期非小细胞肺癌。在一些实施方案中，所述肿瘤为驱动基因阴性的局部晚期或转移性非小细胞肺癌。在一些实施方案中，所述肿瘤为驱动基因阴性的局部晚期不可切除或转移性非小细胞肺癌。
在一些实施方案中，所述肿瘤是驱动基因阴性的非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是驱动基因阴性的晚期非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是驱动基因阴性的局部晚期或转移性非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是驱动基因阴性的局部晚期不可切除或转移性非鳞状非小细胞肺癌。
在一些实施方案中，所述肿瘤是其它驱动基因阳性(除EGFR突变型之外的驱动基因阳性)的非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是其它驱动基因阳性的局部晚期或转移性非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是其它驱动基因阳性的局部晚期不可切除或转移性非鳞状非小细胞肺癌。
在一些实施方案中，所述肿瘤是Nectin-4阳性的非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阳性的晚期非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阳性的局部晚期或转移性非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阳性的局部晚期不可切除或转移性非小细胞肺癌。
在一些实施方案中，所述肿瘤是Nectin-4阴性的非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阴性的晚期非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阴性的局部晚期或转移性非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阴性的局部晚期不可切除或转移性非小细胞肺癌。
在一些实施方案中，所述肿瘤是食管癌。在一些实施方案中，所述肿瘤是晚期食管癌。在一些实施方案中，所述肿瘤是局部晚期或转移性食管癌。在一些实施方案中，所述肿瘤是局部晚期不可切除或转移性食管癌。在一些实施方案中，所述肿瘤是食管鳞癌。在一些实施方案中，所述肿瘤是晚期食管鳞癌。在一些实施方案中，所述肿瘤是局部晚期或转移性食管鳞癌。在一些实施方案中，所述肿瘤是局部晚期不可切除或转移性食管鳞癌。
在一些实施方案中，患有前述任一项所述非小细胞肺癌或食管癌的受试者既往接受过抗肿瘤标准治疗，所述抗肿瘤标准治疗选自化学疗法、免疫疗法、和/或靶向药物疗法，所述化学疗法包含铂类化疗。
在一些实施方案中，患有前述任一项所述驱动基因阴性非小细胞肺癌的受试者既往接受过抗肿瘤标准治疗，所述抗肿瘤标准治疗包含免疫疗法和铂类化疗。在一些实施方案中，所述免疫疗法为PD-1/PD-L1抑制剂治疗。在一些实施方案中，所述受试者既往接受化学疗法(化疗)的线数≤2线。在一些实施方案中，所述受试者既往接受抗肿瘤治疗的线数≤2线。
在一些实施方案中，患有前述任一项所述驱动基因阳性非小细胞肺癌的受试者既往接受过抗肿瘤标准治疗，若针对所述驱动基因尚未有获批靶向治疗药物，其抗肿瘤标准治疗参考驱动基因阴性的受试者。在一些实施方案中，所述抗肿瘤标准治疗包含免疫疗法和铂类化疗，所述免疫疗法为PD-1/PD-L1抑制剂治疗。在一些实施方案中，所述受试者既往接受化学疗法(化疗)的线数≤2线。在一些实施方案中，所述受试者既往接受抗肿瘤治疗的线数≤2线。
在一些实施方案中，患有前述任一项所述驱动基因阳性非小细胞肺癌的受试者既往接受过抗肿瘤标准治疗，若针对所述驱动基因存在获批靶向治疗药物，其抗肿瘤标准治疗包含至少一种靶向药物疗法。在一些实施方案中，所述抗肿瘤标准治疗包含至少一种靶向药物疗法和铂类化疗。在一些实施方案中，所述受试者既往接受化学疗法(化疗)的线数≤2线。在一些实施方案中，所述受试者既往接受抗肿瘤治疗的线数≤2线。
在一些实施方案中，患有前述任一项所述食管癌的受试者既往接受过抗肿瘤标准治疗，所述抗肿瘤标准治疗包含免疫疗法和铂类化疗。在一些实施方案中，所述免疫疗法为PD-1/PD-L1抑制剂治疗。在一些实施方案中，所述受试者既往接受化学疗法(化疗)的线数≤2线。在一些实施方案中，所述受试者既往接受抗肿瘤治疗的线数≤2线。
在一些实施方案中，患有前述任一项所述非小细胞肺癌或食管癌的受试者既往接受抗肿瘤标准治疗失败或不耐受、无标准治疗或拒绝标准治疗，所述抗肿瘤标准治疗选自化学疗法、免疫疗法、和/或靶向药物疗法，所述化学疗法包含铂类化疗。
在一些实施方案中，患有前述任一项所述驱动基因阴性非小细胞肺癌的受试者既往接受抗肿瘤标准治疗失败或不耐受、无标准治疗或拒绝标准治疗，所述抗肿瘤标准治疗包含免疫疗法和铂类化疗。在一些实施方案中，所述免疫疗法为PD-1/PD-L1抑制剂治疗。在一些实施方案中，所述受试者既往接受化学疗法(化疗)的线数≤2线。在一些实施方案中，所述受试者既往接受抗肿瘤治疗的线数≤2线。
在一些实施方案中，患有前述任一项所述驱动基因阳性非小细胞肺癌的受试者既往接受抗肿瘤标准治疗失败或不耐受、无标准治疗或拒绝标准治疗，若针对所述驱动基因尚未有获批靶向治疗药物，其抗肿瘤标准治疗参考驱动基因阴性的受试者。在一些实施方案中，所述抗肿瘤标准治疗包含免疫疗法和铂类化疗，所述免疫疗法为PD-1/PD-L1抑制剂治疗。在一些实施方案中，所述受试者既往接受化学疗法(化疗)的线数≤2线。在一些实施方案中，所述受试者既往接受抗肿瘤治疗的线数≤2线。
在一些实施方案中，患有前述任一项所述驱动基因阳性非小细胞肺癌的受试者既往接受抗肿瘤标准治疗失败或不耐受、无标准治疗或拒绝标准治疗，若针对所述驱动基因存在获批靶向治疗药物，其抗肿瘤标准治疗包含至少一种靶向药物疗法。在一些实施方案中，所述抗肿瘤标准治疗包含至少一种靶向药物疗法和铂类化疗。在一些实施方案中，所述受试者既往接受化学疗法(化疗)的线数≤2线。在一些实施方案中，所述受试者既往接受抗肿瘤治疗的线数≤2线。
在一些实施方案中，患有前述任一项所述食管癌的受试者既往接受抗肿瘤标准治疗失败或不耐受、无标准治疗或拒绝标准治疗，所述抗肿瘤标准治疗包含免疫疗法和铂类化疗。在一些实施方案中，所述免疫疗法为PD-1/PD-L1抑制剂治疗。在一些实施方案中，所述受试者既往接受化学疗法(化疗)的线数≤2线。在一些实施方案中，所述受试者既往接受抗肿瘤治疗的线数≤2线。
在一些实施方案中，患有前述任一项所述非小细胞肺癌或食管癌的受试者既往未经治疗(未接受过系统性抗肿瘤治疗)。在一些实施方案中，患有前述任一项所述驱动基因阳性的非小细胞肺癌的受试者既往未经治疗(未接受过系统性抗肿瘤治疗)，且针对所述驱动基因尚未有获批靶向治疗药物。
在一些实施方案中，患有前述任一项所述非小细胞肺癌的受试者既往未经治疗(未接受过系统性抗肿瘤治疗)，且存在STK11单突变、KEAP1单突变、或STK11/KEAP1共突变。
在一些实施方案中，所述驱动基因阳性包括但不限于EGFR突变、ALK融合、ROS1融合、BRAF V600E突变、NTRK融合、MET14外显子跳跃突变、RET融合、KRAS G12C突变、HER-2突变、EGFR T790M突变、和/或EGFR 20外显子插入。在一些实施方案中，所述驱动基因阳性为EGFR突变或其它驱动基因阳性。
在一些实施方案中，所述肿瘤是驱动基因阴性的鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是驱动基因阴性的局部晚期或转移性鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是驱动基因阴性的局部晚期不可切除或转移性鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是驱动基因阳性的鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是驱动基因阳性的局部晚期或转移性鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是驱动基因阳性的局部晚期不可切除或转移性鳞状非小细胞肺癌。
在一些实施方案中，所述肿瘤是驱动基因阴性的非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是驱动基因阴性的局部晚期或转移性非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是驱动基因阴性的局部晚期不可切除或转移性非鳞状非小细胞肺癌。
在一些实施方案中，所述肿瘤是Nectin-4阳性的鳞状或非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阳性的鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阳性的局部晚期或转移性鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阳性的局部晚期不可切除或转移性鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阳性的非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阳性的局部晚期或转移性非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阳性的局部晚期不可切除或转移性非鳞状非小细胞肺癌。
在一些实施方案中，所述肿瘤是Nectin-4阴性的鳞状或非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阴性的鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阴性的局部晚期或转移性鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阴性的局部晚期不可切除或转移性鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阴性的非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阴性的局部晚期或转移性非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阴性的局部晚期不可切除或转移性非鳞状非小细胞肺癌。
在一些实施方案中，所述肿瘤为Nectin-4阳性和驱动基因阳性的非小细胞肺癌。在一些实施方案中，所述肿瘤为Nectin-4阳性和驱动基因阳性的局部晚期或转移性非小细胞肺癌。在一些实施方案中，所述肿瘤为Nectin-4阳性和驱动基因阳性的局部晚期不可切除或转移性非小细胞肺癌。在一些实施方案中，所述肿瘤为Nectin-4阳性和驱动基因阴性的非小细胞肺癌。在一些实施方案中，所述肿瘤为Nectin-4阳性和驱动基因阴性的局部晚期或转移性非小细胞肺癌。在一些实施方案中，所述肿瘤为Nectin-4阳性和驱动基因阴性的局部晚期不可切除或转移性非小细胞肺癌。在一些实施方案中，所述肿瘤为Nectin-4阳性和EGFR驱动基因阴性(EGFR野生型)的非小细胞肺癌。在一些实施方案中，所述肿瘤为Nectin-4阳性和EGFR驱动基因阴性的局部晚期或转移性非小细胞肺癌。在一些实施方案中，所述肿瘤为Nectin-4阳性和EGFR驱动基因阴性的局部晚期不可切除或转移性非小细胞肺癌。在一些实施方案中，所述肿瘤为Nectin-4阴性和驱动基因阳性的非小细胞肺癌。在一些实施方案中，所述肿瘤为Nectin-4阴性和驱动基因阳性的局部晚期或转移性非小细胞肺癌。在一些实施方案中，所述肿瘤为Nectin-4阴性和驱动基因阳性的局部晚期不可切除或转移性非小细胞肺癌。在一些实施方案中，所述肿瘤为Nectin-4阴性和驱动基因阴性的非小细胞肺癌。在一些实施方案中，所述肿瘤为Nectin-4阴性和驱动基因阴性的局部晚期或转移性非小细胞肺癌。在一些实施方案中，所述肿瘤为Nectin-4阴性和驱动基因阴性的局部晚期不可切除或转移性非小细胞肺癌。在一些实施方案中，所述肿瘤为Nectin-4阴性和EGFR驱动基因阴性的非小细胞肺癌。在一些实施方案中，所述肿瘤为Nectin-4阴性和EGFR驱动基因阴性的局部晚期或转移性非小细胞肺癌。在一些实施方案中，所述肿瘤为Nectin-4阴性和EGFR驱动基因阴性的局部晚期不可切除或转移性非小细胞肺癌。
在一些实施方案中，所述肿瘤为Nectin-4阳性和驱动基因阳性的鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤为Nectin-4阳性和驱动基因阳性的局部晚期或转移性鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤为Nectin-4阳性和驱动基因阳性的局部晚期不可切除或转移性鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤为Nectin-4阳性和驱动基因阴性的鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤为Nectin-4阳性和驱动基因阴性的局部晚期或转移性鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤为Nectin-4阳性和驱动基因阴性的局部晚期不可切除或转移性鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤为Nectin-4阴性和驱动基因阳性的鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤为Nectin-4阴性和驱动基因阳性的局部晚期或转移性鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤为Nectin-4阴性和驱动基因阳性的局部晚期不可切除或转移性鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤为Nectin-4阴性和驱动基因阴性的鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤为Nectin-4阴性和驱动基因阴性的局部晚期或转移性鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤为Nectin-4阴性和驱动基因阴性的局部晚期不可切除或转移性鳞状非小细胞肺癌。
在一些实施方案中，所述肿瘤为Nectin-4阳性和驱动基因阳性的非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤为Nectin-4阳性和驱动基因阳性的局部晚期或转移性非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤为Nectin-4阳性和驱动基因阳性的局部晚期不可切除或转移性非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤为Nectin-4阳性和驱动基因阴性的非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤为Nectin-4阳性和驱动基因阴性的局部晚期或转移性非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤为Nectin-4阳性和驱动基因阴性的局部晚期不可切除或转移性非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤为Nectin-4阳性和EGFR驱动基因阴性(EGFR野生型)的非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤为Nectin-4阳性和EGFR驱动基因阴性的局部晚期或转移性非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤为Nectin-4阳性和EGFR驱动基因阴性的局部晚期不可切除或转移性非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤为Nectin-4阴性和驱动基因阳性的非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤为Nectin-4阴性和驱动基因阳性的局部晚期或转移性非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤为Nectin-4阴性和驱动基因阳性的局部晚期不可切除或转移性非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤为Nectin-4阴性和驱动基因阴性的非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤为Nectin-4阴性和驱动基因阴性的局部晚期或转移性非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤为Nectin-4阴性和驱动基因阴性的局部晚期不可切除或转移性非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤为Nectin-4阴性和EGFR驱动基因阴性的非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤为Nectin-4阴性和EGFR驱动基因阴性的局部晚期或转移性非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤为Nectin-4阴性和EGFR驱动基因阴性的局部晚期不可切除或转移性非鳞状非小细胞肺癌。
在一些实施方案中，所述肿瘤是EGFR突变型鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是EGFR突变型晚期鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是EGFR突变型局部晚期或转移性鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是EGFR突变型局部晚期不可切除或转移性鳞状非小细胞肺癌。
在一些实施方案中，所述肿瘤是Nectin-4阳性和EGFR突变阳性的非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阳性和EGFR突变阳性的局部晚期或转移性非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阳性和EGFR突变阳性的局部晚期不可切除或转移性非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阴性和EGFR突变阳性的非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阴性和EGFR突变阳性的局部晚期或转移性非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阴性和EGFR突变阳性的局部晚期不可切除或转移性非小细胞肺癌。
在一些实施方案中，所述肿瘤是Nectin-4阳性和EGFR突变阳性的鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阳性和EGFR突变阳性的局部晚期或转移性鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阳性和EGFR突变阳性的局部晚期不可切除或转移性鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阳性和EGFR突变阳性的非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阳性和EGFR突变阳性的局部晚期或转移性非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阳性和EGFR突变阳性的局部晚期不可切除或转移性非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阴性和EGFR突变阳性的鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阴性和EGFR突变阳性的局部晚期或转移性鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阴性和EGFR突变阳性的局部晚期不可切除或转移性鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阴性和EGFR突变阳性的非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阴性和EGFR突变阳性的局部晚期或转移性非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阴性和EGFR突变阳性的局部晚期不可切除或转移性非鳞状非小细胞肺癌。
在一些实施方案中，所述肿瘤是其它驱动基因阳性(除EGFR突变型之外的驱动基因阳性)的非小细胞肺癌。在一些实施方案中，所述肿瘤是其它驱动基因阳性的晚期非小细胞肺癌。在一些实施方案中，所述肿瘤是其它驱动基因阳性的局部晚期或转移性非小细胞肺癌。在一些实施方案中，所述肿瘤是其它驱动基因阳性的局部晚期不可切除或转移性非小细胞肺癌。
在一些实施方案中，所述肿瘤是其它驱动基因阳性(除EGFR突变型之外的驱动基因阳性)的鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是其它驱动基因阳性的局部晚期或转移性鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是其它驱动基因阳性的局部晚期不可切除或转移性鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阳性和其它驱动基因阳性的非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阳性和其它驱动基因阳性的局部晚期或转移性非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阳性和其它驱动基因阳性的局部晚期不可切除或转移性非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阴性和其它驱动基因阳性的非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阴性和其它驱动基因阳性的局部晚期或转移性非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阴性和其它驱动基因阳性的局部晚期不可切除或转移性非小细胞肺癌。
在一些实施方案中，所述肿瘤是Nectin-4阳性和其它驱动基因阳性的鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阳性和其它驱动基因阳性的局部晚期或转移性鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阳性和其它驱动基因阳性的局部晚期不可切除或转移性鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阳性和其它驱动基因阳性的非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阳性和其它驱动基因阳性的局部晚期或转移性非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阳性和其它驱动基因阳性的局部晚期不可切除或转移性非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阴性和其它驱动基因阳性的鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阴性和其它驱动基因阳性的局部晚期或转移性鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阴性和其它驱动基因阳性的局部晚期不可切除或转移性鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阴性和其它驱动基因阳性的非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阴性和其它驱动基因阳性的局部晚期或转移性非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阴性和其它驱动基因阳性的局部晚期不可切除或转移性非鳞状非小细胞肺癌。
在一些实施方案中，所述肿瘤是经标准治疗失败或不耐受、无标准治疗或拒绝标准治疗的受试者，所述标准治疗包括：驱动基因阴性的受试者，接受免疫治疗和铂类化疗；驱动基因阳性的受试者，接受靶向治疗与铂类化疗。
在一些实施方案中，所述肿瘤是驱动基因阴性、且经免疫治疗与铂类化疗失败的非小细胞肺癌。在一些实施方案中，所述肿瘤是驱动基因阴性、且经免疫治疗与铂类化疗失败的局部晚期或转移性非小细胞肺癌。在一些实施方案中，所述肿瘤是驱动基因阴性、且经免疫治疗与铂类化疗失败的局部晚期不可切除或转移性非小细胞肺癌。
在一些实施方案中，所述肿瘤是驱动基因阴性、且经免疫治疗与铂类化疗失败的鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是驱动基因阴性、且经免疫治疗与铂类化疗失败的局部晚期或转移性鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是驱动基因阴性、且经免疫治疗与铂类化疗失败的局部晚期不可切除或转移性鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是驱动基因阴性、且经免疫治疗与铂类化疗失败的非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是驱动基因阴性、且经免疫治疗与铂类化疗失败的局部晚期或转移性非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是驱动基因阴性、且经免疫治疗与铂类化疗失败的局部晚期不可切除或转移性非鳞状非小细胞肺癌。
在一些实施方案中，所述肿瘤是Nectin-4阴性和驱动基因阴性、且经免疫治疗与铂类化疗失败的非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阴性和驱动基因阴性、且经免疫治疗与铂类化疗失败的局部晚期或转移性非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阴性和驱动基因阴性、且经免疫治疗与铂类化疗失败的局部晚期不可切除或转移性非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阳性和驱动基因阴性、且经免疫治疗与铂类化疗失败的非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阳性和驱动基因阴性、且经免疫治疗与铂类化疗失败的局部晚期或转移性非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阳性和驱动基因阴性、且经免疫治疗与铂类化疗失败的局部晚期不可切除或转移性非小细胞肺癌。
在一些实施方案中，所述肿瘤是Nectin-4阴性和驱动基因阴性、且经免疫治疗与铂类化疗失败的鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阴性和驱动基因阴性、且经免疫治疗与铂类化疗失败的局部晚期或转移性鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阴性和驱动基因阴性、且经免疫治疗与铂类化疗失败的局部晚期不可切除或转移性鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阳性和驱动基因阴性、且经免疫治疗与铂类化疗失败的鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阳性和驱动基因阴性、且经免疫治疗与铂类化疗失败的局部晚期或转移性鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阳性和驱动基因阴性、且经免疫治疗与铂类化疗失败的局部晚期不可切除或转移性鳞状非小细胞肺癌。
在一些实施方案中，所述肿瘤是Nectin-4阴性和驱动基因阴性、且经免疫治疗与铂类化疗失败的非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阴性和驱动基因阴性、且经免疫治疗与铂类化疗失败的局部晚期或转移性非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阴性和驱动基因阴性、且经免疫治疗与铂类化疗失败的局部晚期不可切除或转移性非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阳性和驱动基因阴性、且经免疫治疗与铂类化疗失败的非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阳性和驱动基因阴性、且经免疫治疗与铂类化疗失败的局部晚期或转移性非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阳性和驱动基因阴性、且经免疫治疗与铂类化疗失败的局部晚期不可切除或转移性非鳞状非小细胞肺癌。
在一些实施方案中，所述肿瘤是驱动基因阳性、且经至少一种靶向药物疗法与铂类化疗失败的非小细胞肺癌。在一些实施方案中，所述肿瘤是驱动基因阳性、且经至少一种靶向药物疗法与铂类化疗失败的局部晚期或转移性非小细胞肺癌。在一些实施方案中，所述肿瘤是驱动基因阳性、且经至少一种靶向药物疗法与铂类化疗失败的局部晚期不可切除或转移性非小细胞肺癌。
在一些实施方案中，所述肿瘤是驱动基因阳性、且经至少一种靶向药物疗法与铂类化疗失败的鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是驱动基因阳性、且经至少一种靶向药物疗法与铂类化疗失败的局部晚期或转移性鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是驱动基因阳性、且经至少一种靶向药物疗法与铂类化疗失败的局部晚期不可切除或转移性鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是驱动基因阳性、且经至少一种靶向药物疗法与铂类化疗失败的非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是驱动基因阳性、且经至少一种靶向药物疗法与铂类化疗失败的局部晚期或转移性非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是驱动基因阳性、且经至少一种靶向药物疗法与铂类化疗失败的局部晚期不可切除或转移性非鳞状非小细胞肺癌。
在一些实施方案中，所述肿瘤是Nectin-4阴性和驱动基因阳性、且经至少一种靶向药物疗法与铂类化疗失败的非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阴性和驱动基因阳性、且经至少一种靶向药物疗法与铂类化疗失败的局部晚期或转移性非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阴性和驱动基因阳性、且经至少一种靶向药物疗法与铂类化疗失败的局部晚期不可切除或转移性非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阳性和驱动基因阳性、且经至少一种靶向药物疗法与铂类化疗失败的非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阳性和驱动基因阳性、且经至少一种靶向药物疗法与铂类化疗失败的局部晚期或转移性非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阳性和驱动基因阳性、且经至少一种靶向药物疗法与铂类化疗失败的局部晚期不可切除或转移性非小细胞肺癌。
在一些实施方案中，所述肿瘤是Nectin-4阴性和驱动基因阳性、且经至少一种靶向药物疗法与铂类化疗失败的鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阴性和驱动基因阳性、且经至少一种靶向药物疗法与铂类化疗失败的局部晚期或转移性鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阴性和驱动基因阳性、且经至少一种靶向药物疗法与铂类化疗失败的局部晚期不可切除或转移性鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阳性和驱动基因阳性、且经至少一种靶向药物疗法与铂类化疗失败的鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阳性和驱动基因阳性、且经至少一种靶向药物疗法与铂类化疗失败的局部晚期或转移性鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阳性和驱动基因阳性、且经至少一种靶向药物疗法与铂类化疗失败的局部晚期不可切除或转移性鳞状非小细胞肺癌。
在一些实施方案中，所述肿瘤是Nectin-4阴性和驱动基因阳性、且经至少一种靶向药物疗法与铂类化疗失败的非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阴性和驱动基因阳性、且经至少一种靶向药物疗法与铂类化疗失败的局部晚期或转移性非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阴性和驱动基因阳性、且经至少一种靶向药物疗法与铂类化疗失败的局部晚期不可切除或转移性非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阳性和驱动基因阳性、且经至少一种靶向药物疗法与铂类化疗失败的非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阳性和驱动基因阳性、且经至少一种靶向药物疗法与铂类化疗失败的局部晚期或转移性非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阳性和驱动基因阳性、且经至少一种靶向药物疗法与铂类化疗失败的局部晚期不可切除或转移性非鳞状非小细胞肺癌。
在一些实施方案中，所述肿瘤是EGFR突变阳性、且经至少一种靶向药物疗法与铂类化疗失败的非小细胞肺癌。在一些实施方案中，所述肿瘤是EGFR突变阳性、且经至少一种靶向药物疗法与铂类化疗失败的局部晚期或转移性非小细胞肺癌。在一些实施方案中，所述肿瘤是EGFR突变阳性、且经至少一种靶向药物疗法与铂类化疗失败的局部晚期不可切除或转移性非小细胞肺癌。
在一些实施方案中，所述肿瘤是EGFR突变阳性、且经至少一种靶向药物疗法与铂类化疗失败的鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是EGFR突变阳性、且经至少一种靶向药物疗法与铂类化疗失败的局部晚期或转移性鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是EGFR突变阳性、且经至少一种靶向药物疗法与铂类化疗失败的局部晚期不可切除或转移性鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是EGFR突变阳性、且经至少一种靶向药物疗法与铂类化疗失败的非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是EGFR突变阳性、且经至少一种靶向药物疗法与铂类化疗失败的局部晚期或转移性非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是EGFR突变阳性、且经至少一种靶向药物疗法与铂类化疗失败的局部晚期不可切除或转移性非鳞状非小细胞肺癌。
在一些实施方案中，所述肿瘤是Nectin-4阴性和EGFR突变阳性、且经至少一种靶向药物疗法与铂类化疗失败的非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阴性和EGFR突变阳性、且经至少一种靶向药物疗法与铂类化疗失败的局部晚期或转移性非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阴性和EGFR突变阳性、且经至少一种靶向药物疗法与铂类化疗失败的局部晚期不可切除或转移性非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阳性和EGFR突变阳性、且经至少一种靶向药物疗法与铂类化疗失败的非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阳性和EGFR突变阳性、且经至少一种靶向药物疗法与铂类化疗失败的局部晚期或转移性非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阳性和EGFR突变阳性、且经至少一种靶向药物疗法与铂类化疗失败的局部晚期不可切除或转移性非小细胞肺癌。
在一些实施方案中，所述肿瘤是Nectin-4阴性和EGFR突变阳性、且经至少一种靶向药物疗法与铂类化疗失败的鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阴性和EGFR突变阳性、且经至少一种靶向药物疗法与铂类化疗失败的局部晚期或转移性鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阴性和EGFR突变阳性、且经至少一种靶向药物疗法与铂类化疗失败的局部晚期不可切除或转移性鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阳性和EGFR突变阳性、且经至少一种靶向药物疗法与铂类化疗失败的鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阳性和EGFR突变阳性、且经至少一种靶向药物疗法与铂类化疗失败的局部晚期或转移性鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阳性和EGFR突变阳性、且经至少一种靶向药物疗法与铂类化疗失败的局部晚期不可切除或转移性鳞状非小细胞肺癌。
在一些实施方案中，所述肿瘤是Nectin-4阴性和EGFR突变阳性、且经至少一种靶向药物疗法与铂类化疗失败的非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阴性和EGFR突变阳性、且经至少一种靶向药物疗法与铂类化疗失败的局部晚期或转移性非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阴性和EGFR突变阳性、且经至少一种靶向药物疗法与铂类化疗失败的局部晚期不可切除或转移性非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阳性和EGFR突变阳性、且经至少一种靶向药物疗法与铂类化疗失败的非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阳性和EGFR突变阳性、且经至少一种靶向药物疗法与铂类化疗失败的局部晚期或转移性非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阳性和EGFR突变阳性、且经至少一种靶向药物疗法与铂类化疗失败的局部晚期不可切除或转移性非鳞状非小细胞肺癌。
在一些实施方案中，所述肿瘤是其它驱动基因阳性(驱动基因阳性除外EGFR突变阳性)、且经至少一种靶向药物疗法与铂类化疗失败的非小细胞肺癌。在一些实施方案中，所述肿瘤是其它驱动基因阳性(驱动基因阳性除外EGFR突变阳性)、且经至少一种靶向药物疗法与铂类化疗失败的局部晚期或转移性非小细胞肺癌。在一些实施方案中，所述肿瘤是其它驱动基因阳性(驱动基因阳性除外EGFR突变阳性)、且经至少一种靶向药物疗法与铂类化疗失败的局部晚期不可切除或转移性非小细胞肺癌。
在一些实施方案中，所述肿瘤是其它驱动基因阳性(驱动基因阳性除外EGFR突变阳性)、且经至少一种靶向药物疗法与铂类化疗失败的鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是其它驱动基因阳性(驱动基因阳性除外EGFR突变阳性)、且经至少一种靶向药物疗法与铂类化疗失败的局部晚期或转移性鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是其它驱动基因阳性(驱动基因阳性除外EGFR突变阳性)、且经至少一种靶向药物疗法与铂类化疗失败的局部晚期不可切除或转移性鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是其它驱动基因阳性、且经至少一种靶向药物疗法与铂类化疗失败的非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是其它驱动基因阳性(驱动基因阳性除外EGFR突变阳性)、且经至少一种靶向药物疗法与铂类化疗失败的局部晚期或转移性非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是其它驱动基因阳性(驱动基因阳性除外EGFR突变阳性)、且经至少一种靶向药物疗法与铂类化疗失败的局部晚期不可切除或转移性非鳞状非小细胞肺癌。
在一些实施方案中，所述肿瘤是Nectin-4阴性和其它驱动基因阳性(驱动基因阳性除外EGFR突变阳性)、且经至少一种靶向药物疗法与铂类化疗失败的非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阴性和其它驱动基因阳性(驱动基因阳性除外EGFR突变阳性)、且经至少一种靶向药物疗法与铂类化疗失败的局部晚期或转移性非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阴性和其它驱动基因阳性(驱动基因阳性除外EGFR突变阳性)、且经至少一种靶向药物疗法与铂类化疗失败的局部晚期不可切除或转移性非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阳性和其它驱动基因阳性(驱动基因阳性除外EGFR突变阳性)、且经至少一种靶向药物疗法与铂类化疗失败的非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阳性和其它驱动基因阳性(驱动基因阳性除外EGFR突变阳性)、且经至少一种靶向药物疗法与铂类化疗失败的局部晚期或转移性非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阳性和其它驱动基因阳性(驱动基因阳性除外EGFR突变阳性)、且经至少一种靶向药物疗法与铂类化疗失败的局部晚期不可切除或转移性非小细胞肺癌。
在一些实施方案中，所述肿瘤是Nectin-4阴性和其它驱动基因阳性(驱动基因阳性除外EGFR突变阳性)、且经至少一种靶向药物疗法与铂类化疗失败的鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阴性和其它驱动基因阳性(驱动基因阳性除外EGFR突变阳性)、且经至少一种靶向药物疗法与铂类化疗失败的局部晚期或转移性鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阴性和其它驱动基因阳性(驱动基因阳性除外EGFR突变阳性)、且经至少一种靶向药物疗法与铂类化疗失败的局部晚期不可切除或转移性鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阳性和其它驱动基因阳性(驱动基因阳性除外EGFR突变阳性)、且经至少一种靶向药物疗法与铂类化疗失败的鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阳性和其它驱动基因阳性(驱动基因阳性除外EGFR突变阳性)、且经至少一种靶向药物疗法与铂类化疗失败的局部晚期或转移性鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阳性和其它驱动基因阳性(驱动基因阳性除外EGFR突变阳性)、且经至少一种靶向药物疗法与铂类化疗失败的局部晚期不可切除或转移性鳞状非小细胞肺癌。
在一些实施方案中，所述肿瘤是Nectin-4阴性和其它驱动基因阳性(驱动基因阳性除外EGFR突变阳性)、且经至少一种靶向药物疗法与铂类化疗失败的非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阴性和其它驱动基因阳性(驱动基因阳性除外EGFR突变阳性)、且经至少一种靶向药物疗法与铂类化疗失败的局部晚期或转移性非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阴性和其它驱动基因阳性(驱动基因阳性除外EGFR突变阳性)、且经至少一种靶向药物疗法与铂类化疗失败的局部晚期不可切除或转移性非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阳性和其它驱动基因阳性(驱动基因阳性除外EGFR突变阳性)、且经至少一种靶向药物疗法与铂类化疗失败的非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阳性和其它驱动基因阳性(驱动基因阳性除外EGFR突变阳性)、且经至少一种靶向药物疗法与铂类化疗失败的局部晚期或转移性非鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阳性和其它驱动基因阳性(驱动基因阳性除外EGFR突变阳性)、且经至少一种靶向药物疗法与铂类化疗失败的局部晚期不可切除或转移性非鳞状非小细胞肺癌。
在一些实施方案中，所述肿瘤是既往接受标准治疗失败或并不耐受标准治疗的非小细胞肺癌受试者。在一些实施方案中，所述肿瘤是既往接受的系统性抗肿瘤治疗线数≤2线的非小细胞肺癌受试者。在一些实施方案中，所述肿瘤是驱动基因阴性的非鳞状非小细胞肺癌受试者。在一些实施方案中，所述肿瘤是非鳞状非小细胞肺癌受试者，驱动基因阴性且既往接受过含铂化疗和PD-(L)1治疗后进展。在一些实施方案中，所述肿瘤是非鳞状非小细胞肺癌受试者，存在驱动基因突变且接受过至少1种的针对该驱动基因突变的靶向药物疗法后进展以及含铂化疗后进展。
在一些实施方案中，所述肿瘤是既往未接受针对非小细胞肺癌的系统性抗肿瘤治疗的受试者。在一些实施方案中，所述肿瘤是既往未接受针对局部晚期或转移性非小细胞肺癌的系统性抗肿瘤治疗的受试者。在一些实施方案中，所述肿瘤是既往未接受针对局部晚期不可切除或转移性非小细胞肺癌的系统性抗肿瘤治疗的受试者。
在一些实施方案中，所述肿瘤是非小细胞肺癌且不带有驱动基因阳性的受试者。在一些实施方案中，所述肿瘤是局部晚期或转移性非小细胞肺癌且不带有驱动基因阳性的受试者。在一些实施方案中，所述肿瘤是非鳞状非小细胞肺癌且不带有驱动基因阳性的受试者。在一些实施方案中，所述肿瘤是局部晚期或转移性非鳞状非小细胞肺癌且不带有驱动基因阳性的受试者。在一些实施方案中，所述肿瘤是局部晚期不可切除或转移性非鳞状非小细胞肺癌且不带有驱动基因阳性的受试者。在一些实施方案中，所述驱动基因阳性包括但不限于EGFR突变、ALK融合、ROS1融合、BRAF V600E突变、NTRK融合、MET14外显子跳跃突变、RET融合、KRAS G12C突变、HER-2突变、EGFR T790M突变、和/或EGFR 20外显子插入。在一些实施方案中，所述驱动基因阳性为EGFR突变阳性或其它驱动基因阳性。
在一些实施方案中，所述肿瘤是Nectin-4阳性、PD-L1 TPS＜50％非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阳性、PD-L1 TPS＜50％的局部晚期或转移性非小细胞肺癌。
在一些实施方案中，所述肿瘤是Nectin-4阳性、PD-L1 TPS＜50％的鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阳性、PD-L1 TPS＜50％的非鳞状非小细胞肺癌。
在一些实施方案中，所述肿瘤是Nectin-4阳性、PD-L1 TPS＜50％的局部晚期或转移性鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阳性、PD-L1 TPS＜50％的局部晚期或转移性非鳞状非小细胞肺癌。
在一些实施方案中，所述肿瘤是Nectin-4阳性和驱动基因阴性、PD-L1 TPS＜50％非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阳性和驱动基因阴性、PD-L1 TPS＜50％的局部晚期或转移性非小细胞肺癌。
在一些实施方案中，所述肿瘤是Nectin-4阳性和驱动基因阴性、PD-L1 TPS＜50％的鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阳性和驱动基因阴性、PD-L1 TPS＜50％的非鳞状非小细胞肺癌。
在一些实施方案中，所述肿瘤是Nectin-4阳性和驱动基因阴性、PD-L1 TPS＜50％的局部晚期或转移性鳞状非小细胞肺癌。在一些实施方案中，所述肿瘤是Nectin-4阳性和驱动基因阴性、PD-L1 TPS＜50％的局部晚期或转移性非鳞状非小细胞肺癌。
在一些实施方案中，所述肿瘤是经含PD-1/PD-L1抑制剂和铂类化疗失败、且既往治疗线数≤2线的受试者。在一些实施方案中，所述肿瘤是既往未接受针对局部晚期不可切除或转移性食管癌的系统性抗肿瘤治疗的受试者。
在一些实施方案中，所述肿瘤是Nectin-4阳性肿瘤。在一些实施方案中，所述肿瘤是Nectin-4阳性晚期实体瘤。在一些实施方案中，所述肿瘤是Nectin-4阳性的食管癌。在一些实施方案中，所述肿瘤是Nectin-4阳性的局部晚期或转移性食管癌。在一些实施方案中，所述肿瘤是Nectin-4阳性的食管鳞癌。在一些实施方案中，所述肿瘤是Nectin-4阳性的局部晚期或转移性食管鳞癌。
在本公开，标准治疗、系统性抗肿瘤治疗(包括一线治疗、二线治、三线治疗、四线治疗)是本领域技术人员所熟知的针对非小细胞肺癌(晚期非小细胞肺癌)或食管癌(晚期食管癌)的治疗方案，例如，经过监管部门批准的治疗指南中所披露的治疗方案；以实体瘤为适应症的临床研究药物的系统性治疗。例如包括但不限于NCCN指南、CSCO指南中提供的关于各种癌症的标准治疗方案、系统性抗肿瘤治疗方案(包括一线治疗、二线治、三线治疗、四线治疗)的详细最新信息。
在一些实施方案中，本公开提供的抗Nectin-4抗体药物偶联物用于治疗非小细胞肺癌经标准治疗失败的患者(既往化疗线数≤2线)，可以显著提高患者的肿瘤客观缓解率和无进展生产时间(ORR为30.4％，DCR为89.1％)。其中针对鳞状非小细胞肺癌患者的ORR为25％，DCR为100％，8mg/kg剂量下的mPFS为6.0个月；针对非鳞状非小细胞肺癌患者的ORR为36.7％，DCR为83.3％，特别是针对EGFR突变型非鳞状非小细胞肺癌患者，在6mg/kg剂量下，可以达到48.6％的ORR和8.5个月的mPFS，在8mg/kg剂量下，可以达到43.8％的ORR和8.5个月的mPFS；针对EGFR野生型(EGFR驱动基因阴性)非鳞状非小细胞肺癌患者，ORR为25％，DCR为72.7％，8mg/kg剂量下的mPFS为5.7个月；针对驱动基因阴性的非鳞状非小细胞肺癌患者，在8mg/kg剂量下的ORR为21.1％，DCR为68.4％，mPFS为5.7个月；与同靶点其它ADC药物以及其它标准治疗方案相比具有显著治疗优势，为非小细胞肺癌经治失败患者提供了积极有效的临床治疗方案。
在一些实施方案中，本公开提供的抗Nectin-4抗体药物偶联物单药施用于实体瘤受试者，所有受试者中35.2％发生了≥3级TRAE，展示出可耐受且可控的临床安全性。
在一些实施方案中，本公开提供的抗Nectin-4抗体药物偶联物联合免疫治疗剂用于治疗非小细胞肺癌经标准治疗失败的患者(既往系统性抗肿瘤治疗线数≤2线)，可以显著提高患者的肿瘤客观缓解率。例如，在剂量水平1(ADC-4，6mg/kg Q3W+抗PD-L1抗体，1200mg Q3W)下的ORR为30％，DCR为80％，在接受剂量水平2(ADC-4，8mg/kg Q3W+抗PD-L1抗体，1200mg Q3W)下的ORR为29.7％，DCR为91.9％，与同靶点其它ADC药物以及其它标准治疗方案相比具有显著治疗优势，为非小细胞肺癌经治失败患者提供了积极有效的临床治疗方案。
在一些实施方案中，本公开提供的抗Nectin-4抗体药物偶联物联合免疫治疗剂用于治疗非小细胞肺癌初治患者(既往未接受过系统性抗肿瘤治疗)，可以显著提高患者的肿瘤客观缓解率。例如，在ADC-4(8mg/kg，Q3W)+抗PD-L1抗体(1200mg，Q3W)剂量水平下，可以达到69.4％的ORR和96.4％的DCR。与同靶点其它ADC药物以及其它标准治疗方案相比具有显著治疗优势，为非小细胞肺癌初治患者提供了积极有效的临床治疗方案。
在一些实施方案中，本公开提供的抗Nectin-4抗体药物偶联物联合免疫治疗剂施用于受试者，在非小细胞肺癌经治受试者中，38％发生了≥3级TRAE；在非小细胞肺癌初治患者中，26.3％发生了≥3级TRAE，与本公开中抗Nectin-4抗体药物偶联物单药治疗相比，联合治疗并未显著增加药物毒性，此联合方案展示出可耐受且可控的安全性优势。
在一些实施方案中，本公开提供的抗Nectin-4抗体药物偶联物单药用于治疗食管癌经标准治疗失败的患者(既往化疗线数≤2线)，可以显著提高患者的肿瘤客观缓解率和无进展生存时间，ORR为20％，DCR为77.5％，mPFS为4.1个月，mOS为9.1个月。与同靶点其它ADC药物以及其它标准治疗方案相比具有显著治疗优势，为食管癌经治失败患者提供了积极有效的临床治疗方案。
在一些实施方案中，本公开提供的抗Nectin-4抗体药物偶联物联合免疫治疗剂用于治疗食管癌经标准治疗失败的患者(既往治疗线数≤2线)，可以显著提高患者的肿瘤客观缓解率。例如，在剂量水平1(ADC-4，6mg/kg Q3W+抗PD-L1抗体，1200mg Q3W)下的ORR为23.5％，DCR为82.4％，在接受剂量水平2(ADC-4，8mg/kg Q3W+抗PD-L1抗体，1200mg Q3W)下的ORR为40.5％，DCR为89.2％，特别是针对既往治疗线数为1L的食管癌经治患者，在剂量水平1下的ORR为30％，DCR为90％，在接受剂量水平2下的ORR为46.4％，DCR为92.9％，与本公开中抗Nectin-4抗体药物偶联物单药治疗、同靶点其它ADC药物以及其它标准治疗方案相比具有显著治疗优势，为食管癌经标准治疗失败患者提供了积极有效的临床治疗方案。
在一些实施方案中，本公开提供的抗Nectin-4抗体药物偶联物联合免疫治疗剂用于治疗食管癌初治患者(既往未接受过系统性抗肿瘤治疗)，可以显著提高患者的肿瘤客观缓解率。例如，在队列A剂量(ADC-4，8mg/kg Q3W+抗PD-L1抗体，1200mg Q3W)下的ORR为64.7％，DCR为91.2％，在队列C剂量(ADC-4，8mg/kg Q3W+抗PD-L1抗体，1200mg Q3W+抗CTLA-4抗体，C1D1 280mg给药一次，C2-C4不给药，C5及后续周期70mg Q6W)下的ORR为61.9％，DCR为95.2％，同靶点其它ADC药物以及其它标准治疗方案相比具有显著治疗优势，为食管癌初治患者提供了积极有效的临床治疗方案。
在一些实施方案中，本公开提供的抗Nectin-4抗体药物偶联物联合免疫治疗剂施用于受试者，在食管癌受试者中展示出可耐受且可控的临床安全性，其中在食管癌的初治受试者中，仅18.8％的受试者发生了≥3级TRAE。与本公开中抗Nectin-4抗体药物偶联物单药治疗相比，联合治疗并未显著增加药物毒性，此联合方案展示出可耐受且可控的安全性优势。
<抗Nectin-4抗体药物偶联物>
在一些实施方案中，所述抗Nectin-4抗体药物偶联物来源于WO2022228406A、WO2023221971A中的任意结构的抗体药物偶联物，本公开通过引用将上述专利中的免疫偶联物的结构、制备方法等相关内容并入本公开。
在一些实施方案中，所述抗Nectin-4抗体药物偶联物具有如下式所示的结构：
其中，n为1至10，n是小数或整数。在一些实施方案中，n为1至8。例如，n为1、2、3、4、5、6、7、8、9、10或前述任意两个数值之间的任意小数或整数。在一些实施方案中，n为3至5的整数或小数，例如，3.1、3.2、3.3、3.4、3.5、3.6、3.7、3.8、3.9、4.0、4.1、4.2、4.3、4.4、4.5、4.6、4.7、4.8、4.9、5.0。在一些实施方案中，n为3.5～4.7。
在一些实施方案中，抗Nectin-4抗体来源于WO2022228406A中的任意种类的抗Nectin-4抗体或其抗原结合片段，本公开通过引用将上述专利中的抗体序列、制备方法等相关内容并入本公开。
在一些实施方案中，所述抗Nectin-4抗体包含重链可变区(VH)和轻链可变区(VL)，其中所述重链可变区包含如SEQ ID NO:1-3所示的HCDR1、HCDR2和HCDR3，所述轻链可变区包含如SEQ ID NO：4-6所示的LCDR1、LCDR2和LCDR3。
其中，前面所述的各CDR序列如下表1所示：
表1.抗Nectin-4抗体的CDR序列(Kabat方案)
在一些实施方案中，抗Nectin-4抗体包含前述HCDR1、HCDR2、HCDR3、LCDR1、LCDR2和LCDR3中任意1个，或任意2、3、4、5或6个的组合。
在一些实施方案中，抗Nectin-4抗体包含重链可变区(VH)和轻链可变区(VL)：其中，所述VH包含SEQ ID NO：7所示氨基酸序列中的HCDR1、HCDR2和HCDR3，所述VL包含如SEQ ID NO：8所示氨基酸序列中的LCDR1、LCDR2和LCDR3。上述的CDR是根据Kabat、IMGT、Chothia、AbM或Contact定义方案定义的。在一些具体的实施方案中，所述CDR是根据Kabat定义方案定义的。
在一些实施方案中，抗Nectin-4抗体为嵌合、人源化、全人抗体或其抗原结合片段。
在一些实施方案中，抗Nectin-4抗体包含重链可变区(VH)和轻链可变区(VL)，其中，所述VH包含如SEQ ID NO：7所示或与之具有至少80％、90％同一性的氨基酸序列，和，所述VL包含如SEQ ID NO：8所示或与之具有至少80％、90％同一性的氨基酸序列。
重链可变区：
轻链可变区：
在一些实施方案中，抗Nectin-4抗体包含前述VH、VL中的任意一个或两个。
在一些实施方案中，抗Nectin-4抗体进一步包含重链恒定区和/或轻链恒定区。其中，抗体的重链恒定区可选自人IgG1、IgG2、IgG3、IgG4及其变体的恒定区。在一些实施方案中，轻链恒定区可选自人源κ、λ链或其变体的轻链恒定区。
在一些实施方案中，抗Nectin-4抗体包含重链和轻链，所述重链包含如SEQ ID NO:9所示或与之具有至少80％、至少90％序列同一性的氨基酸序列；和/或，所述轻链包含如SEQ ID NO:10所示或与之具有至少80％、至少90％同一性的氨基酸序列。
在一些实施方案中，抗Nectin-4抗体包含如SEQ ID NO:9所示氨基酸序列的重链，和如SEQ ID NO:10所示氨基酸序列的轻链。
抗Nectin-4抗体的重链序列：
抗Nectin-4抗体的轻链序列：
注：划线部分为抗体重链或轻链的可变区序列，未划线部分为抗体恒定区序列。
在本公开的上下文中，“至少80％、90％”涵盖80％及以上，例如至少80％、至少81％、至少82％、至少83％、至少84％、至少85％、至少86％、至少87％、至少88％、至少89％、至少90％、至少91％、至少92％、至少93％、至少94％、至少95％、至少96％、至少97％、至少98％、至少99％，以及任意两者之间的数值范围。
在本公开的上下文中，“抗体”以最广义使用，其涵盖各种抗体结构，包括但不限于单克隆抗体，多克隆抗体，多特异性抗体(例如双特异性抗体)，全长抗体或其抗原结合片段(也称“抗原结合部分”)，只要它们展现出期望的抗原结合活性。在一些实施方案中，抗体是全长抗体或其抗原结合片段
在一些实施方案中，抗Nectin-4抗体药物偶联物为实施例1制备的。
在一些实施方案中，所述抗Nectin-4抗体药物偶联物的给药剂量可选为约0.1mg/kg至约50mg/kg，约0.1mg/kg至约40mg/kg，约0.1mg/kg至约30mg/kg，约0.1mg/kg至约20mg/kg，约1.0mg/kg至约20mg/kg，约1.0mg/kg至约19mg/kg，约1.0mg/kg至约18mg/kg，约1.0mg/kg至约17mg/kg，约1.0mg/kg至约16mg/kg，约1.0mg/kg至约15mg/kg，约1.0mg/kg至约14mg/kg，约1.0mg/kg至约13mg/kg，约1.0mg/kg至约12mg/kg，约1.0mg/kg至约11mg/kg，约1.0mg/kg至约10.5mg/kg，约1.0mg/kg至约10mg/kg，约1.0mg/kg至约9mg/kg，约2mg/kg至约15mg，约2mg/kg至约14mg，约2mg/kg至约13mg/kg，约2mg/kg至约12mg/kg，约2mg/kg至约11mg/kg，约2mg/kg至约10mg/kg，约2mg/kg至约9mg/kg，约3mg/kg至约15mg，约3mg/kg至约14mg，约3mg/kg至约13mg/kg，约3mg/kg至约12mg/kg，约3mg/kg至约11mg/kg，约3mg/kg至约10mg/kg，约3.0mg/kg至约9.0mg/kg；约4mg/kg至约15mg，约4mg/kg至约14mg，约4mg/kg至约13mg/kg，约4mg/kg至约12mg/kg，约4mg/kg至约11mg/kg，约4mg/kg至约10mg/kg，约4.0mg/kg至约9.0mg/kg；约4.5mg/kg至约15mg，约4.5mg/kg至约14mg，约4.5mg/kg至约13mg/kg，约4.5mg/kg至约12mg/kg，约4.5mg/kg至约11mg/kg，约4.5mg/kg至约10mg/kg，约4.5mg/kg至约9.0mg/kg；约5mg/kg至约15mg，约5mg/kg至约14mg，约5mg/kg至约13mg/kg，约5mg/kg至约12mg/kg，约5mg/kg至约11mg/kg，约5mg/kg至约10mg/kg，约5mg/kg至约9.0mg/kg；约6mg/kg至约15mg，约6mg/kg至约14mg，约6mg/kg至约13mg/kg，约6mg/kg至约12mg/kg，约6mg/kg至约11mg/kg，约6mg/kg至约10mg/kg，约6.0mg/kg至约9.0mg/kg，约6.0mg/kg至约8.0mg/kg，约5.0mg/kg至约10mg/kg，约5.0mg/kg至约9.0mg/kg，约5.0mg/kg至约8.0mg/kg，约4.0mg/kg至约10.0mg/kg，约4.0mg/kg至约9.0mg/kg，约4.0mg/kg至约8.0mg/kg，约3mg/kg至约8mg/kg，约2mg/kg至约8mg/kg，约2mg/kg至约7mg/kg，约2mg/kg至约6mg/kg，约3mg/kg至约7mg/kg，约4mg/kg至约7mg/kg，或者为这些点值之间的任意范围。
在一些实施方案中，所述抗Nectin-4抗体药物偶联物的给药剂量选自约1.0mg/kg，约1.1mg/kg，约1.2mg/kg，约1.3mg/kg，约1.4mg/kg，约1.5mg/kg，约1.6mg/kg，约1.7mg/kg，约1.8mg/kg，约1.9mg/kg，约2.0mg/kg，约2.1mg/kg，约2.2mg/kg，约2.3mg/kg，约2.4mg/kg，约2.5mg/kg，约2.6mg/kg，约2.7mg/kg，约2.8mg/kg，约2.9mg/kg，约3.0mg/kg，约3.1mg/kg，约3.2mg/kg，约3.4mg/kg，约3.5mg/kg，约3.6mg/kg，约3.7mg/kg，约3.8mg/kg，约3.9mg/kg，约4.0mg/kg，约4.1mg/kg，约4.2mg/kg，约4.3mg/kg，约4.4mg/kg，约4.5mg/kg，约4.6mg/kg，约4.7mg/kg，约4.8mg/kg，约4.9mg/kg，约5.0mg/kg，约5.1mg/kg，约5.2mg/kg，约5.3mg/kg，约5.4mg/kg，约5.5mg/kg，约5.6mg/kg，约5.7mg/kg，约5.8mg/kg，约5.9mg/kg，约6.0mg/kg，约6.1mg/kg，约6.2mg/kg，约6.3mg/kg，约6.4mg/kg，约6.5mg/kg，约6.6mg/kg，约6.7mg/kg，约6.8mg/kg，约6.9mg/kg，约7.0mg/kg，约7.1mg/kg，约7.2mg/kg，约7.3mg/kg，约7.4mg/kg，约7.5mg/kg，约7.6mg/kg，约7.7mg/kg，约7.8mg/kg，约7.9mg/kg，约8.0mg/kg，约8.1mg/kg，约8.2mg/kg，约8.3mg/kg，约8.4mg/kg，约8.5mg/kg，约8.6mg/kg，约8.7mg/kg，约8.8mg/kg，约8.9mg/kg，约9.0mg/kg，约9.1mg/kg，约9.2mg/kg，约9.3mg/kg，约9.4mg/kg，约9.5mg/kg，约9.6mg/kg，约9.7mg/kg，约9.8mg/kg，约9.9mg/kg，约10.0mg/kg，约10.5mg/kg，约11mg/kg，约12mg/kg，约12.5mg/kg，约13mg/kg，约13.5mg/kg，约14mg/kg，约15mg/kg，约16mg/kg，约18mg/kg，约19mg/kg，约20mg/kg，约50mg/kg，或者为这些点值之间的任意范围。
在一些实施方案中，所述抗Nectin-4抗体药物偶联物的给药剂量选自1.0mg/kg，1.1mg/kg，1.2mg/kg，1.3mg/kg，1.4mg/kg，1.5mg/kg，1.6mg/kg，1.7mg/kg，1.8mg/kg，1.9mg/kg，2.0mg/kg，2.1mg/kg，2.2mg/kg，2.3mg/kg，2.4mg/kg，2.5mg/kg，2.6mg/kg，2.7mg/kg，2.8mg/kg，2.9mg/kg，3.0mg/kg，3.1mg/kg，3.2mg/kg，3.4mg/kg，3.5mg/kg，3.6mg/kg，3.7mg/kg，3.8mg/kg，3.9mg/kg，4.0mg/kg，4.1mg/kg，4.2mg/kg，4.3mg/kg，4.4mg/kg，4.5mg/kg，4.6mg/kg，4.7mg/kg，4.8mg/kg，4.9mg/kg，5.0mg/kg，5.1mg/kg，5.2mg/kg，5.3mg/kg，5.4mg/kg，5.5mg/kg，5.6mg/kg，5.7mg/kg，5.8mg/kg，5.9mg/kg，6.0mg/kg，6.1mg/kg，6.2mg/kg，6.3mg/kg，6.4mg/kg，6.5mg/kg，6.6mg/kg，6.7mg/kg，6.8mg/kg，6.9mg/kg，7.0mg/kg，7.1mg/kg，7.2mg/kg，7.3mg/kg，7.4mg/kg，7.5mg/kg，7.6mg/kg，7.7mg/kg，7.8mg/kg，7.9mg/kg，8.0mg/kg，8.1mg/kg，8.2mg/kg，8.3mg/kg，8.4mg/kg，8.5mg/kg，8.6mg/kg，8.7mg/kg，8.8mg/kg，8.9mg/kg，9.0mg/kg，9.1mg/kg，9.2mg/kg，9.3mg/kg，9.4mg/kg，9.5mg/kg，9.6mg/kg，9.7mg/kg，9.8mg/kg，9.9mg/kg，10.0mg/kg，10.5mg/kg，11mg/kg，12mg/kg，12.5mg/kg，13mg/kg，13.5mg/kg，14mg/kg，15mg/kg，16mg/kg，18mg/kg，19mg/kg，20mg/kg，50mg/kg，或者为这些点值之间的任意范围。
在一些实施方案中，所述抗Nectin-4抗体药物偶联物的给药频率为每2周至少1次，每3周至少1次，每4周至少1次，每6周至少1次，或每8周至少1次。在一些实施方案中，所述抗Nectin-4抗体药物偶联物的给药频率为每2周1次，每3周1次，每3周2次，每4周1次，每6周1次，或每8周1次。在一些实施方案中，所述抗Nectin-4抗体药物偶联物的给药频率为为每3周1次或每3周2次。
在一些实施方案中，所述抗Nectin-4抗体药物偶联物的给药剂量为约5mg/kg、约6mg/kg、约7mg/kg、约8mg/kg、约9mg/kg或约10mg/kg，给药频率为每3周1次。在一些实施方案中，所述抗Nectin-4抗体药物偶联物的给药剂量为约1mg/kg、约2mg/kg、约3mg/kg或约4mg/kg，给药频率为每3周2次。在一些实施方案中，所述抗Nectin-4抗体药物偶联物的给药剂量为约4mg/kg，给药频率为每3周2次。在一些实施方案中，所述抗Nectin-4抗体药物偶联物的给药剂量为约1mg/kg、约2mg/kg、约3mg/kg或约4mg/kg，给药频率为每3周2次，每个周期D1、D8天给药。在一些实施方案中，所述抗Nectin-4抗体药物偶联物的给药剂量为约4mg/kg，给药频率为每3周2次，每个周期D1、D8天给药。在一些实施方案中，所述抗Nectin-4抗体药物偶联物的给药剂量为约6mg/kg或约8mg/kg，给药频率为每3周1次。
在一些实施方案中，所述抗Nectin-4抗体药物偶联物的给药途径为经口腔给药、胃肠外给药、经皮给药；所述胃肠外给药包括但不限于静脉注射、皮下注射、肌肉注射。在一些具体的实施方案中，抗Nectin-4抗体药物偶联物的给药途径为静脉注射给药。
在一些实施方案中，抗Nectin-4抗体药物偶联物被配置为可注射的形式。示例性地，抗Nectin-4抗体药物偶联物的可注射的形式是注射液或冻干粉针，其包含抗Nectin-4抗体药物偶联物及一种或多种药学可接受的辅料。在一些实施方案中，抗Nectin-4抗体药物偶联物被配制为选自WO2023221971A的任一组合物。
免疫治疗剂
在一些实施方案中，所述免疫治疗剂包括抗PD-L1抗体和抗CTLA-4抗体中的任意一种或两种的组合。
在一些实施方案中，所述免疫治疗剂包括如下任一种：抗PD-L1抗体、抗CTLA-4抗体、或抗PD-L1抗体和抗CTLA-4抗体的组合。
<抗PD-L1抗体>
在一些实施方案中，所述抗PD-L1抗体包含重链可变区(VH)和轻链可变区(VL)，其中所述重链可变区包含如SEQ ID NO:11-13所示的HCDR1、HCDR2和HCDR3，所述轻链可变区包含如SEQ ID NO:14-16所示的LCDR1、LCDR2和LCDR3。
其中，前面所述的各CDR序列如下表2所示：
表2.抗PD-L1抗体的CDR序列(Kabat方案)
在一些实施方案中，抗PD-L1抗体包含前述HCDR1、HCDR2、HCDR3、LCDR1、LCDR2和LCDR3中任意1个，或任意2、3、4、5或6个的组合。
在一些实施方案中，抗PD-L1抗体包含重链可变区(VH)和轻链可变区(VL)：其中，所述VH包含SEQ ID NO：17所示氨基酸序列中的HCDR1、HCDR2和HCDR3，所述VL包含如SEQ ID NO：18所示氨基酸序列中的LCDR1、LCDR2和LCDR3。上述的CDR是根据Kabat、IMGT、Chothia、AbM或Contact定义方案定义的。在一些具体的实施方案中，所述CDR是根据Kabat定义方案定义的。
在一些实施方案中，抗PD-L1抗体为嵌合、人源化、全人抗体或其抗原结合片段。
在一些实施方案中，抗PD-L1抗体包含重链可变区(VH)和轻链可变区(VL)，其中，所述VH包含如SEQ ID NO：17所示或与之具有至少80％、90％同一性的氨基酸序列，和，所述VL包含如SEQ ID NO：18所示或与之具有至少80％、90％同一性的氨基酸序列。
重链可变区：
轻链可变区：
注：下划线部分为依照Kabat编号规则确定的CDR区。
在一些实施方案中，抗PD-L1抗体包含前述VH、VL中的任意一个或两个。
在一些实施方案中，抗PD-L1抗体进一步包含重链恒定区和/或轻链恒定区。其中，抗体的重链恒定区可选自人IgG1、IgG2、IgG3、IgG4及其变体的恒定区。在一些实施方案中，抗PD-L1抗体包含人源IgG2或IgG4重链恒定区。在一些实施方案中，抗PD-L1抗体包含引入F234A和L235A突变的IgG4重链恒定区。在一些实施方案中，轻链恒定区可选自人源κ、λ链或其变体的轻链恒定区。
在一些实施方案中，抗PD-L1抗体包含重链和轻链，所述重链包含如SEQ IDNO:19所示或与之具有至少80％、至少90％序列同一性的氨基酸序列；和/或，所述轻链包含如SEQ ID NO:20所示或与之具有至少80％、至少90％同一性的氨基酸序列。
在一些实施方案中，抗PD-L1抗体包含如SEQ ID NO:19所示氨基酸序列的重链，和如SEQ ID NO:20所示氨基酸序列的轻链。
抗PD-L1抗体的重链序列：
抗PD-L1抗体的轻链序列：
注：划线部分为抗体重链或轻链的可变区序列，未划线部分为抗体恒定区序列。
在一些实施方案中，上述抗PD-L1抗体或其抗原结合片段的制备可以参考WO2017084495A1、WO2018210230A1，本公开通过引用将WO2017084495A1、WO2018210230A1中抗体序列、制备方法、组合物的相关内容结合至本公开。
在本公开的上下文中，“至少80％、90％”涵盖80％及以上，例如至少80％、至少81％、至少82％、至少83％、至少84％、至少85％、至少86％、至少87％、至少88％、至少89％、至少90％、至少91％、至少92％、至少93％、至少94％、至少95％、至少96％、至少97％、至少98％、至少99％，以及任意两者之间的数值范围。
在一些实施方案中，抗PD-L1抗体的给药剂量可选为约5mg至约5000mg，约50mg至约5000mg，约100mg至约5000mg，约100mg至约4500mg，约100mg至约4000mg，约100mg至约3500mg，约100mg至约3000mg，约100mg至约2500mg，约100mg至约2000mg，约100mg至约1500mg，约500mg至约3500mg，约500mg至约3000mg，约500mg至约2500mg，约500mg至约2000mg，约500mg至约1500mg，约800mg至约3500mg，约800mg至约3000mg，约800mg至约2500mg，约800mg至约2000mg，约800mg至约1500mg，或约1000mg至约1500mg；以及任意两者之间的数值范围。
在一些实施方案中，抗PD-L1抗体的给药剂量为约5mg，约25mg，约50mg、约60mg、约70mg、约75mg、约100mg、约125mg、约150mg、约175mg、约200mg、225mg、约250mg、约375mg、约400mg、约425mg、约450mg、约475mg、约500mg、约550mg、约600mg、650mg、约700mg、约750mg、约800mg、约850mg、约900mg、约950mg、约1000mg、约1050mg、约1100mg、约1150mg、约1200mg、约1250mg、约1300mg、约1350mg、约1400mg、约1450mg、约1500mg、1550mg、约1600mg、约1650mg、约1700mg、约1750mg、约1800mg、约1850mg、约1900mg、约1950mg、2000mg、约2050mg、约2100mg、约2150mg、约2200mg、约2250mg、约2300mg、约2350mg、约2400mg、2450mg、约2500mg、约2550mg、约2600mg、约2650mg、约2700mg、约2750mg、约2800mg、约2850mg、2900mg、约2950mg、约3000mg、约3050mg、约3100mg、约3150mg、约3200mg、约3250mg、约3300mg、约3350mg、约3400mg、3450mg、约3500mg、约3550mg、约3600mg、约3650mg、约3700mg、约3750mg、约3800mg、约3850mg、3900mg、约3950mg、约4000mg、约4500mg、或约5000mg；以及任意两者之间的数值范围。
在一些实施方案中，抗PD-L1抗体的给药剂量为5mg，25mg，50mg、60mg、70mg、75mg、100mg、125mg、150mg、175mg、200mg、225mg、250mg、375mg、400mg、425mg、450mg、475mg、500mg、550mg、600mg、650mg、700mg、750mg、800mg、850mg、900mg、950mg、1000mg、1050mg、1100mg、1150mg、1200mg、1250mg、1300mg、1350mg、1400mg、1450mg、1500mg、1550mg、1600mg、1650mg、1700mg、1750mg、1800mg、1850mg、1900mg、1950mg、2000mg、2050mg、2100mg、2150mg、2200mg、2250mg、2300mg、2350mg、2400mg、2450mg、2500mg、2550mg、2600mg、2650mg、2700mg、2750mg、2800mg、2850mg、2900mg、2950mg、3000mg、3050mg、3100mg、3150mg、3200mg、3250mg、3300mg、3350mg、3400mg、3450mg、3500mg、3550mg、3600mg、3650mg、3700mg、3750mg、3800mg、3850mg、3900mg、3950mg、4000mg、4500mg、或5000mg；以及任意两者之间的数值范围。
在一些实施方案中，所述抗PD-L1抗体的给药剂量为约1200mg。
在一些实施方案中，所述抗PD-L1抗体的给药频率为每2周1次，每3周1次，每4周1次，每5周1次，或每6周1次。在一些具体的实施方案中，所述抗PD-L1抗体的给药频率为每3周1次。
在一些实施方案中，所述抗PD-L1抗体的给药剂量为约1200mg，给药频率为每3周1次。
在一些实施方案中，所述抗PD-L1抗体的给药途径为经口腔给药、胃肠外给药、经皮给药；所述胃肠外给药包括但不限于静脉注射、皮下注射、肌肉注射。在一些实施方案中，所述抗PD-L1抗体的给药方式为静脉注射给药。
<抗CTLA-4抗体>
在一些实施方案中，所述抗CTLA-4抗体包含重链可变区(VH)和轻链可变区(VL)，其中所述重链可变区包含如SEQ ID NO:21-23所示的HCDR1、HCDR2和HCDR3，所述轻链可变区包含如SEQ ID NO:24-26所示的LCDR1、LCDR2和LCDR3。
其中，前面所述的各CDR序列如下表3所示：
表3.抗CTLA-4抗体的CDR序列
在一些实施方案中，抗CTLA-4抗体包含前述HCDR1、HCDR2、HCDR3、LCDR1、LCDR2和LCDR3中任意1个，或任意2、3、4、5或6个的组合。
在一些实施方案中，抗CTLA-4抗体包含重链可变区(VH)和轻链可变区(VL)：其中，所述VH包含SEQ ID NO：27所示氨基酸序列中的HCDR1、HCDR2和HCDR3，所述VL包含如SEQ ID NO：28所示氨基酸序列中的LCDR1、LCDR2和LCDR3。上述的CDR是根据Kabat、IMGT、Chothia、AbM或Contact定义方案定义的。在一些具体的实施方案中，所述CDR是根据Kabat定义方案定义的。
在一些实施方案中，抗CTLA-4抗体为嵌合、人源化、全人抗体或其抗原结合片段。
在一些实施方案中，抗CTLA-4抗体包含重链可变区(VH)和轻链可变区(VL)，其中，所述VH包含如SEQ ID NO：27所示或与之具有至少80％、90％同一性的氨基酸序列，和，所述VL包含如SEQ ID NO：28所示或与之具有至少80％、90％同一性的氨基酸序列。
重链可变区：
轻链可变区：
在一些实施方案中，抗CTLA-4抗体包含前述VH、VL中的任意一个或两个。
在一些实施方案中，抗CTLA-4抗体进一步包含重链恒定区和/或轻链恒定区。其中，抗体的重链恒定区可选自人IgG1、IgG2、IgG3、IgG4及其变体的恒定区。在一些实施方案中，轻链恒定区可选自人源κ、λ链或其变体的轻链恒定区。
在一些实施方案中，抗CTLA-4抗体包含重链和轻链，所述重链包含如SEQ ID NO:29所示或与之具有至少80％、至少90％序列同一性的氨基酸序列；和/或，所述轻链包含如SEQ ID NO:30所示或与之具有至少80％、至少90％同一性的氨基酸序列。
在一些实施方案中，抗CTLA-4抗体包含如SEQ ID NO:29所示氨基酸序列的重链，和如SEQ ID NO:30所示氨基酸序列的轻链。
抗CTLA-4抗体的重链序列：
抗CTLA-4抗体的轻链序列：
注：划线部分为抗体重链或轻链的可变区序列，未划线部分为抗体恒定区序列。
在本公开的上下文中，“至少80％、90％”涵盖80％及以上，例如至少80％、至少81％、至少82％、至少83％、至少84％、至少85％、至少86％、至少87％、至少88％、至少89％、至少90％、至少91％、至少92％、至少93％、至少94％、至少95％、至少96％、至少97％、至少98％、至少99％，以及任意两者之间的数值范围。
在一些实施方案中，所述抗CTLA-4抗体的给药剂量可选为约0.1mg/kg至约100mg/kg，0.1mg/kg至约50mg/kg，0.1mg/kg至约20mg/kg，约0.1mg/kg至约10mg/kg，约0.1mg/kg至约9mg/kg，约0.1mg/kg至约8mg/kg，约0.1mg/kg至约7mg/kg，约0.1mg/kg至约6mg/kg，约0.1mg/kg至约5mg/kg，约0.5mg/kg至约50mg/kg，约0.5mg/kg至约20mg/kg，约0.5mg/kg至约10mg/kg，约0.5mg/kg至约9mg/kg，约0.5mg/kg至约8mg/kg，约0.5mg/kg至约7mg/kg，约0.5mg/kg至约6mg/kg，约0.5mg/kg至约5mg/kg，约1mg/kg至约50mg/kg，约1mg/kg至约20mg/kg，约1mg/kg至约10mg/kg，约1mg/kg至约9mg/kg，约1mg/kg至约8mg/kg，约1mg/kg至约7mg/kg，约1mg/kg至约6mg/kg，约1mg/kg至约5mg/kg，约2mg/kg至约10mg/kg，约2mg/kg至约9mg/kg，约2mg/kg至约8mg/kg，约2mg/kg至约7mg/kg，约2mg/kg至约6mg/kg，约2mg/kg至约5mg/kg，约3mg/kg至约10mg/kg，约3mg/kg至约9mg/kg，约3mg/kg至约8mg/kg，约3mg/kg至约7mg/kg，约3mg/kg至约6mg/kg，约3mg/kg至约5mg/kg，或者为这些点值之间的任意范围。
在一些实施方案中，所述抗CTLA-4抗体的给药剂量为约0.1mg/kg，约0.2mg/kg，约0.3mg/kg，约0.4mg/kg，约0.5mg/kg，约0.6mg/kg，约0.7mg/kg，约0.8mg/kg，约0.9mg/kg，约1.0mg/kg，约1.1mg/kg，约1.2mg/kg，约1.3mg/kg，约1.4mg/kg，约1.5mg/kg，约1.6mg/kg，约1.7mg/kg，约1.8mg/kg，约1.9mg/kg，约2.0mg/kg，约2.1mg/kg，约2.2mg/kg，约2.3mg/kg，约2.4mg/kg，约2.5mg/kg，约2.6mg/kg，约2.7mg/kg，约2.8mg/kg，约2.9mg/kg，约3.0mg/kg，约3.1mg/kg，约3.2mg/kg，约3.3mg/kg，约3.4mg/kg，约3.5mg/kg，约3.6mg/kg，约3.7mg/kg，约3.8mg/kg，约3.9mg/kg，约4.0mg/kg，约4.1mg/kg，约4.2mg/kg，约4.3mg/kg，约4.4mg/kg，约4.5mg/kg，约4.6mg/kg，约4.7mg/kg，约4.8mg/kg，约4.9mg/kg，约5.0mg/kg，约5.1mg/kg，约5.2mg/kg，约5.3mg/kg，约5.4mg/kg，约5.5mg/kg，约5.6mg/kg，约5.7mg/kg，约5.8mg/kg，约5.9mg/kg，约6.0mg/kg，约6.1mg/kg，约6.2mg/kg，约6.3mg/kg，约6.4mg/kg，约6.5mg/kg，约6.6mg/kg，约6.7mg/kg，约6.8mg/kg，约6.9mg/kg，约7.0mg/kg，约7.1mg/kg，约7.2mg/kg，约7.3mg/kg，约7.4mg/kg，约7.5mg/kg，约7.6mg/kg，约7.7mg/kg，约7.8mg/kg，约7.9mg/kg，约8.0mg/kg，约8.1mg/kg，约8.2mg/kg，约8.3mg/kg，约8.4mg/kg，约8.5mg/kg，约8.6mg/kg，约8.7mg/kg，约8.8mg/kg，约8.9mg/kg，约9.0mg/kg，约9.1mg/kg，约9.2mg/kg，约9.3mg/kg，约9.4mg/kg，约9.5mg/kg，约9.6mg/kg，约9.7mg/kg，约9.8mg/kg，约9.9mg/kg，约10.0mg/kg，约10.5mg/kg，约11mg/kg，约11.5mg/kg，约12mg/kg，约12.5mg/kg，约13mg/kg，约13.5mg/kg，约14mg/kg，约14.5mg/kg，约15mg/kg，约15mg/kg，约16mg/kg，约17mg/kg，约18mg/kg，约19mg/kg，约20mg/kg，约21mg/kg，约22mg/kg，约23mg/kg，约24mg/kg，约25mg/kg，约26mg/kg，约27mg/kg，约28mg/kg，约29mg/kg，约30mg/kg，约35mg/kg，约40mg/kg，约45mg/kg，约50mg/kg，约100mg/kg，或者为这些点值之间的任意数值范围。
在一些实施方案中，所述抗CTLA-4抗体的给药剂量为0.1mg/kg，0.2mg/kg，0.3mg/kg，0.4mg/kg，0.5mg/kg，0.6mg/kg，0.7mg/kg，0.8mg/kg，0.9mg/kg，1.0mg/kg，1.1mg/kg，1.2mg/kg，1.3mg/kg，1.4mg/kg，1.5mg/kg，1.6mg/kg，1.7mg/kg，1.8mg/kg，1.9mg/kg，2.0mg/kg，2.1mg/kg，2.2mg/kg，2.3mg/kg，2.4mg/kg，2.5mg/kg，2.6mg/kg，2.7mg/kg，2.8mg/kg，2.9mg/kg，3.0mg/kg，3.1mg/kg，3.2mg/kg，3.3mg/kg，3.4mg/kg，3.5mg/kg，3.6mg/kg，3.7mg/kg，3.8mg/kg，3.9mg/kg，4.0mg/kg，4.1mg/kg，4.2mg/kg，4.3mg/kg，4.4mg/kg，4.5mg/kg，4.6mg/kg，4.7mg/kg，4.8mg/kg，4.9mg/kg，5.0mg/kg，5.1mg/kg，5.2mg/kg，5.3mg/kg，5.4mg/kg，5.5mg/kg，5.6mg/kg，5.7mg/kg，5.8mg/kg，5.9mg/kg，6.0mg/kg，6.1mg/kg，6.2mg/kg，6.3mg/kg，6.4mg/kg，6.5mg/kg，6.6mg/kg，6.7mg/kg，6.8mg/kg，6.9mg/kg，7.0mg/kg，7.1mg/kg，7.2mg/kg，7.3mg/kg，7.4mg/kg，7.5mg/kg，7.6mg/kg，7.7mg/kg，7.8mg/kg，7.9mg/kg，8.0mg/kg，8.1mg/kg，8.2mg/kg，8.3mg/kg，8.4mg/kg，8.5mg/kg，8.6mg/kg，8.7mg/kg，8.8mg/kg，8.9mg/kg，9.0mg/kg，9.1mg/kg，9.2mg/kg，9.3mg/kg，9.4mg/kg，9.5mg/kg，9.6mg/kg，9.7mg/kg，9.8mg/kg，9.9mg/kg，10.0mg/kg，10.5mg/kg，11mg/kg，11.5mg/kg，12mg/kg，12.5mg/kg，13mg/kg，13.5mg/kg，14mg/kg，14.5mg/kg，15mg/kg，15mg/kg，16mg/kg，17mg/kg，18mg/kg，19mg/kg，20mg/kg，21mg/kg，22mg/kg，23mg/kg，24mg/kg，25mg/kg，26mg/kg，27mg/kg，28mg/kg，29mg/kg，30mg/kg，35mg/kg，40mg/kg，45mg/kg，50mg/kg，100mg/kg，或者为这些点值之间的任意数值范围。
在一些实施方案中，所述抗CTLA-4抗体的给药剂量为约4.0mg/kg。
在一些实施方案中，所述抗CTLA-4抗体的给药剂量可选为约1-1000mg，约1-800mg，约1-700mg，约1-600mg，约1-500mg，约5-500mg，约10-500mg，约20-500mg，约30-500mg，约40-500mg，约50-500mg，约60-500mg，约10-400mg，约20-400mg，约30-400mg，约40-400mg，约50-400mg，约60-400mg，约10-350mg，约20-350mg，约30-350mg，约40-350mg，约50-350mg，约60-350mg，约10-300mg，约20-300mg，约30-300mg，约40-300mg，约50-300mg，约60-300mg，约10-150mg，约20-150mg，约30-150mg，约40-150mg，约50-150mg，约60-150mg，约10-100mg，约20-100mg，约30-100mg，约40-100mg，约50-100mg，约60-100mg，约60-90mg，约60-80mg，或者为这些点值之间的任意范围。
在一些实施方案中，所述抗CTLA-4抗体的给药剂量为约1mg，约5mg，约10mg，约15mg，约20mg，约25mg，约30mg，约31mg，约32mg，约33mg，约34mg，约35mg，约36mg，约37mg，约38mg，约39mg，约40mg，约41mg，约42mg，约43mg，约44mg，约45mg，约46mg，约47mg，约48mg，约49mg，约50mg，约51mg，约52mg，约53mg，约54mg，约55mg，约56mg，约57mg，约58mg，约59mg，约60mg，约61mg，约62mg，约63mg，约64mg，约65mg，约66mg，约67mg，约68mg，约69mg，约70mg，约71mg，约72mg，约73mg，约74mg，约75mg，约76mg，约77mg，约78mg，约79mg，约80mg，约81mg，约82mg，约83mg，约84mg，约85mg，约86mg，约87mg，约88mg，约89mg，约90mg，约91mg，约92mg，约93mg，约94mg，约95mg，约96mg，约97mg，约98mg，约99mg，约100mg，约110mg，约120mg，约130mg，约140mg，约150mg，约160mg，约180mg，约200mg，约210mg，约220mg，约230mg，约240mg，约250mg，约260mg，约270mg，约280mg，约290mg，约300mg，约310mg，约320mg，约330mg，约340mg，约350mg，约360mg，约370mg，约380mg，约390mg，约400mg，约450mg，约500mg，约600mg，约700mg，约800mg，约900mg，约1000mg，或者为这些点值之间的任意范围。
在一些实施方案中，所述抗CTLA-4抗体的给药剂量为1mg，5mg，10mg，15mg，20mg，25mg，30mg，31mg，32mg，33mg，34mg，35mg，36mg，37mg，38mg，39mg，40mg，41mg，42mg，43mg，44mg，45mg，46mg，47mg，48mg，49mg，50mg，51mg，52mg，53mg，54mg，55mg，56mg，57mg，58mg，59mg，60mg，61mg，62mg，63mg，64mg，65mg，66mg，67mg，68mg，69mg，70mg，71mg，72mg，73mg，74mg，75mg，76mg，77mg，78mg，79mg，80mg，81mg，82mg，83mg，84mg，85mg，86mg，87mg，88mg，89mg，90mg，91mg，92mg，93mg，94mg，95mg，96mg，97mg，98mg，99mg，100mg，110mg，120mg，130mg，140mg，150mg，160mg，180mg，200mg，210mg，220mg，230mg，240mg，250mg，260mg，270mg，280mg，290mg，300mg，310mg，320mg，330mg，340mg，350mg，360mg，370mg，380mg，390mg，400mg，450mg，500mg，600mg，700mg，800mg，900mg，1000mg，或者为这些点值之间的任意范围。
在一些实施方案中，所述抗CTLA-4抗体的给药剂量为约70mg。
在一些实施方案中，所述抗CTLA-4抗体的给药剂量为约280mg或210mg。
在一些实施方案中，所述抗CTLA-4抗体的给药频次为每2周1次、每3周1次、每4周1次、每6周1次、每8周1次、每10周1次、每12周1次、每14周1次、每16周1次或单次给药。在一些实施方案中，所述抗CTLA-4抗体的给药频率为12周1次。
在一些实施方案中，所述抗CTLA-4抗体的给药频率为每6周1次或单次给药。在一些实施方案中，所述抗CTLA-4抗体在第1周单次给药，给药剂量为约280mg，第2-12周不给药，从第13周开始，给药剂量为约70mg，给药频次为每6周1次。
在一些实施方案中，以21天为1个周期，第1个周期的第1天单次给药280mg或210mg，第2-4个周期不给药，从第5个周期的第1天开始按照70mg、每6周给药一次的频率给药(C1D1 280mg或210mg给药一次，C2-C4不给药，C5及后续周期70mg Q6W)。
在一些实施方案中，所述抗CTLA-4抗体的给药途径为经口腔给药、胃肠外给药、经皮给药；所述胃肠外给药包括但不限于静脉注射、皮下注射、肌肉注射。在一些实施方案中，所述抗CTLA-4抗体的给药方式为静脉注射给药。
<VEGF信号通路抑制剂>
在一些实施例方案中，所述VEGF信号通路抑制剂为抗VEGF抗体。
在一些实施方案中，所述抗VEGF抗体包含重链可变区(VH)和轻链可变区(VL)，其中所述重链可变区包含如SEQ ID NO:31-33所示的HCDR1、HCDR2和HCDR3，所述轻链可变区包含如SEQ ID NO:34-36所示的LCDR1、LCDR2和LCDR3。
在一些实施方案中，如上任一项所述的抗VEGF抗体包含重链可变区和轻链可变区，所述重链可变区的HCDR1的氨基酸序列如SEQ ID NO：31所示，HCDR2的氨基酸序列如SEQ ID NO：32所示，和HCDR3的氨基酸序列如SEQ ID NO：33所示，和所述轻链可变区的LCDR1的氨基酸序列如SEQ ID NO：34所示，LCDR2的氨基酸序列如SEQ ID NO：35所示，和LCDR3的氨基酸序列如SEQ ID NO：36所示。其中，前面所述的各CDR序列如下表4所示：
表4.抗VEGF抗体的CDR序列
上述的CDR是根据Kabat定义方案定义的。
在一些实施方案中，如上任一项所述的抗VEGF抗体包含前述HCDR1、HCDR2、HCDR3、LCDR1、LCDR2和LCDR3中任意1个，或任意2、3、4、5或6个的组合。
在一些实施方案中，如上任一项所述的抗VEGF抗体包含重链可变区和轻链可变区，所述重链可变区包含SEQ ID NO：37所示氨基酸序列中的HCDR1、HCDR2和HCDR3，和所述轻链可变区包含如SEQ ID NO：38所示氨基酸序列中的LCDR1、LCDR2和LCDR3。
在一些实施方案中，如上任一项所述的抗VEGF抗体，其中所述重链可变区的HCDR1、HCDR2和HCDR3以及轻链可变区的LCDR1、LCDR2和LCDR3是根据选自Kabat、IMGT、Chothia、AbM和Contact编号规则定义的。
在一些实施方案中，抗VEGF抗体或其抗原结合片段为嵌合、人源化、全人抗体或其抗原结合片段。
在一些实施方案中，抗VEGF抗体或其抗原结合片段，所述重链可变区包含如SEQ ID NO：37所示的氨基酸序列，或与之具有至少80％、90％序列同一性的氨基酸序列；轻链可变区包含如SEQ ID NO：38所示的氨基酸序列，或与之具有至少80％、90％序列同一性的氨基酸序列。
抗VEGF抗体重链可变区：
抗VEGF抗体轻链可变区：
在一些实施方案中，抗VEGF抗体的重链可变区包含如SEQ ID NO：37所示或与之具有至少80％同一性的氨基酸序列，轻链可变区包含如SEQ ID NO：38所示或与之具有至少80％同一性的氨基酸序列。
在一些实施方案中，抗VEGF抗体进一步包含重链恒定区和/或轻链恒定区，例如，所述抗体恒定区的重链恒定区选自人IgG1、IgG2、IgG3和IgG4恒定区及其变体；所述抗体恒定区的轻链恒定区选自人抗体κ和λ链恒定区及其变体。
在一些实施方案中，抗VEGF抗体包含重链和轻链，所述重链包含如SEQ ID NO:19所示或与之具有至少80％序列同一性的氨基酸序列；和/或，所述轻链包含如SEQ ID NO:20所示或与之具有至少80％同一性的氨基酸序列。
在一些实施方案中，抗VEGF抗体包含如SEQ ID NO:39所示氨基酸序列的重链，和如SEQ ID NO:40所示氨基酸序列的轻链。
抗VEGF抗体的重链序列：
抗VEGF抗体的轻链序列：
注：划线部分为抗体重链或轻链的可变区序列，未划线部分为抗体恒定区序列。
在一些实施方案中，所述抗VEGF抗体的给药剂量可选约1.0mg/kg至约30mg/kg，约1mg/kg至约25mg/kg；约1.0mg/kg至约20mg/kg，约1.0mg/kg至约19mg/kg，约1.0mg/kg至约18mg/kg，约1.0mg/kg至约17mg/kg，约1.0mg/kg至约16mg/kg，约1.0mg/kg至约15mg/kg，约1.0mg/kg至约14mg/kg，约1.0mg/kg至约13mg/kg，约1.0mg/kg至约12mg/kg，约1.0mg/kg至约11mg/kg，约1.0mg/kg至约10mg/kg，约2mg/kg至约25mg/kg；约2.0mg/kg至约20mg/kg，约2.0mg/kg至约19mg/kg，约2.0mg/kg至约18mg/kg，约2.0mg/kg至约17mg/kg，约2.0mg/kg至约16mg/kg，约2.0mg/kg至约15mg/kg，约2.0mg/kg至约14mg/kg，约2.0mg/kg至约13mg/kg，约2.0mg/kg至约12mg/kg，约2.0mg/kg至约11mg/kg，约2.0mg/kg至约10mg/kg，约3.0mg/kg至约25mg/kg，约3.0mg/kg至约20mg/kg，约3.0mg/kg至约19mg/kg，约3.0mg/kg至约18mg/kg，约3.0mg/kg至约17mg/kg，约3.0mg/kg至约16mg/kg，约3.0mg/kg至约15mg/kg，约3.0mg/kg至约14mg/kg，约3.0mg/kg至约13mg/kg，约3.0mg/kg至约12mg/kg，约3.0mg/kg至约11mg/kg，约3.0mg/kg至约10mg/kg，约4.0mg/kg至约25mg/kg，约4.0mg/kg至约20mg/kg，约4.0mg/kg至约19mg/kg，约4.0mg/kg至约18mg/kg，约4.0mg/kg至约17mg/kg，约4.0mg/kg至约16mg/kg，约4.0mg/kg至约15mg/kg，约4.0mg/kg至约14mg/kg，约4.0mg/kg至约13mg/kg，约4.0mg/kg至约12mg/kg，约4.0mg/kg至约11mg/kg，约4.0mg/kg至约10mg/kg，约5.0mg/kg至约25mg/kg，约5.0mg/kg至约20mg/kg，约5.0mg/kg至约19mg/kg，约5.0mg/kg至约18mg/kg，约5.0mg/kg至约17mg/kg，约5.0mg/kg至约16mg/kg，约5.0mg/kg至约15mg/kg，约5.0mg/kg至约14mg/kg，约5.0mg/kg至约13mg/kg，约5.0mg/kg至约12mg/kg，约5.0mg/kg至约11mg/kg，约5.0mg/kg至约10mg/kg，约6.0mg/kg至约25mg/kg，约6.0mg/kg至约20mg/kg，约6.0mg/kg至约19mg/kg，约6.0mg/kg至约18mg/kg，约6.0mg/kg至约17mg/kg，约6.0mg/kg至约16mg/kg，约6.0mg/kg至约15mg/kg，约6.0mg/kg至约14mg/kg，约6.0mg/kg至约13mg/kg，约6.0mg/kg至约12mg/kg，约6.0mg/kg至约11mg/kg，约6.0mg/kg至约10mg/kg，约7.0mg/kg至约25mg/kg，约7.0mg/kg至约23mg/kg，约7.0mg/kg至约20mg/kg，约7.0mg/kg至约19mg/kg，约7.0mg/kg至约18mg/kg，约7.0mg/kg至约17mg/kg，约7.0mg/kg至约16mg/kg，约7.0mg/kg至约15mg/kg，约7.0mg/kg至约14mg/kg，约7.0mg/kg至约13mg/kg，约7.0mg/kg至约12mg/kg，约7.0mg/kg至约11mg/kg，约7.0mg/kg至约10mg/kg，约8mg/kg至约20mg/kg，约8mg/kg至约19mg/kg，约8mg/kg至约18mg/kg，约8mg/kg至约17mg/kg，约8mg/kg至约16mg/kg，约8mg/kg至约15mg/kg；约8mg/kg至约15g/kg，约9mg/kg至约21mg/kg，约10mg/kg至约20mg/kg，约10mg/kg至约19mg/kg，约10mg/kg至约18mg/kg，约10mg/kg至约17mg/kg，约10mg/kg至约16mg/kg，约10mg/kg至约15mg/kg，约11mg/kg至约19mg/kg，约12mg/kg至约18mg/kg，约13mg/kg至约17mg/kg，约14mg/kg至约16mg/kg，约1mg/kg至约9mg/kg，约2mg/kg至约9mg/kg，约3mg/kg至约9mg/kg，约4mg/kg至约9mg/kg，约5mg/kg至约9mg/kg，约6mg/kg至约9mg/kg，约1mg/kg至约8mg/kg，约2mg/kg至约8mg/kg，约3mg/kg至约8mg/kg，约4mg/kg至约8mg/kg，约5mg/kg至约8mg/kg，约6mg/kg至约8mg/kg，约7mg/kg至约8mg/kg。
在一些实施方案中，所述抗VEGF抗体的给药剂量为约2.0mg/kg，约3.0mg/kg，约4.0mg/kg，约5.0mg/kg，约6.0mg/kg，约6.5mg/kg，约7.0mg/kg，约7.5mg/kg，8.0mg/kg，8.5mg/kg，约9.0mg/kg，约9.5mg/kg，约10.0mg/kg，约10.5mg/kg，约11.0mg/kg，约11.5mg/kg，约12.0mg/kg，约12.5mg/kg，约13.0mg/kg，约13.5mg/kg，约14.0mg/kg，约14.5mg/kg，约15.0mg/kg，约15.5mg/kg，约16.0mg/kg，约16.5mg/kg，约17.0mg/kg，约18.0mg/kg，约19.0mg/kg，约20.0mg/kg，约21.0mg/kg，约22.0mg/kg，约23.0mg/kg，约24.0mg/kg，约25.0mg/kg，约30.0mg/kg，或者为这些点值之间的任意范围。在一些实施方案中，所述抗VEGF抗体的给药剂量为2.0mg/kg，3.0mg/kg，4.0mg/kg，5.0mg/kg，6.0mg/kg，6.5mg/kg，7.0mg/kg，7.5mg/kg，8.0mg/kg，8.5mg/kg，9.0mg/kg，9.5mg/kg，10.0mg/kg，10.5mg/kg，11.0mg/kg，11.5mg/kg，12.0mg/kg，12.5mg/kg，13.0mg/kg，13.5mg/kg，14.0mg/kg，14.5mg/kg，15.0mg/kg，15.5mg/kg，16.0mg/kg，16.5mg/kg，17.0mg/kg，18.0mg/kg，19.0mg/kg，20.0mg/kg，21.0mg/kg，22.0mg/kg，23.0mg/kg，24.0mg/kg，25.0mg/kg，30.0mg/kg，或者为这些点值之间的任意范围。
在一些实施方案中，所述抗VEGF抗体的给药频率为每1周1次，每2周1次，每3周1次，每4周1次，每6周1次，每8周1次，每10周1次，或每12周1次。在一些具体的实施方案中，所述抗VEGF抗体的给药频率为每3周1次。
在一些实施方案中，抗VEGF抗体的给药方案选自如下任一项：
所述抗VEGF抗体的给药剂量为约1.0mg/kg至约30mg/kg，给药频率为每1周1次，每2周1次，每3周1次，每4周1次，每6周1次，每8周1次，每10周1次，或每12周1次；
所述抗VEGF抗体的给药剂量为约1.0mg/kg至约25mg/kg，给药频率为每1周1次，每2周1次，每3周1次，每4周1次，每6周1次，每8周1次，每10周1次，或每12周1次；
所述抗VEGF抗体的给药剂量为约2.0mg/kg至约25mg/kg，给药频率为每1周1次，每2周1次，每3周1次，每4周1次，每6周1次，每8周1次，每10周1次，或每12周1次；
所述抗VEGF抗体的给药剂量为约7.0mg/kg至约23mg/kg，给药频率为每1周1次，每2周1次，每3周1次，每4周1次，每6周1次，每8周1次，每10周1次，或每12周1次；
所述抗VEGF抗体的给药剂量为约2.0mg/kg至约20mg/kg，给药频率为每1周1次，每2周1次，每3周1次，每4周1次，每6周1次，每8周1次，每10周1次，或每12周1次；
所述抗VEGF抗体的给药剂量为约5.0mg/kg至约20mg/kg，给药频率为每1周1次，每2周1次，每3周1次，每4周1次，每6周1次，每8周1次，每10周1次，或每12周1次；
所述抗VEGF抗体的给药剂量为约约7.0mg/kg至约20mg/kg，给药频率为每1周1次，每2周1次，每3周1次，每4周1次，每6周1次，每8周1次，每10周1次，或每12周1次；
所述抗VEGF抗体的给药剂量为约8.0mg/kg至约20mg/kg，给药频率为每1周1次，每2周1次，每3周1次，每4周1次，每6周1次，每8周1次，每10周1次，或每12周1次；
所述抗VEGF抗体的给药剂量为约9.0mg/kg至约20mg/kg，给药频率为每1周1次，每2周1次，每3周1次，每4周1次，每6周1次，每8周1次，每10周1次，或每12周1次；
所述抗VEGF抗体的给药剂量为约10mg/kg至约20mg/kg，给药频率为每1周1次，每2周1次，每3周1次，每4周1次，每6周1次，每8周1次，每10周1次，或每12周1次；
所述抗VEGF抗体的给药剂量为约11mg/kg至约19mg/kg，给药频率为每1周1次，每2周1次，每3周1次，每4周1次，每6周1次，每8周1次，每10周1次，或每12周1次；
所述抗VEGF抗体的给药剂量为约12mg/kg至约18mg/kg，给药频率为每1周1次，每2周1次，每3周1次，每4周1次，每6周1次，每8周1次，每10周1次，或每12周1次；
所述抗VEGF抗体的给药剂量为约13mg/kg至约17mg/kg，给药频率为每1周1次，每2周1次，每3周1次，每4周1次，每6周1次，每8周1次，每10周1次，或每12周1次；
所述抗VEGF抗体的给药剂量为约14mg/kg至约16mg/kg，给药频率为每1周1次，每2周1次，每3周1次，每4周1次，每6周1次，每8周1次，每10周1次，或每12周1次；
所述抗VEGF抗体的给药剂量为约14mg/kg至约16mg/kg，给药频率为每1周1次，每2周1次，每3周1次，每4周1次，每6周1次，每8周1次，每10周1次，或每12周1次；
所述抗VEGF抗体的给药剂量为约1mg/kg至约15mg/kg，给药频率为每1周1次，每2周1次，每3周1次，每4周1次，每6周1次，每8周1次，每10周1次，或每12周1次；
所述抗VEGF抗体的给药剂量为约2mg/kg至约14mg/kg，给药频率为每1周1次，每2周1次，每3周1次，每4周1次，每6周1次，每8周1次，每10周1次，或每12周1次；
所述抗VEGF抗体的给药剂量为约2mg/kg至约13mg/kg，给药频率为每1周1次，每2周1次，每3周1次，每4周1次，每6周1次，每8周1次，每10周1次，或每12周1次；
所述抗VEGF抗体的给药剂量为约3mg/kg至约12mg/kg，给药频率为每1周1次，每2周1次，每3周1次，每4周1次，每6周1次，每8周1次，每10周1次，或每12周1次；
所述抗VEGF抗体的给药剂量为约4mg/kg至约11mg/kg，给药频率为每1周1次，每2周1次，每3周1次，每4周1次，每6周1次，每8周1次，每10周1次，或每12周1次；
所述抗VEGF抗体的给药剂量为约5mg/kg至约10mg/kg，给药频率为每1周1次，每2周1次，每3周1次，每4周1次，每6周1次，每8周1次，每10周1次，或每12周1次；
所述抗VEGF抗体的给药剂量为约6mg/kg至约9mg/kg，给药频率为每1周1次，每2周1次，每3周1次，每4周1次，每6周1次，每8周1次，每10周1次，或每12周1次；
所述抗VEGF抗体的给药剂量为约7mg/kg至约8mg/kg，给药频率为每1周1次，每2周1次，每3周1次，每4周1次，每6周1次，每8周1次，每10周1次，或每12周1次；
所述抗VEGF抗体的给药剂量为约2.0mg/kg，约3.0mg/kg，约4.0mg/kg，约5.0mg/kg，约6.0mg/kg，约6.5mg/kg，约7.0mg/kg，约7.5mg/kg，8.0mg/kg，8.5mg/kg，约9.0mg/kg，约9.5mg/kg，约10.0mg/kg，约10.5mg/kg，约11.0mg/kg，约11.5mg/kg，约12.0mg/kg，约12.5mg/kg，约13.0mg/kg，约13.5mg/kg，约14.0mg/kg，约14.5mg/kg，约15.0mg/kg，约15.5mg/kg，约16.0mg/kg，约16.5mg/kg，约17.0mg/kg，约18.0mg/kg，约19.0mg/kg，约20.0mg/kg，约21.0mg/kg，约22.0mg/kg，约23.0mg/kg，约24.0mg/kg，约25.0mg/kg，约30.0mg/kg；给药频率为每1周1次，每2周1次，每3周1次，每4周1次，每6周1次，每8周1次，每10周1次，或每12周1次；
所述抗VEGF抗体的给药剂量为约5.0mg/kg，给药频率为每3周1次；
所述抗VEGF抗体的给药剂量为约5.5mg/kg，给药频率为每3周1次；
所述抗VEGF抗体的给药剂量为约6.0mg/kg，给药频率为每3周1次；
所述抗VEGF抗体的给药剂量为约6.5mg/kg，给药频率为每3周1次；
所述抗VEGF抗体的给药剂量为约7.0mg/kg，给药频率为每3周1次；
所述抗VEGF抗体的给药剂量为约7.5mg/kg，给药频率为每3周1次；
所述抗VEGF抗体的给药剂量为约8.0mg/kg，给药频率为每3周1次；
所述抗VEGF抗体的给药剂量为约8.5mg/kg，给药频率为每3周1次；
所述抗VEGF抗体的给药剂量为约9.0mg/kg，给药频率为每3周1次；
所述抗VEGF抗体的给药剂量为约9.5mg/kg，给药频率为每3周1次；
所述抗VEGF抗体的给药剂量为约10.0mg/kg，给药频率为每3周1次；
所述抗VEGF抗体的给药剂量为约10.5mg/kg，给药频率为每3周1次；
所述抗VEGF抗体的给药剂量为约11.0mg/kg，给药频率为每3周1次；
所述抗VEGF抗体的给药剂量为约11.5mg/kg，给药频率为每3周1次；
所述抗VEGF抗体的给药剂量为约12.0mg/kg，给药频率为每3周1次；
所述抗VEGF抗体的给药剂量为约12.5mg/kg，给药频率为每3周1次；
所述抗VEGF抗体的给药剂量为约13.0mg/kg，给药频率为每3周1次；
所述抗VEGF抗体的给药剂量为约13.5mg/kg，给药频率为每3周1次；
所述抗VEGF抗体的给药剂量为约14.0mg/kg，给药频率为每3周1次；
所述抗VEGF抗体的给药剂量为约14.5mg/kg，给药频率为每3周1次；
所述抗VEGF抗体的给药剂量为约15.0mg/kg，给药频率为每3周1次；
所述抗VEGF抗体的给药剂量为约15.5mg/kg，给药频率为每3周1次；
所述抗VEGF抗体的给药剂量为约16.0mg/kg，给药频率为每3周1次；
所述抗VEGF抗体的给药剂量为约16.5mg/kg，给药频率为每3周1次；
所述抗VEGF抗体的给药剂量为约17.0mg/kg，给药频率为每3周1次；
所述抗VEGF抗体的给药剂量为约17.5mg/kg，给药频率为每3周1次；
所述抗VEGF抗体的给药剂量为约18.0mg/kg，给药频率为每3周1次；
所述抗VEGF抗体的给药剂量为约18.5mg/kg，给药频率为每3周1次；
所述抗VEGF抗体的给药剂量为约19.0mg/kg，给药频率为每3周1次；
所述抗VEGF抗体的给药剂量为约19.5mg/kg，给药频率为每3周1次；
所述抗VEGF抗体的给药剂量为约20.0mg/kg，给药频率为每3周1次；
所述抗VEGF抗体的给药剂量为约21.5mg/kg，给药频率为每3周1次；
所述抗VEGF抗体的给药剂量为约22.0mg/kg，给药频率为每3周1次；
所述抗VEGF抗体的给药剂量为约22.5mg/kg，给药频率为每3周1次；
所述抗VEGF抗体的给药剂量为约23.0mg/kg，给药频率为每3周1次；
所述抗VEGF抗体的给药剂量为约23.5mg/kg，给药频率为每3周1次；
所述抗VEGF抗体的给药剂量为约24.0mg/kg，给药频率为每3周1次；
所述抗VEGF抗体的给药剂量为约24.5mg/kg，给药频率为每3周1次；
所述抗VEGF抗体的给药剂量为约25.0mg/kg，给药频率为每3周1次。
在一些实施方案中，在上述任一项所述的给药方案中，所述抗VEGF抗体的给药频率为每3周1次。
在一些实施方案中，在上述任一项所述的给药方案中，所述抗VEGF抗体的给药途径可以为经口给药、胃肠外给药、经皮给药，所述胃肠外给药包括但不限于静脉注射、皮下注射、肌肉注射。在一些实施方案中，抗VEGF抗体的给药途径为静脉输注给药。
在一些实施方案中，抗VEGF抗体被配置为可注射的形式。示例性地，抗VEGF抗体的可注射的形式是注射液或冻干粉针，其包含抗VEGF抗体及一种或多种药学可接受的辅料。
<铂类药物>
在一些实施方案中，所述铂类药物为卡铂或顺铂。
一些实施方案中，所述铂类药物为顺铂，所述顺铂的给药剂量为约1mg/m2至约500mg/m2，或约50mg/m2至约150mg/m2；例如约1mg/m2至约200mg/m2，约1mg/m2至约150mg/m2，约1mg/m2至约100mg/m2，约15mg/m2至约150mg/m2，约20mg/m2至约150mg/m2，约30mg/m2至约150mg/m2，约30mg/m2至约100mg/m2，约30mg/m2至约85mg/m2，约45mg/m2至约85mg/m2，约50mg/m2至约150mg/m2，约55mg/m2至约100mg/m2，约55mg/m2至约85mg/m2，约60mg/m2至约100mg/m2，约60mg/m2至约85mg/m2，约65mg/m2至约85mg/m2，约70mg/m2至约85mg/m2，或前述任意两个点值之间的任意范围。
示例性地，所述顺铂的给药剂量为约1mg/m2，约5mg/m2，约15mg/m2，约20mg/m2，约25mg/m2，约30mg/m2，约35mg/m2，约40mg/m2，约45mg/m2，约50mg/m2，约51mg/m2，约52mg/m2，约53mg/m2，约55mg/m2，约57mg/m2，约58mg/m2，约60mg/m2，约61mg/m2，约62mg/m2，约63mg/m2，约64mg/m2，约65mg/m2，约66mg/m2，约67mg/m2，约68mg/m2，约69mg/m2，约70mg/m2，约71mg/m2，约72mg/m2，约73mg/m2，约74mg/m2，约75mg/m2，约76mg/m2，约77mg/m2，约78mg/m2，约79mg/m2，约80mg/m2，约81mg/m2，约82mg/m2，约83mg/m2，约84mg/m2，约85mg/m2，约86mg/m2，约87mg/m2，约88mg/m2，约89mg/m2，约90mg/m2，约95mg/m2，约100mg/m2，约105mg/m2，约110mg/m2，约115mg/m2，约120mg/m2，约130mg/m2，约140mg/m2，约150mg/m2，约160mg/m2，约170mg/m2，约180mg/m2，约190mg/m2，约200mg/m2，约220mg/m2，约250mg/m2，约280mg/m2，约300mg/m2；或前述任意两者之间的任意范围。
在一些实施方案中，所述顺铂的给药频率为每2周1次、每3周1次、每4周1次、每5周1次、或每6周1次。在一些具体的实施方案中，所述顺铂的给药频率为每3周1次。
在一些实施方案中，所述顺铂的给药剂量为约1mg/m2至约500mg/m2，给药频率为每2周1次、每3周1次、每4周1次、每5周1次、或每6周1次。在一些具体的实施方案中，所述顺铂的给药剂量为约1mg/m2至约500mg/m2，给药频率为每3周1次。
在一些实施方案中，所述顺铂的给药剂量为约1mg/m2至约200mg/m2，给药频率为每2周1次、每3周1次、每4周1次、每5周1次、或每6周1次。在一些具体的实施方案中，所述顺铂的给药剂量为约1mg/m2至约200mg/m2，给药频率为每3周1次。
在一些实施方案中，所述顺铂的给药剂量为约5mg/m2至约100mg/m2，给药频率为每2周1次、每3周1次、每4周1次、每5周1次、或每6周1次。在一些具体的实施方案中，所述顺铂的给药剂量为约5mg/m2至约100mg/m2，给药频率为每3周1次。
在一些实施方案中，所述顺铂的给药剂量为约50mg/m2至约100mg/m2，给药频率为每2周1次、每3周1次、每4周1次、每5周1次、或每6周1次。在一些具体的实施方案中，所述顺铂的给药剂量为约50mg/m2至约100mg/m2，给药频率为每3周1次。
在一些实施方案中，所述顺铂的给药剂量为约60mg/m2至约85mg/m2，给药频率为每2周1次、每3周1次、每4周1次、每5周1次、或每6周1次。在一些具体的实施方案中，所述顺铂的给药剂量为约60mg/m2至约85mg/m2，给药频率为每3周1次。
在一些实施方案中，所述顺铂的给药剂量为约70mg/m2，给药频率为每3周1次。
在一些实施方案中，所述顺铂的给药剂量为约71mg/m2，给药频率为每3周1次。
在一些实施方案中，所述顺铂的给药剂量为约72mg/m2，给药频率为每3周1次。
在一些实施方案中，所述顺铂的给药剂量为约73mg/m2，给药频率为每3周1次。
在一些实施方案中，所述顺铂的给药剂量为约74mg/m2，给药频率为每3周1次。
在一些实施方案中，所述顺铂的给药剂量为约75mg/m2，给药频率为每3周1次。
在一些实施方案中，所述顺铂的给药剂量为约76mg/m2，给药频率为每3周1次。
在一些实施方案中，所述顺铂的给药剂量为约77mg/m2，给药频率为每3周1次。
在一些实施方案中，所述顺铂的给药剂量为约78mg/m2，给药频率为每3周1次。
在一些实施方案中，所述顺铂的给药剂量为约79mg/m2，给药频率为每3周1次。
在一些实施方案中，所述顺铂的给药剂量为约80mg/m2，给药频率为每3周1次。
在一些实施方案中，所述顺铂的给药剂量为约81mg/m2，给药频率为每3周1次。
在一些实施方案中，所述顺铂的给药剂量为约82mg/m2，给药频率为每3周1次。
在一些实施方案中，所述顺铂的给药剂量为约83mg/m2，给药频率为每3周1次。
在一些实施方案中，所述顺铂的给药剂量为约84mg/m2，给药频率为每3周1次。
在一些实施方案中，所述顺铂的给药剂量为约85mg/m2，给药频率为每3周1次。
在一些实施方案中，顺铂的给药途径可以为经口给药、胃肠外给药、经皮给药，所述胃肠外给药包括但不限于静脉注射、皮下注射、肌肉注射。在一些具体的实施方案中，顺铂的给药途径为静脉注射。在一些具体的实施方案中，顺铂的给药途径为静脉滴注。
在一些实施方案中，所述铂类药物为卡铂，所述卡铂的给药剂量(按AUC计)为约0.1mg/mL/min至约50mg/mL/min，例如，约1mg/mL/min至20mg/mL/min，约1mg/mL/min至10mg/mL/min，约1mg/mL/min至8mg/mL/min，约1mg/mL/min至6mg/mL/min，约2mg/mL/min至10mg/mL/min，约2mg/mL/min至约8mg/mL/min，约2mg/mL/min至约6mg/mL/min，约3mg/mL/min至约8mg/mL/min，约3mg/mL/min至6mg/mL/min，约4mg/mL/min至6mg/mL/min。
在一些实施方案中，所述卡铂的给药剂量(按AUC计)为约0.1mg/mL/min、约0.5mg/mL/min、约0.6mg/mL/min、约0.7mg/mL/min、约0.8mg/mL/min、约0.9mg/mL/min、约1.0mg/mL/min、约1.1mg/mL/min、约1.2mg/mL/min、约1.3mg/mL/min、约1.4mg/mL/min、约1.5mg/mL/min、约1.6mg/mL/min、约1.7mg/mL/min、约1.8mg/mL/min、约1.9mg/mL/min、约2.0mg/mL/min、约2.1mg/mL/min、约2.2mg/mL/min、约2.3mg/mL/min、约2.4mg/mL/min、约2.5mg/mL/min、约2.6mg/mL/min、约2.7mg/mL/min、约2.8mg/mL/min、约2.9mg/mL/min、约3.0mg/mL/min、约3.1mg/mL/min、约3.2mg/mL/min、约3.3mg/mL/min、约3.4mg/mL/min、约3.5mg/mL/min、约3.6mg/mL/min、约3.7mg/mL/min、约3.8mg/mL/min、约3.9mg/mL/min、约4.0mg/mL/min、约4.1mg/mL/min、约4.2mg/mL/min、约4.3mg/mL/min、约4.4mg/mL/min、约4.5mg/mL/min、约4.6mg/mL/min、约4.7mg/mL/min、约4.8mg/mL/min、约4.9mg/mL/min、约5.0mg/mL/min、约5.1mg/mL/min、约5.2mg/mL/min、约5.3mg/mL/min、约5.4mg/mL/min、约5.5mg/mL/min、约5.6mg/mL/min、约5.7mg/mL/min、约5.8mg/mL/min、约5.9mg/mL/min、约6.0mg/mL/min、约6.1mg/mL/min、约6.2mg/mL/min、约6.3mg/mL/min、约6.4mg/mL/min、约6.5mg/mL/min、约6.6mg/mL/min、约6.7mg/mL/min、约6.8mg/mL/min、约6.9mg/mL/min、约7.0mg/mL/min、约7.1mg/mL/min、约7.2mg/mL/min、约7.3mg/mL/min、约7.4mg/mL/min、约7.5mg/mL/min、约7.6mg/mL/min、约7.7mg/mL/min、约7.8mg/mL/min、约7.9mg/mL/min、约8.0mg/mL/min、约8.1mg/mL/min、约8.2mg/mL/min、约8.3mg/mL/min、约8.4mg/mL/min、约8.5mg/mL/min、约8.6mg/mL/min、约8.7mg/mL/min、约8.8mg/mL/min、约8.9mg/mL/min、约9.0mg/mL/min、约9.2mg/mL/min、约9.5mg/mL/min、约9.8mg/mL/min、约10.0mg/mL/min、约15mg/mL/min、约20mg/mL/min、约25mg/mL/min、约30mg/mL/min、约35mg/mL/min、约40mg/mL/min、约45mg/mL/min、约50mg/mL/min，或前述任意两者之间的任意范围。
在一些实施方案中，所述卡铂的给药频率为每2周1次、每3周1次、每4周1次、每5周1次、或每6周1次。在一些具体的实施方案中，所述卡铂的给药频率为每3周1次。
在一些实施方案中，所述卡铂的给药剂量(按AUC计)为约0.1mg/mL/min至约50mg/mL/min，给药频率为每2周1次、每3周1次、每4周1次、每5周1次、或每6周1次。在一些实施方案中，所述卡铂的给药剂量(按AUC计)为约0.1mg/mL/min至约50mg/mL/min，给药频率为每3周1次。
在一些实施方案中，所述卡铂的给药剂量(按AUC计)为约1mg/mL/min至约20mg/mL/min，给药频率为每2周1次、每3周1次、每4周1次、每5周1次、或每6周1次。在一些实施方案中，所述卡铂的给药剂量(按AUC计)为约1mg/mL/min至约20mg/mL/min，给药频率为每3周1次。
在一些实施方案中，所述卡铂的给药剂量(按AUC计)为约1mg/mL/min至约10mg/mL/min，给药频率为每2周1次、每3周1次、每4周1次、每5周1次、或每6周1次。在一些实施方案中，所述卡铂的给药剂量(按AUC计)为约1mg/mL/min至约10mg/mL/min，给药频率为每3周1次。
在一些实施方案中，所述卡铂的给药剂量(按AUC计)为约1mg/mL/min至约8mg/mL/min，给药频率为每2周1次、每3周1次、每4周1次、每5周1次、或每6周1次。在一些实施方案中，所述卡铂的给药剂量(按AUC计)为约1mg/mL/min至约8mg/mL/min，给药频率为每3周1次。
在一些实施方案中，所述卡铂的给药剂量(按AUC计)为约2mg/mL/min至约10mg/mL/min，给药频率为每2周1次、每3周1次、每4周1次、每5周1次、或每6周1次。在一些实施方案中，所述卡铂的给药剂量(按AUC计)为约2mg/mL/min至约10mg/mL/min，给药频率为每3周1次。
在一些实施方案中，所述卡铂的给药剂量(按AUC计)为约2mg/mL/min至约8mg/mL/min，给药频率为每2周1次、每3周1次、每4周1次、每5周1次、或每6周1次。在一些实施方案中，所述卡铂的给药剂量(按AUC计)为约2mg/mL/min至约8mg/mL/min，给药频率为每3周1次。
在一些具体的实施方案中，所述卡铂的给药剂量(按AUC计)为约3mg/mL/min至约8mg/mL/min，给药频率为每2周1次、每3周1次、每4周1次、每5周1次、或每6周1次。在一些具体的实施方案中，所述卡铂的给药剂量(按AUC计)为约3mg/mL/min至约8mg/mL/min，给药频率为每3周1次。
在一些具体的实施方案中，所述卡铂的给药剂量(按AUC计)为约1mg/mL/min至约6mg/mL/min，给药频率为每3周1次。
在一些实施方案中，所述卡铂的给药剂量(按AUC计)为约2mg/mL/min至约6mg/mL/min，给药频率为每3周1次。
在一些实施方案中，所述卡铂的给药剂量(按AUC计)为约3mg/mL/min至约6mg/mL/min，给药频率为每3周1次。
在一些实施方案中，所述卡铂的给药剂量(按AUC计)为约4mg/mL/min至约6mg/mL/min，给药频率为每3周1次。
在一些实施方案中，所述卡铂的给药剂量(按AUC计)为约5mg/mL/min至约6mg/mL/min，给药频率为每3周1次。
在一些实施方案中，所述卡铂的给药剂量(按AUC计)为约2mg/mL/min，给药频率为每3周1次。
在一些实施方案中，所述卡铂的给药剂量(按AUC计)为约3mg/mL/min，给药频率为每3周1次。
在一些实施方案中，所述卡铂的给药剂量(按AUC计)为约4mg/mL/min，给药频率为每3周1次。
在一些实施方案中，所述卡铂的给药剂量(按AUC计)为约5mg/mL/min，给药频率为每3周1次。
在一些实施方案中，所述卡铂的给药剂量(按AUC计)为约6mg/mL/min，给药频率为每3周1次。
在一些实施方案中，所述卡铂的给药剂量(按AUC计)为约7mg/mL/min，给药频率为每3周1次。
在一些实施方案中，所述卡铂的给药剂量(按AUC计)为约8mg/mL/min，给药频率为每3周1次。
在一些实施方案中，卡铂的给药途径可以为经口给药、胃肠外给药、经皮给药，所述胃肠外给药包括但不限于静脉注射、皮下注射、肌肉注射。在一些具体的实施方案中，卡铂的给药途径为静脉注射。在一些具体的实施方案中，卡铂的给药途径为静脉滴注。
给药方案
在一些实施方案中，前述任意的用途、方法或组合物，其选自如下任一项所示的药物给药：
(1)抗Nectin-4抗体药物偶联物单药给药，
(2)抗Nectin-4抗体药物偶联物联合抗PD-L1抗体给药，
(3)抗Nectin-4抗体药物偶联物联合抗CTLA-4抗体给药，
(4)抗Nectin-4抗体药物偶联物联合抗PD-L1抗体和抗CTLA-4抗体给药，
(5)抗Nectin-4抗体药物偶联物联合抗PD-L1抗体和抗VEGF抗体给药，
(6)抗Nectin-4抗体药物偶联物联合抗PD-L1抗体给药、抗CTLA-4抗体和抗VEGF抗体给药
(7)抗Nectin-4抗体药物偶联物联合抗PD-L1抗体给药和卡铂给药。
(8)抗Nectin-4抗体药物偶联物联合抗PD-L1抗体给药和顺铂给药。
在一些实施方案中，抗Nectin-4抗体药物偶联物单药的给药方案为：
a)抗Nectin-4抗体药物偶联物的给药剂量为0.1-50mg/kg，给药频率为每2周至少1次，每3周至少1次，每4周至少1次，每6周至少1次，或每8周至少1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为0.1-20mg/kg，给药频率为每2周至少1次，每3周至少1次，每4周至少1次，每6周至少1次，或每8周至少1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为1-15mg/kg，给药频率为每2周1次，每3周1次，每3周2次，每4周1次，每6周1次，或每8周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为1-10mg/kg，给药频率为每2周1次，每3周1次，每3周2次，每4周1次，每6周1次，或每8周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为约1mg/kg，约2mg/kg，约3mg/kg，约4mg/kg，约5mg/kg，约6mg/kg，约7mg/kg，约8mg/kg或约10mg/kg，给药频率为每2周1次，每3周1次，每3周2次，每4周1次，每6周1次，或每8周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为约1mg/kg，约2mg/kg，约3mg/kg，约4mg/kg，约5mg/kg，约6mg/kg，约7mg/kg，约8mg/kg或约10mg/kg，给药频率为每3周1次或每3周2次；
a)抗Nectin-4抗体药物偶联物的给药剂量为约约5mg/kg，约6mg/kg，约7mg/kg，约8mg/kg，约9mg/kg或约10mg/kg，给药频率为每3周1次；或
a)抗Nectin-4抗体药物偶联物的给药剂量为约1mg/kg，约2mg/kg，约3mg/kg，约4mg/kg，给药频率为每3周2次。
在一些实施方案中，抗Nectin-4抗体药物偶联物联合抗PD-L1抗体的给药方案为：
a)抗Nectin-4抗体药物偶联物的给药剂量为0.1-50mg/kg，给药频率为每2周至少1次，每3周至少1次，每4周至少1次，每6周至少1次，或每8周至少1次；b1)抗PD-L1抗体的给药剂量为5-5000mg，给药频率为每2周1次，每3周1次，每4周1次，每5周1次，或每6周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为0.1-20mg/kg，给药频率为每2周1次，每3周1次，每3周2次，每4周1次，每6周1次，或每8周1次；b1)抗PD-L1抗体的给药剂量为5-5000mg，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为1-10mg/kg，给药频率为每3周2次或每3周1次；b1)抗PD-L1抗体的给药剂量为5-5000mg，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为约1mg/kg，约2mg/kg，约3mg/kg，约4mg/kg，约5mg/kg，约6mg/kg，约7mg/kg，约8mg/kg或约10mg/kg；给药频率为每3周2次或每3周1次；b1)抗PD-L1抗体的给药剂量为5-5000mg，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为约5mg/kg，约6mg/kg，约7mg/kg，约8mg/kg，约9mg/kg或约10mg/kg；给药频率为每3周1次；b1)抗PD-L1抗体的给药剂量为5-5000mg，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为1mg/kg，约2mg/kg，约3mg/kg，或约4mg/kg；给药频率为每3周2次；b1)抗PD-L1抗体的给药剂量为5-5000mg，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为1-10mg/kg，给药频率为每3周2次或每3周1次；b1)抗PD-L1抗体的给药剂量为约100mg，约500mg，约800mg，约900mg，约1000mg，约1100mg，约1200mg，约1300mg，约1400mg，约1500mg，约1600mg，约1800mg，约2000mg，约2200mg，约2500mg，约3000mg，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为约1mg/kg，约2mg/kg，约3mg/kg，约4mg/kg，约5mg/kg，约6mg/kg，约7mg/kg，约8mg/kg，约9mg/kg或约10mg/kg，给药频率为每3周2次或每3周1次；b1)抗PD-L1抗体的给药剂量为约100mg，约500mg，约800mg，约900mg，约1000mg，约1100mg，约1200mg，约1300mg，约1400mg，约1500mg，约1600mg，约1800mg，约2000mg，约2200mg，约2500mg，约3000mg，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为约3mg/kg，或约4mg/kg，给药频率为每3周2次；b1)抗PD-L1抗体的给药剂量为约100mg，约500mg，约800mg，约900mg，约1000mg，约1100mg，约1200mg，约1300mg，约1400mg，约1500mg，约1600mg，约1800mg，约2000mg，约2200mg，约2500mg，约3000mg，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为约3mg/kg，或约4mg/kg，给药频率为每3周2次；b1)抗PD-L1抗体的给药剂量为约1200mg，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为约5mg/kg，约6mg/kg，约7mg/kg，约8mg/kg，约9mg/kg或约10mg/kg，给药频率为每3周1次；b1)抗PD-L1抗体的给药剂量为约100mg，约500mg，约800mg，约900mg，约1000mg，约1100mg，约1200mg，约1300mg，约1400mg，约1500mg，约1600mg，约1800mg，约2000mg，约2200mg，约2500mg，约3000mg，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为约5mg/kg，约6mg/kg，约7mg/kg，约8mg/kg，约9mg/kg或约10mg/kg，给药频率为每3周1次；b1)抗PD-L1抗体的给药剂量为约1200mg，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为约4mg/kg，给药频率为每3周2次，每周期D1、D8给药；b1)抗PD-L1抗体的给药剂量为约1200mg，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为约6mg/kg，给药频率为每3周1次；b1)抗PD-L1抗体的给药剂量为约1200mg，给药频率为每3周1次；或，
a)抗Nectin-4抗体药物偶联物的给药剂量为约8mg/kg，给药频率为每3周1次；b1)抗PD-L1抗体的给药剂量为约1200mg，给药频率为每3周1次。
在一些实施方案中，抗Nectin-4抗体药物偶联物联合抗CTLA-4抗体的给药方案为：
a)抗Nectin-4抗体药物偶联物的给药剂量为0.1-50mg/kg，给药频率为每2周至少1次，每3周至少1次，每4周至少1次，每6周至少1次，或每8周至少1次；b2)抗CTLA-4抗体的给药剂量为1-1000mg，给药频率为每2周1次、每3周1次、每4周1次、每6周1次、每8周1次、每10周1次、每12周1次、每14周1次、每16周1次或单次给药；
a)抗Nectin-4抗体药物偶联物的给药剂量为1-20mg/kg，给药频率为每2周1次，每3周1次，每3周2次，每4周1次，每6周1次，或每8周1次；b2)抗CTLA-4抗体的给药剂量为1-1000mg，给药频率为每6周1次或单次给药；
a)抗Nectin-4抗体药物偶联物的给药剂量为1-10mg/kg，给药频率为每3周2次或每3周1次；b2)抗CTLA-4抗体的给药剂量为1-1000mg，给药频率为每6周1次或单次给药；
a)抗Nectin-4抗体药物偶联物的给药剂量为约1mg/kg，约2mg/kg，约3mg/kg，约4mg/kg，约5mg/kg，约6mg/kg，约7mg/kg，约8mg/kg或约10mg/kg；给药频率为每3周2次或每3周1次；b2)抗CTLA-4抗体的给药剂量为1-1000mg，给药频率为每6周1次或单次给药；
a)抗Nectin-4抗体药物偶联物的给药剂量为约5mg/kg，约6mg/kg，约7mg/kg，约8mg/kg，约9mg/kg或约10mg/kg；给药频率为每3周1次；b2)抗CTLA-4抗体的给药剂量为1-1000mg，给药频率为每6周1次或单次给药；
a)抗Nectin-4抗体药物偶联物的给药剂量为1mg/kg，约2mg/kg，约3mg/kg，或约4mg/kg；给药频率为每3周2次；b2)抗CTLA-4抗体的给药剂量为1-1000mg，给药频率为每6周1次或单次给药；
a)抗Nectin-4抗体药物偶联物的给药剂量为1-10mg/kg，给药频率为每3周2次或每3周1次；b2)抗CTLA-4抗体的给药剂量为约10mg，约20mg，约30mg，约40mg，约50mg，约60mg，约70mg，约80mg，约90mg，约100mg，约150mg，约200mg，约210mg，约220mg，约230mg，约240mg，约250mg，约260mg，约270mg，约280mg，约290mg，约300mg，约350mg，约500mg或约700mg，给药频率为每6周1次或单次给药；
a)抗Nectin-4抗体药物偶联物的给药剂量为约1mg/kg，约2mg/kg，约3mg/kg，约4mg/kg，约5mg/kg，约6mg/kg，约7mg/kg，约8mg/kg，约9mg/kg或约10mg/kg，给药频率为每3周2次或每3周1次；b2)抗CTLA-4抗体的给药剂量为约10mg，约20mg，约30mg，约40mg，约50mg，约60mg，约70mg，约80mg，约90mg，约100mg，约150mg，约200mg，约210mg，约220mg，约230mg，约240mg，约250mg，约260mg，约270mg，约280mg，约290mg，约300mg，约350mg，约500mg或约700mg，给药频率为每6周1次或单次给药；
a)抗Nectin-4抗体药物偶联物的给药剂量为约3mg/kg，或约4mg/kg，给药频率为每3周2次；b2)抗CTLA-4抗体的给药剂量为约10mg，约20mg，约30mg，约40mg，约50mg，约60mg，约70mg，约80mg，约90mg，约100mg，约150mg，约200mg，约210mg，约220mg，约230mg，约240mg，约250mg，约260mg，约270mg，约280mg，约290mg，约300mg，约350mg，约500mg或约700mg，给药频率为每6周1次或单次给药；
a)抗Nectin-4抗体药物偶联物的给药剂量为约5mg/kg，约6mg/kg，约7mg/kg，约8mg/kg，约9mg/kg或约10mg/kg，给药频率为每3周1次；b2)抗CTLA-4抗体的给药剂量为约10mg，约20mg，约30mg，约40mg，约50mg，约60mg，约70mg，约80mg，约90mg，约100mg，约150mg，约200mg，约210mg，约220mg，约230mg，约240mg，约250mg，约260mg，约270mg，约280mg，约290mg，约300mg，约350mg，约500mg或约700mg，给药频率为每6周1次或单次给药；
a)抗Nectin-4抗体药物偶联物的给药剂量为约4mg/kg，给药频率为每3周2次，每周期D1、D8给药；b2)抗CTLA-4抗体在第1周单次给药，给药剂量为约280mg或210mg，第2-12周不给药，从第13周开始，给药剂量为约70mg，给药频次为每6周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为约6mg/kg，给药频率为每3周1次；b2)抗CTLA-4抗体在第1周单次给药，给药剂量为约280mg或210mg，第2-12周不给药，从第13周开始，给药剂量为约70mg，给药频次为每6周1次；或，
a)抗Nectin-4抗体药物偶联物的给药剂量为约8mg/kg，给药频率为每3周1次；b2)抗CTLA-4抗体在第1周单次给药，给药剂量为约280mg或210mg，第2-12周不给药，从第13周开始，给药剂量为约70mg，给药频次为每6周1次。
在一些实施方案中，抗Nectin-4抗体药物偶联物联合抗PD-L1抗体和抗CTLA-4抗体的给药方案为：
a)抗Nectin-4抗体药物偶联物的给药剂量为0.1-50mg/kg，给药频率为每2周至少1次，每3周至少1次，每4周至少1次，每6周至少1次，或每8周至少1次；b1)抗PD-L1抗体的给药剂量为5-5000mg，给药频率为每2周1次，每3周1次，每4周1次，每5周1次，或每6周1次；b2)抗CTLA-4抗体的给药剂量为1-1000mg，给药频率为每2周1次、每3周1次、每4周1次、每6周1次、每8周1次、每10周1次、每12周1次、每14周1次、每16周1次或单次给药；
a)抗Nectin-4抗体药物偶联物的给药剂量为1-20mg/kg，给药频率为每2周1次，每3周1次，每3周2次，每4周1次，每6周1次，或每8周1次；b1)抗PD-L1抗体的给药剂量为5-5000mg，给药频率为每3周1次；b2)抗CTLA-4抗体的给药剂量为1-1000mg，给药频率为每6周1次或单次给药；
a)抗Nectin-4抗体药物偶联物的给药剂量为1-10mg/kg，给药频率为每3周2次或每3周1次；b1)抗PD-L1抗体的给药剂量为5-5000mg，给药频率为每3周1次；b2)抗CTLA-4抗体的给药剂量为1-1000mg，给药频率为每6周1次或单次给药；
a)抗Nectin-4抗体药物偶联物的给药剂量为约1mg/kg，约2mg/kg，约3mg/kg，约4mg/kg，约5mg/kg，约6mg/kg，约7mg/kg，约8mg/kg或约10mg/kg；给药频率为每3周2次或每3周1次；b1)抗PD-L1抗体的给药剂量为5-5000mg，给药频率为每3周1次；b2)抗CTLA-4抗体的给药剂量为1-1000mg，给药频率为每6周1次或单次给药；
a)抗Nectin-4抗体药物偶联物的给药剂量为约5mg/kg，约6mg/kg，约7mg/kg，约8mg/kg，约9mg/kg或约10mg/kg；给药频率为每3周1次；b1)抗PD-L1抗体的给药剂量为5-5000mg，给药频率为每3周1次；b2)抗CTLA-4抗体的给药剂量为1-1000mg，给药频率为每6周1次或单次给药；
a)抗Nectin-4抗体药物偶联物的给药剂量为1mg/kg，约2mg/kg，约3mg/kg，或约4mg/kg；给药频率为每3周2次；b1)抗PD-L1抗体的给药剂量为5-5000mg，给药频率为每3周1次；b2)抗CTLA-4抗体的给药剂量为1-1000mg，给药频率为每6周1次或单次给药；
a)抗Nectin-4抗体药物偶联物的给药剂量为1-10mg/kg，给药频率为每3周2次或每3周1次；b1)抗PD-L1抗体的给药剂量为约100mg，约500mg，约800mg，约900mg，约1000mg，约1100mg，约1200mg，约1300mg，约1400mg，约1500mg，约1600mg，约1800mg，约2000mg，约2200mg，约2500mg，约3000mg，给药频率为每3周1次；b2)抗CTLA-4抗体的给药剂量为约10mg，约20mg，约30mg，约40mg，约50mg，约60mg，约70mg，约80mg，约90mg，约100mg，约150mg，约200mg，约210mg，约220mg，约230mg，约240mg，约250mg，约260mg，约270mg，约280mg，约290mg，约300mg，约350mg，约500mg或约700mg，给药频率为每6周1次或单次给药；
a)抗Nectin-4抗体药物偶联物的给药剂量为约1mg/kg，约2mg/kg，约3mg/kg，约4mg/kg，约5mg/kg，约6mg/kg，约7mg/kg，约8mg/kg，约9mg/kg或约10mg/kg，给药频率为每3周2次或每3周1次；b1)抗PD-L1抗体的给药剂量为约100mg，约500mg，约800mg，约900mg，约1000mg，约1100mg，约1200mg，约1300mg，约1400mg，约1500mg，约1600mg，约1800mg，约2000mg，约2200mg，约2500mg，约3000mg，给药频率为每3周1次；b2)抗CTLA-4抗体的给药剂量为约10mg，约20mg，约30mg，约40mg，约50mg，约60mg，约70mg，约80mg，约90mg，约100mg，约150mg，约200mg，约210mg，约220mg，约230mg，约240mg，约250mg，约260mg，约270mg，约280mg，约290mg，约300mg，约350mg，约500mg或约700mg，给药频率为每6周1次或单次给药；
a)抗Nectin-4抗体药物偶联物的给药剂量为约3mg/kg，或约4mg/kg，给药频率为每3周2次；b1)抗PD-L1抗体的给药剂量为约100mg，约500mg，约800mg，约900mg，约1000mg，约1100mg，约1200mg，约1300mg，约1400mg，约1500mg，约1600mg，约1800mg，约2000mg，约2200mg，约2500mg，约3000mg，给药频率为每3周1次；b2)抗CTLA-4抗体的给药剂量为约10mg，约20mg，约30mg，约40mg，约50mg，约60mg，约70mg，约80mg，约90mg，约100mg，约150mg，约200mg，约210mg，约220mg，约230mg，约240mg，约250mg，约260mg，约270mg，约280mg，约290mg，约300mg，约350mg，约500mg或约700mg，给药频率为每6周1次或单次给药；
a)抗Nectin-4抗体药物偶联物的给药剂量为约5mg/kg，约6mg/kg，约7mg/kg，约8mg/kg，约9mg/kg或约10mg/kg，给药频率为每3周1次；b1)抗PD-L1抗体的给药剂量为约100mg，约500mg，约800mg，约900mg，约1000mg，约1100mg，约1200mg，约1300mg，约1400mg，约1500mg，约1600mg，约1800mg，约2000mg，约2200mg，约2500mg，约3000mg，给药频率为每3周1次；b2)抗CTLA-4抗体的给药剂量为约10mg，约20mg，约30mg，约40mg，约50mg，约60mg，约70mg，约80mg，约90mg，约100mg，约150mg，约200mg，约210mg，约220mg，约230mg，约240mg，约250mg，约260mg，约270mg，约280mg，约290mg，约300mg，约350mg，约500mg或约700mg，给药频率为每6周1次或单次给药；
a)抗Nectin-4抗体药物偶联物的给药剂量为约4mg/kg，给药频率为每3周2次，每周期D1、D8给药；b1)抗PD-L1抗体的给药剂量为约1200mg，给药频率为每3周1次；b2)抗CTLA-4抗体在第1周单次给药，给药剂量为约280mg或210mg，第2-12周不给药，从第13周开始，给药剂量为约70mg，给药频次为每6周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为约6mg/kg，给药频率为每3周1次；b1)抗PD-L1抗体的给药剂量为约1200mg，给药频率为每3周1次；b2)抗CTLA-4抗体在第1周单次给药，给药剂量为约280mg或210mg，第2-12周不给药，从第13周开始，给药剂量为约70mg，给药频次为每6周1次；或，
a)抗Nectin-4抗体药物偶联物的给药剂量为约8mg/kg，给药频率为每3周1次；b1)抗PD-L1抗体的给药剂量为约1200mg，给药频率为每3周1次；b2)抗CTLA-4抗体在第1周单次给药，给药剂量为约280mg或210mg，第2-12周不给药，从第13周开始，给药剂量为约70mg，给药频次为每6周1次。
在一些实施方案中，抗Nectin-4抗体药物偶联物联合抗PD-L1抗体和抗VEGF抗体的给药方案为：
a)抗Nectin-4抗体药物偶联物的给药剂量为0.1-50mg/kg，给药频率为每2周至少1次，每3周至少1次，每4周至少1次，每6周至少1次，或每8周至少1次；b1)抗PD-L1抗体的给药剂量为5-5000mg，给药频率为每2周1次，每3周1次，每4周1次，每5周1次，或每6周1次；b2)抗VEGF抗体的给药剂量为1mg/kg-30mg/kg，给药频率为每1周1次，每2周1次，每3周1次，每4周1次，每6周1次，每8周1次，每10周1次，或每12周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为0.1-20mg/kg，给药频率为每2周1次，每3周1次，每3周2次，每4周1次，每6周1次，或每8周1次；b1)抗PD-L1抗体的给药剂量为5-5000mg，给药频率为每3周1次；b2)抗VEGF抗体的给药剂量为1mg/kg-30mg/kg，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为1-10mg/kg，给药频率为每3周2次或每3周1次；b1)抗PD-L1抗体的给药剂量为5-5000mg，给药频率为每3周1次；b2)抗VEGF抗体的给药剂量为1mg/kg-30mg/kg，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为约1mg/kg，约2mg/kg，约3mg/kg，约4mg/kg，约5mg/kg，约6mg/kg，约7mg/kg，约8mg/kg或约10mg/kg；给药频率为每3周2次或每3周1次；b1)抗PD-L1抗体的给药剂量为5-5000mg，给药频率为每3周1次；b2)抗VEGF抗体的给药剂量为1mg/kg-30mg/kg，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为约5mg/kg，约6mg/kg，约7mg/kg，约8mg/kg，约9mg/kg或约10mg/kg；给药频率为每3周1次；b1)抗PD-L1抗体的给药剂量为5-5000mg，给药频率为每3周1次；b2)抗VEGF抗体的给药剂量为1mg/kg-30mg/kg，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为1mg/kg，约2mg/kg，约3mg/kg，或约4mg/kg；给药频率为每3周2次；b1)抗PD-L1抗体的给药剂量为5-5000mg，给药频率为每3周1次；b2)抗VEGF抗体的给药剂量为1mg/kg-30mg/kg，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为1-10mg/kg，给药频率为每3周2次或每3周1次；b1)抗PD-L1抗体的给药剂量为约100mg，约500mg，约800mg，约900mg，约1000mg，约1100mg，约1200mg，约1300mg，约1400mg，约1500mg，约1600mg，约1800mg，约2000mg，约2200mg，约2500mg，约3000mg，给药频率为每3周1次；b2)抗VEGF抗体的给药剂量为约2.0mg/kg，约3.0mg/kg，约4.0mg/kg，约5mg/kg，约6.0mg/kg，约7.5mg/kg，约8.0mg/kg，约9.0mg/kg，约10mg/kg，约11mg/kg，约12mg/kg，约13mg/kg，约14mg/kg，约15mg/kg，约16mg/kg，约17mg/kg，约18mg/kg，约19mg/kg，约20mg/kg，约21.0mg/kg，约22.0mg/kg，约23.0mg/kg，约24.0mg/kg或约25.0mg/kg，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为约1mg/kg，约2mg/kg，约3mg/kg，约4mg/kg，约5mg/kg，约6mg/kg，约7mg/kg，约8mg/kg，约9mg/kg或约10mg/kg，给药频率为每3周2次或每3周1次；b1)抗PD-L1抗体的给药剂量为约100mg，约500mg，约800mg，约900mg，约1000mg，约1100mg，约1200mg，约1300mg，约1400mg，约1500mg，约1600mg，约1800mg，约2000mg，约2200mg，约2500mg，约3000mg，给药频率为每3周1次；b2)抗VEGF抗体的给药剂量为约2.0mg/kg，约3.0mg/kg，约4.0mg/kg，约5mg/kg，约6.0mg/kg，约7.5mg/kg，约8.0mg/kg，约9.0mg/kg，约10mg/kg，约11mg/kg，约12mg/kg，约13mg/kg，约14mg/kg，约15mg/kg，约16mg/kg，约17mg/kg，约18mg/kg，约19mg/kg，约20mg/kg，约21.0mg/kg，约22.0mg/kg，约23.0mg/kg，约24.0mg/kg或约25.0mg/kg，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为约3mg/kg，或约4mg/kg，给药频率为每3周2次；b1)抗PD-L1抗体的给药剂量为约100mg，约500mg，约800mg，约900mg，约1000mg，约1100mg，约1200mg，约1300mg，约1400mg，约1500mg，约1600mg，约1800mg，约2000mg，约2200mg，约2500mg，约3000mg，给药频率为每3周1次；b2)抗VEGF抗体的给药剂量为约2.0mg/kg，约3.0mg/kg，约4.0mg/kg，约5mg/kg，约6.0mg/kg，约7.5mg/kg，约8.0mg/kg，约9.0mg/kg，约10mg/kg，约11mg/kg，约12mg/kg，约13mg/kg，约14mg/kg，约15mg/kg，约16mg/kg，约17mg/kg，约18mg/kg，约19mg/kg，约20mg/kg，约21.0mg/kg，约22.0mg/kg，约23.0mg/kg，约24.0mg/kg或约25.0mg/kg，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为约3mg/kg，或约4mg/kg，给药频率为每3周2次；b1)抗PD-L1抗体的给药剂量为约1200mg，给药频率为每3周1次；b2)抗VEGF抗体的给药剂量为约7.5mg/kg或约15mg/kg，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为约5mg/kg，约6mg/kg，约7mg/kg，约8mg/kg，约9mg/kg或约10mg/kg，给药频率为每3周1次；b1)抗PD-L1抗体的给药剂量为约100mg，约500mg，约800mg，约900mg，约1000mg，约1100mg，约1200mg，约1300mg，约1400mg，约1500mg，约1600mg，约1800mg，约2000mg，约2200mg，约2500mg，约3000mg，给药频率为每3周1次；b2)抗VEGF抗体的给药剂量为约2.0mg/kg，约3.0mg/kg，约4.0mg/kg，约5mg/kg，约6.0mg/kg，约7.5mg/kg，约8.0mg/kg，约9.0mg/kg，约10mg/kg，约11mg/kg，约12mg/kg，约13mg/kg，约14mg/kg，约15mg/kg，约16mg/kg，约17mg/kg，约18mg/kg，约19mg/kg，约20mg/kg，约21.0mg/kg，约22.0mg/kg，约23.0mg/kg，约24.0mg/kg或约25.0mg/kg，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为约5mg/kg，约6mg/kg，约7mg/kg，约8mg/kg，约9mg/kg或约10mg/kg，给药频率为每3周1次；b1)抗PD-L1抗体的给药剂量为约1200mg，给药频率为每3周1次；b2)抗VEGF抗体的给药剂量为约7.5mg/kg，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为约5mg/kg，约6mg/kg，约7mg/kg，约8mg/kg，约9mg/kg或约10mg/kg，给药频率为每3周1次；b1)抗PD-L1抗体的给药剂量为约1200mg，给药频率为每3周1次；b2)抗VEGF抗体的给药剂量为约15mg/kg，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为约4mg/kg，给药频率为每3周2次，每周期D1、D8给药；b1)抗PD-L1抗体的给药剂量为约1200mg，给药频率为每3周1次；b2)抗VEGF抗体的给药剂量为约7.5mg/kg，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为约4mg/kg，给药频率为每3周2次，每周期D1、D8给药；b1)抗PD-L1抗体的给药剂量为约1200mg，给药频率为每3周1次；b2)抗VEGF抗体的给药剂量为约15mg/kg，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为约6mg/kg，给药频率为每3周1次；b1)抗PD-L1抗体的给药剂量为约1200mg，给药频率为每3周1次；b2)抗VEGF抗体的给药剂量为约7.5mg/kg，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为约6mg/kg，给药频率为每3周1次；b1)抗PD-L1抗体的给药剂量为约1200mg，给药频率为每3周1次；b2)抗VEGF抗体的给药剂量为约15mg/kg，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为约8mg/kg，给药频率为每3周1次；b1)抗PD-L1抗体的给药剂量为约1200mg，给药频率为每3周1次；b2)抗VEGF抗体的给药剂量为约7.5mg/kg，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为约8mg/kg，给药频率为每3周1次；b1)抗PD-L1抗体的给药剂量为约1200mg，给药频率为每3周1次；b2)抗VEGF抗体的给药剂量为约15mg/kg，给药频率为每3周1次。
在一些实施方案中，抗Nectin-4抗体药物偶联物联合抗PD-L1抗体、抗CTLA-4抗体和抗VEGF抗体的给药方案为：
a)抗Nectin-4抗体药物偶联物的给药剂量为0.1-50mg/kg，给药频率为每2周至少1次，每3周至少1次，每4周至少1次，每6周至少1次，或每8周至少1次；b1)抗PD-L1抗体的给药剂量为5-5000mg，给药频率为每2周1次，每3周1次，每4周1次，每5周1次，或每6周1次；b2)抗CTLA-4抗体的给药剂量为1-1000mg，给药频率为每2周1次、每3周1次、每4周1次、每6周1次、每8周1次、每10周1次、每12周1次、每14周1次、每16周1次或单次给药；b3)抗VEGF抗体的给药剂量为1mg/kg-30mg/kg，给药频率为每1周1次，每2周1次，每3周1次，每4周1次，每6周1次，每8周1次，每10周1次，或每12周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为1-20mg/kg，给药频率为每2周1次，每3周1次，每3周2次，每4周1次，每6周1次，或每8周1次；b1)抗PD-L1抗体的给药剂量为5-5000mg，给药频率为每3周1次；b2)抗CTLA-4抗体的给药剂量为1-1000mg，给药频率为每6周1次或单次给药；b3)抗VEGF抗体的给药剂量为1mg/kg-30mg/kg，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为1-10mg/kg，给药频率为每3周2次或每3周1次；b1)抗PD-L1抗体的给药剂量为5-5000mg，给药频率为每3周1次；b2)抗CTLA-4抗体的给药剂量为1-1000mg，给药频率为每6周1次或单次给药；b3)抗VEGF抗体的给药剂量为1mg/kg-30mg/kg，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为约1mg/kg，约2mg/kg，约3mg/kg，约4mg/kg，约5mg/kg，约6mg/kg，约7mg/kg，约8mg/kg或约10mg/kg；给药频率为每3周2次或每3周1次；b1)抗PD-L1抗体的给药剂量为5-5000mg，给药频率为每3周1次；b2)抗CTLA-4抗体的给药剂量为1-1000mg，给药频率为每6周1次或单次给药；b3)抗VEGF抗体的给药剂量为1mg/kg-30mg/kg，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为约5mg/kg，约6mg/kg，约7mg/kg，约8mg/kg，约9mg/kg或约10mg/kg；给药频率为每3周1次；b1)抗PD-L1抗体的给药剂量为5-5000mg，给药频率为每3周1次；b2)抗CTLA-4抗体的给药剂量为1-1000mg，给药频率为每6周1次或单次给药；b3)抗VEGF抗体的给药剂量为1mg/kg-30mg/kg，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为1mg/kg，约2mg/kg，约3mg/kg，或约4mg/kg；给药频率为每3周2次；b1)抗PD-L1抗体的给药剂量为5-5000mg，给药频率为每3周1次；b2)抗CTLA-4抗体的给药剂量为1-1000mg，给药频率为每6周1次或单次给药；b3)抗VEGF抗体的给药剂量为1mg/kg-30mg/kg，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为1-10mg/kg，给药频率为每3周2次或每3周1次；b1)抗PD-L1抗体的给药剂量为约100mg，约500mg，约800mg，约900mg，约1000mg，约1100mg，约1200mg，约1300mg，约1400mg，约1500mg，约1600mg，约1800mg，约2000mg，约2200mg，约2500mg，约3000mg，给药频率为每3周1次；b2)抗CTLA-4抗体的给药剂量为约10mg，约20mg，约30mg，约40mg，约50mg，约60mg，约70mg，约80mg，约90mg，约100mg，约150mg，约200mg，约210mg，约220mg，约230mg，约240mg，约250mg，约260mg，约270mg，约280mg，约290mg，约300mg，约350mg，约500mg或约700mg，给药频率为每6周1次或单次给药；b3)抗VEGF抗体的给药剂量为1mg/kg-30mg/kg，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为约1mg/kg，约2mg/kg，约3mg/kg，约4mg/kg，约5mg/kg，约6mg/kg，约7mg/kg，约8mg/kg，约9mg/kg或约10mg/kg，给药频率为每3周2次或每3周1次；b1)抗PD-L1抗体的给药剂量为约100mg，约500mg，约800mg，约900mg，约1000mg，约1100mg，约1200mg，约1300mg，约1400mg，约1500mg，约1600mg，约1800mg，约2000mg，约2200mg，约2500mg，约3000mg，给药频率为每3周1次；b2)抗CTLA-4抗体的给药剂量为约10mg，约20mg，约30mg，约40mg，约50mg，约60mg，约70mg，约80mg，约90mg，约100mg，约150mg，约200mg，约210mg，约220mg，约230mg，约240mg，约250mg，约260mg，约270mg，约280mg，约290mg，约300mg，约350mg，约500mg或约700mg，给药频率为每6周1次或单次给药；b3)抗VEGF抗体的给药剂量为约2.0mg/kg，约3.0mg/kg，约4.0mg/kg，约5mg/kg，约6.0mg/kg，约7.5mg/kg，约8.0mg/kg，约9.0mg/kg，约10mg/kg，约11mg/kg，约12mg/kg，约13mg/kg，约14mg/kg，约15mg/kg，约16mg/kg，约17mg/kg，约18mg/kg，约19mg/kg，约20mg/kg，约21.0mg/kg，约22.0mg/kg，约23.0mg/kg，约24.0mg/kg或约25.0mg/kg，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为约3mg/kg，或约4mg/kg，给药频率为每3周2次；b1)抗PD-L1抗体的给药剂量为约100mg，约500mg，约800mg，约900mg，约1000mg，约1100mg，约1200mg，约1300mg，约1400mg，约1500mg，约1600mg，约1800mg，约2000mg，约2200mg，约2500mg，约3000mg，给药频率为每3周1次；b2)抗CTLA-4抗体的给药剂量为约10mg，约20mg，约30mg，约40mg，约50mg，约60mg，约70mg，约80mg，约90mg，约100mg，约150mg，约200mg，约210mg，约220mg，约230mg，约240mg，约250mg，约260mg，约270mg，约280mg，约290mg，约300mg，约350mg，约500mg或约700mg，给药频率为每6周1次或单次给药；b3)抗VEGF抗体的给药剂量为约2.0mg/kg，约3.0mg/kg，约4.0mg/kg，约5mg/kg，约6.0mg/kg，约7.5mg/kg，约8.0mg/kg，约9.0mg/kg，约10mg/kg，约11mg/kg，约12mg/kg，约13mg/kg，约14mg/kg，约15mg/kg，约16mg/kg，约17mg/kg，约18mg/kg，约19mg/kg，约20mg/kg，约21.0mg/kg，约22.0mg/kg，约23.0mg/kg，约24.0mg/kg或约25.0mg/kg，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为约5mg/kg，约6mg/kg，约7mg/kg，约8mg/kg，约9mg/kg或约10mg/kg，给药频率为每3周1次；b1)抗PD-L1抗体的给药剂量为约100mg，约500mg，约800mg，约900mg，约1000mg，约1100mg，约1200mg，约1300mg，约1400mg，约1500mg，约1600mg，约1800mg，约2000mg，约2200mg，约2500mg，约3000mg，给药频率为每3周1次；b2)抗CTLA-4抗体的给药剂量为约10mg，约20mg，约30mg，约40mg，约50mg，约60mg，约70mg，约80mg，约90mg，约100mg，约150mg，约200mg，约210mg，约220mg，约230mg，约240mg，约250mg，约260mg，约270mg，约280mg，约290mg，约300mg，约350mg，约500mg或约700mg，给药频率为每6周1次或单次给药；b3)抗VEGF抗体的给药剂量为约2.0mg/kg，约3.0mg/kg，约4.0mg/kg，约5mg/kg，约6.0mg/kg，约7.5mg/kg，约8.0mg/kg，约9.0mg/kg，约10mg/kg，约11mg/kg，约12mg/kg，约13mg/kg，约14mg/kg，约15mg/kg，约16mg/kg，约17mg/kg，约18mg/kg，约19mg/kg，约20mg/kg，约21.0mg/kg，约22.0mg/kg，约23.0mg/kg，约24.0mg/kg或约25.0mg/kg，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为约4mg/kg，给药频率为每3周2次，每周期D1、D8给药；b1)抗PD-L1抗体的给药剂量为约1200mg，给药频率为每3周1次；b2)抗CTLA-4抗体在第1周单次给药，给药剂量为约280mg或210mg，第2-12周不给药，从第13周开始，给药剂量为约70mg，给药频次为每6周1次；b3)抗VEGF抗体的给药剂量为约7.5mg/kg，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为约4mg/kg，给药频率为每3周2次，每周期D1、D8给药；b1)抗PD-L1抗体的给药剂量为约1200mg，给药频率为每3周1次；b2)抗CTLA-4抗体在第1周单次给药，给药剂量为约280mg或210mg，第2-12周不给药，从第13周开始，给药剂量为约70mg，给药频次为每6周1次；b3)抗VEGF抗体的给药剂量为约15mg/kg，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为约6mg/kg，给药频率为每3周1次；b1)抗PD-L1抗体的给药剂量为约1200mg，给药频率为每3周1次；b2)抗CTLA-4抗体在第1周单次给药，给药剂量为约280mg或210mg，第2-12周不给药，从第13周开始，给药剂量为约70mg，给药频次为每6周1次；b3)抗VEGF抗体的给药剂量为约7.5mg/kg，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为约6mg/kg，给药频率为每3周1次；b1)抗PD-L1抗体的给药剂量为约1200mg，给药频率为每3周1次；b2)抗CTLA-4抗体在第1周单次给药，给药剂量为约280mg或210mg，第2-12周不给药，从第13周开始，给药剂量为约70mg，给药频次为每6周1次；b3)抗VEGF抗体的给药剂量为约15mg/kg，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为约8mg/kg，给药频率为每3周1次；b1)抗PD-L1抗体的给药剂量为约1200mg，给药频率为每3周1次；b2)抗CTLA-4抗体在第1周单次给药，给药剂量为约280mg或210mg，第2-12周不给药，从第13周开始，给药剂量为约70mg，给药频次为每6周1次；b3)抗VEGF抗体的给药剂量为约7.5mg/kg，给药频率为每3周1次；或
a)抗Nectin-4抗体药物偶联物的给药剂量为约8mg/kg，给药频率为每3周1次；b1)抗PD-L1抗体的给药剂量为约1200mg，给药频率为每3周1次；b2)抗CTLA-4抗体在第1周单次给药，给药剂量为约280mg或210mg，第2-12周不给药，从第13周开始，给药剂量为约70mg，给药频次为每6周1次；b3)抗VEGF抗体的给药剂量为约15mg/kg，给药频率为每3周1次。
在一些实施方案中，抗Nectin-4抗体药物偶联物联合抗PD-L1抗体和卡铂的给药方案为：
a)抗Nectin-4抗体药物偶联物的给药剂量为0.1-50mg/kg，给药频率为每2周至少1次，每3周至少1次，每4周至少1次，每6周至少1次，或每8周至少1次；b1)抗PD-L1抗体的给药剂量为5-5000mg，给药频率为每2周1次，每3周1次，每4周1次，每5周1次，或每6周1次；b2)卡铂的给药剂量(按AUC计)为约0.1mg/mL/min至约50mg/mL/min，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为0.1-20mg/kg，给药频率为每2周1次，每3周1次，每3周2次，每4周1次，每6周1次，或每8周1次；b1)抗PD-L1抗体的给药剂量为5-5000mg，给药频率为每3周1次；b2)卡铂的给药剂量(按AUC计)为约0.1mg/mL/min至约50mg/mL/min，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为1-10mg/kg，给药频率为每3周2次或每3周1次；b1)抗PD-L1抗体的给药剂量为5-5000mg，给药频率为每3周1次；b2)卡铂的给药剂量(按AUC计)为约0.1mg/mL/min至约50mg/mL/min，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为约1mg/kg，约2mg/kg，约3mg/kg，约4mg/kg，约5mg/kg，约6mg/kg，约7mg/kg，约8mg/kg或约10mg/kg；给药频率为每3周2次或每3周1次；b1)抗PD-L1抗体的给药剂量为5-5000mg，给药频率为每3周1次；b2)卡铂的给药剂量(按AUC计)为约0.1mg/mL/min至约50mg/mL/min，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为约5mg/kg，约6mg/kg，约7mg/kg，约8mg/kg，约9mg/kg或约10mg/kg；给药频率为每3周1次；b1)抗PD-L1抗体的给药剂量为5-5000mg，给药频率为每3周1次；b2)卡铂的给药剂量(按AUC计)为约0.1mg/mL/min至约50mg/mL/min，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为1mg/kg，约2mg/kg，约3mg/kg，或约4mg/kg；给药频率为每3周2次；b1)抗PD-L1抗体的给药剂量为5-5000mg，给药频率为每3周1次；b2)卡铂的给药剂量(按AUC计)为约0.1mg/mL/min至约50mg/mL/min，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为1-10mg/kg，给药频率为每3周2次或每3周1次；b1)抗PD-L1抗体的给药剂量为约100mg，约500mg，约800mg，约900mg，约1000mg，约1100mg，约1200mg，约1300mg，约1400mg，约1500mg，约1600mg，约1800mg，约2000mg，约2200mg，约2500mg，约3000mg，给药频率为每3周1次；b2)卡铂的给药剂量(按AUC计)为约1mg/mL/min，约2mg/mL/min，约3mg/mL/min，约4mg/mL/min，约5mg/mL/min，约6mg/mL/min，约7mg/mL/min，约8mg/mL/min，约9mg/mL/min，约10mg/mL/min，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为约1mg/kg，约2mg/kg，约3mg/kg，约4mg/kg，约5mg/kg，约6mg/kg，约7mg/kg，约8mg/kg，约9mg/kg或约10mg/kg，给药频率为每3周2次或每3周1次；b1)抗PD-L1抗体的给药剂量为约100mg，约500mg，约800mg，约900mg，约1000mg，约1100mg，约1200mg，约1300mg，约1400mg，约1500mg，约1600mg，约1800mg，约2000mg，约2200mg，约2500mg，约3000mg，给药频率为每3周1次；b2)卡铂的给药剂量(按AUC计)为约1mg/mL/min，约2mg/mL/min，约3mg/mL/min，约4mg/mL/min，约5mg/mL/min，约6mg/mL/min，约7mg/mL/min，约8mg/mL/min，约9mg/mL/min，约10mg/mL/min，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为约3mg/kg，或约4mg/kg，给药频率为每3周2次；b1)抗PD-L1抗体的给药剂量为约100mg，约500mg，约800mg，约900mg，约1000mg，约1100mg，约1200mg，约1300mg，约1400mg，约1500mg，约1600mg，约1800mg，约2000mg，约2200mg，约2500mg，约3000mg，给药频率为每3周1次；b2)卡铂的给药剂量(按AUC计)为约1mg/mL/min，约2mg/mL/min，约3mg/mL/min，约4mg/mL/min，约5mg/mL/min，约6mg/mL/min，约7mg/mL/min，约8mg/mL/min，约9mg/mL/min，约10mg/mL/min，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为约3mg/kg，或约4mg/kg，给药频率为每3周2次；b1)抗PD-L1抗体的给药剂量为约1200mg，给药频率为每3周1次；b2)卡铂的给药剂量(按AUC计)为约4mg/mL/min或5mg/mL/min，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为约5mg/kg，约6mg/kg，约7mg/kg，约8mg/kg，约9mg/kg或约10mg/kg，给药频率为每3周1次；b1)抗PD-L1抗体的给药剂量为约100mg，约500mg，约800mg，约900mg，约1000mg，约1100mg，约1200mg，约1300mg，约1400mg，约1500mg，约1600mg，约1800mg，约2000mg，约2200mg，约2500mg，约3000mg，给药频率为每3周1次；b2)卡铂的给药剂量(按AUC计)为约1mg/mL/min，约2mg/mL/min，约3mg/mL/min，约4mg/mL/min，约5mg/mL/min，约6mg/mL/min，约7mg/mL/min，约8mg/mL/min，约9mg/mL/min，约10mg/mL/min，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为约5mg/kg，约6mg/kg，约7mg/kg，约8mg/kg，约9mg/kg或约10mg/kg，给药频率为每3周1次；b1)抗PD-L1抗体的给药剂量为约1200m，给药频率为每3周1次；b2)卡铂的给药剂量(按AUC计)为约4mg/mL/min或5mg/mL/min，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为约4mg/kg，给药频率为每3周2次，每周期D1、D8给药；b1)抗PD-L1抗体的给药剂量为约1200mg，给药频率为每3周1次；b2)卡铂的给药剂量(按AUC计)为约4mg/mL/min，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为约4mg/kg，给药频率为每3周2次，每周期D1、D8给药；b1)抗PD-L1抗体的给药剂量为约1200mg，给药频率为每3周1次；b2)卡铂的给药剂量(按AUC计)为约5mg/mL/min，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为约6mg/kg，给药频率为每3周1次；b1)抗PD-L1抗体的给药剂量为约1200mg，给药频率为每3周1次；b2)卡铂的给药剂量(按AUC计)为约4mg/mL/min，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为约6mg/kg，给药频率为每3周1次；b1)抗PD-L1抗体的给药剂量为约1200mg，给药频率为每3周1次；b2)卡铂的给药剂量(按AUC计)为约5mg/mL/min，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为约8mg/kg，给药频率为每3周1次；b1)抗PD-L1抗体的给药剂量为约1200mg，给药频率为每3周1次；b2)卡铂的给药剂量(按AUC计)为约4mg/mL/min，给药频率为每3周1次；或，
a)抗Nectin-4抗体药物偶联物的给药剂量为约8mg/kg，给药频率为每3周1次；b1)抗PD-L1抗体的给药剂量为约1200mg，给药频率为每3周1次；b2)卡铂的给药剂量(按AUC计)为约5mg/mL/min，给药频率为每3周1次。
在一些实施方案中，抗Nectin-4抗体药物偶联物联合抗PD-L1抗体和顺铂的给药方案为：
a)抗Nectin-4抗体药物偶联物的给药剂量为0.1-50mg/kg，给药频率为每2周至少1次，每3周至少1次，每4周至少1次，每6周至少1次，或每8周至少1次；b1)抗PD-L1抗体的给药剂量为5-5000mg，给药频率为每2周1次，每3周1次，每4周1次，每5周1次，或每6周1次；b2)顺铂的给药剂量为约1mg/m2至约500mg/m2，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为0.1-20mg/kg，给药频率为每2周1次，每3周1次，每3周2次，每4周1次，每6周1次，或每8周1次；b1)抗PD-L1抗体的给药剂量为5-5000mg，给药频率为每3周1次；b2)顺铂的给药剂量为约1mg/m2至约500mg/m2，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为1-10mg/kg，给药频率为每3周2次或每3周1次；b1)抗PD-L1抗体的给药剂量为5-5000mg，给药频率为每3周1次；b2)顺铂的给药剂量为约1mg/m2至约500mg/m2，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为约1mg/kg，约2mg/kg，约3mg/kg，约4mg/kg，约5mg/kg，约6mg/kg，约7mg/kg，约8mg/kg或约10mg/kg；给药频率为每3周2次或每3周1次；b1)抗PD-L1抗体的给药剂量为5-5000mg，给药频率为每3周1次；b2)顺铂的给药剂量为约1mg/m2至约500mg/m2，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为约5mg/kg，约6mg/kg，约7mg/kg，约8mg/kg，约9mg/kg或约10mg/kg；给药频率为每3周1次；b1)抗PD-L1抗体的给药剂量为5-5000mg，给药频率为每3周1次；b2)顺铂的给药剂量为约1mg/m2至约500mg/m2，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为1mg/kg，约2mg/kg，约3mg/kg，或约4mg/kg；给药频率为每3周2次；b1)抗PD-L1抗体的给药剂量为5-5000mg，给药频率为每3周1次；b2)顺铂的给药剂量为约1mg/m2至约500mg/m2，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为1-10mg/kg，给药频率为每3周2次或每3周1次；b1)抗PD-L1抗体的给药剂量为约100mg，约500mg，约800mg，约900mg，约1000mg，约1100mg，约1200mg，约1300mg，约1400mg，约1500mg，约1600mg，约1800mg，约2000mg，约2200mg，约2500mg，约3000mg，给药频率为每3周1次；b2)顺铂的给药剂量为约50mg/m2，约51mg/m2，约52mg/m2，约53mg/m2，约55mg/m2，约57mg/m2，约58mg/m2，约60mg/m2，约61mg/m2，约62mg/m2，约63mg/m2，约64mg/m2，约65mg/m2，约66mg/m2，约67mg/m2，约68mg/m2，约69mg/m2，约70mg/m2，约71mg/m2，约72mg/m2，约73mg/m2，约74mg/m2，约75mg/m2，约76mg/m2，约77mg/m2，约78mg/m2，约79mg/m2，约80mg/m2，约81mg/m2，约82mg/m2，约83mg/m2，约84mg/m2，约85mg/m2，约86mg/m2，约87mg/m2，约88mg/m2，约89mg/m2，约90mg/m2，约95mg/m2，约100mg/m2，约150mg/m2，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为约1mg/kg，约2mg/kg，约3mg/kg，约4mg/kg，约5mg/kg，约6mg/kg，约7mg/kg，约8mg/kg，约9mg/kg或约10mg/kg，给药频率为每3周2次或每3周1次；b1)抗PD-L1抗体的给药剂量为约100mg，约500mg，约800mg，约900mg，约1000mg，约1100mg，约1200mg，约1300mg，约1400mg，约1500mg，约1600mg，约1800mg，约2000mg，约2200mg，约2500mg，约3000mg，给药频率为每3周1次；b2)顺铂的给药剂量为约50mg/m2，约51mg/m2，约52mg/m2，约53mg/m2，约55mg/m2，约57mg/m2，约58mg/m2，约60mg/m2，约61mg/m2，约62mg/m2，约63mg/m2，约64mg/m2，约65mg/m2，约66mg/m2，约67mg/m2，约68mg/m2，约69mg/m2，约70mg/m2，约71mg/m2，约72mg/m2，约73mg/m2，约74mg/m2，约75mg/m2，约76mg/m2，约77mg/m2，约78mg/m2，约79mg/m2，约80mg/m2，约81mg/m2，约82mg/m2，约83mg/m2，约84mg/m2，约85mg/m2，约86mg/m2，约87mg/m2，约88mg/m2，约89mg/m2，约90mg/m2，约95mg/m2，约100mg/m2，约150mg/m2，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为约3mg/kg，或约4mg/kg，给药频率为每3周2次；b1)抗PD-L1抗体的给药剂量为约100mg，约500mg，约800mg，约900mg，约1000mg，约1100mg，约1200mg，约1300mg，约1400mg，约1500mg，约1600mg，约1800mg，约2000mg，约2200mg，约2500mg，约3000mg，给药频率为每3周1次；b2)顺铂的给药剂量为约50mg/m2，约51mg/m2，约52mg/m2，约53mg/m2，约55mg/m2，约57mg/m2，约58mg/m2，约60mg/m2，约61mg/m2，约62mg/m2，约63mg/m2，约64mg/m2，约65mg/m2，约66mg/m2，约67mg/m2，约68mg/m2，约69mg/m2，约70mg/m2，约71mg/m2，约72mg/m2，约73mg/m2，约74mg/m2，约75mg/m2，约76mg/m2，约77mg/m2，约78mg/m2，约79mg/m2，约80mg/m2，约81mg/m2，约82mg/m2，约83mg/m2，约84mg/m2，约85mg/m2，约86mg/m2，约87mg/m2，约88mg/m2，约89mg/m2，约90mg/m2，约95mg/m2，约100mg/m2，约150mg/m2，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为约3mg/kg，或约4mg/kg，给药频率为每3周2次；b1)抗PD-L1抗体的给药剂量为约1200mg，给药频率为每3周1次；b2)顺铂的给药剂量为约75mg/m2，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为约5mg/kg，约6mg/kg，约7mg/kg，约8mg/kg，约9mg/kg或约10mg/kg，给药频率为每3周1次；b1)抗PD-L1抗体的给药剂量为约100mg，约500mg，约800mg，约900mg，约1000mg，约1100mg，约1200mg，约1300mg，约1400mg，约1500mg，约1600mg，约1800mg，约2000mg，约2200mg，约2500mg，约3000mg，给药频率为每3周1次；b2)顺铂的给药剂量为约50mg/m2，约51mg/m2，约52mg/m2，约53mg/m2，约55mg/m2，约57mg/m2，约58mg/m2，约60mg/m2，约61mg/m2，约62mg/m2，约63mg/m2，约64mg/m2，约65mg/m2，约66mg/m2，约67mg/m2，约68mg/m2，约69mg/m2，约70mg/m2，约71mg/m2，约72mg/m2，约73mg/m2，约74mg/m2，约75mg/m2，约76mg/m2，约77mg/m2，约78mg/m2，约79mg/m2，约80mg/m2，约81mg/m2，约82mg/m2，约83mg/m2，约84mg/m2，约85mg/m2，约86mg/m2，约87mg/m2，约88mg/m2，约89mg/m2，约90mg/m2，约95mg/m2，约100mg/m2，约150mg/m2，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为约5mg/kg，约6mg/kg，约7mg/kg，约8mg/kg，约9mg/kg或约10mg/kg，给药频率为每3周1次；b1)抗PD-L1抗体的给药剂量为约1200m，给药频率为每3周1次；b2)顺铂的给药剂量为约75mg/m2，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为约4mg/kg，给药频率为每3周2次，每周期D1、D8给药；b1)抗PD-L1抗体的给药剂量为约1200mg，给药频率为每3周1次；b2)顺铂的给药剂量为约75mg/m2，给药频率为每3周1次；
a)抗Nectin-4抗体药物偶联物的给药剂量为约6mg/kg，给药频率为每3周1次；b1)抗PD-L1抗体的给药剂量为约1200mg，给药频率为每3周1次；b2)顺铂的给药剂量为约75mg/m2，给药频率为每3周1次；或，
a)抗Nectin-4抗体药物偶联物的给药剂量为约8mg/kg，给药频率为每3周1次；b1)抗PD-L1抗体的给药剂量为约1200mg，给药频率为每3周1次；b2)顺铂的给药剂量为约75mg/m2，给药频率为每3周1次。
在一些实施方案中，抗Nectin-4抗体药物偶联物联合抗PD-L1抗体的给药顺序：建议先给予抗Nectin-4抗体药物偶联物，再给予抗PD-L1抗体。两药给药时间间隔应＞30分钟，尽量在同一天内完成给药。
在一些实施方案中，抗Nectin-4抗体药物偶联物联合抗PD-L1抗体、抗VEGF抗体的给药顺序：建议先给予抗Nectin-4抗体药物偶联物，再给予抗PD-L1抗体，最后给予抗VEGF抗体。两药给药时间间隔应＞30分钟，尽量在同一天内完成给药。
在一些实施方案中，抗Nectin-4抗体药物偶联物联合抗PD-L1抗体、铂类药物的给药顺序：建议先给予抗Nectin-4抗体药物偶联物，再给予抗PD-L1抗体，最后给予铂类药物。两药给药时间间隔应＞30分钟，尽量在同一天内完成给药。
在一些实施方案中，抗Nectin-4抗体药物偶联物联合抗PD-L1抗体、抗CTLA-4抗体的给药顺序：建议先给予抗Nectin-4抗体药物偶联物，再给予抗PD-L1抗体，最后再给予抗CTLA-4抗体。两药给药时间间隔应＞30分钟，尽量在同一天内完成给药。
在一些实施方案中，抗Nectin-4抗体药物偶联物联合抗PD-L1抗体、抗CTLA-4抗体、抗VEGF抗体的给药顺序：建议先给予抗Nectin-4抗体药物偶联物，再给予抗PD-L1抗体，再给予抗CTLA-4抗体，最后给予抗VEGF抗体。两药给药时间间隔应＞30分钟，尽量在同一天内完成给药。
抗Nectin-4抗体药物偶联物及其联用其它治疗剂在靶向治疗非小细胞肺癌和食管癌中展露出一定的临床获益，为患者带来优于现有治疗的临床获益，病情得到控制或者缓解。
术语
为了更容易理解本公开，以下具体定义了某些技术和科学术语。除非在本文中另有明确定义，本文使用的所有其它技术和科学术语都具有本公开所属领域的一般技术人员通常理解的含义。
除非上下文另外清楚要求，否则在整个说明书和权利要求书中，应将词语“包含”、“具有”、“包括”等理解为具有包含意义，而不是排他性或穷举性意义；也即，“包括但不仅限于”的意义。
“任选”或“任选地”意味着随后所描述地事件或环境可以但不必发生，该说明包括该事件或环境发生或不发生的场合。
“约”、“大约”是指数值在由本领域一般技术人员所测定的具体值的可接受误差范围内，所述数值部分取决于怎样测量或测定(即测量体系的限度)。例如，“约”可意味着在1内或超过1的标准差。或者，“约”或“基本上包含”可意味着至多20％的范围，例如1％至15％之间、在1％至10％之间、在1％至5％之间、在0.5％至5％之间、在0.5％至1％之间变化，本公开中，数字或数值范围之前有术语“约”的每种情况也包括给定数的实施方案。除非另外说明，否则当具体值在本申请和权利要求中出现时，“约”或“基本上包含”的含义应该假定为在该具体值的可接受误差范围内。
术语“和/或”，例如“X和/或Y”应当理解为意指“X和Y”或“X或Y”并且应当被用来提供对两种含义或任一含义的明确支持。
在一些实施方案中，本公开进行如下定义：
“抗体药物偶联物(antibody drug conjugate，ADC)”是把抗体或者抗体片段通过稳定的化学接头化合物与具有生物活性的细胞毒素或具有细胞杀伤活性的小分子药物相连，充分利用了抗体对肿瘤细胞特异或高表达抗原结合的特异性和细胞毒素的高效性，避免对正常细胞的毒副作用。与以往传统的化疗药物相比，抗体药物偶联物能精准地结合肿瘤细胞并降低对正常细胞的影响。
如果抗体药物偶联物没有显示出显著的化学改变，那么所述抗体在药物制剂中“保留它的化学稳定性”。通过检测和定量化学上改变的形式的蛋白，可以评估化学稳定性。经常改变蛋白化学结构的降解过程包括水解或截短(通过诸如尺寸排阻色谱法和CE-SDS等方法来评价)、氧化(通过诸如与质谱法或MALDI/TOF/MS结合的肽谱法等方法来评价)、脱酰胺作用(通过诸如离子交换色谱法、毛细管等电聚焦、肽谱法、异天冬氨酸测量等方法来评价)和异构化(通过测量异天冬氨酸含量、肽谱法等来评价)。
如果抗体药物偶联物在给定时间的生物活性是在制备药物制剂时表现出的生物活性的预定范围内，那么所述抗体药物偶联物在药物制剂中“保留它的生物活性”。
本公开所用氨基酸三字母代码和单字母代码如J.biol.chem，243，p3558(1968)中所述。
如本文所用，术语“抗体”以最广义使用，涵盖各种抗体结构，包括但不限于单克隆抗体，多克隆抗体；单特异性抗体，多特异性抗体(例如双特异性抗体)，全长抗体和抗体片段(或抗原结合片段，或抗原结合部分)，只要它们展现出期望的抗原结合活性。抗体可以指免疫球蛋白，是由两条相同的重链和两条相同的轻链通过链间二硫键连接而成的四肽链结构。免疫球蛋白重链恒定区的氨基酸组成和排列顺序不同，故其抗原性也不同。据此，可将免疫球蛋白分为五类，或称为免疫球蛋白的同种型，即IgM、IgD、IgG、IgA和IgE，其相应的重链分别为μ链、δ链、γ链、α链和ε链。同一类Ig根据其铰链区氨基酸组成和重链二硫键的数目和位置的差别，又可分为不同的亚类，如IgG可分为IgG1、IgG2、IgG3、IgG4。轻链通过恒定区的不同分为κ链或λ链。五类Ig中第每类Ig都可以有κ链或λ链。抗体重链和轻链靠近N端的约110个氨基酸的序列变化很大，为可变区(V区)；靠近C端的其余氨基酸序列相对稳定，为恒定区(C区)。可变区包括3个高变区(CDR)和4个序列相对保守的骨架区(FR)。3个高变区决定抗体的特异性，又称为互补性决定区(CDR)。每条轻链可变区(VL)和重链可变区(VH)由3个CDR区4个FR区组成，从氨基端到羧基端依次排列的顺序为：FR1，CDR1，FR2，CDR2，FR3，CDR3，FR4。轻链的3个CDR区指LCDR1，LCDR2，和LCDR3；重链的3个CDR区指HCDR1，HCDR2和HCDR3。
对于CDR的确定或定义，能够通过分辨抗体的结构和/或分辨抗体-配体复合物的结构来完成CDR的确定性描绘和包含抗体的结合位点的残基的鉴定。这可通过本领域技术人员已知的各种技术中的任一种，例如X射线晶体学来实现。多种分析方法可用于鉴定CDR，包括但不限于Kabat编号系统、Chothia编号系统、AbM编号系统、IMGT编号系统、接触定义、构象定义。
可以通过各种公知方案来确定CDR的氨基酸序列边界，例如：“Kabat”编号规则(参见Kabat等(1991)，“Sequences of Proteins of Immunological Interest”，第5版，Public Health Service，National Institutes of Health，Bethesda，MD)、“Chothia”编号规则、“ABM”编号规则、“contact”编号规则(参见Martin,ACR.Protein Sequence and Structure Analysis of Antibody Variable Domains[J].2001)和ImMunoGenTics(IMGT)编号规则(Lefranc，M.P.等，Dev.Comp.Immunol.，27，55-77(2003)；Front Immunol.2018 Oct 16；9:2278)等。
术语“抗原结合片段”或“功能片段”或“抗原结合部分”是指保持特异性结合抗原的能力的完整抗体的一个或更多个片段。已显示可利用全长抗体的片段来进行抗体的抗原结合功能。示例性的，涵盖在术语“抗原结合片段”的结合片段的实例包括：(i)Fab片段，一种由VL、VH、CL和CH1结构域组成的单价片段；(ii)F(ab')2片段，一种包含通过铰链区上的二硫键桥连接的两个Fab片段的二价片段，(iii)由VH和CH1结构域组成的Fd片段；(iv)由抗体的单臂的VH和VL结构域组成的Fv片段；(v)dsFv，由VH和VL经链间二硫键形成的稳定的抗原结合片段；(vi)scFv；(vii)包含scFv、dsFv、Fab等片段的双抗体、双特异性抗体和多特异性抗体。
术语“特异性结合”、“选择性结合”、“选择性地结合”和“特异性地结合”是指抗体对预先确定的抗原上的表位的结合。通常，抗体以大约小于10-8M，例如大约小于10-9M、10-10M、10-11M或更小的亲和力(KD)结合。
术语"KD"是指特定抗体-抗原相互作用的解离平衡常数。通常，本公开的抗体以小于大约10-7M，例如小于大约10-8M、10-9M或10-10M或更小的解离平衡常数(KD)结合IL-5，例如，如使用表面等离子体共振(SPR)技术在BIACORE仪中测定的。
“同源性”是指两个多核苷酸序列之间或两个多肽之间的序列相似性。当两个比较序列中的位置均被相同碱基或氨基酸单体亚基占据时，例如如果两个DNA分子的每一个位置都被腺嘌呤占据时，那么所述分子在该位置是同源的。两个序列之间的同源性百分率是两个序列共有的匹配或同源位置数除以比较的位置数×100的函数。例如，在序列最佳比对时，如果两个序列中的10个位置有6个匹配或同源，那么两个序列为60％同源；如果两个序列中的100个位置有95个匹配或同源，那么两个序列为95％同源。通常，当比对两个序列时进行比较以给出最大百分比同源性。例如，可以通过BLAST算法执行比较，其中选择算法的参数以在各个参考序列的整个长度上给出各个序列之间的最大匹配。以下参考文献涉及经常用于序列分析的BLAST算法：BLAST算法(BLAST ALGORITHMS)：Altschul，S.F.等人，(1990)J.Mol.Biol.215:403-410；Gish，W.等人，(1993)Nature Genet.3:266-272；Madden，T.L.等人，(1996)Meth.Enzymol.266:131-141；Altschul，S.F.等人，(1997)Nucleic Acids Res.25:3389-3402；Zhang，J.等人，(1997)Genome Res.7:649-656。其他如NCBI BLAST提供的常规BLAST算法也为本领域技术人员所熟知。
“给予”和“处理”当应用于动物、人、实验受试者、细胞、组织、器官或生物流体时，是指外源性药物、治疗剂、诊断剂或组合物与动物、人、受试者、细胞、组织、器官或生物流体的接触。“给予”和“处理”可以指例如治疗、药物代谢动力学、诊断、研究和实验方法。细胞的处理包括试剂与细胞的接触，以及试剂与流体的接触，其中所述流体与细胞接触。“给予”和“处理”还意指通过试剂、诊断、结合组合物或通过另一种细胞体外和离体处理例如细胞。“处理”当应用于人、兽医学或研究受试者时，是指治疗处理、预防或预防性措施，研究和诊断应用。
“治疗”意指给予患者内用或外用治疗剂，例如包含本公开的任一种结合化合物的组合物，所述患者具有一种或多种疾病症状，而已知所述治疗剂对这些症状具有治疗作用。通常，在受治疗患者或群体中以有效缓解一种或多种疾病症状的量给予治疗剂，以诱导这类症状退化或抑制这类症状发展到任何临床可测量的程度。有效缓解任何具体疾病症状的治疗剂的量(也称作“治疗有效量”)可根据多种因素变化，例如患者的疾病状态、年龄和体重，以及药物在患者产生需要疗效的能力。通过医生或其它专业卫生保健人士通常用于评价该症状的严重性或进展状况的任何临床检测方法，可评价疾病症状是否已被减轻。尽管本公开的实施方案(例如治疗方法或制品)在缓解每个目标疾病症状方面可能无效，但是根据本领域已知的任何统计学检验方法如Student t检验、卡方检验、依据Mann和Whitney的U检验、Kruskal-Wallis检验(H检验)、Jonckheere-Terpstra检验和Wilcoxon检验确定，其在统计学显著数目的患者中应当减轻目标疾病症状。
“有效量”包含足以改善或预防医学疾病的症状或病症的量。有效量还意指足以允许或促进诊断的量。用于特定患者或兽医学受试者的有效量可依据以下因素而变化：例如，待治疗的病症、患者的总体健康情况、给药的方法途径和剂量以及副作用严重性。有效量可以是避免显著副作用或毒性作用的最大剂量或给药方案。
术语“受试者”、“患者”意指哺乳动物，尤其灵长类动物，尤其是人。
本公开“Nectin-4阳性”是指用免疫组化的方法检测细胞膜或细胞质nectin-4表达，如果表达数值≥1，则为nectin-4阳性。
本公开“驱动基因”包括但不限于EGFR突变、ALK融合、ROS1融合、BRAF V600E突变、NTRK融合、MET14外显子跳跃突变、RET融合、KRAS G12C突变、HER-2突变等、EGFR敏感突变、EGFR T790M突变、EGFR 20外显子插入等。本公开“驱动基因阳性”是指基因检测或免疫组化等方法检测到非小细胞肺癌特定的基因突变。所述“驱动基因阳性”包括但不限于EGFR突变、EGFR敏感突变、EGFR T790M突变、EGFR 20外显子插入、ALK融合、ROS1融合、BRAF V600E突变、NTRK融合、MET14外显子跳跃突变、RET融合、KRAS G12C突变、HER-2突变等。本公开“驱动基因阳性”还包括其它待发现的非小细胞肺癌特定的基因突变。
本公开“驱动基因阴性”是指基因检测或免疫组化等方法未检测到非小细胞肺癌“驱动基因”。本公开中“驱动基因阳性但是尚未有获批靶向药物疗法”的患者人群参照“驱动基因阴性”的患者人群进行治疗。
本公开“免疫治疗”是指免疫治疗指的是以免疫检查点抑制剂(ICIs)为代表的肿瘤免疫治疗，包括但不限于程序性细胞死亡蛋白受体1(Programmed cell death receptor 1,PD-1)、程序性细胞死亡蛋白配体1(Programmed cell death ligand 1，PD-L1)以及毒性T淋巴细胞相关抗原4(Cytotoxic T lymphocyte associated antigen 4，CTLA-4)等。
本公开“铂类化疗”，包括顺铂、卡铂等铂类药物的治疗。
本公开“靶向药物疗法”，是指针对“驱动基因阳性”的已获批或未来新获批的靶向药物疗法，包括但不限于获批的针对EGFR突变、KRAS G12C突变、HER-2突变、EGFR敏感突变、EGFR T790M突变、EGFR 20外显子插入、ALK融合、ROS1融合、NTRK融合、BRAF V600E突变、MET 14外显子跳跃突变、RET融合等的靶向药物疗法。
本公开抗体药物偶联物中“n”是指抗体药物偶联物分子中每个抗体或其抗原结合片段上加载的细胞毒性药物平均数量，也可以表示为药物量和抗体量的比值，为经疏水色谱法(HIC)质谱鉴定偶联反应后每个ADC分子的药物平均数量。
“药物组合物”表示含有一种或多种本文所述化合物或其生理学上/可药用的盐或前体药物与其他化学组分的混合物，所述其他组分例如生理学/可药用的载体和赋形剂。药物组合物的目的是促进对生物体的给药，利于活性成分的吸收进而发挥生物活性。
具体实施方式
以下结合实施例进一步描述本公开，但这些实施例并非是对本公开范围的限制。本公开实施例中未注明具体条件的实验方法，通常按照常规条件，如参照冷泉港实验室出版的《抗体技术实验手册》，《分子克隆手册》；或按照原料或商品制造厂商所建议的条件。未注明具体来源的试剂，为市场购买的常规试剂。
实施例1.抗Nectin-4抗体药物偶联物的制备
抗Nectin-4抗体药物偶联物为WO2023221971A(通过引用全文并入本公开)中的实施例3-4制备的ADC-4，结构如下：
反相色谱计算平均值：n＝3.5～4.7。
抗Nectin-4抗体来源于抗体NEC49，其CDR序列如表1所示。抗体NEC49的重链全长如SEQ ID NO：9所示，轻链全长如SEQ ID NO:10所示。
实施例2.ADC-4在晚期实体瘤患者中的安全性、耐受性、疗效及药代动力学的开放、单臂、多中心的I期临床研究
1.试验药物
实施例1制备的ADC-4。剂型为注射剂(注射用无菌粉末)。
2.入组受试者
1)年龄18周岁以上，性别不限；
2)东部肿瘤协作组(ECOG)体能状态评分为0～1分；
3)预计生存期≥3个月；
4)经病理学确诊的不可切除局部晚期或晚期实体瘤患者，经标准治疗失败或不耐受、无标准治疗或拒绝标准治疗。各队列入组标准如下：
队列A：经病理学确认的不可切除局部晚期/转移性非小细胞肺癌：包括i)驱动基因阴性的NSCLC受试者须接受过以PD-(L)1和铂类化疗为基础的治疗，除非不适合或拒绝接受该治疗；ii)已知存在驱动基因阳性的NSCLC受试者，针对该驱动基因阳性突变若已获批靶向药物，须接受过至少1种靶向药物疗法；iii)若接受化疗，既往化疗线数≤2线。
队列D：经病理学确认的不可切除局部晚期/转移性食管鳞癌；针对局部晚期/转移性疾病，受试者须接受过以PD-(L)1和铂类化疗为基础的治疗，且既往化疗线数≤2线；
疗效拓展阶段各队列细分入组标准如下：
队列A1入组EGFR突变型非鳞状非小细胞肺癌(NSCLC)；
队列A2入组驱动基因阴性非鳞状非小细胞肺癌(NSCLC)；
队列A3入组其他驱动基因阳性非鳞状非小细胞肺癌(NSCLC)；
队列A4入组鳞状非小细胞肺癌；
队列A5入组Nectin-4表达阴性非小细胞肺癌。
队列A1、A2、A3的非鳞癌(非鳞状非小细胞肺癌)受试者，必须进行驱动基因突变检测，包括但不限于EGFR基因检测和其它驱动基因(是指除EGFR基因之外的驱动基因)检测和/或免疫组化检测，依据检测结果入组不同队列。
5)能够提供存档或新鲜肿瘤组织，且队列A1、A2、A3、A4入组受试者的肿瘤组织Nectin-4表达阳性。对于无法提供满足上述要求肿瘤组织样本的受试者，需与申办方讨论后确定是否入组。
6)根据RECIST v1.1标准至少有一个可测量病灶。
3.临床方案
3.1研究设计
剂量递增阶段
ADC-4的起始剂量为1mg/kg，静脉滴注给药，静脉滴注给药，每3周1次(Q3W)，21天为一个治疗周期。
采用贝叶斯最优区间(BOIN)设计，以1mg/kg为起始剂量开始剂量递增研究。BOIN设计阶段：预设5个剂量组(2mg/kg、4mg/kg、6mg/kg、8mg/kg、10mg/kg)。从试验起始剂量开始入组受试者，受试者以每队列3-6例入组接受治疗。在每个队列受试者完成DLT观察期(即研究给药第1周期)安全性评估后，根据BOIN设计剂量升降决策表决定下一队列受试者的给药剂量，直至方案规定的单剂量组最大样本量(12例)或总最大样本量(36例)或由安全监查委员会(SMC)决定提前终止剂量递增。如有必要，将由主要研究者和申办方根据已获得的安全性、耐受性、PK、免疫原性数据和疗效信息共同讨论决定是否需要增加其他剂量组(更高剂量或中间剂量或更低剂量)和/或调整给药频率(如每周1次，QW)。
PK拓展阶段
依据剂量递增阶段不同剂量组的安全性、耐受性、PK等数据，选择约3个剂量组进行PK拓展。计划每个剂量组拓展至8～12例受试者(包括剂量递增阶段同剂量组完成第二周期给药前所有PK采血的受试者)。同时，若剂量递增阶段剂量组完成安全性评估，该剂量组可同步开始PK拓展受试者的入组。
疗效拓展阶段
疗效拓展阶段将根据肿瘤种类分为6个主要队列，即：
队列A1：接受6mg/kg或8mg/kg Q3W ADC-4给药治疗EGFR突变型非鳞状非小细胞肺癌(NSCLC)受试者；
队列A2：接受6mg/kg或8mg/kg Q3W ADC-4给药治疗驱动基因阴性(例如EGFR驱动基因阴性等)非鳞状非小细胞肺癌(NSCLC)受试者；
队列A3：接受6mg/kg或8mg/kg Q3W ADC-4给药治疗其他驱动基因阳性(除EGFR基因之外的驱动基因阳性)非鳞状非小细胞肺癌(NSCLC)受试者；
队列A4：接受6mg/kg或8mg/kg Q3W ADC-4给药治疗鳞状非小细胞肺癌受试者；
队列A5：接受6mg/kg或8mg/kg Q3W ADC-4给药治疗Nectin-4表达阴性非小细胞肺癌受试者(鳞状非小细胞肺癌和非鳞状非小细胞肺癌)。
3.2给药方式
ADC-4：静脉滴注，2mg/kg，4mg/kg，6mg/kg、8mg/kg，10mg/kg，Q3W或探索/确定的其他剂量。
4.结果评价
4.1有效性指标
肿瘤评估采用RECIST v1.1标准，所有受试者在筛选期进行基线肿瘤影像学评估。采用RECIST v1.1标准进行疗效评价，疗效评价指标包括：经研究者评估的ORR、DCR、DoR、PFS、OS。
共入组395例受试者，其中包括197例非小细胞肺癌受试者和77例食管鳞癌受试者。
部分入组受试者的基线特征如表5所示：165例入组受试者(包括83例非小细胞肺癌)中所有入组人群中位年龄为60岁，86.1％ ECOG评分1分，65.5％患者既往系统性抗肿瘤治疗≥2线；对于非小细胞肺癌人群，中位年龄为61岁，95.2％ECOG评分1分，78.3％患者既往系统性抗肿瘤治疗≥2线。
表5.受试者基线特征
在剂量递增阶段，17名患者接受了2至10mg/kg的ADC-4药物治疗。仅在10mg/kg组出现1例DLT(血小板计数降低4级)，MTD尚未达到。选择6mg/kg与8mg/kg进行PK拓展与疗效拓展。
4.1.1针对非小细胞肺癌的有效性评价
针对非小细胞肺癌入组受试者的治疗疗效评价统计结果如表2-4所示。
如表6所示，在所有完成至少1次肿瘤评估的46例非小细胞肺癌患者中，ORR为30.4％(其中非鳞癌36.7％，鳞癌18.8％)，DCR为89.1％(其中非鳞癌83.3％，鳞癌100％)PR 14例(30.4％)，SD 27例(58.7％)，PD 4例(8.7％)：其中非鳞癌PR 11例(36.7％)，SD 14例(46.7％)，PD 4例(13.3％)；鳞癌PR 3例(18.8％)，SD 13例(81.3％)，PD 0例。
表6.疗效评价

*ORR,客观缓解率.DCR,疾病控制率
如表7所示，在69例EGFR突变型非鳞状非小细胞肺癌患者中，ORR为43.5％，DCR为84.1％，mPFS为5.7个月(截止至2024年12月20日，6mg/kg剂量下mPFS为8.5个月，8mg/kg剂量下mPFS为5.7个月)。在44例EGFR野生型(EGFR驱动基因阴性)非鳞状非小细胞肺癌患者中，ORR为25.0％，DCR为72.7％，其中有1例患者疾病达到完全缓解CR(2.3％)，mPFS为4.3个月(截止至2024年12月20日，6mg/kg剂量下mPFS为2.6个月，8mg/kg剂量下mPFS为4.3个月，截止至2025年5月，8mg/kg剂量下mPFS为5.7个月)。在44例鳞状非小细胞肺癌患者中，ORR为25％，DCR为100％，mPFS为4.5个月(截止至2024年12月20日，6mg/kg剂量下mPFS为4.4个月，8mg/kg剂量下mPFS为6.0个月)。
表7.疗效评价


*包括未确认的ORR
*EGFR驱动基因阴性非鳞状NSCLC：又称“EGFR野生型非鳞状NSCLC”，包括驱动基因
阴性的非鳞状NSCLC以及非EGFR突变的其它驱动基因阳性的非鳞状NSCLC
如下表8所示，在105例非鳞状非小细胞肺癌受试者中，EGFR突变型非鳞状非小细胞肺癌受试者在6mg/kg剂量下的ORR为48.6％，DCR为80％，mPFS为8.5个月(截止至2025年5月的数据)；在8mg/kg剂量下的ORR为43.8％，DCR为90.6％，mPFS为8.5个月(截止至2025年5月的数据)。驱动基因阴性的非鳞状非小细胞肺癌受试者在8mg/kg剂量下的ORR为21.1％，DCR为68.4％，mPFS为5.7个月(截止至2025年5月的数据)。
表8.疗效评价

*包括未确认的ORR
*EGFR驱动基因阴性非鳞状NSCLC：又称“EGFR野生型非鳞状NSCLC”，包括驱动
基因阴性的非鳞状NSCLC以及非EGFR突变的其它驱动基因阳性的非鳞状NSCLC
4.1.2针对食管鳞癌的有效性评价
在76例食管鳞癌(ESCC)受试者中，在6mg/kg剂量下的ORR为25％，DCR为77.5％，mPFS为4.1个月(截止至2025年5月)，mOS为9.1个月(截止至2025年5月)。
4.2安全性评价
所有受试者入组研究后，每个治疗周期都将进行安全性评估。包括AE、严重不良事件(SAE)发生率和级别等(依据NCI-CTCAEv5.0标准判断)、生命体征变化、实验室检查指标异常和试验期间因研究药物相关毒性导致的剂量暂停、剂量下调及剂量终止的发生率。
部分受试者(165例)的安全性评价结果如表9所示，其中35.2％(58/165)的患者发生了≥3级TRAE，最常见(≥10％)的TRAE包括中性粒细胞计数降低(16.4％)和白细胞计数降低(13.3％)。所有入组受试者(395例)的安全性评价结果显示，ADC-4抗体偶联物耐受性良好，间质性肺疾病(ILD)和≥3级的皮肤毒性发生率极低(均为0.3％)，未发现新的安全问题。
表9.安全性评价结果
综上所述，ADC-4抗体偶联物展示出可耐受且可控的安全性，在非小细胞肺癌中显示出具有前景的抗肿瘤活性。
实施例3.ADC-4联合免疫治疗剂联合或不联合其它抗肿瘤治疗在局部晚期或转移性非小细胞肺癌受试者中的安全性、耐受性及有效性的多中心、开放IB/II期临床研究
1.试验药物
(1)实施例1制备的ADC-4。剂型为注射剂(冻干粉)。
(2)抗PD-L1抗体，其重链如SEQ ID NO：19所示，轻链如SEQ ID NO：20所示。剂型为注射剂。
(3)注射用卡铂注射液、顺铂注射液为已上市药物。
(4)抗VEGF抗体，其重链如SEQ ID NO：39所示，轻链如SEQ ID NO：40所示。剂型为注射剂。
2.入组受试者
1)年龄18周岁以上，性别不限；
2)东部肿瘤协作组(ECOG)体能状态评分为0～1分；
3)预计生存期≥12周；
4)经病理学确诊的局部晚期不可切除或转移性非小细胞肺癌患者：
-IB期阶段受试者经标准治疗失败或不耐受或拒绝标准治疗，同时须满足：驱动基因阴性的受试者，必须接受过免疫治疗与铂类化疗，且既往系统性抗肿瘤治疗线数≤2；驱动基因阳性的受试者，必须接受过靶向治疗与铂类化疗，且既往系统性抗肿瘤治疗线数≤2。
-II期阶段队列A和队列C纳入鳞癌(鳞状非小细胞肺癌)受试者，队列B和队列D纳入非鳞癌(非鳞状非小细胞肺癌)受试者。所有受试者须未接受过针对局部晚期不可切除或转移性非小细胞肺癌的系统性抗肿瘤治疗，包括以实体瘤为适应症的临床研究药物的系统性治疗。既往接受过以治愈为目的的新辅助/辅助性化疗、根治性手术放疗或放化疗治疗非转移性肿瘤的受试者可以入组，但需满足以下条件：自末次化疗、根治性手术、放疗或放化疗最后一次疗程结束后至首次用药之前，至少超过6个月；自末次免疫治疗最后一次疗程结束后至首次用药之前，至少超过12个月。
队列B和队列D的非鳞癌(非鳞状非小细胞肺癌)受试者，必须进行EGFR基因检测和ALK基因和/或免疫组化检测，带有EGFR突变阳性或者ALK融合阳性的受试者不能入组。同时，如存在其它驱动基因突变(除EGFR或ALK基因)、且针对所述驱动基因突变有获批靶向药物疗法的受试者也不能入组。
5)能够提供存档或新鲜肿瘤组织，且肿瘤组织Nectin-4表达阳性，II期阶段的受试者PD-L1 TPS≥1％(均基于中心实验室的免疫组织化学[IHC]检测)。对于无法提供满足上述要求肿瘤组织样本的受试者，需与申办方讨论后确定是否入组。
6)根据RECIST v1.1标准至少有一个可测量病灶。
3.临床方案
3.1研究设计
Ib期阶段
(1)IB期第一部分(IB-Part1)，ADC-4联合抗PD-L1抗体探索：
o剂量水平1：ADC-4 6mg/kg Q3W+抗PD-L1抗体1200mg Q3W，
o剂量水平2：ADC-4 8mg/kg Q3W+抗PD-L1抗体1200mg Q3W。
(2)IB期第二部分(IB-Part2)，ADC-4联合抗PD-L1抗体和铂类药物(卡铂或顺铂)探索：
o剂量水平1:
ADC-4 4mg/kg Q3W+抗PD-L1抗体1200mg Q3W+顺铂75mg/m2 Q3W；或
ADC-4 4mg/kg Q3W+抗PD-L1抗体1200mg Q3W+卡铂AUC4 Q3W；或
ADC-4 4mg/kg Q3W+抗PD-L1抗体1200mg Q3W+卡铂AUC5 Q3W。
o剂量水平2:
ADC-4 6mg/kg Q3W+抗PD-L1抗体1200mg Q3W+顺铂75mg/m2 Q3W；或
ADC-4 6mg/kg Q3W+抗PD-L1抗体1200mg Q3W+卡铂AUC4 Q3W；或
ADC-4 6mg/kg Q3W+抗PD-L1抗体1200mg Q3W+卡铂AUC5 Q3W。
(3)IB期第三部分(IB-Part3)，ADC-4联合抗PD-L1抗体和抗VEGF抗体探索:
o剂量水平1：ADC-4 8mg/kg Q3W+抗PD-L1抗体1200mg Q3W+抗VEGF抗体7.5mg/kg Q3W；
o剂量水平2：ADC-4 8mg/kg Q3W+抗PD-L1抗体1200mg Q3W+抗VEGF抗体15mg/kg Q3W。
II期阶段(疗效拓展)
队列A：接受ADC-4(选定剂量，Q3W)+抗PD-L1抗体(1200mg，Q3W)治疗鳞癌(鳞状非小细胞肺癌)受试者；
队列B：接受ADC-4(选定剂量，Q3W)+抗PD-L1抗体(1200mg，Q3W)治疗非鳞癌(非鳞状非小细胞肺癌)受试者；
队列C：接受ADC-4(选定剂量，Q3W)+抗PD-L1抗体(1200mg，Q3W)+卡铂(AUC4或AUC5，Q3W)治疗鳞癌(鳞状非小细胞肺癌)受试者；或
接受ADC-4(选定剂量，Q3W)+抗PD-L1抗体(1200mg，Q3W)+顺铂(75mg/m2，Q3W)治疗鳞癌(鳞状非小细胞肺癌)受试者；
队列D：接受ADC-4(选定剂量，Q3W)+抗PD-L1抗体(1200mg，Q3W)+卡铂(AUC4或AUC5，Q3W)治疗非鳞癌(非鳞状非小细胞肺癌)受试者；或
接受ADC-4(选定剂量，Q3W)+抗PD-L1抗体(1200mg，Q3W)+顺铂(75mg/m2，Q3W)治疗非鳞癌(非鳞状非小细胞肺癌)受试者；
队列E：接受ADC-4(8mg/kg，Q3W)+抗PD-L1抗体(1200mg，Q3W)+抗VEGF抗体(选定剂量，Q3W)治疗非小细胞肺癌受试者。
3.2给药方式
ADC-4：静脉滴注，4mg/kg，6mg/kg、8mg/kg，Q3W或探索/确定的其他剂量。
抗PD-L1抗体：静脉滴注，1200mg，每3周给药1次，每次滴注时间为30-60分钟，21天为一个周期(Q3W)。
卡铂(按Calvert公式给药)：静脉滴注，按AUC4或AUC 5计算剂量给药，每3周给药1次，具体药物可按照处方信息或按研究中心诊疗常规进行滴注。Calvert公式：卡铂剂量(mg)＝所设定的AUC(mg/mL·min)×[内生肌酐清除率(mL/min)+25]。内生肌酐清除率的计算采用Cockcroft-Gault公式：
血清肌酐浓度：mg/dL
血清肌酐浓度：μmol/L
年龄单位为岁，体重单位为千克(kg)。
顺铂：静脉滴注，75mg/m2，每3周给药1次，每次建议输注1-2小时。
抗VEGF抗体：静脉滴注，7.5mg/kg、15mg/kg，每3周为1个给药周期。
给药顺序：1)两药联合建议先给予ADC-4，再给予抗PD-L1抗体；2)三药联合建议先给予ADC-4，再给予抗PD-L1抗体，最后给予卡铂或顺铂或抗VEGF抗体。两药给药时间间隔应>30分钟。尽量在同一天内完成给药。不同药物的输液需使用单独的输液袋和过滤器。
最大用药疗程：抗PD-L1抗体累计用药满35次需终止用药。卡铂/顺铂使用2-4周期。若因毒性不耐受提前终止某一研究用药，可考虑继续使用其他研究用药。
4.结果评价
4.1有效性指标
肿瘤评估采用RECIST v1.1标准，所有受试者在筛选期进行基线肿瘤影像学评估。有效性指标包括：经研究者评估的ORR、DCR、DoR、PFS、OS。
临床试验还在进行中，在所有完成至少1次肿瘤评估的103例非小细胞肺癌受试者中，IB期入组的受试者(包含非鳞癌受试者和鳞癌受试者)：在IB-Part1剂量水平1下的ORR为30％，DCR为80％，在IB-Part1剂量水平2下的ORR为29.7％，DCR为91.9％；II期入组的受试者(包括30例非鳞癌受试者和26例鳞癌受试者)：在ADC-4(8mg/kg，Q3W)+抗PD-L1抗体(1200mg，Q3W)剂量水平下的ORR达到69.6％，DCR达到96.4％(如表2所示)。
表10.疗效评价


*包括未确认的ORR
4.2安全性评价
所有受试者入组研究后，每个治疗周期都将进行安全性评估。包括AE、严重不良事件(SAE)发生率和级别等(依据NCI-CTCAEv5.0标准判断)、生命体征变化、实验室检查指标异常和试验期间因研究药物相关毒性导致的剂量暂停、剂量下调及剂量终止的发生率。
入组受试者的安全性评价显示，IB期入组的受试者中发生≥3级TRAE的受试者比例为38％，最常见(≥10％)的TRAE包括中性粒细胞计数降低(24％)和贫血(14％)。II期入组的受试者中发生≥3级TRAE的受试者比例为26.3％，最常见(≥10％)的TRAE包括中性粒细胞计数降低(22.8％)和白细胞计数降低(10.5％)。
综上所述，ADC-4抗体偶联物联用其它治疗剂(例如免疫治疗剂)展示出可耐受且可控的安全性，在非小细胞肺癌的后线治疗及一线治疗中显示出具有前景的抗肿瘤活性。
实施例4.ADC-4联合免疫治疗剂联合或不联合其它抗肿瘤治疗在晚期实体瘤受试者中的安全性、耐受性及有效性的多中心、开放IB/II期临床研究
1.试验药物
(1)实施例1制备的ADC-4。剂型为注射剂(冻干粉)。
(2)抗PD-L1抗体，其重链如SEQ ID NO：19所示，轻链如SEQ ID NO：20所示。剂型为注射剂。
(3)抗CTLA-4抗体，其重链如SEQ ID NO：29所示，轻链如SEQ ID NO：30所示。剂型为注射剂。
(4)抗VEGF抗体，其重链如SEQ ID NO：39所示，轻链如SEQ ID NO：40所示。剂型为注射剂。
2.入组受试者
1)年龄18周岁以上，性别不限；
2)东部肿瘤协作组(ECOG)体能状态评分为0～1分；
3)预计生存期≥12周；
4)经病理学确诊的不可切除局部晚期或转移性非小细胞肺癌患者，
-Ib期阶段受试者，经标准治疗失败或不耐受或拒绝标准治疗的局部晚期或转移性非小细胞肺癌患者；既往接受的系统性抗肿瘤治疗线数不超过2线。若为非鳞癌受试者，要求已获得基因检测结果。
-II期阶段：队列A纳入鳞癌受试者，队列B纳入非鳞癌受试者，队列C纳入STK11单突变、KEAP1单突变、或STK11/KEAP1共突变的非小细胞肺癌受试者，队列D纳入非小细胞肺癌受试者。
所有受试者须未接受过针对局部晚期不可切除或转移性非小细胞肺癌的系统性抗肿瘤治疗，包括以实体瘤为适应症的临床研究药物的系统性治疗。既往接受过新辅助/辅助治疗非转移性肿瘤的受试者可以入组(末次新辅助或辅助治疗距本研究首次用药时间须＞6个月；如果新辅助或辅助含免疫治疗，末次免疫治疗至本研究首次用药须≥12个月)。
NSCLC非鳞癌受试者，必须进行EGFR基因检测和ALK基因和/或免疫组化检测；带有EGFR突变阳性或者ALK阳性的受试者不能入组。同时，如存在其它驱动基因突变(除EGFR或ALK基因阳性突变)、且针对所述其它基因突变有获批靶向药物疗法的受试者也不能入组。
5)能够提供存档或新鲜肿瘤组织，用于检测Nectin-4和PD-L1 TPS表达水平。对于无法提供满足上述要求肿瘤组织样本的受试者，需与申办方讨论后确定是否入组。
6)根据RECIST v1.1标准至少有一个可测量病灶。
3.临床方案
3.1研究设计
Ib期阶段(Part A)
剂量组1：ADC-4(6mg/kg，Q3W)+抗PD-L1抗体(1200mg，Q3W)+抗CTLA-4抗体(C1D1 280mg给药一次，C2-C4不给药，C5及后续周期70mg Q6W)
剂量组2：ADC-4(8mg/kg，Q3W)+抗PD-L1抗体(1200mg，Q3W)+抗CTLA-4抗体(C1D1 280mg给药一次，C2-C4不给药，C5及后续周期70mg Q6W)。
Ib期阶段(Part B)
ADC-4(8mg/kg，Q3W)+抗PD-L1抗体(1200mg，Q3W)+抗CTLA-4抗体(C1D1 280mg给药一次，C2-C4不给药，C5及后续周期70mg Q6W)+抗VEGF抗体(15mg/kg，Q3W)。
SMC将根据取得的安全性疗效等数据决定是否探索ADC-4或抗VEGF抗体或抗CTLA-4抗体下调剂量组联合治疗，或以目前方案开展II期。
II期阶段(疗效拓展)
队列A：接受ADC-4(选定剂量，Q3W)+抗PD-L1抗体(1200mg，Q3W)+抗CTLA-4抗体(C1D1 280mg给药一次，C2-C4不给药，C5及后续周期70mg Q6W)治疗鳞癌(鳞状非小细胞肺癌)受试者；
队列B：接受ADC-4(选定剂量，Q3W)+抗PD-L1抗体(1200mg，Q3W)+抗CTLA-4抗体(C1D1 280mg给药一次，C2-C4不给药，C5及后续周期70mg Q6W)治疗非鳞癌(非鳞状非小细胞肺癌)受试者；
队列C：接受ADC-4(选定剂量，Q3W)+抗PD-L1抗体(1200mg，Q3W)+抗CTLA-4抗体(C1D1 280mg给药一次，C2-C4不给药，C5及后续周期70mg Q6W)治疗STK11单突变、KEAP1单突变、或STK11/KEAP1共突变的非小细胞肺癌受试者；
队列D：接受ADC-4(选定剂量，Q3W)+抗PD-L1抗体(1200mg，Q3W)+抗CTLA-4抗体(C1D1 280mg给药一次，C2-C4不给药，C5及后续周期70mg Q6W)+贝伐珠单抗15mg/kg Q3W，用于非小细胞肺癌受试者。
所述抗CTLA-4抗体的给药方式“C1D1 280mg给药一次，C2-C4不给药，C5及后续周期70mg Q6W”是指“以21天为1个周期，第1个周期的第1天单次给药280mg，第2-4个周期不给药，从第5个周期的第1天开始按照70mg、每6周(又称“每隔一个周期”)给药一次的频率给药”。
3.2给药方式
ADC-4：静脉滴注，6mg/kg、8mg/kg，Q3W；或探索/确定的其他剂量。首次静脉滴注时长90±10min，如首次用药后未发生输注相关反应，其后的每次输注可缩短至约30min(不少于20min，不超过60min，包括冲洗阶段)。
抗PD-L1抗体：静脉滴注，1200mg，每3周给药1次，每次滴注时间为30-60分钟，21天为一个周期(Q3W)。累计用药不超过35次。
抗CTLA-4抗体：静脉滴注，C1D1 280mg给药一次，C2-C4不给药，C5及后续周期70mg Q6W(第1个周期的第1天单次给药280mg，第2-4个周期不给药，从第5个周期的第1天开始按照70mg、每6周给药一次的频率给药)。每次静脉滴注时长30±10min，21天为一个周期。累计用药不超过2年。
抗VEGF抗体：静脉滴注，15mg/kg或探索/确定的其它剂量，每3周为1个给药周期，每个周期第一天给药。
给药顺序：建议先给予ADC-4，再给予抗PD-L1抗体，再给予抗CTLA-4抗体，最后再给予抗VEGF抗体(如需)。两药给药时间间隔应>30分钟。尽量在同一天内完成给药。不同药物的输液需使用单独的输液袋和过滤器。
最大用药疗程：抗PD-L1抗体累计用药满35次需终止用药。抗CTLA-4抗体累计用药不超过2年。若因毒性不耐受提前终止某一研究用药，可考虑继续使用其他研究用药。
4.结果评价
4.1有效性评价
肿瘤评估采用RECIST v1.1标准，所有受试者在筛选期进行基线肿瘤影像学评估。有效性指标包括：经研究者评估的标准评价的客观缓解率(ORR)、疾病控制率(DCR)、缓解持续时间(DoR)、无进展生存期(PFS)、总生存期(OS)。
临床试验还在进行中，II期的6例受试者(包括1例非鳞癌受试者和5例鳞癌受试者)，在ADC-4(8mg/kg，Q3W)+抗PD-L1抗体(1200mg，Q3W)+抗CTLA-4抗体(C1D1 280mg给药一次，C2-C4不给药，C5及后续周期70mg Q6W)给药剂量下的ORR达到50％，DCR达到100％。
4.2安全性评价
所有受试者入组研究后，每个治疗周期都将进行安全性评估。包括AE、严重不良事件(SAE)发生率和级别等(依据NCI-CTCAEv5.0标准判断)、生命体征变化、实验室检查指标异常和试验期间因研究药物相关毒性导致的剂量暂停、剂量下调及剂量终止的发生率。
入组受试者的安全性评价显示，受试者中最常见(≥10％)的TRAE包括低钠血症(15.8％)、虚弱(15.8％)、白细胞计数降低(10.5％)、中性粒细胞计数降低(10.5％)和贫血(10.5％)。II期入组的17例受试者发生≥3级TRAE的受试者比例为11.8％。
综上所述，ADC-4抗体偶联物联用其它治疗剂(例如免疫治疗剂)展示出可耐受且可控的安全性，在非小细胞肺癌的后线治疗及一线治疗中显示出具有前景的抗肿瘤活性。
实施例5.ADC-4联合或者不联合其它抗肿瘤治疗在局部晚期或转移性食管癌受试者中的安全性、耐受性及有效性的多中心、开放IB/II期临床研究
1.试验药物
(1)实施例1制备的ADC-4。剂型为注射剂(冻干粉)。
(2)抗PD-L1抗体，其重链如SEQ ID NO：19所示，轻链如SEQ ID NO：20所示。剂型为注射剂。
(3)抗CTLA-4抗体，其重链如SEQ ID NO：29所示，轻链如SEQ ID NO：30所示。剂型为注射剂。
(4)注射用顺铂注射液为已上市药物。
2.入组受试者
1)年龄18-70周岁，性别不限；
2)东部肿瘤协作组(ECOG)体能状态评分为0～1分；
3)预计生存期≥12周；
4)经病理学确诊的局部晚期不可切除或转移性食管鳞癌患者，Ib期阶段受试者经标准治疗失败或不耐受或拒绝标准治疗，受试者须接受过以PD-(L)1和铂类化疗为基础的治疗，且既往治疗线数≤2线。既往接受过新辅助/辅助化疗、根治性放化疗治疗非转移性肿瘤的受试者，如治疗结束后≤6个月内发生疾病复发或转移，该治疗可视作一线治疗。
II期阶段受试者为未接受针对局部晚期不可切除或转移性食管癌的系统性抗肿瘤治疗，包括以实体瘤为适应症的临床研究药物的系统性治疗；如果既往接受过以治愈为目的的新辅助/辅助性化疗、免疫治疗、根治性手术放疗或放化疗治疗非转移性肿瘤的受试者，自末次化疗、根治性手术、放疗或放化疗最后一次疗程结束后至首次用药之前，至少超过6个月；自末次免疫治疗最后一次疗程结束后至首次用药之前，至少超过12个月。
5)能够提供可用于Nectin-4和PD-L1表达检测的存档或新鲜肿瘤组织。
6)根据RECIST v1.1标准至少有一个可测量病灶。
3.临床方案
3.1研究设计
Ib期阶段
(1)IB期第一部分(IB-Part1)，ADC-4联合抗PD-L1抗体探索：
o Part1剂量水平1：ADC-4 6mg/kg Q3W+抗PD-L1抗体1200mg Q3W，
o Part1剂量水平2：ADC-4 8mg/kg Q3W+抗PD-L1抗体1200mg Q3W。
(2)IB期第二部分(IB-Part2)，ADC-4联合抗PD-L1抗体和顺铂探索：
o Part2剂量水平1:ADC-4 4mg/kg Q3W+抗PD-L1抗体1200mg Q3W+顺铂75mg/m2 Q3W，
o Part2剂量水平2:ADC-4 6mg/kg Q3W+抗PD-L1抗体1200mg Q3W+顺铂75mg/m2 Q3W。
(3)IB期第三部分(IB-Part3)，ADC-4联合抗PD-L1抗体和抗CTLA-4抗体探索：
Part3剂量水平1：ADC-4(6mg/kg，Q3W)+抗PD-L1抗体(1200mg，Q3W)+抗CTLA-4抗体(C1D1 280mg给药一次，C2-C4不给药，C5及后续周期70mg Q6W)。
Part3剂量水平2：ADC-4(8mg/kg，Q3W)+抗PD-L1抗体(1200mg，Q3W)+抗CTLA-4抗体(C1D1 280mg给药一次，C2-C4不给药，C5及后续周期70mg Q6W)。
所述抗CTLA-4抗体的给药方式“C1D1 280mg给药一次，C2-C4不给药，C5及后续周期70mg Q6W”是指“以21天为1个周期，第1个周期的第1天单次给药280mg，第2-4个周期不给药，从第5个周期的第1天开始按照70mg、每6周(又称“每隔一个周期”)给药一次的频率给药”。
II期阶段(疗效拓展)
队列A：接受ADC-4(选定剂量，Q3W)+抗PD-L1抗体(1200mg，Q3W)治疗食管鳞癌；
队列B：接受ADC-4(选定剂量，Q3W)+抗PD-L1抗体(1200mg，Q3W)+顺铂(75mg/m2，Q3W)治疗食管鳞癌。
队列C：接受ADC-4(选定剂量，Q3W)+抗PD-L1抗体(1200mg，Q3W)+抗CTLA-4抗体(C1D1 280mg给药一次，C2-C4不给药，C5及后续周期70mg Q6W)治疗食管鳞癌。
3.2给药方式
ADC-4：静脉滴注，4mg/kg，6mg/kg、8mg/kg，Q3W或探索/确定的其他剂量。
抗PD-L1抗体：静脉滴注，1200mg，每3周给药1次，每次滴注时间为30-60分钟，21天为一个周期(Q3W)。
顺铂：静脉滴注，75mg/m2，每3周给药1次，每次滴注时间约60min，化疗用药最长4周期。
抗CTLA-4抗体：静脉滴注，C1D1 280mg给药一次，C2-C4不给药，C5及后续周期70mg Q6W(第1个周期的第1天单次给药280mg，第2-4个周期不给药，从第5个周期的第1天开始按照70mg、每6周(又称“每隔一个周期”)给药一次的频率给药)。每次静脉滴注时长30±10min，21天为一个周期。累计用药不超过2年。
给药顺序：1)两药联合建议先给予ADC-4，再给予抗PD-L1抗体；2)三药联合建议先给予ADC-4，再给予抗PD-L1抗体，最后给予顺铂或抗CTLA-4抗体。两药给药时间间隔应>30分钟。尽量在同一天内完成给药。不同药物的输液需使用单独的输液袋和过滤器。
最大用药疗程：抗PD-L1抗体累计用药满35次、抗CTLA-4抗体从首次用药时间开始用药满2年后需终止用药。若因毒性不耐受提前终止某一研究用药，可考虑继续使用其他研究用药。
4.结果评价
4.1有效性指标
肿瘤评估采用RECIST v1.1标准，所有受试者在筛选期进行基线肿瘤影像学评估。有效性指标包括：经研究者评估的ORR、DCR、DoR、PFS、OS。
临床试验还在进行中，如表11所示，IB期入组的受试者：在Part1剂量水平1(part1-1)下的ORR为30％，DCR为90％，在Part1剂量水平2(part1-2)下的ORR为46.4％，DCR为92.9％。II期入组的受试者：在队列A(II-A，其中ADC-4的剂量为8mg/kg)剂量下的ORR为64.7％，DCR为91.2％，在队列C(II-C，其中ADC-4的剂量为8mg/kg)剂量下的ORR为61.9％，DCR为95.2％。
此外，IB-part3还有8例受试者完成了至少1次肿瘤评估，其中，part3剂量水平1下有4例受试者，包括3例SD(疾病稳定)，1例PD(疾病进展)；part3剂量水平2下有4例受试者，包括2例PR(部分缓解)，2例SD(疾病稳定)。
表11.疗效评价

*ORR：客观缓解率，包括未确认ORR
4.2安全性评价
所有受试者入组研究后，每个治疗周期都将进行安全性评估。包括AE、严重不良事件(SAE)发生率和级别等(依据NCI-CTCAEv5.0标准判断)、生命体征变化、实验室检查指标异常和试验期间因研究药物相关毒性导致的剂量暂停、剂量下调及剂量终止的发生率。
入组受试者的安全性评价显示，入组的受试者中最常见(≥20％)的TRAE包括贫血、食欲减退、恶心、白细胞计数降低、中性粒细胞计数降低、低白蛋白血症、淋巴细胞计数降低、血小板计数降低、脱发、虚弱、呕吐。II期入组的受试者接受1线治疗过程中发生≥3级TRAE的受试者比例为18.8％。
综上所述，ADC-4抗体偶联物联用免疫治疗剂展示出可耐受且可控的安全性，在食管鳞癌的后线治疗及一线治疗中显示出具有前景的抗肿瘤活性。

Claims (29)

  1. 抗Nectin-4抗体药物偶联物在制备用于治疗肿瘤的药物中的用途，所述抗Nectin-4抗体药物偶联物包含如下所示结构：
    其中：
    n为1至10的小数或整数，优选为1至8，更优选为3至5；NEC49为抗Nectin-4抗体；所述肿瘤为非小细胞肺癌或食管癌。
  2. 根据权利要求1所述的用途，其中，所述非小细胞肺癌为晚期非小细胞肺癌；优选为局部晚期或转移性非小细胞肺癌。
  3. 根据权利要求1或2所述的用途，其中，所述非小细胞肺癌为鳞状非小细胞肺癌或非鳞状非小细胞肺癌；
    优选地，所述非鳞状非小细胞肺癌为EGFR突变型非鳞状非小细胞肺癌或EGFR野生型非鳞状非小细胞肺癌；优选为EGFR突变型非鳞状非小细胞肺癌或驱动基因阴性非鳞状非小细胞肺癌。
  4. 根据权利要求1所述的用途，其中，所述食管癌为食管鳞癌，优选为晚期食管鳞癌，更优选为局部晚期或转移性食管鳞癌。
  5. 根据权利要求1-4任一项所述的用途，其中，患有所述非小细胞肺癌或食管癌的受试者既往接受过抗肿瘤标准治疗，所述抗肿瘤标准治疗选自化学疗法、免疫疗法、和/或靶向药物疗法，所述化学疗法包含铂类化疗。
  6. 根据权利要求1-5任一项所述的用途，其中，所述患有所述非小细胞肺癌或食管癌的受试者既往接受抗肿瘤标准治疗后失败或不耐受，优选为接受化学疗法、免疫疗法、和/或靶向药物疗法治疗失败或不耐受的受试者，所述化学疗法包含铂类化疗。
  7. 根据权利要求1-6任一项所述的用途，其中，所述抗Nectin-4抗体包含重链可变区(VH)和轻链可变区(VL)，所述重链可变区包含分别如SEQ ID NO:1、SEQ ID NO:2和SEQ ID NO:3所示的HCDR1、HCDR2和HCDR3；和所述轻链可变区包含分别如SEQ ID NO:4、SEQ ID NO:5和SEQ ID NO:6所示的LCDR1、LCDR2和LCDR3；
    优选地，所述抗Nectin-4抗体包含重链可变区(VH)和轻链可变区(VL)，所述重链可变区包含如SEQ ID NO:7所示或与之具有至少80％、90％同一性的氨基酸序列，所述轻链可变区包含如SEQ ID NO:8所示或与之具有至少80％、90％同一性的氨基酸序列；
    更优选地，所述抗Nectin-4抗体包含重链和轻链，所述重链包含如SEQ ID NO:9所示或与之具有至少80％、90％同一性的氨基酸序列，所述轻链包含如SEQ ID NO:10所示或与之具有至少80％、90％同一性的氨基酸序列。
  8. 根据权利要求1-7任一项所述的用途，其中，所述抗Nectin-4抗体药物偶联物的给药剂量为0.1-20mg/kg，优选为1-10mg/kg，更优选为约1mg/kg，约2mg/kg，约3mg/kg，约4mg/kg，约5mg/kg，约6mg/kg，约7mg/kg，约8mg/kg或约10mg/kg；和/或
    所述抗Nectin-4抗体药物偶联物的给药频率为每2周至少1次，每3周至少1次，每4周至少1次，每6周至少1次，或每8周至少1次；优选为每3周1次，或每3周2次；
    优选地，所述抗Nectin-4抗体药物偶联物的给药剂量为约5mg/kg、约6mg/kg、约7mg/kg，约8mg/kg，约9mg/kg或约10mg/kg，给药频率为每3周1次；或，所述抗Nectin-4抗体药物偶联物的给药剂量为约1mg/kg，约2mg/kg，约3mg/kg，约4mg/kg，给药频率为每3周2次。
  9. 抗Nectin-4抗体药物偶联物联合免疫治疗剂在制备治疗非小细胞肺癌或食管癌的药物中的用途；所述抗Nectin-4抗体药物偶联物包含如下所示结构：
    其中：
    n为1至10的小数或整数，优选为1至8，更优选为3至5；NEC49为抗Nectin-4抗体；
    优选地，所述免疫治疗剂为抗PD-L1抗体、和/或抗CTLA-4抗体；
    优选地，所述抗Nectin-4抗体如权利要求7所定义，所述抗Nectin-4抗体药物偶联物的给药剂量和给药频率如权利要求8所定义。
  10. 根据权利要求9所述的用途，其中，所述非小细胞肺癌为晚期非小细胞肺癌；优选为局部晚期或转移性非小细胞肺癌。
  11. 根据权利要9或10所述的用途，其中，所述非小细胞肺癌为鳞状非小细胞肺癌或非鳞状非小细胞肺癌。
  12. 根据权利要求9所述的用途，其中，所述食管癌为食管鳞癌，优选为晚期食管鳞癌，更优选为局部晚期或转移性食管鳞癌。
  13. 根据权利要求9-12任一项所述的用途，其中，患有所述非小细胞肺癌或食管癌的受试者既往未经治疗，或既往接受抗肿瘤治疗；
    优选地，所述受试者既往接受抗肿瘤治疗后失败或不耐受；
    更优选地，所述受试者既往接受化学疗法、免疫疗法、和/或靶向药物疗法治疗后失败或不耐受，所述化学疗法包含铂类化疗。
  14. 根据权利要求9-13任一项所述的用途，所述抗PD-L1抗体包含重链可变区(VH)和轻链可变区(VL)，所述重链可变区包含分别如SEQ ID NO:11，SEQ ID NO:12和SEQ ID NO:13所示的HCDR1，HCDR2和HCDR3，和所述轻链可变区包含分别如SEQ ID NO:14，SEQ ID NO:15和SEQ ID NO:16所示的LCDR1，LCDR2和LCDR3；
    优选地，所述重链可变区包含如SEQ ID NO：17所示或与之具有至少80％、90％同一性的氨基酸序列，和，所述轻链可变区包含如SEQ ID NO：18所示或与之具有至少80％、90％同一性的氨基酸序列；
    更优选地，所述抗PD-L1抗体包含重链和轻链，所述重链包含SEQ ID NO：19所示或与之具有至少80％、90％同一性的氨基酸序列，和，所述轻链包含如SEQ ID NO：20所示或与之具有至少80％、90％同一性的氨基酸序列。
  15. 根据权利要求9-14任一项所述的用途，其中，所述抗PD-L1抗体的给药剂量为5-5000mg，优选为约100mg，约500mg，约800mg，约900mg，约1000mg，约1100mg，约1200mg，约1300mg，约1400mg，约1500mg，约1600mg，约1800mg，约2000mg，约2200mg，约2500mg，约3000mg；和/或，所述抗PD-L1抗体的给药频率为每2周1次，每3周1次，每4周1次，每5周1次，或每6周1次，优选为每3周1次；
    优选地，所述抗PD-L1抗体的给药剂量为约100mg，约500mg，约800mg，约900mg，约1000mg，约1100mg，约1200mg，约1300mg，约1400mg，约1500mg，约1600mg，约1800mg，约2000mg，约2200mg，约2500mg，约3000mg；所述抗PD-L1抗体的给药频率为每3周1次；
    更优选地，所述抗PD-L1抗体的给药剂量为约1200mg，给药频率为每3周1次。
  16. 根据权利要求9-15任一项所述的用途，其中，所述抗CTLA-4抗体包含重链可变区(VH)和轻链可变区(VL)，所述重链可变区包含分别如SEQ ID NO:21，SEQ ID NO:22和SEQ ID NO:23所示的HCDR1，HCDR2和HCDR3，所述轻链可变区包含分别如SEQ ID NO:24，SEQ ID NO:25和SEQ ID NO:26所示的LCDR1，LCDR2和LCDR3；
    优选地，所述重链可变区包含如SEQ ID NO:27所示或与之具有至少90％同一性的氨基酸序列，所述轻链可变区包含如SEQ ID NO:28所示或与之具有至少90％同一性的氨基酸序列；
    更优选地，所述抗CTLA-4抗体包含重链和轻链，所述重链包含如SEQ ID NO:29所示或与之具有至少80％、90％同一性的氨基酸序列，所述轻链包含如SEQ ID NO:30所示或与之具有至少80％、90％同一性的氨基酸序列。
  17. 根据权利要求9-16任一项所述的用途，其中，所述抗CTLA-4抗体的给药剂量为所述抗CTLA-4抗体的给药剂量为1mg-1000mg，优选为约10mg，约20mg，约30mg，约40mg，约50mg，约60mg，约70mg，约80mg，约90mg，约100mg，约150mg，约200mg，约210mg，约220mg，约230mg，约240mg，约250mg，约260mg，约270mg，约280mg，约290mg，约300mg，约350mg，约500mg或约700mg；和/或
    所述抗CTLA-4抗体的给药频次为每2周1次、每3周1次、每4周1次、每6周1次、每8周1次、每10周1次、每12周1次、每14周1次、每16周1次或单次给药，优选为每6周1次或单次给药；
    优选地，所述抗CTLA-4抗体的给药剂量为约10mg，约20mg，约30mg，约40mg，约50mg，约60mg，约70mg，约80mg，约90mg，约100mg，约150mg，约200mg，约210mg，约220mg，约230mg，约240mg，约250mg，约260mg，约270mg，约280mg，约290mg，约300mg，约350mg，约500mg或约700mg；所述抗CTLA-4抗体的给药频次为每6周1次或单次给药；
    更优选地，所述抗CTLA-4抗体在第1周单次给药，给药剂量为约280mg或210mg，第2-12周不给药，从第13周开始，给药剂量为约70mg，给药频次为每6周1次。
  18. 根据权利要求9-17任一项所述的用途，其选自如下任一项所示的联用：
    (1)抗Nectin-4抗体药物偶联物联合抗PD-L1抗体，
    (2)抗Nectin-4抗体药物偶联物联合抗PD-L1抗体和抗CTLA-4抗体；
    优选地，(1)抗Nectin-4抗体药物偶联物联合抗PD-L1抗体的给药方案为：
    (a)抗Nectin-4抗体药物偶联物的给药剂量为1-10mg/kg，给药频率为每3周1次或每三周2次；(b1)抗PD-L1抗体的给药剂量为5-5000mg，给药频率为每3周1次；或，
    (a)抗Nectin-4抗体药物偶联物的给药剂量为约1mg/kg，约2mg/kg，约3mg/kg，约4mg/kg，约5mg/kg，约6mg/kg，约7mg/kg，约8mg/kg，约9mg/kg或约10mg/kg，给药频率为每3周1次或每3周2次；(b1)抗PD-L1抗体的给药剂量为5-5000mg，给药频率为每3周1次；
    (a)所述抗Nectin-4抗体药物偶联物的给药剂量为约5mg/kg、约6mg/kg、约7mg/kg、约8mg/kg、约9mg/kg或约10mg/kg，给药频率为每3周1次；(b1)抗PD-L1抗体的给药剂量为5-5000mg，给药频率为每3周1次；
    (a)所述抗Nectin-4抗体药物偶联物的给药剂量为约1mg/kg、约2mg/kg、约3mg/kg或约4mg/kg，给药频率为每3周2次；(b1)抗PD-L1抗体的给药剂量为5-5000mg，给药频率为每3周1次；
    (a)所述抗Nectin-4抗体药物偶联物的给药剂量为约6mg/kg或约8mg/kg，给药频率为每3周1次；(b1)抗PD-L1抗体的给药剂量为1200mg，给药频率为每3周1次；或
    (a)所述抗Nectin-4抗体药物偶联物的给药剂量为约4mg/kg，给药频率为每3周2次；(b1)抗PD-L1抗体的给药剂量为1200mg，给药频率为每3周1次；
    优选地，(2)抗Nectin-4抗体药物偶联物联合抗PD-L1抗体和抗CTLA-4抗体的给药方案为：
    (a)抗Nectin-4抗体药物偶联物的给药剂量为1-10mg/kg，给药频率为每3周1次或每三周2次；(b1)抗PD-L1抗体的给药剂量为5-5000mg，给药频率为每3周1次；(b2)抗CTLA-4抗体的给药剂量为1mg-1000mg，给药频率为每6周1次或单次给药；
    (a)抗Nectin-4抗体药物偶联物的给药剂量为约1mg/kg，约2mg/kg，约3mg/kg，约4mg/kg，约5mg/kg，约6mg/kg，约7mg/kg，约8mg/kg，约9mg/kg或约10mg/kg，给药频率为每3周1次或每三周2次；(b1)抗PD-L1抗体的给药剂量为5-5000mg，给药频率为每3周1次；(b2)抗CTLA-4抗体的给药剂量为1mg-1000mg，给药频率为每6周1次或单次给药；
    (a)所述抗Nectin-4抗体药物偶联物的给药剂量为约5mg/kg、约6mg/kg、约7mg/kg、约8mg/kg、约9mg/kg或约10mg/kg，给药频率为每3周1次；(b1)抗PD-L1抗体的给药剂量为5-5000mg，给药频率为每3周1次；(b2)抗CTLA-4抗体的给药剂量为1mg-1000mg，给药频率为每6周1次或单次给药；
    (a)所述抗Nectin-4抗体药物偶联物的给药剂量为约1mg/kg，约2mg/kg，约3mg/kg或约4mg/kg，给药频率为每3周2次；(b1)抗PD-L1抗体的给药剂量为5-5000mg，给药频率为每3周1次；(b2)抗CTLA-4抗体的给药剂量为1mg-1000mg，给药频率为每6周1次或单次给药；
    (a)所述抗Nectin-4抗体药物偶联物的给药剂量为约6mg/kg或约8mg/kg，给药频率为每3周1次；(b1)抗PD-L1抗体的给药剂量为1200mg，给药频率为每3周1次；(b2)抗CTLA-4抗体在第1周单次给药，给药剂量为约210mg或280mg，第2-12周不给药，从第13周开始，给药剂量为约70mg，给药频次为每6周1次；或
    (a)所述抗Nectin-4抗体药物偶联物的给药剂量为约4mg/kg，给药频率为每3周2次；(b1)抗PD-L1抗体的给药剂量为1200mg，给药频率为每3周1次；(b2)抗CTLA-4抗体在第1周单次给药，给药剂量为约210mg或280mg，第2-12周不给药，从第13周开始，给药剂量为约70mg，给药频次为每6周1次。
  19. 根据权利要求9-18任一项所述的用途，其中，所述用途为抗Nectin-4抗体药物偶联物联合免疫治疗剂和VEGF信号通路抑制剂在制备治疗非小细胞肺癌或食管癌的药物中的用途。
  20. 根据权利要求19所述的用途，其中，所述VEGF信号通路抑制剂为抗VEGF抗体；优选地，所述抗VEGF抗体包含重链可变区(VH)和轻链可变区(VL)，所述VH包含分别如SEQ ID NO:31，SEQ ID NO:32和SEQ ID NO:33所示的HCDR1，HCDR2和HCDR3，和所述VL包含分别如SEQ ID NO:34，SEQ ID NO:35和SEQ ID NO:36所示的LCDR1，LCDR2和LCDR3；
    更优选地，所述VH包含如SEQ ID NO：37所示或与之具有至少80％同一性的氨基酸序列，和所述VL包含如SEQ ID NO：38所示或与之具有至少80％同一性的氨基酸序列；
    最优选地，所述抗VEGF抗体包含重链和轻链，所述重链包含SEQ ID NO：39所示或与之具有至少80％同一性的氨基酸序列，和所述轻链包含如SEQ ID NO：40所示或与之具有至少80％同一性的氨基酸序列。
  21. 根据权利要求19或20所述的用途，所述抗VEGF抗体的给药剂量为约1mg/kg至约30mg/kg；优选为约约3.0mg/kg，约4.0mg/kg，约5mg/kg，约6.0mg/kg，约7.5mg/kg，约8.0mg/kg，约9.0mg/kg，约10mg/kg，约11mg/kg，约12mg/kg，约13mg/kg，约14mg/kg，约15mg/kg，约16mg/kg，约17mg/kg，约18mg/kg，约19mg/kg，约20mg/kg；和/或
    所述抗VEGF抗体的给药频率为每1周1次，每2周1次，每3周1次，每4周1次，每6周1次，每8周1次，每10周1次，或每12周1次；优选为每3周1次；
    优选地，
    所述抗Nectin-4抗体药物偶联物的给药剂量为约6mg/kg或约8mg/kg，给药频率为每3周1次；所述抗PD-L1抗体的给药剂量为1200mg，给药频率为每3周1次；所述抗VEGF抗体的给药剂量为约7.5mg/kg；给药频率为每3周1次；
    所述抗Nectin-4抗体药物偶联物的给药剂量为约6mg/kg或约8mg/kg，给药频率为每3周1次；所述抗PD-L1抗体的给药剂量为1200mg，给药频率为每3周1次；所述抗VEGF抗体的给药剂量为约15mg/kg；给药频率为每3周1次；
    所述抗Nectin-4抗体药物偶联物的给药剂量为约6mg/kg或约8mg/kg，给药频率为每3周1次；所述抗PD-L1抗体的给药剂量为1200mg，给药频率为每3周1次；所述抗CTLA-4抗体在第1周单次给药，给药剂量为约210mg或280mg，第2-12周不给药，从第13周开始，给药剂量为约70mg，给药频次为每6周1次；所述抗VEGF抗体的给药剂量为约7.5mg/kg；给药频率为每3周1次；或
    所述抗Nectin-4抗体药物偶联物的给药剂量为约6mg/kg或约8mg/kg，给药频率为每3周1次；所述抗PD-L1抗体的给药剂量为1200mg，给药频率为每3周1次；抗CTLA-4抗体在第1周单次给药，给药剂量为约210mg或280mg，第2-12周不给药，从第13周开始，给药剂量为约70mg，给药频次为每6周1次；所述抗VEGF抗体的给药剂量为约15mg/kg；给药频率为每3周1次。
  22. 根据权利要求9-18任一项所述的用途，其中，所述用途为抗Nectin-4抗体药物偶联物联合免疫治疗剂和铂类药物在制备治疗非小细胞肺癌或食管癌的药物中的用途。
  23. 根据权利要求22所述的用途，所述铂类药物为卡铂或顺铂。
  24. 根据权利要求23所述的用途，所述卡铂的给药剂量(按AUC计)为约0.1mg/mL/min至约50mg/mL/min，或约1mg/mL/min至10mg/mL/min；优选约1mg/mL/min，约2mg/mL/min，约3mg/mL/min，约4mg/mL/min，约5mg/mL/min，约6mg/mL/min，约7mg/mL/min，约8mg/mL/min，约9mg/mL/min，约10mg/mL/min；给药频率为每2周1次、每3周1次、每4周1次、每5周1次、或每6周1次，优选为每3周1次；
    优选地，
    所述抗Nectin-4抗体药物偶联物的给药剂量为约4mg/kg或约6mg/kg，给药频率为每3周1次；所述抗PD-L1抗体的给药剂量为1200mg，给药频率为每3周1次；所述卡铂的给药剂量(按AUC计)为约4mg/mL/min，给药频率为每3周1次；或
    所述抗Nectin-4抗体药物偶联物的给药剂量为约4mg/kg或约6mg/kg，给药频率为每3周1次；所述抗PD-L1抗体的给药剂量为1200mg，给药频率为每3周1次；所述卡铂的给药剂量(按AUC计)为约5mg/mL/min，给药频率为每3周1次。
  25. 根据权利要求23所述的用途，所述顺铂的给药剂量为1mg/m2至500mg/m2，或50mg/m2至150mg/m2；优选约10mg/m2，约20mg/m2，约30mg/m2，约50mg/m2，约65mg/m2，约70mg/m2，约75mg/m2，约80mg/m2，约85mg/m2，约90mg/m2，约100mg/m2，约150mg/m2；给药频率为每2周1次、每3周1次、每4周1次、每5周1次、或每6周1次，优选为每3周1次；
    优选地，
    所述抗Nectin-4抗体药物偶联物的给药剂量为约4mg/kg或约6mg/kg，给药频率为每3周1次；所述抗PD-L1抗体的给药剂量为1200mg，给药频率为每3周1次；所述顺铂的给药剂量为约75mg/m2，给药频率为每3周1次。
  26. 一种药剂盒或制品，其包含如权利要求1、7-8和18中任一项所定义的抗Nectin-4抗体药物偶联物，如权利要求9、14-18中任一项所定义的免疫治疗剂，如权利要求20-21中任一项所定义的VEGF信号通路抑制剂，和/或如权利要求23-25中任一项所定义的铂类药物；
    优选地，所述药剂盒或制品包含抗Nectin-4抗体药物偶联物，抗Nectin-4抗体药物偶联物和抗PD-L1抗体，抗Nectin-4抗体药物偶联物、抗PD-L1抗体和抗VEGF抗体，抗Nectin-4抗体药物偶联物、抗PD-L1抗体和卡铂，抗Nectin-4抗体药物偶联物、抗PD-L1抗体和顺铂，抗Nectin-4抗体药物偶联物、抗PD-L1抗体和抗CTLA-4抗体，抗Nectin-4抗体药物偶联物、抗PD-L1抗体、抗CTLA-4抗体和抗VEGF抗体。
  27. 一种药物组合物，其包含如权利要求1、7-8和18中任一项所定义的抗Nectin-4抗体药物偶联物，如权利要求9、14-18中任一项所定义的免疫治疗剂，如权利要求20-21中任一项所定义的VEGF信号通路抑制剂，和/或如权利要求23-25中任一项所定义的铂类药物；
    优选地，所述药物组合物包含抗Nectin-4抗体药物偶联物，抗Nectin-4抗体药物偶联物和抗PD-L1抗体，抗Nectin-4抗体药物偶联物、抗PD-L1抗体和抗VEGF抗体，抗Nectin-4抗体药物偶联物、抗PD-L1抗体和卡铂，抗Nectin-4抗体药物偶联物、抗PD-L1抗体和顺铂，抗Nectin-4抗体药物偶联物、抗PD-L1抗体和抗CTLA-4抗体，抗Nectin-4抗体药物偶联物、抗PD-L1抗体、抗CTLA-4抗体和抗VEGF抗体。
  28. 权利要求26所述的药剂盒或制品，或权利要求27所述的药物组合物在制备用于治疗肿瘤的药物中的用途；
    优选地，所述肿瘤如权利要求2-6和13中任一项所定义。
  29. 预防或治疗肿瘤的方法，包括向有需要的受试者施用：1)抗Nectin-4抗体药物偶联物，2)抗Nectin-4抗体药物偶联物和免疫治疗剂，3)抗Nectin-4抗体药物偶联物、免疫治疗剂和VEGF信号通路抑制剂，或4)抗Nectin-4抗体药物偶联物、免疫治疗剂和铂类药物；所述抗Nectin-4抗体药物偶联物的给药剂量为0.1-20mg/kg，优选为1-10mg/kg；
    所述抗Nectin-4抗体药物偶联物包含如下所示结构：
    其中：n为1至10的小数或整数，优选为1至8，更优选为3至5；NEC49为抗Nectin-4抗体；
    优选地，所述抗Nectin-4抗体药物偶联物如权利要求1、7-8和18中任一项所定义，所述免疫治疗剂如权利要求9、14-18中任一项所定义，所述VEGF信号通路抑制剂如权利要求20-21中任一项所定义，所述铂类药物如权利要求23-25中任一项所定义；
    所述肿瘤如权利要求2-6和13中任一项所定义。
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