Use of Anti-her2 antibody-drug conjugate in combination with immunotherapeutic agent in preparation of antitumor drug

Abstract

The present disclosure relates to the use of an anti-HER2 antibody-drug conjugate in combination with an immunotherapeutic agent in the preparation of an antitumor drug. More specifically, the present disclosure relates to the use of an anti-HER2 antibody-drug conjugate in combination with an immunotherapeutic agent and a VEGF signaling pathway inhibitor in the preparation of a drug for treating cervical cancer.

Description

Use of anti-HER2 antibody-drug conjugates in combination with immunotherapeutic agents in the preparation of antitumor drugs

[0001] This disclosure claims priority to the following patent application: Chinese Patent Application No. 202510178692.7, filed on February 18, 2025, the entire contents of which are incorporated herein by reference. Technical Field

[0002] This disclosure pertains to the pharmaceutical field and relates to the use of anti-HER2 antibody-drug conjugates (ADCs) in combination with immunotherapeutic agents in the preparation of medicaments for treating cervical cancer; it also relates to the use of anti-HER2 antibody-drug conjugates (ADCs) in combination with immunotherapeutic agents and VEGF signaling pathway inhibitors in the preparation of medicaments for treating cervical cancer; further, it relates to the use of anti-HER2 antibody-drug conjugates (ADCs) in combination with immunotherapeutic agents, VEGF signaling pathway inhibitors, and platinum-based drugs in the preparation of medicaments for treating cervical cancer. Background Technology

[0003] HER2 is a member of the type I transmembrane tyrosine kinase receptor family. It is essentially inactive in its monomeric state, but it can polymerize with the other three transmembrane tyrosine kinase members of the family, HER1, HER3, and HER4, leading to phosphorylation of receptor tyrosine residues and activation of multiple signaling pathways (such as MAPK, PI3K / Akt, etc.), thereby promoting cell proliferation and tumor development.

[0004] HER2-targeting antibody-drug conjugates (ADCs) exert their effects through the following mechanism: First, the antibody in the ADC specifically recognizes and binds to the HER2 receptor on the surface of target cells. Then, it 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 induces apoptosis by damaging DNA or acting on microtubules, thereby exerting its anti-tumor effect. If the cytotoxic drug has high membrane permeability, it may penetrate into the extracellular space after being released from the target cell, killing surrounding HER2-negative cells; this effect is known as bypass killing. This effect may also occur if the cytotoxic drug is released before ADC endocytosis. WO2020063676A discloses a class of ADCs targeting HER2. Given the excellent efficacy of the already approved HER-2 ADC drugs Trastuzumab emtansine (T-DM1) and Trastuzumab Deruxtecan (DS-8201a) in the treatment of cervical cancer and gastric cancer, it is of great significance to conduct research on the indications of the antibody-drug conjugates in WO2020063676A. Summary of the Invention

[0005] This disclosure provides the use of an anti-HER2 antibody drug conjugate in the preparation of a medicament for treating tumors.

[0006] In a first aspect, this disclosure provides the use of an anti-HER2 antibody drug conjugate, an immunotherapy agent, or a combination of an anti-HER2 antibody drug conjugate, an immunotherapy agent, and a VEGF signaling pathway inhibitor, or a combination of an anti-HER2 antibody drug conjugate, an immunotherapy agent, a VEGF signaling pathway inhibitor, and a platinum-based drug in the preparation of a medicament for treating tumors.

[0007] Secondly, this disclosure provides the use of an anti-HER2 antibody drug conjugate, an immunotherapy agent, or a combination of an anti-HER2 antibody drug conjugate, an immunotherapy agent and a VEGF signaling pathway inhibitor, or a combination of an anti-HER2 antibody drug conjugate, an immunotherapy agent, a VEGF signaling pathway inhibitor and a platinum-based drug in the preparation of a medicament for treating tumors.

[0008] Thirdly, this disclosure provides an anti-HER2 antibody-drug conjugate for treating a subject with a tumor, wherein the subject is also administered an immunotherapy agent, or an immunotherapy agent and a VEGF signaling pathway inhibitor, or an immunotherapy agent, a VEGF signaling pathway inhibitor and a platinum-based drug.

[0009] Fourthly, this disclosure provides the use of a pharmaceutical composition in the preparation of a medicament for treating tumors; wherein the pharmaceutical composition comprises an anti-HER2 antibody drug conjugate, an immunotherapy agent, or an anti-HER2 antibody drug conjugate, an immunotherapy agent and a VEGF signaling pathway inhibitor, or an anti-HER2 antibody drug conjugate, an immunotherapy agent, a VEGF signaling pathway inhibitor and a platinum-based drug.

[0010] Fifthly, this disclosure provides a method for treating tumors, including administering to a patient an anti-HER2 antibody drug conjugate, an immunotherapy agent, or an anti-HER2 antibody drug conjugate, an immunotherapy agent, and a VEGF signaling pathway inhibitor, or including administering to a patient an anti-HER2 antibody drug conjugate, an immunotherapy agent, a VEGF signaling pathway inhibitor, and a platinum-based drug.

[0011] Sixthly, this disclosure provides a combination of the aforementioned anti-HER2 antibody drug conjugate and immunotherapy agent for the treatment of tumors, or a combination of the aforementioned anti-HER2 antibody drug conjugate, immunotherapy agent and VEGF signaling pathway inhibitor, or a combination of the aforementioned anti-HER2 antibody drug conjugate, immunotherapy agent, VEGF signaling pathway inhibitor and platinum-based drugs.

[0012] In a seventh aspect, this disclosure provides a VEGF signaling pathway inhibitor for treating tumors, wherein the VEGF signaling pathway inhibitor is used in combination with the aforementioned anti-HER2 antibody drug conjugate and immunotherapy agent, or the VEGF signaling pathway inhibitor is used in combination with the aforementioned anti-HER2 antibody drug conjugate, immunotherapy agent and platinum-based drug.

[0013] Eighthly, this disclosure provides an immunotherapy agent for treating tumors, wherein the immunotherapy agent is used in combination with the aforementioned anti-HER2 antibody drug conjugate, or the immunotherapy agent is used in combination with the aforementioned anti-HER2 antibody drug conjugate and a VEGF signaling pathway inhibitor, or the immunotherapy agent is used in combination with the aforementioned anti-HER2 antibody drug conjugate, a VEGF signaling pathway inhibitor, and a platinum-based drug.

[0014] In a ninth aspect, this disclosure provides a pharmaceutical composition comprising an anti-HER2 antibody-drug conjugate, an immunotherapeutic agent, or comprising an anti-HER2 antibody-drug conjugate, an immunotherapeutic agent and a VEGF signaling pathway inhibitor, or comprising an anti-HER2 antibody-drug conjugate, an immunotherapeutic agent, a VEGF signaling pathway inhibitor and a platinum-based drug.

[0015] In a tenth aspect, this disclosure provides a kit or article comprising an anti-HER2 antibody-drug conjugate, an immunotherapeutic agent, or comprising an anti-HER2 antibody-drug conjugate, an immunotherapeutic agent, and a VEGF signaling pathway inhibitor, or comprising an anti-HER2 antibody-drug conjugate, an immunotherapeutic agent, a VEGF signaling pathway inhibitor, and a platinum-based drug. In some embodiments, the kit or article further comprises one or more containers, each independently containing an anti-HER2 antibody-drug conjugate, an immunotherapeutic agent, a VEGF signaling pathway inhibitor, and / or a platinum-based drug.

[0016] In some implementations, this disclosure provides for any of the following uses:

[0017] (1) Use of antiHER2 antibody-drug conjugates in the preparation of antitumor drugs;

[0018] (2) Use of anti-HER2 antibody drug conjugates in combination with immunotherapy agents in the preparation of antitumor drugs;

[0019] (3) The use of combinations of anti-HER2 antibody drug conjugates and immunotherapeutic agents in the preparation of antitumor drugs;

[0020] (4) The use of anti-HER2 antibody drug conjugates in combination with immunotherapeutic agents and VEGF signaling pathway inhibitors in the preparation of antitumor drugs;

[0021] (5) The use of combinations of anti-HER2 antibody drug conjugates, immunotherapeutic agents and VEGF signaling pathway inhibitors in the preparation of antitumor drugs;

[0022] (6) Use of antiHER2 antibody drug conjugates in combination with immunotherapeutic agents, VEGF signaling pathway inhibitors and platinum drugs in the preparation of antitumor drugs;

[0023] (7) Use of combinations of antiHER2 antibody drug conjugates and immunotherapeutic agents, VEGF signaling pathway inhibitors and platinum drugs in the preparation of antitumor drugs;

[0024] (8) Anti-HER2 antibody-drug conjugates used to treat subjects with tumors;

[0025] (9) Anti-HER2 antibody drug conjugates combined with immunotherapeutic agents, used to treat subjects with tumors;

[0026] (10) Anti-HER2 antibody drug conjugate combined with immunotherapy agents and VEGF signaling pathway inhibitors, used to treat subjects with tumors;

[0027] (11) Anti-HER2 antibody drug conjugates combined with immunotherapeutic agents, VEGF signaling pathway inhibitors and platinum drugs, used to treat subjects with tumors;

[0028] (12) The anti-HER2 antibody drug conjugate is used to treat tumors, wherein the anti-HER2 antibody drug conjugate is administered in combination with an immunotherapy agent to the subject;

[0029] (13) The anti-HER2 antibody drug conjugate is used to treat tumors, wherein the anti-HER2 antibody drug conjugate is administered to the subject in combination with an immunotherapy agent and a VEGF signaling pathway inhibitor;

[0030] (14) The anti-HER2 antibody drug conjugate is used to treat tumors, wherein the anti-HER2 antibody drug conjugate is administered to the subject in combination with an immunotherapy agent, a VEGF signaling pathway inhibitor and a platinum-based drug;

[0031] (15) An immunotherapy agent is used to treat tumors, wherein the immunotherapy agent is administered to a subject in combination with an anti-HER2 antibody drug conjugate;

[0032] (16) An immunotherapy agent is used to treat tumors, wherein the immunotherapy agent is administered to a subject in combination with an anti-HER2 antibody drug conjugate and a VEGF signaling pathway inhibitor;

[0033] (17) An immunotherapy agent is used to treat tumors, wherein the immunotherapy agent is administered to the subject in combination with an anti-HER2 antibody drug conjugate, a VEGF signaling pathway inhibitor and a platinum-based drug;

[0034] (18) Anti-HER2 antibody drug conjugates for anti-tumor purposes, wherein the anti-HER2 antibody drug conjugates are used in combination with immunotherapeutic agents;

[0035] (19) Anti-HER2 antibody drug conjugate for anti-tumor purposes, wherein the anti-HER2 antibody drug conjugate is used in combination with an immunotherapy agent and a VEGF signaling pathway inhibitor;

[0036] (20) Anti-HER2 antibody drug conjugates for anti-tumor purposes, wherein the anti-HER2 antibody drug conjugates are used in combination with immunotherapeutic agents, VEGF signaling pathway inhibitors and platinum-based drugs;

[0037] (21) An antitumor immunotherapy agent, wherein the immunotherapy agent is used in combination with an antiHER2 antibody drug conjugate;

[0038] (22) For use in antitumor immunotherapy agents, wherein the immunotherapy agent is used in combination with an antiHER2 antibody drug conjugate and a VEGF signaling pathway inhibitor;

[0039] (23) For use in antitumor immunotherapy agents, wherein the immunotherapy agent is used in combination with antiHER2 antibody drug conjugates, VEGF signaling pathway inhibitors and platinum drugs;

[0040] (24) For use in antitumor drug compositions, kits or articles, wherein the drug composition, kit or article includes an antiHER2 antibody drug conjugate;

[0041] (25) For use in antitumor drug compositions, kits or articles, wherein the drug composition, kit or article comprises antiHER2 antibody drug conjugates and immunotherapeutic agents;

[0042] (26) For use in antitumor drug compositions, kits or articles, wherein the drug composition, kit or article includes antiHER2 antibody drug conjugates, immunotherapeutic agents and VEGF signaling pathway inhibitors;

[0043] (27) For use in antitumor drug compositions, kits or articles, wherein the drug composition, kit or article includes antiHER2 antibody drug conjugates, immunotherapeutic agents, VEGF signaling pathway inhibitors and platinum drugs;

[0044] (28) Use of a pharmaceutical composition, kit or article in the preparation of an antitumor drug, wherein the pharmaceutical composition, kit or article includes an antiHER2 antibody drug conjugate;

[0045] (29) Use of a pharmaceutical composition, kit or article in the preparation of an antitumor drug, wherein the pharmaceutical composition, kit or article includes an antiHER2 antibody drug conjugate and an immunotherapy agent;

[0046] (30) Use of a pharmaceutical composition, kit or article in the preparation of an antitumor drug, wherein the pharmaceutical composition, kit or article includes an antiHER2 antibody drug conjugate, an immunotherapy agent and a VEGF signaling pathway inhibitor;

[0047] (31) Use of a pharmaceutical composition, kit or article in the preparation of an antitumor drug, wherein the pharmaceutical composition, kit or article includes antiHER2 antibody drug conjugates, immunotherapeutic agents, VEGF signaling pathway inhibitors and platinum drugs.

[0048] In some embodiments, the use described in any of the foregoing embodiments may be in the preparation of perioperative treatment drugs for tumors, including in the preparation of neoadjuvant drugs for tumor surgery and / or adjuvant drugs for tumor surgery.

[0049] In some embodiments, the treatment of tumors or treatment of a subject with tumors described in any of the foregoing embodiments may be perioperative treatment for tumors, including neoadjuvant therapy before tumor surgery and / or adjuvant therapy after tumor surgery.

[0050] In some implementations, this disclosure provides a method as shown in any of the following:

[0051] (1) Methods of treating tumors, including administering a therapeutically effective amount of an anti-HER2 antibody-drug conjugate to subjects in need;

[0052] (2) Methods of treating tumors, including administering therapeutically effective doses of antiHER2 antibody-drug conjugates and immunotherapeutic agents to subjects in need;

[0053] (3) Methods of treating tumors, including administering therapeutically effective doses of antiHER2 antibody-drug conjugates, immunotherapeutic agents and VEGF signaling pathway inhibitors to subjects in need;

[0054] (4) Methods of treating tumors, including administering therapeutically effective doses of antiHER2 antibody-drug conjugates, immunotherapeutic agents, VEGF signaling pathway inhibitors and platinum-based drugs to subjects in need;

[0055] (5) 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-HER2 antibody-drug conjugate;

[0056] (6) 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-HER2 antibody-drug conjugate and an immunotherapeutic agent;

[0057] (7) 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 includes an anti-HER2 antibody drug conjugate, an immunotherapy agent and a VEGF signaling pathway inhibitor.

[0058] (8) 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 includes anti-HER2 antibody-drug conjugates, immunotherapeutic agents, VEGF signaling pathway inhibitors, and platinum-based drugs.

[0059] In some embodiments, the treatment method described in any of the foregoing embodiments can be a perioperative treatment method for tumors, including neoadjuvant therapy before tumor surgery and / or adjuvant therapy after tumor surgery.

[0060] In some implementations, this disclosure provides a product as shown in any of the following:

[0061] (1) A pharmaceutical composition comprising an anti-HER2 antibody-drug conjugate;

[0062] (2) A kit containing an anti-HER2 antibody drug conjugate;

[0063] (3) Products, including anti-HER2 antibody-drug conjugates;

[0064] (4) A pharmaceutical composition comprising an anti-HER2 antibody-drug conjugate and an immunotherapeutic agent;

[0065] (5) A kit containing an anti-HER2 antibody drug conjugate and an immunotherapy agent;

[0066] (6) Products, including anti-HER2 antibody-drug conjugates and immunotherapeutic agents;

[0067] (7) A pharmaceutical composition comprising an anti-HER2 antibody-drug conjugate, an immunotherapeutic agent and a VEGF signaling pathway inhibitor;

[0068] (8) A kit containing an anti-HER2 antibody drug conjugate, an immunotherapy agent and a VEGF signaling pathway inhibitor;

[0069] (9) Products, including anti-HER2 antibody-drug conjugates, immunotherapeutic agents and VEGF signaling pathway inhibitors;

[0070] (10) Pharmaceutical compositions comprising anti-HER2 antibody-drug conjugates, immunotherapeutic agents, and VEGF signaling pathways.

[0071] Inhibitors and platinum-based drugs;

[0072] (11) A kit containing anti-HER2 antibody-drug conjugates, immunotherapeutic agents, and VEGF signaling pathway inhibitors.

[0073] Antibiotics and platinum-based drugs;

[0074] (12) Products, including anti-HER2 antibody drug conjugates, immunotherapeutic agents, VEGF signaling pathway inhibitors and platinum-based drugs.

[0075] In some embodiments, the tumor is cervical cancer. In some embodiments, the cervical cancer is cervical squamous cell carcinoma, cervical adenocarcinoma, or cervical adenosquamous carcinoma. In some embodiments, the cervical cancer is cervical squamous cell carcinoma. In some embodiments, the cervical cancer is cervical adenocarcinoma. In some embodiments, the cervical cancer is cervical adenosquamous carcinoma.

[0076] In some embodiments, the cervical cancer is recurrent or metastatic cervical cancer. In some embodiments, the cervical cancer is recurrent or metastatic cervical squamous cell carcinoma, recurrent or metastatic cervical adenocarcinoma, or recurrent or metastatic cervical adenosquamous carcinoma. In some embodiments, the cervical cancer is recurrent or metastatic cervical squamous cell carcinoma. In some embodiments, the cervical cancer is recurrent or metastatic cervical adenocarcinoma. In some embodiments, the cervical cancer is recurrent or metastatic cervical adenosquamous carcinoma.

[0077] In some embodiments, the cervical cancer is recurrent or metastatic cervical cancer that is unsuitable for radical surgery, radical radiotherapy, and / or radical chemoradiotherapy. In some embodiments, the cervical cancer is recurrent or metastatic cervical cancer that is unsuitable for radical surgery, radical radiotherapy, and / or radical chemoradiotherapy, and the recurrent or metastatic cervical cancer is recurrent or metastatic squamous cell carcinoma of the cervix, recurrent or metastatic adenocarcinoma of the cervix, or recurrent or metastatic adenosquamous carcinoma of the cervix. In some embodiments, the cervical cancer is recurrent or metastatic squamous cell carcinoma of the cervix that is unsuitable for radical surgery, radical radiotherapy, and / or radical chemoradiotherapy. In some embodiments, the cervical cancer is recurrent or metastatic adenosquamous carcinoma of the cervix that is unsuitable for radical surgery, radical radiotherapy, and / or radical chemoradiotherapy. In some embodiments, the cervical cancer is recurrent or metastatic adenosquamous carcinoma of the cervix that is unsuitable for radical surgery, radical radiotherapy, and / or radical chemoradiotherapy.

[0078] In some embodiments, the cervical cancer is recurrent or metastatic cervical cancer, and the patient has received ≤1 line of systemic therapy or has not received systemic therapy during the recurrence and metastasis stage. In some embodiments, the cervical cancer is recurrent or metastatic cervical cancer, and the patient has received ≤1 line of systemic therapy or has not received systemic therapy during the recurrence and metastasis stage; the recurrent or metastatic cervical cancer is recurrent or metastatic squamous cell carcinoma of the cervix, recurrent or metastatic adenocarcinoma of the cervix, or recurrent or metastatic adenosquamous carcinoma of the cervix. In some embodiments, the cervical cancer is recurrent or metastatic squamous cell carcinoma of the cervix, and the patient has received ≤1 line of systemic therapy or has not received systemic therapy during the recurrence and metastasis stage. In some embodiments, the cervical cancer is recurrent or metastatic adenosquamous carcinoma of the cervix, and the patient has received ≤1 line of systemic therapy or has not received systemic therapy during the recurrence and metastasis stage. In some embodiments, the cervical cancer is HER2-expressing cervical cancer or HER2-non-expressing cervical cancer. In some embodiments, the HER2-expressing cervical cancer includes HER2-positive and HER2-low-expressing cervical cancer. In some implementations, the cervical cancer has HER2 expression IHC ≥ 1+ or IHC < 1+.

[0079] In this disclosure, treatment options for recurrent or metastatic cervical cancer (e.g., systemic therapy, ≤1-line systemic therapy) are well known to those skilled in the art, for example, as disclosed in treatment guidelines approved by regulatory authorities. Examples include, but are not limited to, detailed and up-to-date information on cervical cancer treatment options provided in the NCCN guidelines and CSCO guidelines.

[0080] <Anti-HER2 antibody-drug conjugate>

[0081] In some embodiments, the structure of the antibody-drug conjugate is shown in formula (I):

[0082] in:

[0083] n is between 3 and 8, and n is a decimal or an integer;

[0084] Pc is an anti-HER2 antibody.

[0085] In some implementations, n is 5.3-6.4, such as 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6.0, 6.1, 6.2, 6.3 or 6.4.

[0086] In the context of this disclosure, "antibody" is used in the broadest sense and encompasses a 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. In some embodiments, the antibody is a full-length antibody or an antigen-binding fragment thereof.

[0087] Anti-HER2 antibody

[0088] In some embodiments, the anti-HER2 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.

[0089] The CDR sequences mentioned above are shown in Table 1 below:

[0090] Table 1. CDR sequences of anti-HER2 antibodies (Kabat protocol)

[0091] In some implementations, the anti-HER2 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.

[0092] In some embodiments, the anti-HER2 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. 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.

[0093] In some implementations, the anti-HER2 antibody is a chimeric, humanized, fully human antibody or its antigen-binding fragment.

[0094] In some embodiments, the anti-HER2 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.

[0095] Heavy chain variable region:

[0096] Light chain variable region:

[0097] In some implementations, the anti-HER2 antibody comprises any one or both of the aforementioned VH and VL.

[0098] In some embodiments, the anti-HER2 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. In some embodiments, the light chain constant region may be selected from the light chain constant region of human κ, λ chains, or their variants.

[0099] In some embodiments, the anti-HER2 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.

[0100] In some embodiments, the anti-HER2 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.

[0101] Heavy chain sequence of anti-HER2 antibody:

[0102] Light chain sequence of anti-HER2 antibody:

[0103] Note: The underlined portion is the variable region sequence of the antibody heavy or light chain, and the ununderlined portion is the constant region sequence of the antibody.

[0104] In some implementations, the anti-HER2 antibody is selected from Trastuzumab and Pertuzumab.

[0105] In some implementations, the anti-HER2 antibody is Trastuzumab.

[0106] In some embodiments, the antibody-drug conjugate has the structure shown in the following formula:

[0107] Where n is between 3 and 8, and n is a decimal or an integer.

[0108] In some implementations, n is 6 in the anti-HER2 antibody drug conjugate.

[0109] In some embodiments, n in the anti-HER2 antibody drug conjugate is 5.3-6.4, for example, n is 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6.0, 6.1, 6.2, 6.3 or 6.4.

[0110] In some embodiments, the anti-HER2 antibody drug conjugate is trastuzumab rezetecan.

[0111] In some embodiments, the single-dose dose of the anti-HER2 antibody-drug conjugate may be, optionally, about 0.1 mg / kg to about 20.0 mg / kg, about 1.0 mg / kg to about 10.0 mg / kg, about 1.0 mg / kg to about 8.0 mg / kg, about 1.0 mg / kg to about 6.0 mg / kg, about 1.0 mg / kg to about 5.0 mg / kg, about 1.0 mg / kg to about 4.0 mg / kg, about 2.0 mg / kg to about 10.0 mg / kg, about 2.0 mg / kg to about 8.0 mg / kg, about 2.0 mg / kg to about 6.0 mg / kg, about 2.0 mg / kg to about 5.0 mg / kg, about 2.0 mg / kg to about 4.0 mg / kg, about 3.2 mg / kg to about 8.0 mg / kg, about 3.2 mg / kg to about 6.4 mg / kg, or about 2.0 mg / kg to about 6.4 mg / kg.

[0112] In some embodiments, the single-dose dose of the anti-HER2 antibody-drug conjugate may be selected from about 0.1 mg / kg, 1.0 mg / kg, about 1.2 mg / kg, about 1.4 mg / kg, about 1.6 mg / kg, about 1.8 mg / kg, about 2.0 mg / kg, about 2.2 mg / kg, about 2.4 mg / kg, about 2.6 mg / kg, about 2.8 mg / kg, about 3.0 mg / kg, about 3.2 mg / kg, about 3.4 mg / kg, about 3.6 mg / kg, about 3.8 mg / kg, about 4.0 mg / kg, about 4.2 mg / kg, about 4.4 mg / kg, about 4.6 mg / kg, about 4.8 mg / kg, about 5.0 mg / kg, about 5.2 mg / kg, about 5.4 mg / kg, and about 5 mg / kg. 6 mg / kg, approximately 5.8 mg / kg, approximately 6.0 mg / kg, approximately 6.2 mg / kg, approximately 6.4 mg / kg, approximately 6.6 mg / kg, approximately 6.8 mg / kg, approximately 7.0 mg / kg, approximately 7.2 mg / kg, approximately 7.4 mg / kg, approximately 7.6 mg / kg, approximately 7.8 mg / kg, approximately 8.0 mg / kg, approximately 8.2 mg / kg, approximately 8.4 mg / kg, approximately 8.6 mg / kg, approximately 8.8 mg / kg, approximately 9.0 mg / kg, approximately 9.2 mg / kg, approximately 9.4 mg / kg, approximately 9.6 mg / kg, approximately 9.8 mg / kg, approximately 10.0 mg / kg, approximately 12.0 mg / kg, approximately 15.0 mg / kg, approximately 20.0 mg / kg, or any range between these values.In some embodiments, the single-dose dose of the anti-HER2 antibody-drug conjugate may be selected from 1.0 mg / kg, 1.2 mg / kg, 1.4 mg / kg, 1.6 mg / kg, 1.8 mg / kg, 2.0 mg / kg, 2.2 mg / kg, 2.4 mg / kg, 2.6 mg / kg, 2.8 mg / kg, 3.0 mg / kg, 3.2 mg / kg, 3.4 mg / kg, 3.6 mg / kg, 3.8 mg / kg, 4.0 mg / kg, 4.2 mg / kg, 4.4 mg / kg, 4.6 mg / kg, 4.8 mg / kg, 5.0 mg / kg, 5.2 mg / kg, 5.4 mg / kg, 5.6 mg / kg, etc. The values ​​are 5.8 mg / kg, 6.0 mg / kg, 6.2 mg / kg, 6.4 mg / kg, 6.6 mg / kg, 6.8 mg / kg, 7.0 mg / kg, 7.2 mg / kg, 7.4 mg / kg, 7.6 mg / kg, 7.8 mg / kg, 8.0 mg / kg, 8.2 mg / kg, 8.4 mg / kg, 8.6 mg / kg, 8.8 mg / kg, 9.0 mg / kg, 9.2 mg / kg, 9.4 mg / kg, 9.6 mg / kg, 9.8 mg / kg, 10.0 mg / kg, 12.0 mg / kg, 15.0 mg / kg, 20.0 mg / kg, or any range between these values.

[0113] In some embodiments, the anti-HER3 antibody-drug conjugate 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-HER3 antibody-drug conjugate is administered once every 3 weeks.

[0114] In some embodiments, the dosing regimen of the anti-HER3 antibody-drug conjugate is selected from any of the following:

[0115] The dosage is from about 0.1 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.

[0116] The dosage is from about 1.0 mg / kg to about 10 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.

[0117] The dosage is from about 1.0 mg / kg to about 8.0 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.

[0118] The dosage is from about 1.0 mg / kg to about 6.0 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.

[0119] The dosage is from about 1.0 mg / kg to about 5.0 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.

[0120] The dosage is from about 1.0 mg / kg to about 4.0 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.

[0121] The dosage is from about 2.0 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.

[0122] The dosage is from about 2.0 mg / kg to about 8.0 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.

[0123] The dosage is from about 2.0 mg / kg to about 6.4 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.

[0124] The dosage is from about 2.0 mg / kg to about 6.0 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.

[0125] The dosage is from about 2.0 mg / kg to about 5.0 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.

[0126] The dosage is from about 2.0 mg / kg to about 4.0 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.

[0127] The dosage is from about 3.2 mg / kg to about 8.0 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.

[0128] The dosage is from about 3.2 mg / kg to about 6.4 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.

[0129] The dosage is approximately 1.0 mg / kg, approximately 2.0 mg / kg, approximately 3.0 mg / kg, approximately 3.2 mg / kg, approximately 4.0 mg / kg, approximately 4.5 mg / kg, approximately 4.8 mg / kg, approximately 5.0 mg / kg, approximately 5.5 mg / kg, approximately 5.6 mg / kg, approximately 6.0 mg / kg, approximately 6.4 mg / kg, approximately 7 mg / kg, approximately 8.0 mg / kg, approximately 9.0 mg / kg, and approximately 10 mg / kg; 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.

[0130] In some embodiments, the single dose of the anti-HER2 antibody-drug conjugate is about 1.0 mg / kg, and the dosing frequency is once every 3 weeks.

[0131] In some embodiments, the single dose of the anti-HER2 antibody-drug conjugate is about 2.0 mg / kg, and the dosing frequency is once every 3 weeks.

[0132] In some embodiments, the single dose of the anti-HER2 antibody-drug conjugate is approximately 3.2 mg / kg, and the dosing frequency is once every 3 weeks.

[0133] In some embodiments, the single dose of the anti-HER2 antibody-drug conjugate is approximately 4.0 mg / kg, and the dosing frequency is once every 3 weeks.

[0134] In some embodiments, the single dose of the anti-HER2 antibody drug conjugate is approximately 4.8 mg / kg, and the dosing frequency is once every 3 weeks.

[0135] In some embodiments, the single-dose of the anti-HER2 antibody-drug conjugate is about 5.6 mg / kg, and the dosing frequency is once every three weeks.

[0136] In some embodiments, the single-dose of the anti-HER2 antibody-drug conjugate is about 6.4 mg / kg, and the dosing frequency is once every three weeks.

[0137] In some embodiments, the single-dose of the anti-HER2 antibody-drug conjugate is about 8.0 mg / kg, and the dosing frequency is once every three weeks.

[0138] In some embodiments, the single-dose of the anti-HER2 antibody-drug conjugate is about 10 mg / kg, and the dosing frequency is once every three weeks.

[0139] In some embodiments, the administration route of the anti-HER2 antibody-drug conjugate can be oral administration, parenteral administration, or transdermal administration. The parenteral administration includes, but is not limited to, intravenous injection, subcutaneous injection, and intramuscular injection. In some specific embodiments, the administration route of the anti-HER2 antibody-drug conjugate is intravenous infusion.

[0140] In some embodiments, the anti-HER2 antibody-drug conjugate is configured in an injectable form. Exemplarily, the injectable form of the antibody-drug conjugate is an injection solution or a lyophilized powder for injection, which contains the antibody-drug conjugate and one or more pharmaceutically acceptable excipients.

[0141] <VEGF signaling pathway inhibitor>

[0142] In some embodiments, the VEGF signaling pathway inhibitor is an anti-VEGF antibody.

[0143] In some embodiments, 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: 1-3, and the light-chain variable region comprises LCDR1, LCDR2, and LCDR3 as shown in SEQ ID NO: 4-6.

[0144] In some embodiments, 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 HCDR1 in the heavy chain variable region is shown in SEQ ID NO: 1, the amino acid sequence of HCDR2 is shown in SEQ ID NO: 2, and the amino acid sequence of HCDR3 is shown in SEQ ID NO: 3, and the amino acid sequence of LCDR1 in the light chain variable region is shown in SEQ ID NO: 4, the amino acid sequence of LCDR2 is shown in SEQ ID NO: 5, and the amino acid sequence of LCDR3 is shown in SEQ ID NO: 6. The CDR sequences described above are shown in Table 2 below:

[0145] Table 2. CDR sequences of anti-VEGF antibodies

[0146] The CDR mentioned above is defined according to the Kabat definition scheme.

[0147] In some embodiments, 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.

[0148] In some embodiments, 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 heavy chain variable region comprises HCDR1, HCDR2 and HCDR3 of the amino acid sequence shown in SEQ ID NO: 7, and the light chain variable region comprises LCDR1, LCDR2 and LCDR3 of the amino acid sequence shown in SEQ ID NO: 8.

[0149] In some embodiments, such as the anti-VEGF antibody described in any of the preceding embodiments, 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.

[0150] In some implementations, the anti-VEGF antibody or its antigen-binding fragment is a chimeric, humanized, or fully human antibody or its antigen-binding fragment.

[0151] In some embodiments, 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: 7, 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: 8, or an amino acid sequence having at least 80% or 90% sequence identity with it.

[0152] Anti-VEGF antibody heavy chain variable region:

[0153] Anti-VEGF antibody light chain variable region:

[0154] In some embodiments, 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: 7, and the light chain variable region contains an amino acid sequence as shown in or having at least 80% identity with SEQ ID NO: 8.

[0155] In some embodiments, the anti-VEGF antibody further comprises a heavy chain constant region and / or a light chain constant region. For example, 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 κ and λ chain constant regions and their variants.

[0156] In some embodiments, the anti-VEGF 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% 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% sequence identity with it.

[0157] In some embodiments, the anti-VEGF 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.

[0158] Heavy chain sequence of anti-VEGF antibody:

[0159] Light chain sequence of anti-VEGF antibody:

[0160] Note: The underlined portion is the variable region sequence of the antibody heavy or light chain, and the ununderlined portion is the constant region sequence of the antibody.

[0161] In some implementations, the anti-VEGF antibody is bevacizumab.

[0162] In some embodiments, 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 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. mg / kg, about 2.0 mg / kg to about 17 mg / kg, about 2.0 mg / kg to about 16 mg / kg, about 2.0 mg / kg to about 15 mg / kg, about 3.0 mg / kg to about 25 mg / kg, about 3.0 mg / kg to about 20 mg / kg, about 3.0 mg / kg to about 19 mg / kg, about 3.0 mg / kg to about 18 mg / kg, about 3.0 mg / kg to about 17 mg / kg, about 3.0 mg / kg to about 16 mg / kg, about 3.0 mg / kg to about 15 mg / kg, about 4.0 mg / kg to about 25 mg / kg, about 4.0 mg / kg to about 20 mg / kg, about 4.0 mg / kg to Approximately 19 mg / kg, approximately 4.0 mg / kg to approximately 18 mg / kg, approximately 4.0 mg / kg to approximately 17 mg / kg, approximately 4.0 mg / kg to approximately 16 mg / kg, approximately 4.0 mg / kg to approximately 15 mg / kg, approximately 5.0 mg / kg to approximately 25 mg / kg, approximately 5.0 mg / kg to approximately 20 mg / kg, approximately 5.0 mg / kg to approximately 19 mg / kg, approximately 5.0 mg / kg to approximately 18 mg / kg, approximately 5.0 mg / kg to approximately 17 mg / kg, approximately 5.0 mg / kg to approximately 16 mg / kg, approximately 5.0 mg / kg to approximately 15 mg / kg, approximately 6.0 mg / kg to approximately 25 mg / kg, approximately 6.0 mg / kg to about 20 mg / kg, about 6.0 mg / kg to about 19 mg / kg, about 6.0 mg / kg to about 18 mg / kg, about 6.0 mg / kg to about 17 mg / kg, about 6.0 mg / kg to about 16 mg / kg, about 6.0 mg / kg to about 15 mg / kg, about 7.0 mg / kg to about 25 mg / kg, about 7.0 mg / kg to about 23 mg / kg, about 7.0 mg / kg to about 20 mg / kg, about 7.0 mg / kg to about 19 mg / kg, about 7.0 mg / kg to about 18 mg / kg, about 7.0 mg / kg to about 17 mg / kg, about 7.0 mg / kg to about 16 mg / kg, about 7.0 mg / kg to about 15 mg / kg, about 8 mg / kg to about 20 mg / kg, about 8 mg / kg to about 19 mg / kg, about 8 mg / kg to about 18 mg / kg, about 8 mg / kg to about 17 mg / kg, about 8 mg / kg to about 16 mg / kg, about 8 mg / kg to about 15 mg / kg; about 8 mg / kg to about 15 mg / kg, about 9 mg / kg to about 21 mg / kg, about 10 mg / kg to about 20 mg / kg, about 10 mg / kg to about 19 mg / kg, about 10 mg / kg to about 18 mg / kg, about 10 mg / kg to about 17 mg / kg, about 10 mg / kg to about 16 mg / kg, about 10 mg / kg to about 15 mg / kg, about 11 mg / kg to about 19 mg / kg, about 12 mg / kg to about 18 mg / kg, about 13 mg / kg to about 17 mg / kg, about 14 mg / kg to about 16 mg / kg.

[0163] In some embodiments, the dosage of the anti-VEGF antibody is about 1.0 mg / kg, 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. kg, approximately 13.0 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, approximately 30.0 mg / kg, or any range between these values. In some embodiments, the dosage of the anti-VEGF antibody is 1.0 mg / kg, 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, etc. The values ​​are 13.0 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.

[0164] In some embodiments, 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.

[0165] In some implementations, the dosing regimen for the anti-VEGF antibody is selected from any of the following:

[0166] 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.

[0167] 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.

[0168] 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.

[0169] 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.

[0170] 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.

[0171] 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.

[0172] 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.

[0173] 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.

[0174] 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.

[0175] 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.

[0176] 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.

[0177] 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.

[0178] 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.

[0179] 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.

[0180] 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.

[0181] The dosage of the anti-VEGF antibody is approximately 6.0 mg / kg, and the dosing frequency is once every 3 weeks;

[0182] The dosage of the anti-VEGF antibody is approximately 6.5 mg / kg, and the dosing frequency is once every 3 weeks;

[0183] The dosage of the anti-VEGF antibody is approximately 7.0 mg / kg, and the dosing frequency is once every 3 weeks;

[0184] The dosage of the anti-VEGF antibody is approximately 7.5 mg / kg, and the dosing frequency is once every 3 weeks;

[0185] The dosage of the anti-VEGF antibody is approximately 8.0 mg / kg, and the dosing frequency is once every 3 weeks;

[0186] The dosage of the anti-VEGF antibody is approximately 8.5 mg / kg, and the dosing frequency is once every 3 weeks;

[0187] The dosage of the anti-VEGF antibody is approximately 9.0 mg / kg, and the dosing frequency is once every 3 weeks;

[0188] The dosage of the anti-VEGF antibody is approximately 9.5 mg / kg, and the dosing frequency is once every 3 weeks;

[0189] The dosage of the anti-VEGF antibody is approximately 10.0 mg / kg, and the dosing frequency is once every 3 weeks;

[0190] The dosage of the anti-VEGF antibody is approximately 10.5 mg / kg, and the dosing frequency is once every 3 weeks;

[0191] The dosage of the anti-VEGF antibody is approximately 11.0 mg / kg, and the dosing frequency is once every 3 weeks;

[0192] The dosage of the anti-VEGF antibody is approximately 11.5 mg / kg, and the dosing frequency is once every 3 weeks;

[0193] The dosage of the anti-VEGF antibody is approximately 12.0 mg / kg, and the dosing frequency is once every 3 weeks;

[0194] The dosage of the anti-VEGF antibody is approximately 12.5 mg / kg, and the dosing frequency is once every 3 weeks;

[0195] The dosage of the anti-VEGF antibody is approximately 13.0 mg / kg, and the dosing frequency is once every 3 weeks;

[0196] The dosage of the anti-VEGF antibody is approximately 13.5 mg / kg, and the dosing frequency is once every 3 weeks;

[0197] The dosage of the anti-VEGF antibody is approximately 14.0 mg / kg, and the dosing frequency is once every 3 weeks;

[0198] The dosage of the anti-VEGF antibody is approximately 14.5 mg / kg, and the dosing frequency is once every 3 weeks;

[0199] The dosage of the anti-VEGF antibody is approximately 15.0 mg / kg, and the dosing frequency is once every 3 weeks;

[0200] The dosage of the anti-VEGF antibody is approximately 15.5 mg / kg, and the dosing frequency is once every 3 weeks;

[0201] The dosage of the anti-VEGF antibody is approximately 16.0 mg / kg, and the dosing frequency is once every 3 weeks;

[0202] The dosage of the anti-VEGF antibody is approximately 16.5 mg / kg, and the dosing frequency is once every 3 weeks;

[0203] The dosage of the anti-VEGF antibody is approximately 17.0 mg / kg, and the dosing frequency is once every 3 weeks;

[0204] The dosage of the anti-VEGF antibody is approximately 17.5 mg / kg, and the dosing frequency is once every 3 weeks;

[0205] The dosage of the anti-VEGF antibody is approximately 18.0 mg / kg, and the dosing frequency is once every 3 weeks;

[0206] The dosage of the anti-VEGF antibody is approximately 18.5 mg / kg, and the dosing frequency is once every 3 weeks;

[0207] The dosage of the anti-VEGF antibody is approximately 19.0 mg / kg, and the dosing frequency is once every 3 weeks;

[0208] The dosage of the anti-VEGF antibody is approximately 19.5 mg / kg, and the dosing frequency is once every 3 weeks;

[0209] The dosage of the anti-VEGF antibody is approximately 20.0 mg / kg, and the dosing frequency is once every 3 weeks;

[0210] The dosage of the anti-VEGF antibody is approximately 21.5 mg / kg, and the dosing frequency is once every 3 weeks;

[0211] The dosage of the anti-VEGF antibody is approximately 22.0 mg / kg, and the dosing frequency is once every 3 weeks;

[0212] The dosage of the anti-VEGF antibody is approximately 22.5 mg / kg, and the dosing frequency is once every 3 weeks;

[0213] The dosage of the anti-VEGF antibody is approximately 23.0 mg / kg, and the dosing frequency is once every 3 weeks;

[0214] The dosage of the anti-VEGF antibody is approximately 23.5 mg / kg, and the dosing frequency is once every 3 weeks;

[0215] The dosage of the anti-VEGF antibody is approximately 24.0 mg / kg, and the dosing frequency is once every 3 weeks;

[0216] The dosage of the anti-VEGF antibody is approximately 24.5 mg / kg, and the dosing frequency is once every 3 weeks;

[0217] The dosage of the anti-VEGF antibody is approximately 25.0 mg / kg, and the dosing frequency is once every 3 weeks.

[0218] In some implementations, in any of the dosing regimens described above, the anti-VEGF antibody is administered once every 3 weeks.

[0219] In some embodiments, in any of the above-described dosing regimens, the anti-VEGF antibody 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.

[0220] In some implementations, the anti-VEGF antibody is configured in an injectable form. Exemplarily, 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.

[0221] <Immunotherapy Agents>

[0222] In some embodiments, the immunotherapeutic agent comprises any one or a combination of two of anti-PD-L1 antibodies and anti-CTLA-4 antibodies.

[0223] In some embodiments, 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.

[0224] Anti-PD-L1 antibody

[0225] In some embodiments, 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:21-23, and the light chain variable region comprises LCDR1, LCDR2 and LCDR3 as shown in SEQ ID NO:24-26.

[0226] The CDR sequences mentioned above are shown in Table 3 below:

[0227] Table 3. CDR sequences of anti-PD-L1 antibodies (Kabat protocol)

[0228] In some implementations, 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.

[0229] In some embodiments, 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: 27, and the VL comprises LCDR1, LCDR2, and LCDR3 of the amino acid sequence shown in SEQ ID NO: 28. 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.

[0230] In some implementations, the anti-PD-L1 antibody is a chimeric, humanized, fully human antibody or its antigen-binding fragment.

[0231] In some embodiments, 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: 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.

[0232] Heavy chain variable region:

[0233] Light chain variable region:

[0234] Note: The underlined part is the CDR area determined according to the Kabat numbering rules.

[0235] In some implementations, the anti-PD-L1 antibody comprises any one or both of the aforementioned VH and VL.

[0236] In some embodiments, 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. In some embodiments, the anti-PD-L1 antibody comprises a human IgG2 or IgG4 heavy chain constant region. In some embodiments, the anti-PD-L1 antibody comprises an IgG4 heavy chain constant region incorporating F234A and L235A mutations. In some embodiments, the light chain constant region may be selected from the light chain constant region of human κ, λ chains, or their variants.

[0237] In some embodiments, 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: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.

[0238] In some embodiments, the anti-PD-L1 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.

[0239] Heavy chain sequence of anti-PD-L1 antibody:

[0240] Light chain sequence of anti-PD-L1 antibody:

[0241] Note: The underlined portion is the variable region sequence of the antibody heavy or light chain, and the ununderlined portion is the constant region sequence of the antibody.

[0242] In some embodiments, the anti-PD-L1 antibody is adebrelimab.

[0243] In some embodiments, 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.

[0244] In the context of this disclosure, "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.

[0245] In some embodiments, the dosage of the anti-PD-L1 antibody is from about 50 mg to about 5000 mg, for example, from about 100 mg to about 5000 mg, from about 100 mg to about 4500 mg, from about 100 mg to about 4000 mg, from about 100 mg to about 3500 mg, from about 100 mg to about 3000 mg, from about 100 mg to about 2500 mg, from about 100 mg to about 2000 mg, from about 100 mg to about 1500 mg, from about 500 mg to about 3500 mg. 0 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 a range of values ​​between any two.

[0246] In some implementations, the dosage of the anti-PD-L1 antibody is 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, approximately 750 mg, approximately 800 mg, etc. Approximately 850mg, approximately 900mg, approximately 950mg, approximately 1000mg, approximately 1050mg, approximately 1100mg, approximately 1150mg, approximately 1200mg, approximately 1250mg, approximately 1300mg, approximately 1350mg, approximately 1400mg, approximately 1450mg, approximately 1500mg, 1550mg, approximately 1600mg, approximately 1650mg, approximately 1700mg, approximately 1750mg, approximately 1800mg, approximately 1850mg, approximately 1900mg, approximately 1950mg g, 2000mg, approximately 2050mg, approximately 2100mg, approximately 2150mg, approximately 2200mg, approximately 2250mg, approximately 2300mg, approximately 2350mg, approximately 2400mg, 2450mg, approximately 2500mg, approximately 2550mg, approximately 2600mg, approximately 2650mg, approximately 2700mg, approximately 2750mg, approximately 2800mg, approximately 2850mg, 2900mg, approximately 2950mg, approximately 3000mg, approximately 3050mg, approximately 31 00 mg, approximately 3150 mg, approximately 3200 mg, approximately 3250 mg, approximately 3300 mg, approximately 3350 mg, approximately 3400 mg, 3450 mg, approximately 3500 mg, approximately 3550 mg, approximately 3600 mg, approximately 3650 mg, approximately 3700 mg, approximately 3750 mg, approximately 3800 mg, approximately 3850 mg, 3900 mg, approximately 3950 mg, approximately 4000 mg, approximately 4500 mg, or approximately 4800 mg; and any range of values ​​between the two.In some implementations, the dosage of the anti-PD-L1 antibody is 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, 800 mg, 850mg, 900mg, 950mg, 1000mg, 1050mg, 1100mg, 1150mg, 1200mg, 1250mg, 1300mg, 1350mg, 1400m g, 1450mg, 1500mg, 1550mg, 1600mg, 1650mg, 1700mg, 1750mg, 1800mg, 1850mg, 1900mg, 1950mg, 2000mg, 2050mg, 2100mg, 2150mg, 2200mg, 2250mg, 2300mg, 2350mg, 2400mg, 2450mg, 2500mg, 25 50mg, 2600mg, 2650mg, 2700mg, 2750mg, 2800mg, 2850mg, 2900mg, 2950mg, 3000mg, 3050mg, 3100 mg, 3150mg, 3200mg, 3250mg, 3300mg, 3350mg, 3400mg, 3450mg, 3500mg, 3550mg, 3600mg, 3650mg, 3700mg, 3750mg, 3800mg, 3850mg, 3900mg, 3950mg, 4000mg, 4500mg, or 4800mg; and any range of values ​​between any two.

[0247] In some embodiments, the dosage of the anti-PD-L1 antibody is approximately 1200 mg.

[0248] In some embodiments, 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.

[0249] In some embodiments, the dose of the anti-PD-L1 antibody is about 1200 mg, administered once every 3 weeks.

[0250] In some embodiments, in any of the above-described dosing regimens, the anti-PD-L1 antibody 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-PD-L1 antibody is administered via intravenous infusion.

[0251] In some embodiments, the anti-PD-L1 antibody is configured in an injectable form. Exemplarily, the injectable form of the anti-PD-L1 antibody is a solution or lyophilized powder for injection, comprising the anti-PD-L1 antibody and one or more pharmaceutically acceptable excipients.

[0252] Anti-CTLA-4 antibody

[0253] In some embodiments, 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:31-33, and the light chain variable region comprises LCDR1, LCDR2 and LCDR3 as shown in SEQ ID NO:34-36.

[0254] The CDR sequences mentioned above are shown in Table 4 below:

[0255] Table 4. CDR sequences of anti-CTLA-4 antibodies

[0256] In some implementations, 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.

[0257] In some embodiments, 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: 37, and the VL comprises LCDR1, LCDR2, and LCDR3 of the amino acid sequence shown in SEQ ID NO: 38. 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.

[0258] In some implementations, the anti-CTLA-4 antibody is a chimeric, humanized, fully human antibody or its antigen-binding fragment.

[0259] In some embodiments, 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: 37, and the VL comprises an amino acid sequence as shown in or having at least 80% or 90% identity with SEQ ID NO: 38.

[0260] Heavy chain variable region:

[0261] Light chain variable region:

[0262] In some implementations, the anti-CTLA-4 antibody comprises any one or both of the aforementioned VH and VL.

[0263] In some embodiments, 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. In some embodiments, the light chain constant region may be selected from the light chain constant region of human κ, λ chains, or their variants.

[0264] In some embodiments, 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:39 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:40 or having at least 80% or at least 90% sequence identity therewith.

[0265] In some embodiments, the anti-CTLA-4 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.

[0266] Heavy chain sequence of anti-CTLA-4 antibody:

[0267] Light chain sequence of anti-CTLA-4 antibody:

[0268] Note: The underlined portion is the variable region sequence of the antibody heavy or light chain, and the ununderlined portion is the constant region sequence of the antibody.

[0269] In some embodiments, the dosage of the anti-CTLA-4 antibody is about 1-1000 mg, about 1-500 mg, about 10-500 mg, about 20-500 mg, about 30-500 mg, about 40-500 mg, about 50-500 mg, about 60-500 mg, about 40-400 mg, about 50-400 mg, about 60-400 mg, about 40-350 mg, about 50-350 mg, about 60-350 mg, about 40-300mg, approximately 50-300mg, approximately 60-300mg, approximately 10-150mg, approximately 20-150mg, approximately 30-150mg, approximately 40-150mg, approximately 50-150mg, approximately 60-150mg, approximately 10-100mg, approximately 20-100mg, approximately 30-100mg, approximately 40-100mg, approximately 50-100mg, approximately 60-100mg, approximately 60-90mg, approximately 60-80mg.

[0270] In some embodiments, the dosage of the anti-CTLA-4 antibody is about 1 mg, about 10 mg, about 15 mg, about 20 mg, about 25 mg, about 30 mg, about 35 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, about 51 mg, about 52 mg, about 53 mg, about 54 mg, about 55 mg, about 56 mg, about 57 mg, about 58 mg, about 59 mg, about 60 mg, about 61 mg, about 62 mg, about 63 mg, about 64 mg, about 65 mg, about 66 mg, about 67 mg, about 68 mg, about 69 mg, about 70 mg, about 71 mg, about 72 mg, about 73 mg, about 74 mg, about 75 mg, about 76 mg, about 77 mg, about 78 mg, about... 79mg, approximately 80mg, approximately 81mg, approximately 82mg, approximately 83mg, approximately 84mg, approximately 85mg, approximately 86mg, approximately 87mg, approximately 88mg, approximately 89mg, approximately 90mg, approximately 91mg, approximately 92mg, approximately 93mg, approximately 94mg, approximately 95mg, approximately 96mg, approximately 97mg, approximately 98mg, approximately 99mg, approximately 100mg, approximately 120mg, approximately 140mg, approximately 150mg g, approximately 160 mg, approximately 180 mg, approximately 200 mg, approximately 220 mg, approximately 240 mg, approximately 250 mg, approximately 260 mg, approximately 280 mg, approximately 300 mg, approximately 320 mg, approximately 350 mg, approximately 400 mg, approximately 450 mg, approximately 500 mg, approximately 600 mg, approximately 700 mg, approximately 800 mg, approximately 900 mg, or approximately 1000 mg; or any range between these point values.In some embodiments, the dosage of the anti-CTLA-4 antibody is 1 mg, 10 mg, 15 mg, 20 mg, 25 mg, 30 mg, 35 mg, 40 mg, 41 mg, 42 mg, 43 mg, 44 mg, 45 mg, 46 mg, 47 mg, 48 mg, 49 mg, 50 mg, 51 mg, 52 mg, 53 mg, 54 mg, 55 mg, 56 mg, 57 mg, 58 mg, 59 mg, 60 mg, 61 mg, 62 mg, 63 mg, 64 mg, 65 mg, 66 mg, 67 mg, 68 mg, 69 mg, 70 mg, 71 mg, 72 mg, 73 mg, 74 mg, 75 mg, 76 mg, 77 mg, 78 mg, 79 mg. mg, 80mg, 81mg, 82mg, 83mg, 84mg, 85mg, 86mg, 87mg, 88mg, 89mg, 90mg, 91mg, 92mg, 93mg, 94mg, 95mg, 96mg, 97mg, 98mg, 99mg, 100mg, 120mg, 140mg, 150mg, 160mg, 180mg, 200mg, 220mg, 240mg, 250mg, 260mg, 280mg, 300mg, 320mg, 350mg, 400mg, 450mg, 500mg, 600mg, 700mg, 800mg, 900mg, or 1000mg; or any range between these point values.

[0271] In some implementations, the dose of the anti-CTLA-4 antibody is approximately 70 mg.

[0272] In some implementations, the dosage of the anti-CTLA-4 antibody is approximately 280 mg.

[0273] In some embodiments, 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 6 weeks or as a single dose.

[0274] In some embodiments, the anti-CTLA-4 antibody is administered once in week 1 at a dose of about 280 mg, with no administration from week 2 to week 12, and from week 13 onwards, at a dose of about 70 mg, administered once every 6 weeks.

[0275] In some implementation schemes, a 21-day cycle is used. On the first day of the first cycle, a single dose of 280 mg is administered. No doses are administered in cycles 2-4. Starting from the first day of the fifth cycle, the dose is administered at a frequency of 70 mg every 6 weeks (C1D1 280 mg once, C2-C4 no doses, C5 and subsequent cycles 70 mg Q6W).

[0276] In some embodiments, in any of the dosing regimens described above, the anti-CTLA-4 antibody 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-CTLA-4 antibody is administered via intravenous infusion.

[0277] In some implementations, the anti-CTLA-4 antibody is configured in an injectable form. Exemplarily, the injectable form of the anti-CTLA-4 antibody is a solution or lyophilized powder for injection, comprising the anti-CTLA-4 antibody and one or more pharmaceutically acceptable excipients.

[0278] Platinum-based drugs

[0279] In some implementations, the platinum-based drug is carboplatin or cisplatin.

[0280] In some implementations, the platinum-based drug is carboplatin.

[0281] In some implementations, the platinum-based drug is cisplatin.

[0282] <Carboplatin>

[0283] In some embodiments, the dosage (AUC) of the carboplatin may be selected from about 0.1 mg / mL / min to about 50 mg / mL / min, about 1 mg / mL / min to 20 mg / mL / min, about 1 mg / mL / min to 10 mg / mL / min, about 1 mg / mL / min to 8 mg / mL / min, about 1 mg / mL / min to 6 mg / mL / min, about 2 mg / mL / min to 10 mg / mL / min, about 2 mg / mL / min to about 8 mg / mL / min, about 2 mg / mL / min to about 6 mg / mL / min, about 3 mg / mL / min to about 10 mg / mL / min, about 3 mg / mL / min to about 8 mg / mL / min, about 3 mg / mL / min to 7 mg / mL / min, about 4 mg / mL / min to about 10 mg / mL / min, about 4 mg / mL / min to about 8 mg / mL / min, and about 4 mg / mL / min to 6 mg / mL / min.

[0284] In some embodiments, the AUC of carboplatin 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, about 1.4 mg / mL / min, about 1.5 mg / mL / min, about 1.6 mg / mL / min, about 1.7 mg / mL / min, about 1.8 mg / mL / min, about 1.9 mg / mL / min, etc. Approximately 2.0 mg / mL / min, approximately 2.1 mg / mL / min, approximately 2.2 mg / mL / min, approximately 2.3 mg / mL / min, approximately 2.4 mg / mL / min, approximately 2.5 mg / mL / min, approximately 2.6 mg / mL / min, approximately 2.7 mg / mL / min, approximately 2.8 mg / mL / min, approximately 2.9 mg / mL / min, approximately 3.0 mg / mL / min, approximately 3.1 mg / mL / min, approximately 3.2 mg / mL / min, approximately 3.3 mg / mL / min, approximately 3.4 mg / mL / min, approximately 3.5 mg / mL / min, approximately 3.6 mg / mL / min, approximately 3.7 mg / mL / min approx. 3.8 mg / mL / min, approx. 3.9 mg / mL / min, approx. 4.0 mg / mL / min, approx. 4.1 mg / mL / min, approx. 4.2 mg / mL / min, approx. 4.3 mg / mL / min, approx. 4.4 mg / mL / min, approx. 4.5 mg / mL / min, approx. 4.6 mg / mL / min, approx. 4.7 mg / mL / min, approx. 4.8 mg / mL / min, approx. 4.9 mg / mL / min, approx. 5.0 mg / mL / min, approx. 5.1 mg / mL / min, approx. 5.2 mg / mL / min, approx. 5.3 mg / mL / min, approx. 5.4 mg / mL / min, approx. 5.5 mg / mL / min / mL / min, approximately 5.6 mg / mL / min, approximately 5.7 mg / mL / min, approximately 5.8 mg / mL / min, approximately 5.9 mg / mL / min, approximately 6.0 mg / mL / min, approximately 6.1 mg / mL / min, approximately 6.2 mg / mL / min, approximately 6.3 mg / mL / min, approximately 6.4 mg / mL / min, approximately 6.5 mg / mL / min, approximately 6.6 mg / mL / min, approximately 6.7 mg / mL / min, approximately 6.8 mg / mL / min, approximately 6.9 mg / mL / min, approximately 7.0 mg / mL / min, approximately 7.1 mg / mL / min, approximately 7.2 mg / mL / min, approximately 7.3 mg / mL / min, approximately 7.4 mg / mL / min, approximately 7.5 mg / mL / min, approximately 7.6 mg / mL / min, approximately 7.7 mg / mL / min, approximately 7.8 mg / mL / min, approximately 7.9 mg / mL / min, approximately 8.0 mg / mL / min, approximately 8.1 mg / mL / min, approximately 8.2 mg / mL / min, approximately 8.3 mg / mL / min, approximately 8.4 mg / mL / min, approximately 8.5 mg / mL / min, approximately 8.6 mg / mL / min, approximately 8.7 mg / mL / min, approximately 8.8 mg / mL / min g / mL / min, about 8.9 mg / mL / min, about 9.0 mg / mL / min, about 9.2 mg / mL / min, about 9.5 mg / mL / min, about 9.8 mg / mL / min, about 10.0 mg / mL / min, about 15 mg / mL / min, about 20 mg / mL / min, about 25 mg / mL / min, about 30 mg / mL / min, about 35 mg / mL / min, about 40 mg / mL / min, about 45 mg / mL / min, about 50 mg / mL / min, or any range between any two of the foregoing. In some embodiments, the AUC of carboplatin is 0.1 mg / mL / min, 0.5 mg / mL / min, 0.6 mg / mL / min, 0.7 mg / mL / min, 0.8 mg / mL / min, 0.9 mg / mL / min, 1.0 mg / mL / min, 1.1 mg / mL / min, 1.2 mg / mL / min, 1.3 mg / mL / min, 1.4 mg / mL / min, 1.5 mg / mL / min, 1.6 mg / mL / min, 1.7 mg / mL / min, 1.8 mg / mL / min, 1.9 mg / mL / min, 2.0 mg / mL / min, 2.1 mg / mL / min, 2.2 mg / mL / min, 2.3 mg / mL / min, and 2. 4mg / mL / min, 2.5mg / mL / min, 2.6mg / mL / min, 2.7mg / mL / min, 2.8mg / mL / min, 2.9mg / mL / min, 3.0mg / mL / min, 3.1mg / mL / min, 3.2mg / mL / min, 3.3mg / mL / min, 3.4mg / mL / min, 3. 5mg / mL / min, 3.6mg / mL / min, 3.7mg / mL / min, 3.8mg / mL / min, 3.9mg / mL / min, 4.0mg / mL / min, 4.1mg / mL / min, 4.2mg / mL / min, 4.3mg / mL / min, 4.4mg / mL / min, 4.5mg / mL / min, 4.6mg / mL / min, 4.7mg / mL / min, 4.8mg / mL / min, 4.9mg / mL / min, 5.0mg / mL / min, 5.1mg / mL / min, 5.2mg / mL / min, 5.3m g / mL / min, 5.4mg / mL / min, 5.5mg / mL / min, 5.6mg / mL / min, 5.7mg / mL / min, 5.8mg / mL / min, 5.9mg / mL / min, 6.0mg / mL / min, 6.1mg / mL / min, 6.2mg / mL / min, 6.3mg / mL / min, 6.4mg / mL / min, 6.5mg / mL / min, 6.6mg / mL / min, 6.7mg / mL / min, 6.8mg / mL / min, 6.9mg / mL / min, 7.0mg / mL / min, 7.1mg / mL / min, 7.2mg / mL / min, 7.3mg / mL / min, 7.4mg / mL / mi n, 7.5mg / mL / min, 7.6mg / mL / min, 7.7mg / mL / min, 7.8mg / mL / min, 7.9mg / mL / min, 8.0mg / mL / min, 8.1mg / mL / min, 8.2mg / mL / min, 8.3mg / mL / min, 8.4mg / mL / min, 8.5mg / mL / min, 8.6mg / mL / min, 8.7mg / mL / min, 8.8mg / mL / min, 8.9 mg / mL / min, 9.0 mg / mL / min, 9.2 mg / mL / min, 9.5 mg / mL / min, 9.8 mg / mL / min, 10.0 mg / mL / min, 15 mg / mL / min, 20 mg / mL / min, 25 mg / mL / min, 30 mg / mL / min, 35 mg / mL / min, 40 mg / mL / min, 45 mg / mL / min, 50 mg / mL / min, or any range between any two of the foregoing.

[0285] In some embodiments, 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 embodiments, the carboplatin is administered once every 3 weeks.

[0286] In some embodiments, the carboplatin dosage (AUC) 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 carboplatin dosage (AUC) is from about 0.1 mg / mL / min to about 50 mg / mL / min, and the dosing frequency is once every 3 weeks.

[0287] In some embodiments, the carboplatin dosage (AUC) 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 carboplatin dosage (AUC) is from about 1 mg / mL / min to about 20 mg / mL / min, and the dosing frequency is once every 3 weeks.

[0288] In some embodiments, the carboplatin dosage (AUC) 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 carboplatin dosage (AUC) is from about 1 mg / mL / min to about 10 mg / mL / min, and the dosing frequency is once every 3 weeks.

[0289] In some embodiments, the carboplatin dosage (AUC) 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 carboplatin dosage (AUC) is from about 1 mg / mL / min to about 8 mg / mL / min, and the dosing frequency is once every 3 weeks.

[0290] In some embodiments, the carboplatin dosage (AUC) is from about 1 mg / mL / min to about 6 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 carboplatin dosage (AUC) is from about 1 mg / mL / min to about 6 mg / mL / min, and the dosing frequency is once every 3 weeks.

[0291] In some embodiments, the carboplatin dosage (AUC) 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 carboplatin dosage (AUC) is from about 2 mg / mL / min to about 10 mg / mL / min, and the dosing frequency is once every 3 weeks.

[0292] In some embodiments, the carboplatin dosage (AUC) 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 carboplatin dosage (AUC) is from about 2 mg / mL / min to about 8 mg / mL / min, and the dosing frequency is once every 3 weeks.

[0293] In some embodiments, the AUC of carboplatin is from about 2 mg / mL / min to about 6 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 AUC of carboplatin is from about 2 mg / mL / min to about 6 mg / mL / min, and the dosing frequency is once every 3 weeks.

[0294] In some embodiments, the dosage (AUC) of carboplatin is from about 3 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 (AUC) of carboplatin is from about 3 mg / mL / min to about 10 mg / mL / min, and the dosing frequency is once every 3 weeks.

[0295] In some embodiments, the carboplatin dosage (AUC) is from about 3 mg / mL / min to about 7 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 carboplatin dosage (AUC) is from about 3 mg / mL / min to about 7 mg / mL / min, and the dosing frequency is once every 3 weeks.

[0296] In some embodiments, the carboplatin dosage (AUC) is from about 4 mg / mL / min to about 6 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 carboplatin dosage (AUC) is from about 4 mg / mL / min to about 6 mg / mL / min, and the dosing frequency is once every 3 weeks.

[0297] In some embodiments, the carboplatin dosage (AUC) is about 2 mg / mL / min, and the dosing frequency is once every 3 weeks.

[0298] In some embodiments, the carboplatin dosage (AUC) is about 3 mg / mL / min, and the dosing frequency is once every 3 weeks.

[0299] In some embodiments, the carboplatin dosage (AUC) is about 4 mg / mL / min, and the dosing frequency is once every 3 weeks.

[0300] In some embodiments, the carboplatin dosage (AUC) is about 5 mg / mL / min, and the dosing frequency is once every 3 weeks.

[0301] In some embodiments, the carboplatin dosage (AUC) is about 6 mg / mL / min, and the dosing frequency is once every 3 weeks.

[0302] In some embodiments, the carboplatin dosage (AUC) is about 7 mg / mL / min, and the dosing frequency is once every 3 weeks.

[0303] In some embodiments, the carboplatin dosage (AUC) is about 8 mg / mL / min, and the dosing frequency is once every 3 weeks.

[0304] In some embodiments, the carboplatin dosage (AUC) is about 9 mg / mL / min, and the dosing frequency is once every 3 weeks.

[0305] In some embodiments, the carboplatin dosage (AUC) is about 10 mg / mL / min, and the dosing frequency is once every 3 weeks.

[0306] In some embodiments, 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 embodiments, carboplatin is administered via intravenous injection. In some embodiments, carboplatin is administered via intravenous infusion.

[0307] In some embodiments, a dosing cycle is defined as every 2 weeks, 3 weeks, 4 weeks, 5 weeks, or 6 weeks, with a maximum of 4, 5, or 6 cycles for carboplatin. In some embodiments, a dosing cycle is defined as every 3 weeks, with each cycle consisting of one dose every 3 weeks, and a maximum of 6 cycles for carboplatin.

[0308] In some embodiments, carboplatin is administered via intravenous infusion in a 3-week cycle, with the dosing frequency being once every 3 weeks, starting on the first day of each cycle, for a maximum of 6 cycles.

[0309] In this disclosure, the formula for calculating carboplatin dosage is as follows:

[0310] The dosage of carboplatin injection needs to be calculated based on the area under the plasma concentration-time curve (AUC) and endogenous creatinine clearance. The maximum dose of carboplatin should not exceed 600 mg. If the calculated dose of carboplatin is greater than 600 mg, it should be administered at 600 mg.

[0311] Calvert formula for carboplatin dosage based on AUC: Carboplatin dose (mg) = set AUC (mg / mL / min) × [creatinine clearance (mL / min) + 25]

[0312] The endogenous creatinine clearance rate was calculated using the Cockcroft formula.

[0313] Serum creatinine concentration (mg / dL)

[0314] Serum creatinine concentration (mol / L):

[0315] Cisplatin

[0316] In some embodiments, the dosage of cisplatin may be about 1 mg / m². 2 Approximately 500 mg / m 2 Approximately 5mg / m 2 Approximately 500 mg / m 2 Approximately 1 mg / m 2 Approximately 200 mg / m 2 Approximately 1 mg / m 2 Approximately 150 mg / m 2 Approximately 1 mg / m 2 Approximately 100 mg / m 2 Approximately 10 mg / m 2 Approximately 200 mg / m 2 Approximately 10 mg / m 2 Approximately 150 mg / m 2 Approximately 10 mg / m 2 Approximately 100 mg / m 2 Approximately 15 mg / m 2 Approximately 200 mg / m 2 Approximately 15 mg / m 2 Approximately 150 mg / m 2 Approximately 15 mg / m 2 Approximately 100 mg / m 2 Approximately 20 mg / m 2 Approximately 200 mg / m 2 Approximately 20 mg / m 2 Approximately 150 mg / m 2 Approximately 20 mg / m 2 Approximately 100 mg / m2 Approximately 30 mg / m 2 Approximately 200 mg / m 2 Approximately 30 mg / m 2 Approximately 150 mg / m 2 Approximately 30 mg / m 2 Approximately 100 mg / m 2 Approximately 10 mg / m 2 Approximately 90 mg / m 2 Approximately 10 mg / m 2 Approximately 80 mg / m 2 Approximately 10 mg / m 2 Approximately 70 mg / m 2 Approximately 10 mg / m 2 Approximately 60 mg / m 2 Approximately 20 mg / m 2 Approximately 90 mg / m 2 Approximately 20 mg / m 2 Approximately 80 mg / m 2 Approximately 20 mg / m 2 Approximately 70 mg / m 2 Approximately 20 mg / m 2 Approximately 60 mg / m 2 Approximately 30 mg / m 2 Approximately 90 mg / m 2 Approximately 30 mg / m 2 Approximately 80 mg / m 2 Approximately 30 mg / m 2 Approximately 70 mg / m 2 Approximately 40 mg / m 2 Approximately 60 mg / m 2 Approximately 40 mg / m 2 Approximately 90 mg / m 2 Approximately 40 mg / m 2 Approximately 80 mg / m 2 Approximately 40 mg / m 2 Approximately 70 mg / m 2 Approximately 40 mg / m 2 Approximately 60 mg / m 2 Approximately 30 mg / m 2 Approximately 85 mg / m 2 Approximately 45 mg / m 2 Approximately 85 mg / m 2 Approximately 55 mg / m 2 Approximately 85 mg / m 2 Approximately 65 mg / m 2 Approximately 85 mg / m 2 Approximately 50 mg / m 2Approximately 150 mg / m 2 Approximately 55 mg / m 2 Approximately 100 mg / m 2 Approximately 55 mg / m 2 Approximately 85 mg / m 2 Approximately 60 mg / m 2 Approximately 100 mg / m 2 Approximately 60 mg / m 2 Approximately 85 mg / m 2 Approximately 65 mg / m 2 Approximately 85 mg / m 2 or about 70mg / m 2 Approximately 85 mg / m 2 .

[0317] In some embodiments, the dosage of cisplatin is about 1 mg / m². 2 Approximately 5mg / m 2 Approximately 15 mg / m 2 Approximately 20 mg / m 2 Approximately 21 mg / m 2 Approximately 22 mg / m 2 Approximately 23 mg / m 2 Approximately 24 mg / m 2 Approximately 25 mg / m 2 Approximately 26 mg / m 2 Approximately 27 mg / m 2 Approximately 28 mg / m 2 Approximately 29 mg / m 2 Approximately 30 mg / m 2 Approximately 31 mg / m 2 Approximately 32 mg / m 2 Approximately 33 mg / m 2 Approximately 34 mg / m 2 Approximately 35 mg / m 2 Approximately 36 mg / m 2 Approximately 37 mg / m 2 Approximately 38 mg / m 2 Approximately 39 mg / m 2 Approximately 40 mg / m 2 Approximately 41 mg / m 2 Approximately 42 mg / m 2 Approximately 43 mg / m 2 Approximately 44 mg / m 2 Approximately 45 mg / m 2 Approximately 46 mg / m 2 Approximately 47 mg / m 2 Approximately 48 mg / m 2 Approximately 49 mg / m2 Approximately 50 mg / m 2 Approximately 51 mg / m 2 Approximately 52 mg / m 2 Approximately 53 mg / m 2 Approximately 54 mg / m 2 Approximately 55 mg / m 2 Approximately 56 mg / m 2 Approximately 57 mg / m 2 Approximately 58 mg / m 2 Approximately 59 mg / m 2 Approximately 60 mg / m 2 Approximately 61 mg / m³ 2 Approximately 62 mg / m 2 Approximately 63 mg / m 2 Approximately 64 mg / m 2 Approximately 65 mg / m 2 Approximately 66 mg / m 2 Approximately 67 mg / m 2 Approximately 68 mg / m 2 Approximately 69 mg / m 2 Approximately 70 mg / m 2 Approximately 71 mg / m³ 2 Approximately 72 mg / m 2 Approximately 73 mg / m 2 Approximately 74 mg / m 2 Approximately 75 mg / m 2 Approximately 76 mg / m 2 Approximately 77 mg / m 2 Approximately 78 mg / m 2 Approximately 79 mg / m 2 Approximately 80 mg / m 2 Approximately 81 mg / m³ 2 Approximately 82 mg / m 2 Approximately 83 mg / m 2 Approximately 84 mg / m 2 Approximately 85 mg / m 2 Approximately 86 mg / m 2 Approximately 87 mg / m 2 Approximately 88 mg / m 2 Approximately 89 mg / m³ 2 Approximately 90 mg / m 2 Approximately 95 mg / m 2 Approximately 100 mg / m 2 Approximately 105 mg / m³ 2 Approximately 110 mg / m 2 Approximately 115 mg / m³ 2 Approximately 120 mg / m 2Approximately 130 mg / m 2 Approximately 140 mg / m 2 Approximately 150 mg / m 2 Approximately 160 mg / m 2 Approximately 170 mg / m 2 Approximately 180 mg / m 2 Approximately 190 mg / m 2 Approximately 200 mg / m 2 Approximately 220 mg / m 2 Approximately 250 mg / m 2 Approximately 280 mg / m 2 Approximately 300 mg / m 2 Or any range between the two mentioned above. In some embodiments, the dosage of cisplatin is 1 mg / m². 2 5mg / m 2 15mg / m 2 20mg / m 2 21mg / m 2 22mg / m 2 23mg / m 2 24mg / m 2 25mg / m 2 26mg / m 2 27mg / m 2 28mg / m 2 29mg / m 2 30mg / m 2 31mg / m 2 32mg / m 2 33mg / m 2 34mg / m 2 35mg / m 2 36mg / m 2 37mg / m 2 38mg / m 2 39mg / m 2 40mg / m 2 41mg / m 2 42mg / m 2 43mg / m 2 44mg / m 2 45mg / m 2 46mg / m 2 47mg / m 2 48mg / m 2 49mg / m 2 50mg / m 2 51mg / m 2,52mg / m 2 ,53mg / m 2 ,54mg / m 2 ,55mg / m 2 ,56mg / m 2 ,57mg / m 2 ,58mg / m 2 ,59mg / m 2 ,60mg / m 2 ,61mg / m 2 ,62mg / m 2 ,63mg / m 2 ,64mg / m 2 ,65mg / m 2 ,66mg / m 2 ,67mg / m 2 ,68mg / m 2 ,69mg / m 2 ,70mg / m 2 ,71mg / m 2 ,72mg / m 2 ,73mg / m 2 ,74mg / m 2 ,75mg / m 2 ,76mg / m 2 ,77mg / m 2 ,78mg / m 2 ,79mg / m 2 ,80mg / m 2 ,81mg / m 2 ,82mg / m 2 ,83mg / m 2 ,84mg / m 2 ,85mg / m 2 ,86mg / m 2 ,87mg / m 2 ,88mg / m 2 ,89mg / m 2 ,90mg / m 2 ,95mg / m 2 ,100mg / m 2 ,105mg / m 2 ,110mg / m 2 ,115mg / m 2 ,120mg / m 2 ,130mg / m 2 ,140mg / m 2 ,150mg / m 2 ,160mg / m 2 ,170mg / m2 180mg / m 2 190mg / m 2 200mg / m 2 220mg / m 2 250mg / m 2 280mg / m 2 300mg / m 2 ; or any range between any two of the aforementioned.

[0318] In some embodiments, 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 embodiments, the cisplatin is administered once every 3 weeks.

[0319] In some embodiments, the dosage of cisplatin is about 1 mg / m². 2 Approximately 500 mg / m 2 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 of cisplatin is about 1 mg / m². 2 Approximately 500 mg / m 2 The administration frequency is once every 3 weeks.

[0320] In some embodiments, the dosage of cisplatin is about 1 mg / m². 2 Approximately 200 mg / m 2 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 of cisplatin is about 1 mg / m². 2 Approximately 200 mg / m 2 The administration frequency is once every 3 weeks.

[0321] In some embodiments, the dosage of cisplatin is about 1 mg / m². 2 Approximately 150 mg / m 2 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 of cisplatin is about 1 mg / m². 2 Approximately 150 mg / m 2 The administration frequency is once every 3 weeks.

[0322] In some embodiments, the dosage of cisplatin is about 1 mg / m². 2 Approximately 100 mg / m 2The 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 of cisplatin is about 1 mg / m². 2 Approximately 100 mg / m 2 The administration frequency is once every 3 weeks.

[0323] In some embodiments, the dosage of cisplatin is about 10 mg / m². 2 Approximately 200 mg / m 2 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 of cisplatin is about 10 mg / m². 2 Approximately 200 mg / m 2 The administration frequency is once every 3 weeks.

[0324] In some embodiments, the dosage of cisplatin is about 10 mg / m². 2 Approximately 150 mg / m 2 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 of cisplatin is about 10 mg / m². 2 Approximately 150 mg / m 2 The administration frequency is once every 3 weeks.

[0325] In some embodiments, the dosage of cisplatin is about 10 mg / m². 2 Approximately 100 mg / m 2 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 of cisplatin is about 10 mg / m². 2 Approximately 100 mg / m 2 The administration frequency is once every 3 weeks.

[0326] In some embodiments, the dosage of cisplatin is about 20 mg / m². 2 Approximately 200 mg / m 2 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 of cisplatin is about 20 mg / m². 2 Approximately 200 mg / m 2 The administration frequency is once every 3 weeks.

[0327] In some embodiments, the dosage of cisplatin is about 20 mg / m². 2 Approximately 150 mg / m 2The 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 of cisplatin is about 20 mg / m². 2 Approximately 150 mg / m 2 The administration frequency is once every 3 weeks.

[0328] In some embodiments, the dosage of cisplatin is about 20 mg / m². 2 Approximately 100 mg / m 2 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 of cisplatin is about 20 mg / m². 2 Approximately 100 mg / m 2 The administration frequency is once every 3 weeks.

[0329] In some embodiments, the dosage of cisplatin is approximately 30 mg / m². 2 Approximately 200 mg / m 2 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 cisplatin dosage is approximately 30 mg / m². 2 Approximately 200 mg / m 2 The administration frequency is once every 3 weeks.

[0330] In some embodiments, the dosage of cisplatin is approximately 30 mg / m². 2 Approximately 150 mg / m 2 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 cisplatin dosage is approximately 30 mg / m². 2 Approximately 150 mg / m 2 The administration frequency is once every 3 weeks.

[0331] In some embodiments, the dosage of cisplatin is approximately 30 mg / m². 2 Approximately 100 mg / m 2 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 cisplatin dosage is approximately 30 mg / m². 2 Approximately 100 mg / m 2 The administration frequency is once every 3 weeks.

[0332] In some embodiments, the dosage of cisplatin is about 10 mg / m². 2 Approximately 90 mg / m 2The 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 of cisplatin is about 10 mg / m². 2 Approximately 90 mg / m 2 The administration frequency is once every 3 weeks.

[0333] In some embodiments, the dosage of cisplatin is about 20 mg / m². 2 Approximately 80 mg / m 2 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 of cisplatin is about 20 mg / m². 2 Approximately 80 mg / m 2 The administration frequency is once every 3 weeks.

[0334] In some embodiments, the dosage of cisplatin is approximately 30 mg / m². 2 Approximately 70 mg / m 2 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 cisplatin dosage is approximately 30 mg / m². 2 Approximately 70 mg / m 2 The administration frequency is once every 3 weeks.

[0335] In some embodiments, the dosage of cisplatin is approximately 40 mg / m². 2 Approximately 60 mg / m 2 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 of cisplatin is approximately 40 mg / m². 2 Approximately 60 mg / m 2 The administration frequency is once every 3 weeks.

[0336] In some embodiments, the dosage of cisplatin is approximately 40 mg / m². 2 The administration frequency is once every 3 weeks.

[0337] In some embodiments, the dosage of cisplatin is approximately 41 mg / m². 2 The administration frequency is once every 3 weeks.

[0338] In some embodiments, the dosage of cisplatin is approximately 42 mg / m². 2 The administration frequency is once every 3 weeks.

[0339] In some embodiments, the dosage of cisplatin is approximately 43 mg / m². 2The administration frequency is once every 3 weeks.

[0340] In some embodiments, the dosage of cisplatin is approximately 44 mg / m². 2 The administration frequency is once every 3 weeks.

[0341] In some embodiments, the dosage of cisplatin is approximately 45 mg / m². 2 The administration frequency is once every 3 weeks.

[0342] In some embodiments, the dosage of cisplatin is approximately 46 mg / m². 2 The administration frequency is once every 3 weeks.

[0343] In some embodiments, the dosage of cisplatin is approximately 47 mg / m². 2 The administration frequency is once every 3 weeks.

[0344] In some embodiments, the dosage of cisplatin is approximately 48 mg / m². 2 The administration frequency is once every 3 weeks.

[0345] In some embodiments, the dosage of cisplatin is approximately 49 mg / m². 2 The administration frequency is once every 3 weeks.

[0346] In some embodiments, the dosage of cisplatin is approximately 50 mg / m². 2 The administration frequency is once every 3 weeks.

[0347] In some embodiments, the dosage of cisplatin is approximately 51 mg / m². 2 The administration frequency is once every 3 weeks.

[0348] In some embodiments, the dosage of cisplatin is approximately 52 mg / m². 2 The administration frequency is once every 3 weeks.

[0349] In some embodiments, the dosage of cisplatin is approximately 53 mg / m². 2 The administration frequency is once every 3 weeks.

[0350] In some embodiments, the dosage of cisplatin is approximately 54 mg / m². 2 The administration frequency is once every 3 weeks.

[0351] In some embodiments, the dosage of cisplatin is approximately 55 mg / m². 2 The administration frequency is once every 3 weeks.

[0352] In some embodiments, the dosage of cisplatin is approximately 56 mg / m². 2The administration frequency is once every 3 weeks.

[0353] In some embodiments, the dosage of cisplatin is approximately 57 mg / m². 2 The administration frequency is once every 3 weeks.

[0354] In some embodiments, the dosage of cisplatin is approximately 58 mg / m². 2 The administration frequency is once every 3 weeks.

[0355] In some embodiments, the dosage of cisplatin is approximately 59 mg / m². 2 The administration frequency is once every 3 weeks.

[0356] In some embodiments, the dosage of cisplatin is approximately 60 mg / m². 2 The administration frequency is once every 3 weeks.

[0357] In some embodiments, 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 embodiments, cisplatin is administered via intravenous injection. In some embodiments, cisplatin is administered via intravenous infusion.

[0358] Dosing regimen

[0359] In some implementation schemes, the anti-HER2 antibody-drug conjugate and immunotherapy agent are administered simultaneously, separately, or sequentially.

[0360] In some implementation schemes, the combination of anti-HER2 antibody drug conjugates, immunotherapeutic agents, and VEGF signaling pathway inhibitors is administered simultaneously, separately, or sequentially.

[0361] In some implementation schemes, the combination of anti-HER2 antibody drug conjugates, immunotherapeutic agents, VEGF signaling pathway inhibitors, and platinum-based drugs is administered simultaneously, separately, or sequentially.

[0362] In some implementations, the VEGF signaling pathway inhibitor described above is an anti-VEGF antibody.

[0363] In some implementations, the immunotherapeutic agent described above is any one or a combination of two of anti-PD-L1 antibodies and anti-CTLA-4 antibodies.

[0364] In some implementations, the platinum-based drugs described above are carboplatin or cisplatin.

[0365] In some implementations, when anti-HER2 antibody-drug conjugates and anti-PD-L1 antibodies are used in combination, the dosing order is: anti-HER2 antibody-drug conjugate, then anti-PD-L1 antibody. In some implementations, the time interval between the two drug administrations should be >30 minutes, and the anti-HER2 antibody-drug conjugate and anti-PD-L1 antibody can be administered on the same day or divided into two days.

[0366] In some implementations, when anti-HER2 antibody-drug conjugate, anti-PD-L1 antibody, and anti-VEGF antibody are used in combination, the dosing order is: anti-HER2 antibody-drug conjugate, anti-PD-L1 antibody, and anti-VEGF antibody. In some implementations, the time interval between the dosing of the two drugs should be >30 minutes, and the anti-HER2 antibody-drug conjugate, anti-PD-L1 antibody, and anti-VEGF antibody should be administered on the same day or divided into two days.

[0367] In some implementations, when anti-HER2 antibody-drug conjugate, anti-PD-L1 antibody, anti-CTLA-4 antibody, and anti-VEGF antibody are used in combination, the dosing order is: anti-HER2 antibody-drug conjugate, anti-PD-L1 antibody, anti-CTLA-4 antibody, and anti-VEGF antibody. In some implementations, the time interval between the dosing of the two drugs should be >30 minutes, and the anti-HER2 antibody-drug conjugate, anti-PD-L1 antibody, anti-CTLA-4 antibody, and anti-VEGF antibody should be administered on the same day or divided into two days.

[0368] In some implementations, when anti-HER2 antibody-drug conjugate, anti-PD-L1 antibody, anti-CTLA-4 antibody, anti-VEGF antibody, and cisplatin are used in combination, the dosing order is: anti-HER2 antibody-drug conjugate, anti-PD-L1 antibody, anti-CTLA-4 antibody, cisplatin, and anti-VEGF antibody. In some implementations, the time interval between the two drug administrations should be >30 minutes, and the anti-HER2 antibody-drug conjugate, anti-PD-L1 antibody, anti-CTLA-4 antibody, anti-VEGF antibody, and cisplatin should be administered on the same day or divided into two days.

[0369] In some implementations, when anti-HER2 antibody-drug conjugate, anti-PD-L1 antibody, anti-CTLA-4 antibody, anti-VEGF antibody, and carboplatin are used in combination, the dosing order is: anti-HER2 antibody-drug conjugate, anti-PD-L1 antibody, anti-CTLA-4 antibody, carboplatin, and anti-VEGF antibody. In some implementations, the time interval between the dosing of the two drugs should be >30 minutes, and the anti-HER2 antibody-drug conjugate, anti-PD-L1 antibody, anti-CTLA-4 antibody, anti-VEGF antibody, and carboplatin should be administered on the same day or divided into two days.

[0370] In this disclosure, "combination" refers to a method of administration that includes various situations where two drugs are administered sequentially or simultaneously. Simultaneous administration, independently prepared and co-administered drugs, or independently prepared and sequentially administered drugs all fall under the category of combined administration as described in this disclosure. "Simultaneous" here means administering at least one dose of an anti-HER2 antibody-drug conjugate, an anti-PD-L1 antibody and / or an anti-CTLA-4 antibody, an anti-VEGF antibody, carboplatin, or cisplatin within a certain time period, for example, administering three drugs within 2 days or 1 day, wherein all three substances exhibit pharmacological effects. "Sequential" administration includes administering the anti-HER2 antibody-drug conjugate, anti-PD-L1 antibody and / or an anti-CTLA-4 antibody, an anti-VEGF antibody, carboplatin, or cisplatin separately within different dosing cycles. The time period can be within a dosing cycle, optionally within 4 weeks, 3 weeks, 2 weeks, 1 week, within 24 hours, or within 2 hours. This period includes treatments in which anti-PD-L1 antibodies and / or anti-CTLA-4 antibodies, anti-VEGF antibodies, carboplatin, or cisplatin are administered via the same or different routes of administration.

[0371] In some implementations, the treatment cycle is every 2 weeks, every 3 weeks, or every 4 weeks, preferably every 3 weeks.

[0372] In some implementations, the dosing regimen of the anti-HER2 antibody-drug conjugate in combination with the anti-PD-L1 antibody is selected from any of the following:

[0373] a) The dosage of anti-HER2 antibody drug conjugate is 0.1 mg / kg-20.0 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, or once every 10 weeks; b) The dosage of anti-PD-L1 antibody is 5-5000 mg, 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;

[0374] a) The dosage of anti-HER2 antibody drug conjugate is 1 mg / kg-10.0 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, or once every 10 weeks; b) 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.

[0375] a) The dosage of anti-HER2 antibody drug conjugate is 1 mg / kg-8.0 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, or once every 10 weeks; b) 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.

[0376] a) The dosage of anti-HER2 antibody drug conjugate is 1 mg / kg-6.0 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, or once every 10 weeks; b) 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.

[0377] a) The dosage of anti-HER2 antibody drug conjugate is 1 mg / kg-5.0 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, or once every 10 weeks; b) 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.

[0378] a) The dosage of anti-HER2 antibody drug conjugate is 1 mg / kg-4.0 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, or once every 10 weeks; b) The dosage of anti-PD-L1 antibody is 5-5000 mg, 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;

[0379] a) The dosage of anti-HER2 antibody drug conjugate is 2 mg / kg-8.0 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, or once every 10 weeks; b) 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.

[0380] a) The dosage of anti-HER2 antibody drug conjugate is 2 mg / kg-6.4 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, or once every 10 weeks; b) 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.

[0381] a) The dosage of anti-HER2 antibody drug conjugate is 2 mg / kg-5.0 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, or once every 10 weeks; b) 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.

[0382] a) The dosage of anti-HER2 antibody drug conjugate is 3.2 mg / kg-8.0 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, or once every 10 weeks; b) 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;

[0383] a) The dosage of anti-HER2 antibody drug conjugate is 3.2 mg / kg-6.4 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, or once every 10 weeks; b) The dosage of anti-PD-L1 antibody is 5-5000 mg, 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;

[0384] a) The dosage of the anti-HER2 antibody drug conjugate is 1.0 mg / kg to 10.0 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, or once every 10 weeks; b) The dosage of the anti-PD-L1 antibody is about 500 mg, about 800 mg, about 1000 mg, about 1200 mg, about 1500 mg, about 1800 mg, or about 2000 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;

[0385] a) The dosage of the anti-HER2 antibody drug conjugate is 1.0 mg / kg-10.0 mg / kg, and the frequency of administration is once every 3 weeks; b) The dosage of the anti-PD-L1 antibody is approximately 500 mg, approximately 800 mg, approximately 1000 mg, approximately 1200 mg, approximately 1500 mg, approximately 1800 mg, or approximately 2000 mg, and the frequency of administration is once every 3 weeks;

[0386] a) The dosage of the anti-HER2 antibody drug conjugate is 1.0 mg / kg to 8.0 mg / kg, and the frequency of administration is once every 3 weeks; b) The dosage of the anti-PD-L1 antibody is approximately 500 mg, approximately 800 mg, approximately 1000 mg, approximately 1200 mg, approximately 1500 mg, approximately 1800 mg, or approximately 2000 mg, and the frequency of administration is once every 3 weeks;

[0387] a) The dosage of the anti-HER2 antibody drug conjugate is 1.0 mg / kg to 6.0 mg / kg, and the frequency of administration is once every 3 weeks; b) The dosage of the anti-PD-L1 antibody is approximately 500 mg, approximately 800 mg, approximately 1000 mg, approximately 1200 mg, approximately 1500 mg, approximately 1800 mg, or approximately 2000 mg, and the frequency of administration is once every 3 weeks;

[0388] a) The dosage of the anti-HER2 antibody drug conjugate is 1.0 mg / kg to 5.0 mg / kg, and the frequency of administration is once every 3 weeks; b) The dosage of the anti-PD-L1 antibody is approximately 500 mg, approximately 800 mg, approximately 1000 mg, approximately 1200 mg, approximately 1500 mg, approximately 1800 mg, or approximately 2000 mg, and the frequency of administration is once every 3 weeks;

[0389] a) The dosage of the anti-HER2 antibody drug conjugate is 2.0 mg / kg-8.0 mg / kg, and the frequency of administration is once every 3 weeks; b) The dosage of the anti-PD-L1 antibody is approximately 500 mg, approximately 800 mg, approximately 1000 mg, approximately 1200 mg, approximately 1500 mg, approximately 1800 mg, or approximately 2000 mg, and the frequency of administration is once every 3 weeks;

[0390] a) The dosage of the anti-HER2 antibody drug conjugate is 2.0 mg / kg-6.4 mg / kg, and the frequency of administration is once every 3 weeks; b) The dosage of the anti-PD-L1 antibody is approximately 500 mg, approximately 800 mg, approximately 1000 mg, approximately 1200 mg, approximately 1500 mg, approximately 1800 mg, or approximately 2000 mg, and the frequency of administration is once every 3 weeks;

[0391] a) The dosage of the anti-HER2 antibody drug conjugate is 3.2 mg / kg-8.0 mg / kg, and the frequency of administration is once every 3 weeks; b) The dosage of the anti-PD-L1 antibody is approximately 500 mg, approximately 800 mg, approximately 1000 mg, approximately 1200 mg, approximately 1500 mg, approximately 1800 mg, or approximately 2000 mg, and the frequency of administration is once every 3 weeks;

[0392] a) The dosage of the anti-HER2 antibody drug conjugate is 3.2 mg / kg-6.4 mg / kg, and the frequency of administration is once every 3 weeks; b) The dosage of the anti-PD-L1 antibody is approximately 500 mg, approximately 800 mg, approximately 1000 mg, approximately 1200 mg, approximately 1500 mg, approximately 1800 mg, or approximately 2000 mg, and the frequency of administration is once every 3 weeks.

[0393] a) The dosage of the anti-HER2 antibody drug conjugate is approximately 1.0 mg / kg, approximately 2.0 mg / kg, approximately 3.0 mg / kg, approximately 3.2 mg / kg, approximately 4.0 mg / kg, approximately 4.5 mg / kg, approximately 4.8 mg / kg, approximately 5.0 mg / kg, approximately 5.5 mg / kg, approximately 5.6 mg / kg, approximately 6.0 mg / kg, approximately 6.4 mg / kg, approximately 7 mg / kg, approximately 8.0 mg / kg, approximately 9.0 mg / kg, or approximately 10 mg / kg; the frequency of administration is once every 3 weeks; b) The dosage of the anti-PD-L1 antibody is approximately 500 mg, approximately 800 mg, approximately 1000 mg, approximately 1200 mg, approximately 1500 mg, approximately 1800 mg, or approximately 2000 mg; the frequency of administration is once every 3 weeks.

[0394] a) The dosage of the anti-HER2 antibody drug conjugate is approximately 3.2 mg / kg, 4.0 mg / kg, or approximately 4.8 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.

[0395] In some implementations, the dosing regimen of the anti-HER2 antibody-drug conjugate in combination with the anti-PD-L1 antibody and the anti-CTLA-4 antibody is selected from any of the following:

[0396] a) The dosage of anti-HER2 antibody drug conjugate is 0.1 mg / kg-20.0 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, or once every 10 weeks; b1) 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; b2) The dosage of anti-CTLA-4 antibody is 1-1000 mg, and the frequency of administration is once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, once every 6 weeks, once every 7 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;

[0397] a) The dosage of anti-HER2 antibody drug conjugate is 1 mg / kg-10.0 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, or once every 10 weeks; b1) 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; b2) The dosage of anti-CTLA-4 antibody is 1-1000 mg, and the frequency of administration is once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, once every 6 weeks, once every 7 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;

[0398] a) The dosage of anti-HER2 antibody-drug conjugate is 1 mg / kg-8.0 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, or once every 10 weeks; b1) 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; b2) The dosage of anti-CTLA-4 antibody is 1-1000 mg, and the frequency of administration is once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, once every 6 weeks, once every 7 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;

[0399] a) The dosage of anti-HER2 antibody drug conjugate is 1 mg / kg-6.0 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, or once every 10 weeks; b1) 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; b2) The dosage of anti-CTLA-4 antibody is 1-1000 mg, and the frequency of administration is once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, once every 6 weeks, once every 7 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;

[0400] a) The dosage of anti-HER2 antibody drug conjugate is 1 mg / kg-5.0 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, or once every 10 weeks; b1) 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; b2) The dosage of anti-CTLA-4 antibody is 1-1000 mg, and the frequency of administration is once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, once every 6 weeks, once every 7 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;

[0401] a) The dosage of anti-HER2 antibody drug conjugate is 1 mg / kg-4.0 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, or once every 10 weeks; b1) 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; b2) The dosage of anti-CTLA-4 antibody is 1-1000 mg, and the frequency of administration is once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, once every 6 weeks, once every 7 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;

[0402] a) The dosage of anti-HER2 antibody drug conjugate is 2 mg / kg-8.0 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, or once every 10 weeks; b1) 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; b2) The dosage of anti-CTLA-4 antibody is 1-1000 mg, and the frequency of administration is once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, once every 6 weeks, once every 7 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;

[0403] a) The dosage of anti-HER2 antibody drug conjugate is 2 mg / kg-6.4 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, or once every 10 weeks; b1) 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; b2) The dosage of anti-CTLA-4 antibody is 1-1000 mg, and the frequency of administration is once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, once every 6 weeks, once every 7 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;

[0404] a) The dosage of anti-HER2 antibody-drug conjugate is 2 mg / kg-5.0 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, or once every 10 weeks; b1) 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; b2) The dosage of anti-CTLA-4 antibody is 1-1000 mg, and the frequency of administration is once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, once every 6 weeks, once every 7 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;

[0405] a) The dosage of anti-HER2 antibody drug conjugate is 3.2 mg / kg-8.0 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, or once every 10 weeks; b1) 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; b2) The dosage of anti-CTLA-4 antibody is 1-1000 mg, and the frequency of administration is once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, once every 6 weeks, once every 7 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;

[0406] a) The dosage of anti-HER2 antibody drug conjugate is 3.2 mg / kg-6.4 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, or once every 10 weeks; b1) 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; b2) The dosage of anti-CTLA-4 antibody is 1-1000 mg, and the frequency of administration is once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, once every 6 weeks, once every 7 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;

[0407] a) The dosage of anti-HER2 antibody-drug conjugate is 1.0 mg / kg-10.0 mg / kg, 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, or once every 10 weeks; b1) The dosage of anti-PD-L1 antibody is approximately 500 mg, approximately 800 mg, approximately 1000 mg, approximately 1200 mg, approximately 1500 mg, approximately 1800 mg, or approximately 2000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks; b2) Anti-CTLA-4 The dosage of the 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 250 mg, approximately 280 mg, approximately 300 mg, approximately 350 mg, approximately 500 mg, or approximately 700 mg, and the dosing frequency is once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, once every 6 weeks, once every 7 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;

[0408] a) The dosage of anti-HER2 antibody drug conjugate is 1.0 mg / kg-10.0 mg / kg, administered once every 3 weeks; b1) The dosage of anti-PD-L1 antibody is approximately 500 mg, approximately 800 mg, approximately 1000 mg, approximately 1200 mg, approximately 1500 mg, approximately 1800 mg, or approximately 2000 mg, administered once every 3 weeks; b2) 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 250 mg, approximately 280 mg, approximately 300 mg, approximately 350 mg, approximately 500 mg, or approximately 700 mg, administered once every 6 weeks or as a single dose;

[0409] a) The dosage of anti-HER2 antibody drug conjugate is 1.0 mg / kg-8.0 mg / kg, administered once every 3 weeks; b1) The dosage of anti-PD-L1 antibody is approximately 500 mg, approximately 800 mg, approximately 1000 mg, approximately 1200 mg, approximately 1500 mg, approximately 1800 mg, or approximately 2000 mg, administered once every 3 weeks; b2) 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 250 mg, approximately 280 mg, approximately 300 mg, approximately 350 mg, approximately 500 mg, or approximately 700 mg, administered once every 6 weeks or as a single dose;

[0410] a) The dosage of anti-HER2 antibody drug conjugate is 1.0 mg / kg-6.0 mg / kg, administered once every 3 weeks; b1) The dosage of anti-PD-L1 antibody is approximately 500 mg, approximately 800 mg, approximately 1000 mg, approximately 1200 mg, approximately 1500 mg, approximately 1800 mg, or approximately 2000 mg, administered once every 3 weeks; b2) 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 250 mg, approximately 280 mg, approximately 300 mg, approximately 350 mg, approximately 500 mg, or approximately 700 mg, administered once every 6 weeks or as a single dose;

[0411] a) The dosage of anti-HER2 antibody drug conjugate is 1.0 mg / kg-5.0 mg / kg, administered once every 3 weeks; b1) The dosage of anti-PD-L1 antibody is approximately 500 mg, approximately 800 mg, approximately 1000 mg, approximately 1200 mg, approximately 1500 mg, approximately 1800 mg, or approximately 2000 mg, administered once every 3 weeks; b2) 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 250 mg, approximately 280 mg, approximately 300 mg, approximately 350 mg, approximately 500 mg, or approximately 700 mg, administered once every 6 weeks or as a single dose;

[0412] a) The dosage of anti-HER2 antibody drug conjugate is 2.0 mg / kg-8.0 mg / kg, administered once every 3 weeks; b1) The dosage of anti-PD-L1 antibody is approximately 500 mg, approximately 800 mg, approximately 1000 mg, approximately 1200 mg, approximately 1500 mg, approximately 1800 mg, or approximately 2000 mg, administered once every 3 weeks; b2) 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 250 mg, approximately 280 mg, approximately 300 mg, approximately 350 mg, approximately 500 mg, or approximately 700 mg, administered once every 6 weeks or as a single dose;

[0413] a) The dosage of anti-HER2 antibody drug conjugate is 2.0 mg / kg-6.4 mg / kg, administered once every 3 weeks; b1) The dosage of anti-PD-L1 antibody is approximately 500 mg, approximately 800 mg, approximately 1000 mg, approximately 1200 mg, approximately 1500 mg, approximately 1800 mg, or approximately 2000 mg, administered once every 3 weeks; b2) 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 250 mg, approximately 280 mg, approximately 300 mg, approximately 350 mg, approximately 500 mg, or approximately 700 mg, administered once every 6 weeks or as a single dose;

[0414] a) The dosage of anti-HER2 antibody drug conjugate is 3.2 mg / kg-8.0 mg / kg, administered once every 3 weeks; b1) The dosage of anti-PD-L1 antibody is approximately 500 mg, approximately 800 mg, approximately 1000 mg, approximately 1200 mg, approximately 1500 mg, approximately 1800 mg, or approximately 2000 mg, administered once every 3 weeks; b2) 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 250 mg, approximately 280 mg, approximately 300 mg, approximately 350 mg, approximately 500 mg, or approximately 700 mg, administered once every 6 weeks or as a single dose;

[0415] a) The dosage of anti-HER2 antibody drug conjugate is 3.2 mg / kg-6.4 mg / kg, administered once every 3 weeks; b1) The dosage of anti-PD-L1 antibody is approximately 500 mg, approximately 800 mg, approximately 1000 mg, approximately 1200 mg, approximately 1500 mg, approximately 1800 mg, or approximately 2000 mg, administered once every 3 weeks; b2) 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 250 mg, approximately 280 mg, approximately 300 mg, approximately 350 mg, approximately 500 mg, or approximately 700 mg, administered once every 6 weeks or as a single dose;

[0416] a) The dosage of the anti-HER2 antibody-drug conjugate is approximately 1.0 mg / kg, approximately 2.0 mg / kg, approximately 3.0 mg / kg, approximately 3.2 mg / kg, approximately 4.0 mg / kg, approximately 4.5 mg / kg, approximately 4.8 mg / kg, approximately 5.0 mg / kg, approximately 5.5 mg / kg, approximately 5.6 mg / kg, approximately 6.0 mg / kg, approximately 6.4 mg / kg, approximately 7 mg / kg, approximately 8.0 mg / kg, approximately 9.0 mg / kg, or approximately 10 mg / kg; the frequency of administration is once every 3 weeks; b1) The dosage of the anti-PD-L1 antibody is approximately 500 mg / kg. a) The dosage of anti-CTLA-4 antibody is approximately 800 mg, 1000 mg, 1200 mg, 1500 mg, 1800 mg, or 2000 mg, administered once every 3 weeks; b2) 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, 250 mg, 280 mg, 300 mg, 350 mg, 500 mg, or 700 mg, administered once every 6 weeks or as a single dose;

[0417] a) The dosage of the anti-HER2 antibody-drug conjugate is approximately 1.0 mg / kg, approximately 2.0 mg / kg, approximately 3.0 mg / kg, approximately 3.2 mg / kg, approximately 4.0 mg / kg, approximately 4.5 mg / kg, approximately 4.8 mg / kg, approximately 5.0 mg / kg, approximately 5.5 mg / kg, approximately 5.6 mg / kg, approximately 6.0 mg / kg, approximately 6.4 mg / kg, approximately 7 mg / kg, approximately 8.0 mg / kg, approximately 9.0 mg / kg, or approximately 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 anti-CTLA-4 antibody is administered as a single dose of approximately 280 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.

[0418] a) The dosage of the anti-HER2 antibody drug conjugate is approximately 3.2 mg / kg, 4.0 mg / kg, or 4.8 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 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.

[0419] In some implementations, the dosing regimen of the anti-HER2 antibody-drug conjugate in combination with the anti-PD-L1 antibody and the anti-VEGF antibody is selected from any of the following:

[0420] a) The dosage of anti-HER2 antibody drug conjugate is 0.1 mg / kg-20.0 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, or once every 10 weeks; b) 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; c) 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.

[0421] a) The dosage of anti-HER2 antibody drug conjugate is 1 mg / kg-10.0 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, or once every 10 weeks; b) 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; c) The dosage of anti-VEGF antibody is 1 mg / kg-25 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.

[0422] a) The dosage of anti-HER2 antibody drug conjugate is 1 mg / kg-8.0 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, or once every 10 weeks; b) 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; c) The dosage of anti-VEGF antibody is 1 mg / kg-25 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.

[0423] a) The dosage of anti-HER2 antibody drug conjugate is 1 mg / kg-6.0 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, or once every 10 weeks; b) 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; c) The dosage of anti-VEGF antibody is 1 mg / kg-25 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.

[0424] a) The dosage of anti-HER2 antibody drug conjugate is 1 mg / kg-5.0 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, or once every 10 weeks; b) 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; c) The dosage of anti-VEGF antibody is 1 mg / kg-25 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.

[0425] a) The dosage of anti-HER2 antibody drug conjugate is 1 mg / kg-4.0 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, or once every 10 weeks; b) 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; c) The dosage of anti-VEGF antibody is 1 mg / kg-25 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.

[0426] a) The dosage of anti-HER2 antibody drug conjugate is 2 mg / kg-8.0 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, or once every 10 weeks; b) 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; c) The dosage of anti-VEGF antibody is 1 mg / kg-25 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.

[0427] a) The dosage of anti-HER2 antibody drug conjugate is 2 mg / kg-6.4 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, or once every 10 weeks; b) 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; c) The dosage of anti-VEGF antibody is 1 mg / kg-25 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.

[0428] a) The dosage of anti-HER2 antibody drug conjugate is 2 mg / kg-5.0 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, or once every 10 weeks; b) 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; c) The dosage of anti-VEGF antibody is 1 mg / kg-25 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.

[0429] a) The dosage of anti-HER2 antibody drug conjugate is 3.2 mg / kg-8.0 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, or once every 10 weeks; b) 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; c) The dosage of anti-VEGF antibody is 1 mg / kg-25 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.

[0430] a) The dosage of anti-HER2 antibody drug conjugate is 3.2 mg / kg-6.4 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, or once every 10 weeks; b) 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; c) The dosage of anti-VEGF antibody is 1 mg / kg-25 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.

[0431] a) The dosage of anti-HER2 antibody drug conjugate is 1.0 mg / kg to 10.0 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, or once every 10 weeks; b) The dosage of anti-PD-L1 antibody is about 500 mg, about 800 mg, about 1000 mg, about 1200 mg, about 1500 mg, about 1800 mg, or about 2000 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; c) The dosage of anti-VEGF antibody is 10 mg / kg to 20 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.

[0432] a) The dosage of anti-HER2 antibody drug conjugate is 1.0 mg / kg-10.0 mg / kg, administered once every 3 weeks; b) The dosage of anti-PD-L1 antibody is approximately 500 mg, 800 mg, 1000 mg, 1200 mg, 1500 mg, 1800 mg, or 2000 mg, administered once every 3 weeks; c) The dosage of anti-VEGF antibody is 10 mg / kg-20 mg / kg, administered once every 3 weeks.

[0433] a) The dosage of anti-HER2 antibody drug conjugate is 1.0 mg / kg-8.0 mg / kg, administered once every 3 weeks; b) The dosage of anti-PD-L1 antibody is approximately 500 mg, 800 mg, 1000 mg, 1200 mg, 1500 mg, 1800 mg, or 2000 mg, administered once every 3 weeks; c) The dosage of anti-VEGF antibody is 10 mg / kg-20 mg / kg, administered once every 3 weeks.

[0434] a) The dosage of anti-HER2 antibody drug conjugate is 1.0 mg / kg-6.0 mg / kg, administered once every 3 weeks; b) The dosage of anti-PD-L1 antibody is approximately 500 mg, 800 mg, 1000 mg, 1200 mg, 1500 mg, 1800 mg, or 2000 mg, administered once every 3 weeks; c) The dosage of anti-VEGF antibody is 10 mg / kg-20 mg / kg, administered once every 3 weeks.

[0435] a) The dosage of anti-HER2 antibody drug conjugate is 1.0 mg / kg-5.0 mg / kg, administered once every 3 weeks; b) The dosage of anti-PD-L1 antibody is approximately 500 mg, 800 mg, 1000 mg, 1200 mg, 1500 mg, 1800 mg, or 2000 mg, administered once every 3 weeks; c) The dosage of anti-VEGF antibody is 10 mg / kg-20 mg / kg, administered once every 3 weeks.

[0436] a) The dosage of anti-HER2 antibody drug conjugate is 2.0 mg / kg-8.0 mg / kg, administered once every 3 weeks; b) The dosage of anti-PD-L1 antibody is approximately 500 mg, 800 mg, 1000 mg, 1200 mg, 1500 mg, 1800 mg, or 2000 mg, administered once every 3 weeks; c) The dosage of anti-VEGF antibody is 10 mg / kg-20 mg / kg, administered once every 3 weeks.

[0437] a) The dosage of anti-HER2 antibody drug conjugate is 2.0 mg / kg-6.4 mg / kg, administered once every 3 weeks; b) The dosage of anti-PD-L1 antibody is approximately 500 mg, 800 mg, 1000 mg, 1200 mg, 1500 mg, 1800 mg, or 2000 mg, administered once every 3 weeks; c) The dosage of anti-VEGF antibody is 10 mg / kg-20 mg / kg, administered once every 3 weeks.

[0438] a) The dosage of anti-HER2 antibody drug conjugate is 3.2 mg / kg-8.0 mg / kg, administered once every 3 weeks; b) The dosage of anti-PD-L1 antibody is approximately 500 mg, 800 mg, 1000 mg, 1200 mg, 1500 mg, 1800 mg, or 2000 mg, administered once every 3 weeks; c) The dosage of anti-VEGF antibody is 10 mg / kg-20 mg / kg, administered once every 3 weeks.

[0439] a) The dosage of anti-HER2 antibody drug conjugate is 3.2 mg / kg-6.4 mg / kg, administered once every 3 weeks; b) The dosage of anti-PD-L1 antibody is approximately 500 mg, 800 mg, 1000 mg, 1200 mg, 1500 mg, 1800 mg, or 2000 mg, administered once every 3 weeks; c) The dosage of anti-VEGF antibody is 10 mg / kg-20 mg / kg, administered once every 3 weeks.

[0440] a) The dosage of the anti-HER2 antibody-drug conjugate is approximately 1.0 mg / kg, approximately 2.0 mg / kg, approximately 3.0 mg / kg, approximately 3.2 mg / kg, approximately 4.0 mg / kg, approximately 4.5 mg / kg, approximately 4.8 mg / kg, approximately 5.0 mg / kg, approximately 5.5 mg / kg, approximately 5.6 mg / kg, approximately 6.0 mg / kg, approximately 6.4 mg / kg, approximately 7 mg / kg, approximately 8.0 mg / kg, approximately 9.0 mg / kg, or approximately 10 mg / kg; the frequency of administration is once every 3 weeks; b) The dosage of the anti-PD-L1 antibody is approximately 500 mg, approximately 800 mg, approximately 1000 mg, approximately 1200 mg, approximately 1500 mg, approximately 1800 mg, or approximately 2000 mg. The dosing frequency is once every 3 weeks; c) The dosage of anti-VEGF antibody is about 2.0 mg / kg, about 3.0 mg / kg, about 5 mg / kg, about 6.0 mg / kg, about 7.5 mg / kg, about 8.0 mg / kg, about 9.0 mg / kg, about 10 mg / kg, about 11 mg / kg, about 12 mg / kg, about 13 mg / kg, about 14 mg / kg, about 15 mg / kg, about 16 mg / kg, about 17 mg / kg, about 18 mg / kg, about 19 mg / kg, about 20 mg / kg, about 21.0 mg / kg, about 22.0 mg / kg, about 23.0 mg / kg, about 24.0 mg / kg, or about 25.0 mg / kg, and the dosing frequency is once every 3 weeks;

[0441] a) The dosage of the anti-HER2 antibody drug conjugate is approximately 3.2 mg / kg, 4.0 mg / kg, or approximately 4.8 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; c) The dosage of the anti-VEGF antibody is approximately 15 mg / kg, administered once every 3 weeks.

[0442] In some implementations, the dosing regimen of the anti-HER2 antibody-drug conjugate in combination with anti-PD-L1 antibody, anti-CTLA-4 antibody, and anti-VEGF antibody is selected from any of the following:

[0443] a) The dosage of anti-HER2 antibody-drug conjugates is 0.1 mg / kg-20.0 mg / kg, 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, or once every 10 weeks; b1) The dosage of anti-PD-L1 antibody is 5-5000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks; b2) The dosage of anti-CTLA-4 antibody is 1-10 mg / kg-20.0 mg / kg. 0.00 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, once every 6 weeks, once every 7 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; c) The dosage of anti-VEGF antibody is 1 mg / kg-30 mg / kg, 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;

[0444] a) The dosage of anti-HER2 antibody drug conjugate is 1 mg / kg-10.0 mg / kg, 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, or once every 10 weeks; b1) The dosage of anti-PD-L1 antibody is 5-5000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks; b2) The dosage of anti-CTLA-4 antibody is 1-100 mg / kg. 0 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, once every 6 weeks, once every 7 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; c) The dosage of anti-VEGF antibody is 1 mg / kg-25 mg / kg, 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;

[0445] a) The dosage of anti-HER2 antibody-drug conjugates is 1 mg / kg-8.0 mg / kg, 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, or once every 10 weeks; b1) The dosage of anti-PD-L1 antibodies is 5-5000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks; b2) The dosage of anti-CTLA-4 antibodies is 1-100 mg / kg. 0 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, once every 6 weeks, once every 7 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; c) The dosage of anti-VEGF antibody is 1 mg / kg-25 mg / kg, 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;

[0446] a) The dosage of anti-HER2 antibody-drug conjugates is 1 mg / kg-6.0 mg / kg, 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, or once every 10 weeks; b1) The dosage of anti-PD-L1 antibody is 5-5000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks; b2) The dosage of anti-CTLA-4 antibody is 1-100 mg / kg. 0 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, once every 6 weeks, once every 7 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; c) The dosage of anti-VEGF antibody is 1 mg / kg-25 mg / kg, 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;

[0447] a) The dosage of anti-HER2 antibody-drug conjugates is 1 mg / kg-5.0 mg / kg, 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, or once every 10 weeks; b1) The dosage of anti-PD-L1 antibody is 5-5000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks; b2) The dosage of anti-CTLA-4 antibody is 1-100 mg / kg. 0 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, once every 6 weeks, once every 7 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; c) The dosage of anti-VEGF antibody is 1 mg / kg-25 mg / kg, 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;

[0448] a) The dosage of anti-HER2 antibody-drug conjugates is 1 mg / kg-4.0 mg / kg, 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, or once every 10 weeks; b1) The dosage of anti-PD-L1 antibodies is 5-5000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks; b2) The dosage of anti-CTLA-4 antibodies is 1-100 mg / kg. 0 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, once every 6 weeks, once every 7 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; c) The dosage of anti-VEGF antibody is 1 mg / kg-25 mg / kg, 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;

[0449] a) The dosage of anti-HER2 antibody-drug conjugates is 2 mg / kg-8.0 mg / kg, 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, or once every 10 weeks; b1) The dosage of anti-PD-L1 antibodies is 5-5000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks; b2) The dosage of anti-CTLA-4 antibodies is 1-100 mg / kg. 0 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, once every 6 weeks, once every 7 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; c) The dosage of anti-VEGF antibody is 1 mg / kg-25 mg / kg, 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;

[0450] a) The dosage of anti-HER2 antibody-drug conjugates is 2 mg / kg-6.4 mg / kg, 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, or once every 10 weeks; b1) The dosage of anti-PD-L1 antibodies is 5-5000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks; b2) The dosage of anti-CTLA-4 antibodies is 1-100 mg / kg. 0 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, once every 6 weeks, once every 7 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; c) The dosage of anti-VEGF antibody is 1 mg / kg-25 mg / kg, 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;

[0451] a) The dosage of anti-HER2 antibody-drug conjugates is 2 mg / kg-5.0 mg / kg, 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, or once every 10 weeks; b1) The dosage of anti-PD-L1 antibodies is 5-5000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks; b2) The dosage of anti-CTLA-4 antibodies is 1-100 mg / kg. 0 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, once every 6 weeks, once every 7 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; c) The dosage of anti-VEGF antibody is 1 mg / kg-25 mg / kg, 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;

[0452] a) The dosage of anti-HER2 antibody-drug conjugates is 3.2 mg / kg-8.0 mg / kg, 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, or once every 10 weeks; b1) The dosage of anti-PD-L1 antibody is 5-5000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks; b2) The dosage of anti-CTLA-4 antibody is 1-10 mg / kg-8.0 mg / kg. 0.00 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, once every 6 weeks, once every 7 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; c) The dosage of anti-VEGF antibody is 1 mg / kg-25 mg / kg, 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;

[0453] a) The dosage of anti-HER2 antibody-drug conjugates is 3.2 mg / kg-6.4 mg / kg, 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, or once every 10 weeks; b1) The dosage of anti-PD-L1 antibody is 5-5000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks; b2) The dosage of anti-CTLA-4 antibody is 1-10 mg / kg-6.4 mg / kg. 0.00 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, once every 6 weeks, once every 7 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; c) The dosage of anti-VEGF antibody is 1 mg / kg-25 mg / kg, 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;

[0454] a) The dosage of anti-HER2 antibody-drug conjugate is 1.0 mg / kg-10.0 mg / kg, 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, or once every 10 weeks; b1) The dosage of anti-PD-L1 antibody is approximately 500 mg, 800 mg, 1000 mg, 1200 mg, 1500 mg, 1800 mg, or 2000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks; b2) The dosage of anti-CTLA-4 antibody is approximately 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, or 60 mg. The dosage of anti-VEGF antibody is approximately 70 mg, 80 mg, 90 mg, 100 mg, 150 mg, 200 mg, 250 mg, 280 mg, 300 mg, 350 mg, 500 mg, or 700 mg, administered at a frequency of once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, once every 6 weeks, once every 7 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; c) The dosage of anti-VEGF antibody is 10 mg / kg-20 mg / kg, administered at a frequency of 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;

[0455] a) The dosage of anti-HER2 antibody drug conjugate is 1.0 mg / kg-10.0 mg / kg, administered once every 3 weeks; b1) The dosage of anti-PD-L1 antibody is approximately 500 mg, 800 mg, 1000 mg, 1200 mg, 1500 mg, 1800 mg, or 2000 mg, administered once every 3 weeks; b2) The dosage of anti-CTLA-4 antibody is approximately 10 mg, approximately 20 mg, ... Approximately 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 150 mg, 200 mg, 250 mg, 280 mg, 300 mg, 350 mg, 500 mg, or 700 mg, administered once every 6 weeks or as a single dose; c) The dosage of anti-VEGF antibody is 10 mg / kg-20 mg / kg, administered once every 3 weeks;

[0456] a) The dosage of anti-HER2 antibody drug conjugate is 1.0 mg / kg-8.0 mg / kg, administered once every 3 weeks; b1) The dosage of anti-PD-L1 antibody is approximately 500 mg, 800 mg, 1000 mg, 1200 mg, 1500 mg, 1800 mg, or 2000 mg, administered once every 3 weeks; b2) The dosage of anti-CTLA-4 antibody is approximately 10 mg, approximately 20 mg, ... Approximately 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 150 mg, 200 mg, 250 mg, 280 mg, 300 mg, 350 mg, 500 mg, or 700 mg, administered once every 6 weeks or as a single dose; c) The dosage of anti-VEGF antibody is 10 mg / kg-20 mg / kg, administered once every 3 weeks;

[0457] a) The dosage of anti-HER2 antibody drug conjugate is 1.0 mg / kg-6.0 mg / kg, administered once every 3 weeks; b1) The dosage of anti-PD-L1 antibody is approximately 500 mg, 800 mg, 1000 mg, 1200 mg, 1500 mg, 1800 mg, or 2000 mg, administered once every 3 weeks; b2) The dosage of anti-CTLA-4 antibody is approximately 10 mg, approximately 20 mg, ... Approximately 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 150 mg, 200 mg, 250 mg, 280 mg, 300 mg, 350 mg, 500 mg, or 700 mg, administered once every 6 weeks or as a single dose; c) The dosage of anti-VEGF antibody is 10 mg / kg-20 mg / kg, administered once every 3 weeks;

[0458] a) The dosage of anti-HER2 antibody drug conjugate is 1.0 mg / kg-5.0 mg / kg, administered once every 3 weeks; b1) The dosage of anti-PD-L1 antibody is approximately 500 mg, 800 mg, 1000 mg, 1200 mg, 1500 mg, 1800 mg, or 2000 mg, administered once every 3 weeks; b2) The dosage of anti-CTLA-4 antibody is approximately 10 mg, approximately 20 mg, Approximately 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 150 mg, 200 mg, 250 mg, 280 mg, 300 mg, 350 mg, 500 mg, or 700 mg, administered once every 6 weeks or as a single dose; c) The dosage of anti-VEGF antibody is 10 mg / kg-20 mg / kg, administered once every 3 weeks;

[0459] a) The dosage of anti-HER2 antibody-drug conjugate is 2.0 mg / kg-8.0 mg / kg, administered once every 3 weeks; b1) The dosage of anti-PD-L1 antibody is approximately 500 mg, 800 mg, 1000 mg, 1200 mg, 1500 mg, 1800 mg, or 2000 mg, administered once every 3 weeks; b2) The dosage of anti-CTLA-4 antibody is approximately 10 mg, approximately 20 mg, Approximately 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 150 mg, 200 mg, 250 mg, 280 mg, 300 mg, 350 mg, 500 mg, or 700 mg, administered once every 6 weeks or as a single dose; c) The dosage of anti-VEGF antibody is 10 mg / kg-20 mg / kg, administered once every 3 weeks;

[0460] a) The dosage of anti-HER2 antibody drug conjugate is 2.0 mg / kg-6.4 mg / kg, administered once every 3 weeks; b1) The dosage of anti-PD-L1 antibody is approximately 500 mg, 800 mg, 1000 mg, 1200 mg, 1500 mg, 1800 mg, or 2000 mg, administered once every 3 weeks; b2) The dosage of anti-CTLA-4 antibody is approximately 10 mg, approximately 20 mg, Approximately 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 150 mg, 200 mg, 250 mg, 280 mg, 300 mg, 350 mg, 500 mg, or 700 mg, administered once every 6 weeks or as a single dose; c) The dosage of anti-VEGF antibody is 10 mg / kg-20 mg / kg, administered once every 3 weeks;

[0461] a) The dosage of anti-HER2 antibody-drug conjugate is 3.2 mg / kg-8.0 mg / kg, administered once every 3 weeks; b1) The dosage of anti-PD-L1 antibody is approximately 500 mg, 800 mg, 1000 mg, 1200 mg, 1500 mg, 1800 mg, or 2000 mg, administered once every 3 weeks; b2) The dosage of anti-CTLA-4 antibody is approximately 10 mg, approximately 20 mg, Approximately 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 150 mg, 200 mg, 250 mg, 280 mg, 300 mg, 350 mg, 500 mg, or 700 mg, administered once every 6 weeks or as a single dose; c) The dosage of anti-VEGF antibody is 10 mg / kg-20 mg / kg, administered once every 3 weeks;

[0462] a) The dosage of anti-HER2 antibody-drug conjugate is 3.2 mg / kg-6.4 mg / kg, administered once every 3 weeks; b1) The dosage of anti-PD-L1 antibody is approximately 500 mg, 800 mg, 1000 mg, 1200 mg, 1500 mg, 1800 mg, or 2000 mg, administered once every 3 weeks; b2) The dosage of anti-CTLA-4 antibody is approximately 10 mg, approximately 20 mg, Approximately 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 150 mg, 200 mg, 250 mg, 280 mg, 300 mg, 350 mg, 500 mg, or 700 mg, administered once every 6 weeks or as a single dose; c) The dosage of anti-VEGF antibody is 10 mg / kg-20 mg / kg, administered once every 3 weeks;

[0463] a) The dosage of the anti-HER2 antibody-drug conjugate is approximately 1.0 mg / kg, approximately 2.0 mg / kg, approximately 3.0 mg / kg, approximately 3.2 mg / kg, approximately 4.0 mg / kg, approximately 4.5 mg / kg, approximately 4.8 mg / kg, approximately 5.0 mg / kg, approximately 5.5 mg / kg, approximately 5.6 mg / kg, approximately 6.0 mg / kg, approximately 6.4 mg / kg, approximately 7 mg / kg, approximately 8.0 mg / kg, and approximately 9.0 mg / kg. Or approximately 10 mg / kg; the dosing frequency is once every 3 weeks; b1) The dosing dose of anti-PD-L1 antibody is approximately 500 mg, approximately 800 mg, approximately 1000 mg, approximately 1200 mg, approximately 1500 mg, approximately 1800 mg, or approximately 2000 mg, and the dosing frequency is once every 3 weeks; b2) The dosing dose 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, or approximately 10 mg / kg; the dosing frequency is once every 3 weeks; g, approximately 90 mg, approximately 100 mg, approximately 150 mg, approximately 200 mg, approximately 250 mg, approximately 280 mg, approximately 300 mg, approximately 350 mg, approximately 500 mg, or approximately 700 mg, administered once every 6 weeks or as a single dose; c) The dosage of anti-VEGF antibody is approximately 2.0 mg / kg, approximately 3.0 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. g, 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 / kg, approximately 22.0 mg / kg, approximately 23.0 mg / kg, approximately 24.0 mg / kg, or approximately 25.0 mg / kg, administered once every 3 weeks;

[0464] a) The dosage of the anti-HER2 antibody-drug conjugate is approximately 1.0 mg / kg, approximately 2.0 mg / kg, approximately 3.0 mg / kg, approximately 3.2 mg / kg, approximately 4.0 mg / kg, approximately 4.5 mg / kg, approximately 4.8 mg / kg, approximately 5.0 mg / kg, approximately 5.5 mg / kg, approximately 5.6 mg / kg, approximately 6.0 mg / kg, approximately 6.4 mg / kg, approximately 7 mg / kg, approximately 8.0 mg / kg, and approximately 9.0 mg / kg. g, or about 10 mg / kg, administered once every 3 weeks; b1) Anti-PD-L1 antibody administered at a dose of about 1200 mg, administered once every 3 weeks; b2) Anti-CTLA-4 antibody administered once in week 1 at a dose of about 280 mg, with no administration from week 2 to week 12, and from week 13 onwards at a dose of about 70 mg, administered once every 6 weeks; c) Anti-VEGF antibody administered at a dose of about 15 mg / kg, administered once every 3 weeks.

[0465] a) The dosage of the anti-HER2 antibody-drug conjugate is approximately 3.2 mg / kg, 4.0 mg / kg, or 4.8 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 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; c) The dosage of the anti-VEGF antibody is approximately 15 mg / kg, administered once every 3 weeks.

[0466] In some implementations, the dosing regimen of the anti-HER2 antibody-drug conjugate in combination with anti-PD-L1 antibody, anti-VEGF antibody, and cisplatin is selected from any of the following:

[0467] a) The dosage of anti-HER2 antibody-drug conjugates is 0.1 mg / kg to 20.0 mg / kg, 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, or once every 10 weeks; b) The dosage of anti-PD-L1 antibody is 5 to 5000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks; c) The dosage of anti-VEGF antibody is 1 mg / kg to 30 mg / kg, 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; d) The dosage of cisplatin is approximately 1 mg / kg. 2 Approximately 500 mg / m 2 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;

[0468] a) The dosage of anti-HER2 antibody-drug conjugates is 1 mg / kg to 10.0 mg / kg, 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, or once every 10 weeks; b) The dosage of anti-PD-L1 antibodies is 5 to 5000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks; c) The dosage of anti-VEGF antibodies is 1 mg / kg to 25 mg / kg, 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; d) The dosage of cisplatin is approximately 1 mg / kg. 2 Approximately 200 mg / m 2 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;

[0469] a) The dosage of anti-HER2 antibody-drug conjugates is 1 mg / kg-8.0 mg / kg, 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, or once every 10 weeks; b1) The dosage of anti-PD-L1 antibodies is 5-5000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks; c) The dosage of anti-VEGF antibodies is 1 mg / kg-25 mg / kg, 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; d) The dosage of cisplatin is approximately 1 mg / m 2 Approximately 200 mg / m 2 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;

[0470] a) The dosage of anti-HER2 antibody-drug conjugates is 1 mg / kg-6.0 mg / kg, 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, or once every 10 weeks; b1) The dosage of anti-PD-L1 antibodies is 5-5000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks; c) The dosage of anti-VEGF antibodies is 1 mg / kg-25 mg / kg, 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; d) The dosage of cisplatin is approximately 1 mg / m 2 Approximately 200 mg / m 2The dosing frequency is once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks;

[0471] a) The dosage of anti-HER2 antibody-drug conjugates is 1 mg / kg-5.0 mg / kg, 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, or once every 10 weeks; b1) The dosage of anti-PD-L1 antibodies is 5-5000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks; c) The dosage of anti-VEGF antibodies is 1 mg / kg-25 mg / kg, 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; d) The dosage of cisplatin is approximately 1 mg / kg. 2 Approximately 200 mg / m 2 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;

[0472] a) The dosage of anti-HER2 antibody-drug conjugates is 1 mg / kg-4.0 mg / kg, 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, or once every 10 weeks; b1) The dosage of anti-PD-L1 antibodies is 5-5000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks; c) The dosage of anti-VEGF antibodies is 1 mg / kg-25 mg / kg, 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; d) The dosage of cisplatin is approximately 1 mg / m 2 Approximately 200 mg / m 2 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;

[0473] a) The dosage of anti-HER2 antibody-drug conjugates is 2 mg / kg-8.0 mg / kg, 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, or once every 10 weeks; b1) The dosage of anti-PD-L1 antibodies is 5-5000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks; c) The dosage of anti-VEGF antibodies is 1 mg / kg-25 mg / kg, 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; d) The dosage of cisplatin is approximately 1 mg / kg. 2 Approximately 200 mg / m 2 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;

[0474] a) The dosage of anti-HER2 antibody-drug conjugates is 2 mg / kg-6.4 mg / kg, 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, or once every 10 weeks; b1) The dosage of anti-PD-L1 antibodies is 5-5000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks; c) The dosage of anti-VEGF antibodies is 1 mg / kg-25 mg / kg, 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; d) The dosage of cisplatin is approximately 1 mg / m 2 Approximately 200 mg / m 2 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;

[0475] a) The dosage of anti-HER2 antibody-drug conjugates is 2 mg / kg-5.0 mg / kg, 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, or once every 10 weeks; b) The dosage of anti-PD-L1 antibodies is 5-5000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks; c) The dosage of anti-VEGF antibodies is 1 mg / kg-25 mg / kg, 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; d) The dosage of cisplatin is approximately 1 mg / m². 2 Approximately 200 mg / m 2The dosing frequency is once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks;

[0476] a) The dosage of anti-HER2 antibody-drug conjugates is 3.2 mg / kg-8.0 mg / kg, 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, or once every 10 weeks; b1) The dosage of anti-PD-L1 antibodies is 5-5000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks; c) The dosage of anti-VEGF antibodies is 1 mg / kg-25 mg / kg, 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; d) The dosage of cisplatin is approximately 1 mg / m 2 Approximately 200 mg / m 2 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;

[0477] a) The dosage of anti-HER2 antibody-drug conjugates is 3.2 mg / kg-6.4 mg / kg, 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, or once every 10 weeks; b) The dosage of anti-PD-L1 antibodies is 5-5000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks; c) The dosage of anti-VEGF antibodies is 1 mg / kg-25 mg / kg, 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; d) The dosage of cisplatin is approximately 1 mg / m². 2 Approximately 200 mg / m 2 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;

[0478] a) The dosage of the anti-HER2 antibody-drug conjugate is 1.0 mg / kg-10.0 mg / kg, 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, or once every 10 weeks; b1) The dosage of the anti-PD-L1 antibody is approximately 500 mg, approximately 800 mg, approximately 1000 mg, approximately 1200 mg, approximately 1500 mg, and approximately 1800 mg. a) The dosage of anti-VEGF antibody is 10 mg / kg-20 mg / kg, administered once a 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; d) The dosage of cisplatin is approximately 1 mg / m². 2 Approximately 100 mg / m 2 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;

[0479] a) The dosage of anti-HER2 antibody-drug conjugate is 1.0 mg / kg-10.0 mg / kg, administered once every 3 weeks; b) The dosage of anti-PD-L1 antibody is approximately 500 mg, 800 mg, 1000 mg, 1200 mg, 1500 mg, 1800 mg, or 2000 mg, administered once every 3 weeks; c) The dosage of anti-VEGF antibody is 10 mg / kg-20 mg / kg, administered once every 3 weeks; d) The dosage of cisplatin is approximately 1 mg / kg. 2 Approximately 100 mg / m 2 The dosing frequency is once every 3 weeks;

[0480] a) The dosage of anti-HER2 antibody-drug conjugate is 1.0 mg / kg–8.0 mg / kg, administered once every 3 weeks; b) The dosage of anti-PD-L1 antibody is approximately 500 mg, 800 mg, 1000 mg, 1200 mg, 1500 mg, 1800 mg, or 2000 mg, administered once every 3 weeks; c) The dosage of anti-VEGF antibody is 10 mg / kg–20 mg / kg, administered once every 3 weeks; d) The dosage of cisplatin is approximately 1 mg / kg. 2 Approximately 100 mg / m 2 The dosing frequency is once every 3 weeks;

[0481] a) The dosage of anti-HER2 antibody-drug conjugate is 1.0 mg / kg–6.0 mg / kg, administered once every 3 weeks; b) The dosage of anti-PD-L1 antibody is approximately 500 mg, 800 mg, 1000 mg, 1200 mg, 1500 mg, 1800 mg, or 2000 mg, administered once every 3 weeks; c) The dosage of anti-VEGF antibody is 10 mg / kg–20 mg / kg, administered once every 3 weeks; d) The dosage of cisplatin is approximately 1 mg / kg. 2 Approximately 100 mg / m 2 The dosing frequency is once every 3 weeks;

[0482] a) The dosage of anti-HER2 antibody-drug conjugate is 1.0 mg / kg–5.0 mg / kg, administered once every 3 weeks; b) The dosage of anti-PD-L1 antibody is approximately 500 mg, 800 mg, 1000 mg, 1200 mg, 1500 mg, 1800 mg, or 2000 mg, administered once every 3 weeks; c) The dosage of anti-VEGF antibody is 10 mg / kg–20 mg / kg, administered once every 3 weeks; d) The dosage of cisplatin is approximately 1 mg / kg. 2 Approximately 100 mg / m 2 The dosing frequency is once every 3 weeks;

[0483] a) The dosage of anti-HER2 antibody-drug conjugate is 2.0 mg / kg-8.0 mg / kg, administered once every 3 weeks; b) The dosage of anti-PD-L1 antibody is approximately 500 mg, 800 mg, 1000 mg, 1200 mg, 1500 mg, 1800 mg, or 2000 mg, administered once every 3 weeks; c) The dosage of anti-VEGF antibody is 10 mg / kg-20 mg / kg, administered once every 3 weeks; d) The dosage of cisplatin is approximately 1 mg / kg. 2 Approximately 100 mg / m 2 The dosing frequency is once every 3 weeks;

[0484] a) The dosage of anti-HER2 antibody-drug conjugate is 2.0 mg / kg–6.4 mg / kg, administered once every 3 weeks; b) The dosage of anti-PD-L1 antibody is approximately 500 mg, 800 mg, 1000 mg, 1200 mg, 1500 mg, 1800 mg, or 2000 mg, administered once every 3 weeks; c) The dosage of anti-VEGF antibody is 10 mg / kg–20 mg / kg, administered once every 3 weeks; d) The dosage of cisplatin is approximately 1 mg / kg. 2 Approximately 100 mg / m2 The dosing frequency is once every 3 weeks;

[0485] a) The dosage of anti-HER2 antibody-drug conjugate is 3.2 mg / kg-8.0 mg / kg, administered once every 3 weeks; b) The dosage of anti-PD-L1 antibody is approximately 500 mg, 800 mg, 1000 mg, 1200 mg, 1500 mg, 1800 mg, or 2000 mg, administered once every 3 weeks; c) The dosage of anti-VEGF antibody is 10 mg / kg-20 mg / kg, administered once every 3 weeks; d) The dosage of cisplatin is approximately 1 mg / kg. 2 Approximately 100 mg / m 2 The dosing frequency is once every 3 weeks;

[0486] a) The dosage of anti-HER2 antibody-drug conjugate is 3.2 mg / kg-6.4 mg / kg, administered once every 3 weeks; b) The dosage of anti-PD-L1 antibody is approximately 500 mg, 800 mg, 1000 mg, 1200 mg, 1500 mg, 1800 mg, or 2000 mg, administered once every 3 weeks; c) The dosage of anti-VEGF antibody is 10 mg / kg-20 mg / kg, administered once every 3 weeks; d) The dosage of cisplatin is approximately 1 mg / kg. 2 Approximately 100 mg / m 2 The dosing frequency is once every 3 weeks;

[0487] a) The dosage of the anti-HER2 antibody-drug conjugate is approximately 1.0 mg / kg, approximately 2.0 mg / kg, approximately 3.0 mg / kg, approximately 3.2 mg / kg, approximately 4.0 mg / kg, approximately 4.5 mg / kg, approximately 4.8 mg / kg, approximately 5.0 mg / kg, approximately 5.5 mg / kg, approximately 5.6 mg / kg, approximately 6.0 mg / kg, approximately 6.4 mg / kg, approximately 7 mg / kg, approximately 8.0 mg / kg, approximately 9.0 mg / kg, or approximately 10 mg / kg; the frequency of administration is once every 3 weeks; b1) The dosage of the anti-PD-L1 antibody is approximately 500 mg, approximately 800 mg, approximately 1000 mg, approximately 1200 mg, approximately 1500 mg, approximately 1800 mg, or approximately 2000 mg; the frequency of administration is once every 3 weeks. c) The dosage of anti-VEGF antibody is approximately 2.0 mg / kg, approximately 3.0 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 / kg, approximately 22.0 mg / kg, approximately 23.0 mg / kg, approximately 24.0 mg / kg, or approximately 25.0 mg / kg, administered once every 3 weeks; d) The dosage of cisplatin is approximately 1 mg / m². 2 10mg / m 2 Approximately 20 mg / m 2 Approximately 30 mg / m 2 Approximately 40 mg / m 2 Approximately 45 mg / m 2 Approximately 50 mg / m 2 Approximately 55 mg / m 2 Approximately 60 mg / m 2 Approximately 65 mg / m 2 Approximately 70 mg / m 2 Approximately 75 mg / m 2 Approximately 80 mg / m 2 Approximately 85 mg / m 2 Approximately 90 mg / m 2 Approximately 100 mg / m 2 Approximately 150 mg / m 2 The dosing frequency is once every 3 weeks;

[0488] a) The dosage of the anti-HER2 antibody-drug conjugate is approximately 1.0 mg / kg, approximately 2.0 mg / kg, approximately 3.0 mg / kg, approximately 3.2 mg / kg, approximately 4.0 mg / kg, approximately 4.5 mg / kg, approximately 4.8 mg / kg, approximately 5.0 mg / kg, approximately 5.5 mg / kg, approximately 5.6 mg / kg, approximately 6.0 mg / kg, approximately 6.4 mg / kg, approximately 7 mg / kg, approximately 8.0 mg / kg, approximately 9.0 mg / kg, or approximately 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; d) The dosage of cisplatin is approximately 50 mg / m². 2 The dosing frequency is once every 3 weeks;

[0489] a) The dosage of the anti-HER2 antibody-drug conjugate is approximately 3.2 mg / kg, 4.0 mg / kg, or 4.8 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; c) The dosage of the anti-VEGF antibody is approximately 15 mg / kg, administered once every 3 weeks; d) The dosage of cisplatin is approximately 50 mg / kg. 2 The administration frequency is once every 3 weeks.

[0490] In some implementations, the dosing regimen of the anti-HER2 antibody-drug conjugate in combination with anti-PD-L1 antibody, anti-CTLA-4 antibody, anti-VEGF antibody, and carboplatin is selected from any of the following:

[0491] a) The dosage of anti-HER2 antibody-drug conjugates is 0.1 mg / kg-20.0 mg / kg, 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, or once every 10 weeks; b1) The dosage of anti-PD-L1 antibodies is 5-5000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks; c) Anti-VEGF The dosage of the antibody is 1 mg / kg to 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; d) the dosage (AUC) of carboplatin is about 0.1 mg / mL / min to about 50 mg / mL / min, 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;

[0492] a) The dosage of anti-HER2 antibody-drug conjugates is 1 mg / kg-10.0 mg / kg, 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, or once every 10 weeks; b1) The dosage of anti-PD-L1 antibodies is 5-5000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks; c) Anti-VEGF The dosage of the antibody is 1 mg / kg to 25 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; d) The dosage (AUC) of carboplatin is about 1 mg / mL / min to about 20 mg / mL / min, 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;

[0493] a) The dosage of anti-HER2 antibody-drug conjugates is 1 mg / kg-8.0 mg / kg, 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, or once every 10 weeks; b1) The dosage of anti-PD-L1 antibodies is 5-5000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks; c) Anti-VEGF antibodies... The dosage of the drug is 1 mg / kg to 25 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; d) the dosage (AUC) of carboplatin is about 1 mg / mL / min to about 20 mg / mL / min, 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;

[0494] a) The dosage of anti-HER2 antibody-drug conjugates is 1 mg / kg-6.0 mg / kg, 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, or once every 10 weeks; b1) The dosage of anti-PD-L1 antibodies is 5-5000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks; c) Anti-VEGF antibodies... The dosage of the drug is 1 mg / kg to 25 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; d) the dosage (AUC) of carboplatin is about 1 mg / mL / min to about 20 mg / mL / min, 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;

[0495] a) The dosage of anti-HER2 antibody-drug conjugates is 1 mg / kg-5.0 mg / kg, 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, or once every 10 weeks; b1) The dosage of anti-PD-L1 antibodies is 5-5000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks; c) Anti-VEGF antibodies... The dosage of the drug is 1 mg / kg to 25 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; d) the dosage (AUC) of carboplatin is about 1 mg / mL / min to about 20 mg / mL / min, 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;

[0496] a) The dosage of anti-HER2 antibody-drug conjugates is 1 mg / kg-4.0 mg / kg, 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, or once every 10 weeks; b1) The dosage of anti-PD-L1 antibodies is 5-5000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks; c) Anti-VEGF antibodies... The dosage of the drug is 1 mg / kg to 25 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; d) the dosage (AUC) of carboplatin is about 1 mg / mL / min to about 20 mg / mL / min, 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;

[0497] a) The dosage of anti-HER2 antibody-drug conjugates is 2 mg / kg-8.0 mg / kg, 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, or once every 10 weeks; b1) The dosage of anti-PD-L1 antibodies is 5-5000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks; c) Anti-VEGF antibodies... The dosage of the drug is 1 mg / kg to 25 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; d) the dosage (AUC) of carboplatin is about 1 mg / mL / min to about 20 mg / mL / min, 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;

[0498] a) The dosage of anti-HER2 antibody-drug conjugates is 2 mg / kg-6.4 mg / kg, 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, or once every 10 weeks; b1) The dosage of anti-PD-L1 antibodies is 5-5000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks; c) Anti-VEGF antibodies... The dosage of the drug is 1 mg / kg to 25 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; d) the dosage (AUC) of carboplatin is about 1 mg / mL / min to about 20 mg / mL / min, 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;

[0499] a) The dosage of anti-HER2 antibody-drug conjugates is 2 mg / kg-5.0 mg / kg, 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, or once every 10 weeks; b1) The dosage of anti-PD-L1 antibodies is 5-5000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks; c) Anti-VEGF antibodies... The dosage of the drug is 1 mg / kg to 25 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; d) the dosage (AUC) of carboplatin is about 1 mg / mL / min to about 20 mg / mL / min, 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;

[0500] a) The dosage of anti-HER2 antibody-drug conjugates is 3.2 mg / kg-8.0 mg / kg, 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, or once every 10 weeks; b1) The dosage of anti-PD-L1 antibodies is 5-5000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks; c) Anti-VEGF The dosage of the antibody is 1 mg / kg to 25 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; d) The dosage (AUC) of carboplatin is about 1 mg / mL / min to about 20 mg / mL / min, 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;

[0501] a) The dosage of anti-HER2 antibody-drug conjugates is 3.2 mg / kg-6.4 mg / kg, 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, or once every 10 weeks; b1) The dosage of anti-PD-L1 antibodies is 5-5000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks; c) Anti-VEGF The dosage of the antibody is 1 mg / kg to 25 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; d) The dosage (AUC) of carboplatin is about 1 mg / mL / min to about 20 mg / mL / min, 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;

[0502] a) The dosage of the anti-HER2 antibody-drug conjugate is 1.0 mg / kg–10.0 mg / kg, 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, or once every 10 weeks; b) The dosage of the anti-PD-L1 antibody is approximately 500 mg, 800 mg, 1000 mg, 1200 mg, 1500 mg, 1800 mg, or 2000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, or once every 5 weeks. a) Once every 5 weeks, or once every 6 weeks; c) The dosage of anti-VEGF antibody is 10 mg / kg-20 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; d) The dosage (AUC) of carboplatin is about 1 mg / mL / min to about 20 mg / mL / min, 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.

[0503] a) The dosage of anti-HER2 antibody-drug conjugate is 1.0 mg / kg to 10.0 mg / kg, administered once every 3 weeks; b1) The dosage of anti-PD-L1 antibody is approximately 500 mg, 800 mg, 1000 mg, 1200 mg, 1500 mg, 1800 mg, or 2000 mg, administered once every 3 weeks; c) The dosage of anti-VEGF antibody is 10 mg / kg to 20 mg / kg, administered once every 3 weeks; d) The dosage (AUC) of carboplatin is approximately 1 mg / mL / min to approximately 20 mg / mL / min, administered once every 3 weeks.

[0504] a) The dosage of anti-HER2 antibody-drug conjugate is 1.0 mg / kg to 8.0 mg / kg, administered once every 3 weeks; b1) The dosage of anti-PD-L1 antibody is approximately 500 mg, 800 mg, 1000 mg, 1200 mg, 1500 mg, 1800 mg, or 2000 mg, administered once every 3 weeks; c) The dosage of anti-VEGF antibody is 10 mg / kg to 20 mg / kg, administered once every 3 weeks; d) The dosage (AUC) of carboplatin is approximately 1 mg / mL / min to approximately 20 mg / mL / min, administered once every 3 weeks.

[0505] a) The dosage of anti-HER2 antibody-drug conjugate is 1.0 mg / kg to 6.0 mg / kg, administered once every 3 weeks; b1) The dosage of anti-PD-L1 antibody is approximately 500 mg, 800 mg, 1000 mg, 1200 mg, 1500 mg, 1800 mg, or 2000 mg, administered once every 3 weeks; c) The dosage of anti-VEGF antibody is 10 mg / kg to 20 mg / kg, administered once every 3 weeks; d) The dosage (AUC) of carboplatin is approximately 1 mg / mL / min to approximately 20 mg / mL / min, administered once every 3 weeks.

[0506] a) The dosage of anti-HER2 antibody-drug conjugate is 1.0 mg / kg to 5.0 mg / kg, administered once every 3 weeks; b1) The dosage of anti-PD-L1 antibody is approximately 500 mg, 800 mg, 1000 mg, 1200 mg, 1500 mg, 1800 mg, or 2000 mg, administered once every 3 weeks; c) The dosage of anti-VEGF antibody is 10 mg / kg to 20 mg / kg, administered once every 3 weeks; d) The dosage (AUC) of carboplatin is approximately 1 mg / mL / min to approximately 20 mg / mL / min, administered once every 3 weeks.

[0507] a) The dosage of the anti-HER2 antibody-drug conjugate is 2.0 mg / kg to 8.0 mg / kg, administered once every 3 weeks; b1) The dosage of the anti-PD-L1 antibody is approximately 500 mg, 800 mg, 1000 mg, 1200 mg, 1500 mg, 1800 mg, or 2000 mg, administered once every 3 weeks; c) The dosage of the anti-VEGF antibody is 10 mg / kg to 20 mg / kg, administered once every 3 weeks; d) The dosage (AUC) of carboplatin is approximately 1 mg / mL / min to approximately 20 mg / mL / min, administered once every 3 weeks.

[0508] a) The dosage of anti-HER2 antibody-drug conjugate is 2.0 mg / kg to 6.4 mg / kg, administered once every 3 weeks; b1) The dosage of anti-PD-L1 antibody is approximately 500 mg, 800 mg, 1000 mg, 1200 mg, 1500 mg, 1800 mg, or 2000 mg, administered once every 3 weeks; c) The dosage of anti-VEGF antibody is 10 mg / kg to 20 mg / kg, administered once every 3 weeks; d) The dosage (AUC) of carboplatin is approximately 1 mg / mL / min to approximately 20 mg / mL / min, administered once every 3 weeks.

[0509] a) The dosage of anti-HER2 antibody-drug conjugate is 3.2 mg / kg to 8.0 mg / kg, administered once every 3 weeks; b1) The dosage of anti-PD-L1 antibody is approximately 500 mg, 800 mg, 1000 mg, 1200 mg, 1500 mg, 1800 mg, or 2000 mg, administered once every 3 weeks; c) The dosage of anti-VEGF antibody is 10 mg / kg to 20 mg / kg, administered once every 3 weeks; d) The dosage (AUC) of carboplatin is approximately 1 mg / mL / min to approximately 20 mg / mL / min, administered once every 3 weeks.

[0510] a) The dosage of anti-HER2 antibody-drug conjugate is 3.2 mg / kg to 6.4 mg / kg, administered once every 3 weeks; b1) The dosage of anti-PD-L1 antibody is approximately 500 mg, 800 mg, 1000 mg, 1200 mg, 1500 mg, 1800 mg, or 2000 mg, administered once every 3 weeks; c) The dosage of anti-VEGF antibody is 10 mg / kg to 20 mg / kg, administered once every 3 weeks; d) The dosage (AUC) of carboplatin is approximately 1 mg / mL / min to approximately 20 mg / mL / min, administered once every 3 weeks.

[0511] a) The dosage of the anti-HER2 antibody-drug conjugate is approximately 1.0 mg / kg, approximately 2.0 mg / kg, approximately 3.0 mg / kg, approximately 3.2 mg / kg, approximately 4.0 mg / kg, approximately 4.5 mg / kg, approximately 4.8 mg / kg, approximately 5.0 mg / kg, approximately 5.5 mg / kg, approximately 5.6 mg / kg, approximately 6.0 mg / kg, approximately 6.4 mg / kg, approximately 7 mg / kg, approximately 8.0 mg / kg, approximately 9.0 mg / kg, or approximately 10 mg / kg. a) The dosage of anti-PD-L1 antibody is approximately 500 mg, 800 mg, 1000 mg, 1200 mg, 1500 mg, 1800 mg, or 2000 mg, administered once every 3 weeks; b) The dosage of anti-PD-L1 antibody is approximately 2.0 mg / kg, 3.0 mg / kg, 5 mg / kg, 6.0 mg / kg, 7.5 mg / kg, 8.0 mg / kg, or 9 mg / kg; the dosing frequency is once every 3 weeks; c) The dosage of anti-VEGF antibody is approximately 2.0 mg / kg, 3.0 mg / kg, 5 mg / kg, 6.0 mg / kg, 7.5 mg / kg, 8.0 mg / kg, or 9 mg / kg. 0.0 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 / kg, approximately 22.0 mg / kg, approximately 23.0 mg / kg, approximately 24.0 mg / kg, or approximately 25.0 mg / kg, administered once every 3 weeks; d) The AUC of carboplatin 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, approximately 10 mg / mL / min, approximately 15 mg / mL / min, or approximately 20 mg / mL / min; the dosing frequency is once every 3 weeks.

[0512] a) The dosage of the anti-HER2 antibody-drug conjugate is approximately 1.0 mg / kg, approximately 2.0 mg / kg, approximately 3.0 mg / kg, approximately 3.2 mg / kg, approximately 4.0 mg / kg, approximately 4.5 mg / kg, approximately 4.8 mg / kg, approximately 5.0 mg / kg, approximately 5.5 mg / kg, approximately 5.6 mg / kg, approximately 6.0 mg / kg, approximately 6.4 mg / kg, approximately 7 mg / kg, approximately 8.0 mg / kg, approximately 9.0 mg / kg, or approximately 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; c) The dosage of the anti-VEGF antibody is approximately 15 mg / kg, administered once every 3 weeks; d) The dosage (AUC) of carboplatin is approximately 5 mg / mL / min, administered once every 3 weeks.

[0513] a) The dosage of the anti-HER2 antibody-drug conjugate is approximately 3.2 mg / kg, 4.0 mg / kg, or 4.8 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; c) The dosage of the anti-VEGF antibody is approximately 15 mg / kg, administered once every 3 weeks; d) The dosage (AUC) of carboplatin is approximately 5 mg / mL / min, administered once every 3 weeks.

[0514] In some implementations, the dosing regimen of the anti-HER2 antibody-drug conjugate in combination with anti-PD-L1 antibody, anti-CTLA-4 antibody, anti-VEGF antibody, and cisplatin is selected from any of the following:

[0515] a) The dosage of anti-HER2 antibody-drug conjugates is 0.1 mg / kg-20.0 mg / kg, 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, or once every 10 weeks; b1) The dosage of anti-PD-L1 antibody is 5-5000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks; b2) The dosage of anti-CTLA-4 antibody is 1-1000 mg, administered once every 10 weeks, ... The dosage of anti-VEGF antibody is 1 mg / kg-30 mg / kg, administered once every 1 week, 2 weeks, 3 weeks, 4 weeks, 6 weeks, 6 weeks, 8 weeks, 14 weeks, 16 weeks, or once every 12 weeks; c) the dosage of anti-VEGF antibody is 1 mg / kg-30 mg / kg, administered once every 1 week, 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, 10 weeks, or 12 weeks; d) the dosage of cisplatin is approximately 1 mg / kg. 2 Approximately 500 mg / m2 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;

[0516] a) The dosage of anti-HER2 antibody-drug conjugates is 1 mg / kg-10.0 mg / kg, 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, or once every 10 weeks; b1) The dosage of anti-PD-L1 antibody is 5-5000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks; b2) The dosage of anti-CTLA-4 antibody is 1-1000 mg, administered at a frequency of... The dosage of anti-VEGF antibody is 1 mg / kg-25 mg / kg, administered once every 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 10 weeks, 12 weeks, 14 weeks, 16 weeks, or once a single dose; c) The dosage of anti-VEGF antibody is 1 mg / kg-25 mg / kg, administered once every 1 week, 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, 10 weeks, or 12 weeks; d) The dosage of cisplatin is approximately 1 mg / m². 2 Approximately 200 mg / m 2 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;

[0517] a) The dosage of anti-HER2 antibody-drug conjugates is 1 mg / kg-8.0 mg / kg, 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, or once every 10 weeks; b1) The dosage of anti-PD-L1 antibody is 5-5000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks; b2) The dosage of anti-CTLA-4 antibody is 1-1000 mg, administered at a frequency of... The dosage of anti-VEGF antibody is 1 mg / kg-25 mg / kg, administered once every 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 10 weeks, 12 weeks, 14 weeks, 16 weeks, or once a single dose; c) The dosage of anti-VEGF antibody is 1 mg / kg-25 mg / kg, administered once every 1 week, 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, 10 weeks, or 12 weeks; d) The dosage of cisplatin is approximately 1 mg / m². 2 Approximately 200 mg / m 2 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;

[0518] a) The dosage of anti-HER2 antibody-drug conjugates is 1 mg / kg-6.0 mg / kg, 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, or once every 10 weeks; b1) The dosage of anti-PD-L1 antibody is 5-5000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks; b2) The dosage of anti-CTLA-4 antibody is 1-1000 mg, administered at a frequency of... The dosage of anti-VEGF antibody is 1 mg / kg-25 mg / kg, administered once every 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 10 weeks, 12 weeks, 14 weeks, 16 weeks, or once a single dose; c) The dosage of anti-VEGF antibody is 1 mg / kg-25 mg / kg, administered once every 1 week, 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, 10 weeks, or 12 weeks; d) The dosage of cisplatin is approximately 1 mg / m². 2 Approximately 200 mg / m 2 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;

[0519] a) The dosage of anti-HER2 antibody-drug conjugates is 1 mg / kg-5.0 mg / kg, 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, or once every 10 weeks; b1) The dosage of anti-PD-L1 antibody is 5-5000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks; b2) The dosage of anti-CTLA-4 antibody is 1-1000 mg, administered at a frequency of... The dosage of anti-VEGF antibody is 1 mg / kg-25 mg / kg, administered once every 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 10 weeks, 12 weeks, 14 weeks, 16 weeks, or once a single dose; c) The dosage of anti-VEGF antibody is 1 mg / kg-25 mg / kg, administered once every 1 week, 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, 10 weeks, or 12 weeks; d) The dosage of cisplatin is approximately 1 mg / m². 2 Approximately 200 mg / m 2 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;

[0520] a) The dosage of anti-HER2 antibody-drug conjugates is 1 mg / kg-4.0 mg / kg, 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, or once every 10 weeks; b1) The dosage of anti-PD-L1 antibody is 5-5000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks; b2) The dosage of anti-CTLA-4 antibody is 1-1000 mg, administered at a frequency of... The dosage of anti-VEGF antibody is 1 mg / kg-25 mg / kg, administered once every 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 10 weeks, 12 weeks, 14 weeks, 16 weeks, or once a single dose; c) The dosage of anti-VEGF antibody is 1 mg / kg-25 mg / kg, administered once every 1 week, 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, 10 weeks, or 12 weeks; d) The dosage of cisplatin is approximately 1 mg / m². 2 Approximately 200 mg / m 2 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;

[0521] a) The dosage of anti-HER2 antibody-drug conjugates is 2 mg / kg-8.0 mg / kg, 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, or once every 10 weeks; b1) The dosage of anti-PD-L1 antibody is 5-5000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks; b2) The dosage of anti-CTLA-4 antibody is 1-1000 mg, administered at a frequency of... The dosage of anti-VEGF antibody is 1 mg / kg-25 mg / kg, administered once every 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 10 weeks, 12 weeks, 14 weeks, 16 weeks, or once a single dose; c) The dosage of anti-VEGF antibody is 1 mg / kg-25 mg / kg, administered once every 1 week, 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, 10 weeks, or 12 weeks; d) The dosage of cisplatin is approximately 1 mg / m². 2 Approximately 200 mg / m 2 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;

[0522] a) The dosage of anti-HER2 antibody-drug conjugates is 2 mg / kg-6.4 mg / kg, 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, or once every 10 weeks; b1) The dosage of anti-PD-L1 antibody is 5-5000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks; b2) The dosage of anti-CTLA-4 antibody is 1-1000 mg, administered at a frequency of... The dosage of anti-VEGF antibody is 1 mg / kg-25 mg / kg, administered once every 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 10 weeks, 12 weeks, 14 weeks, 16 weeks, or once a single dose; c) The dosage of anti-VEGF antibody is 1 mg / kg-25 mg / kg, administered once every 1 week, 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, 10 weeks, or 12 weeks; d) The dosage of cisplatin is approximately 1 mg / m². 2 Approximately 200 mg / m 2 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;

[0523] a) The dosage of anti-HER2 antibody-drug conjugates is 2 mg / kg-5.0 mg / kg, 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, or once every 10 weeks; b1) The dosage of anti-PD-L1 antibody is 5-5000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks; b2) The dosage of anti-CTLA-4 antibody is 1-1000 mg, administered at a frequency of... The dosage of anti-VEGF antibody is 1 mg / kg-25 mg / kg, administered once every 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 10 weeks, 12 weeks, 14 weeks, 16 weeks, or once a single dose; c) The dosage of anti-VEGF antibody is 1 mg / kg-25 mg / kg, administered once every 1 week, 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, 10 weeks, or 12 weeks; d) The dosage of cisplatin is approximately 1 mg / m². 2 Approximately 200 mg / m 2 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;

[0524] a) The dosage of anti-HER2 antibody-drug conjugates is 3.2 mg / kg-8.0 mg / kg, 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, or once every 10 weeks; b1) The dosage of anti-PD-L1 antibody is 5-5000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks; b2) The dosage of anti-CTLA-4 antibody is 1-1000 mg, administered once every 10 weeks, once every 10 weeks, once every 10 weeks, once every 10 weeks, once every 10 weeks, once every 10 weeks, once every 11 weeks, once every 12 weeks, once every 13 weeks, once every 14 weeks, once every 15 weeks, or once every 10 weeks. The dosage of anti-VEGF antibody is 1 mg / kg-25 mg / kg, administered once every 1 week, once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 6 weeks, once every 6 weeks, once every 8 weeks, once every 14 weeks, once every 16 weeks, or once every 12 weeks; d) the dosage of cisplatin is approximately 1 mg / m². 2 Approximately 200 mg / m 2 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;

[0525] a) The dosage of anti-HER2 antibody-drug conjugates is 3.2 mg / kg-6.4 mg / kg, 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, or once every 10 weeks; b1) The dosage of anti-PD-L1 antibody is 5-5000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks; b2) The dosage of anti-CTLA-4 antibody is 1-1000 mg, administered once every 10 weeks, once every 10 weeks, once every 10 weeks, once every 10 weeks, once every 10 weeks, once every 10 weeks, once every 11 weeks, once every 12 weeks, once every 13 weeks, once every 14 weeks, once every 15 weeks, or once every 10 weeks. The dosage of anti-VEGF antibody is 1 mg / kg-25 mg / kg, administered once every 1 week, once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 6 weeks, once every 6 weeks, once every 8 weeks, once every 14 weeks, once every 16 weeks, or once every 12 weeks; d) the dosage of cisplatin is approximately 1 mg / m². 2 Approximately 200 mg / m 2 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;

[0526] a) The dosage of anti-HER2 antibody-drug conjugate is 1.0 mg / kg-10.0 mg / kg, 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, or once every 10 weeks; b1) The dosage of anti-PD-L1 antibody is approximately 500 mg, approximately 800 mg, approximately 1000 mg, approximately 1200 mg, approximately 1500 mg, approximately 1800 mg, or approximately 2000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks; b2) 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, or approximately... 80 mg, approximately 90 mg, approximately 100 mg, approximately 150 mg, approximately 200 mg, approximately 250 mg, approximately 280 mg, approximately 300 mg, approximately 350 mg, approximately 500 mg, or approximately 700 mg, administered at frequencies of once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, once every 6 weeks, once every 7 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; c) Anti-VEGF antibody dosage is 10 mg / kg-20 mg / kg, administered at frequencies of 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; d) Cisplatin dosage is approximately 1 mg / m 2 Approximately 100 mg / m 2 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;

[0527] a) The dosage of anti-HER2 antibody-drug conjugate is 1.0 mg / kg-10.0 mg / kg, administered once every 3 weeks; b1) The dosage of anti-PD-L1 antibody is approximately 500 mg, 800 mg, 1000 mg, 1200 mg, 1500 mg, 1800 mg, or 2000 mg, administered once every 3 weeks; b2) The dosage of anti-CTLA-4 antibody is approximately 10 mg, 20 mg, 30 mg, or 4 mg / kg. 0 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 250 mg, approximately 280 mg, approximately 300 mg, approximately 350 mg, approximately 500 mg, or approximately 700 mg, administered once every 6 weeks or as a single dose; c) Anti-VEGF antibody dosage is 10 mg / kg-20 mg / kg, administered once every 3 weeks; d) Cisplatin dosage is approximately 1 mg / m 2 Approximately 100 mg / m 2 The dosing frequency is once every 3 weeks;

[0528] a) The dosage of anti-HER2 antibody-drug conjugate is 1.0 mg / kg-8.0 mg / kg, administered once every 3 weeks; b1) The dosage of anti-PD-L1 antibody is approximately 500 mg, 800 mg, 1000 mg, 1200 mg, 1500 mg, 1800 mg, or 2000 mg, administered once every 3 weeks; b2) The dosage of anti-CTLA-4 antibody is approximately 10 mg, 20 mg, 30 mg, or 4 mg / kg. 0 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 250 mg, approximately 280 mg, approximately 300 mg, approximately 350 mg, approximately 500 mg, or approximately 700 mg, administered once every 6 weeks or as a single dose; c) Anti-VEGF antibody dosage is 10 mg / kg-20 mg / kg, administered once every 3 weeks; d) Cisplatin dosage is approximately 1 mg / m 2 Approximately 100 mg / m 2 The dosing frequency is once every 3 weeks;

[0529] a) The dosage of the anti-HER2 antibody-drug conjugate is 1.0 mg / kg-6.0 mg / kg, administered once every 3 weeks; b1) The dosage of the anti-PD-L1 antibody is approximately 500 mg, 800 mg, 1000 mg, 1200 mg, 1500 mg, 1800 mg, or 2000 mg, administered once every 3 weeks; b2) The dosage of the anti-CTLA-4 antibody is approximately 10 mg, 20 mg, 30 mg, or 4 mg / kg. 0 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 250 mg, approximately 280 mg, approximately 300 mg, approximately 350 mg, approximately 500 mg, or approximately 700 mg, administered once every 6 weeks or as a single dose; c) Anti-VEGF antibody dosage is 10 mg / kg-20 mg / kg, administered once every 3 weeks; d) Cisplatin dosage is approximately 1 mg / m 2 Approximately 100 mg / m 2 The dosing frequency is once every 3 weeks;

[0530] a) The dosage of anti-HER2 antibody-drug conjugate is 1.0 mg / kg-5.0 mg / kg, administered once every 3 weeks; b1) The dosage of anti-PD-L1 antibody is approximately 500 mg, 800 mg, 1000 mg, 1200 mg, 1500 mg, 1800 mg, or 2000 mg, administered once every 3 weeks; b2) The dosage of anti-CTLA-4 antibody is approximately 10 mg, 20 mg, 30 mg, or 4 mg / kg. 0 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 250 mg, approximately 280 mg, approximately 300 mg, approximately 350 mg, approximately 500 mg, or approximately 700 mg, administered once every 6 weeks or as a single dose; c) Anti-VEGF antibody dosage is 10 mg / kg-20 mg / kg, administered once every 3 weeks; d) Cisplatin dosage is approximately 1 mg / m 2 Approximately 100 mg / m 2 The dosing frequency is once every 3 weeks;

[0531] a) The dosage of the anti-HER2 antibody-drug conjugate is 2.0 mg / kg-8.0 mg / kg, administered once every 3 weeks; b1) The dosage of the anti-PD-L1 antibody is approximately 500 mg, 800 mg, 1000 mg, 1200 mg, 1500 mg, 1800 mg, or 2000 mg, administered once every 3 weeks; b2) The dosage of the anti-CTLA-4 antibody is approximately 10 mg, 20 mg, 30 mg, or 4 mg / kg. 0 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 250 mg, approximately 280 mg, approximately 300 mg, approximately 350 mg, approximately 500 mg, or approximately 700 mg, administered once every 6 weeks or as a single dose; c) Anti-VEGF antibody dosage is 10 mg / kg-20 mg / kg, administered once every 3 weeks; d) Cisplatin dosage is approximately 1 mg / m 2 Approximately 100 mg / m 2 The dosing frequency is once every 3 weeks;

[0532] a) The dosage of the anti-HER2 antibody-drug conjugate is 2.0 mg / kg-6.4 mg / kg, administered once every 3 weeks; b1) The dosage of the anti-PD-L1 antibody is approximately 500 mg, 800 mg, 1000 mg, 1200 mg, 1500 mg, 1800 mg, or 2000 mg, administered once every 3 weeks; b2) The dosage of the anti-CTLA-4 antibody is approximately 10 mg, 20 mg, 30 mg, or 4 mg / kg. 0 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 250 mg, approximately 280 mg, approximately 300 mg, approximately 350 mg, approximately 500 mg, or approximately 700 mg, administered once every 6 weeks or as a single dose; c) Anti-VEGF antibody dosage is 10 mg / kg-20 mg / kg, administered once every 3 weeks; d) Cisplatin dosage is approximately 1 mg / m 2 Approximately 100 mg / m 2 The dosing frequency is once every 3 weeks;

[0533] a) The dosage of anti-HER2 antibody-drug conjugate is 3.2 mg / kg-8.0 mg / kg, administered once every 3 weeks; b1) The dosage of anti-PD-L1 antibody is approximately 500 mg, 800 mg, 1000 mg, 1200 mg, 1500 mg, 1800 mg, or 2000 mg, administered once every 3 weeks; b2) The dosage of anti-CTLA-4 antibody is approximately 10 mg, 20 mg, 30 mg, or 4 mg / kg. 0 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 250 mg, approximately 280 mg, approximately 300 mg, approximately 350 mg, approximately 500 mg, or approximately 700 mg, administered once every 6 weeks or as a single dose; c) Anti-VEGF antibody dosage is 10 mg / kg-20 mg / kg, administered once every 3 weeks; d) Cisplatin dosage is approximately 1 mg / m 2 Approximately 100 mg / m 2 The dosing frequency is once every 3 weeks;

[0534] a) The dosage of the anti-HER2 antibody drug conjugate is 3.2 mg / kg-6.4 mg / kg, administered once every 3 weeks; b1) The dosage of the anti-PD-L1 antibody is approximately 500 mg, 800 mg, 1000 mg, 1200 mg, 1500 mg, 1800 mg, or 2000 mg, administered once every 3 weeks; b2) The dosage of the anti-CTLA-4 antibody is approximately 10 mg, 20 mg, 30 mg, or 4 mg / kg. 0 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 250 mg, approximately 280 mg, approximately 300 mg, approximately 350 mg, approximately 500 mg, or approximately 700 mg, administered once every 6 weeks or as a single dose; c) Anti-VEGF antibody dosage is 10 mg / kg-20 mg / kg, administered once every 3 weeks; d) Cisplatin dosage is approximately 1 mg / m 2 Approximately 100 mg / m 2 The dosing frequency is once every 3 weeks;

[0535] a) The dosage of the anti-HER2 antibody-drug conjugate is approximately 1.0 mg / kg, approximately 2.0 mg / kg, approximately 3.0 mg / kg, approximately 3.2 mg / kg, approximately 4.0 mg / kg, approximately 4.5 mg / kg, approximately 4.8 mg / kg, approximately 5.0 mg / kg, approximately 5.5 mg / kg, approximately 5.6 mg / kg, approximately 6.0 mg / kg, approximately 6.4 mg / kg, approximately 7 mg / kg, approximately 8.0 mg / kg, approximately 9.0 mg / kg, or approximately 10 mg / kg. mg / kg; dosing frequency is once every 3 weeks; b1) The dosage of anti-PD-L1 antibody is approximately 500 mg, approximately 800 mg, approximately 1000 mg, approximately 1200 mg, approximately 1500 mg, approximately 1800 mg, or approximately 2000 mg, dosing frequency is once every 3 weeks; b2) 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 250 mg, approximately 280 mg, approximately 300 mg, approximately 350 mg, approximately 500 mg, or approximately 700 mg, administered once every 6 weeks or as a single dose; c) The dosage of anti-VEGF antibody is approximately 2.0 mg / kg, approximately 3.0 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 / kg, approximately 22.0 mg / kg, approximately 23.0 mg / kg, approximately 24.0 mg / kg, or approximately 25.0 mg / kg, administered once every 3 weeks; d) Cisplatin was administered at a dose of approximately 1 mg / m². 2 10mg / m 2 Approximately 20 mg / m 2 Approximately 30 mg / m 2 Approximately 40 mg / m 2 Approximately 45 mg / m 2 Approximately 50 mg / m 2 Approximately 55 mg / m 2 Approximately 60 mg / m 2 Approximately 65 mg / m 2 Approximately 70 mg / m 2 Approximately 75 mg / m 2 Approximately 80 mg / m 2 Approximately 85 mg / m 2 Approximately 90 mg / m 2Approximately 100 mg / m 2 Approximately 150 mg / m 2 The dosing frequency is once every 3 weeks;

[0536] a) The dosage of the anti-HER2 antibody-drug conjugate is approximately 1.0 mg / kg, approximately 2.0 mg / kg, approximately 3.0 mg / kg, approximately 3.2 mg / kg, approximately 4.0 mg / kg, approximately 4.5 mg / kg, approximately 4.8 mg / kg, approximately 5.0 mg / kg, approximately 5.5 mg / kg, approximately 5.6 mg / kg, approximately 6.0 mg / kg, approximately 6.4 mg / kg, approximately 7 mg / kg, approximately 8.0 mg / kg, approximately 9.0 mg / kg, or approximately 10 mg / kg. a) The dosage of anti-PD-L1 antibody is approximately 1200 mg, administered once every 3 weeks; b) The dosage of anti-CTLA-4 antibody is approximately 280 mg once 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; c) The dosage of anti-VEGF antibody is approximately 15 mg / kg, administered once every 3 weeks; d) The dosage of cisplatin is approximately 50 mg / kg. 2 The dosing frequency is once every 3 weeks;

[0537] a) The dosage of the anti-HER2 antibody-drug conjugate is approximately 3.2 mg / kg, 4.0 mg / kg, or 4.8 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 in week 1, with no administration from weeks 2 to 12, and from week 13 onwards, a dose of approximately 70 mg is administered once every 6 weeks; c) The dosage of the anti-VEGF antibody is approximately 15 mg / kg, administered once every 3 weeks; d) The dosage of cisplatin is approximately 50 mg / kg. 2 The administration frequency is once every 3 weeks.

[0538] In some implementations, the dosing regimen of the anti-HER2 antibody-drug conjugate in combination with anti-PD-L1 antibody, anti-CTLA-4 antibody, anti-VEGF antibody, and carboplatin is selected from any of the following:

[0539] a) The dosage of anti-HER2 antibody-drug conjugates is 0.1 mg / kg-20.0 mg / kg, 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, or once every 10 weeks; b1) The dosage of anti-PD-L1 antibody is 5-5000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks; b2) The dosage of anti-CTLA-4 antibody is 1-1000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks. a) Once every 7 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; c) The dosage of anti-VEGF antibody is 1 mg / kg-30 mg / kg, 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; d) The dosage (AUC) of carboplatin is about 0.1 mg / mL / min to about 50 mg / mL / min, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks;

[0540] a) The dosage of anti-HER2 antibody-drug conjugates is 1 mg / kg-10.0 mg / kg, 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, or once every 10 weeks; b1) The dosage of anti-PD-L1 antibody is 5-5000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks; b2) The dosage of anti-CTLA-4 antibody is 1-1000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks. a) Once every 7 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; c) The dosage of anti-VEGF antibody is 1 mg / kg-25 mg / kg, 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; d) The dosage (AUC) of carboplatin is about 1 mg / mL / min to about 20 mg / mL / min, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks;

[0541] a) The dosage of anti-HER2 antibody-drug conjugates is 1 mg / kg-8.0 mg / kg, 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, or once every 10 weeks; b1) The dosage of anti-PD-L1 antibody is 5-5000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks; b2) The dosage of anti-CTLA-4 antibody is 1-1000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks. a) Once every 7 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; c) The dosage of anti-VEGF antibody is 1 mg / kg-25 mg / kg, 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; d) The dosage (AUC) of carboplatin is about 1 mg / mL / min to about 20 mg / mL / min, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks;

[0542] a) The dosage of anti-HER2 antibody-drug conjugates is 1 mg / kg-6.0 mg / kg, 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, or once every 10 weeks; b1) The dosage of anti-PD-L1 antibody is 5-5000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks; b2) The dosage of anti-CTLA-4 antibody is 1-1000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks. a) Once every 7 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; c) The dosage of anti-VEGF antibody is 1 mg / kg-25 mg / kg, 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; d) The dosage (AUC) of carboplatin is about 1 mg / mL / min to about 20 mg / mL / min, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks;

[0543] a) The dosage of anti-HER2 antibody-drug conjugates is 1 mg / kg-5.0 mg / kg, 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, or once every 10 weeks; b1) The dosage of anti-PD-L1 antibody is 5-5000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks; b2) The dosage of anti-CTLA-4 antibody is 1-1000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks. a) Once every 7 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; c) The dosage of anti-VEGF antibody is 1 mg / kg-25 mg / kg, 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; d) The dosage (AUC) of carboplatin is about 1 mg / mL / min to about 20 mg / mL / min, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks;

[0544] a) The dosage of anti-HER2 antibody-drug conjugates is 1 mg / kg-4.0 mg / kg, 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, or once every 10 weeks; b1) The dosage of anti-PD-L1 antibody is 5-5000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks; b2) The dosage of anti-CTLA-4 antibody is 1-1000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks. a) Once every 7 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; c) The dosage of anti-VEGF antibody is 1 mg / kg-25 mg / kg, 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; d) The dosage (AUC) of carboplatin is about 1 mg / mL / min to about 20 mg / mL / min, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks;

[0545] a) The dosage of anti-HER2 antibody-drug conjugates is 2 mg / kg-8.0 mg / kg, 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, or once every 10 weeks; b1) The dosage of anti-PD-L1 antibody is 5-5000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks; b2) The dosage of anti-CTLA-4 antibody is 1-1000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks. a) Once every 7 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; c) The dosage of anti-VEGF antibody is 1 mg / kg-25 mg / kg, 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; d) The dosage (AUC) of carboplatin is about 1 mg / mL / min to about 20 mg / mL / min, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks;

[0546] a) The dosage of anti-HER2 antibody-drug conjugates is 2 mg / kg-6.4 mg / kg, 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, or once every 10 weeks; b1) The dosage of anti-PD-L1 antibody is 5-5000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks; b2) The dosage of anti-CTLA-4 antibody is 1-1000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks. a) Once every 7 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; c) The dosage of anti-VEGF antibody is 1 mg / kg-25 mg / kg, 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; d) The dosage (AUC) of carboplatin is about 1 mg / mL / min to about 20 mg / mL / min, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks;

[0547] a) The dosage of anti-HER2 antibody-drug conjugates is 2 mg / kg-5.0 mg / kg, 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, or once every 10 weeks; b1) The dosage of anti-PD-L1 antibody is 5-5000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks; b2) The dosage of anti-CTLA-4 antibody is 1-1000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks. a) Once every 7 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; c) The dosage of anti-VEGF antibody is 1 mg / kg-25 mg / kg, 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; d) The dosage (AUC) of carboplatin is about 1 mg / mL / min to about 20 mg / mL / min, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks;

[0548] a) The dosage of anti-HER2 antibody-drug conjugates is 3.2 mg / kg-8.0 mg / kg, 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, or once every 10 weeks; b1) The dosage of anti-PD-L1 antibody is 5-5000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks; b2) The dosage of anti-CTLA-4 antibody is 1-1000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks. a) The dosage of anti-VEGF antibody is 1 mg / kg to 25 mg / kg, 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; d) The dosage (AUC) of carboplatin is about 1 mg / mL / min to about 20 mg / mL / min, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks.

[0549] a) The dosage of anti-HER2 antibody-drug conjugates is 3.2 mg / kg-6.4 mg / kg, 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, or once every 10 weeks; b1) The dosage of anti-PD-L1 antibody is 5-5000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks; b2) The dosage of anti-CTLA-4 antibody is 1-1000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks. a) The dosage of anti-VEGF antibody is 1 mg / kg to 25 mg / kg, 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; d) The dosage (AUC) of carboplatin is about 1 mg / mL / min to about 20 mg / mL / min, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks.

[0550] a) The dosage of anti-HER2 antibody-drug conjugate is 1.0 mg / kg-10.0 mg / kg, 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, or once every 10 weeks; b1) The dosage of anti-PD-L1 antibody is approximately 500 mg, 800 mg, 1000 mg, 1200 mg, 1500 mg, 1800 mg, or 2000 mg, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks; b2) 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, or 200 mg. g, approximately 250 mg, approximately 280 mg, approximately 300 mg, approximately 350 mg, approximately 500 mg, or approximately 700 mg, administered at frequencies of once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, once every 6 weeks, once every 7 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; c) The dose of anti-VEGF antibody is 10 mg. / kg-20mg / kg, 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; d) Carboplatin dosage (AUC) is from about 1 mg / mL / min to about 20 mg / mL / min, administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, or once every 6 weeks;

[0551] a) The dosage of anti-HER2 antibody-drug conjugate is 1.0 mg / kg-10.0 mg / kg, administered once every 3 weeks; b1) The dosage of anti-PD-L1 antibody is approximately 500 mg, 800 mg, 1000 mg, 1200 mg, 1500 mg, 1800 mg, or 2000 mg, administered once every 3 weeks; b2) The dosage of anti-CTLA-4 antibody is approximately 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, or 60 mg, administered once every 3 weeks. 70 mg, approximately 80 mg, approximately 90 mg, approximately 100 mg, approximately 150 mg, approximately 200 mg, approximately 250 mg, approximately 280 mg, approximately 300 mg, approximately 350 mg, approximately 500 mg, or approximately 700 mg, administered once every 6 weeks or as a single dose; c) Anti-VEGF antibody administered at a dose of 10 mg / kg-20 mg / kg, administered once every 3 weeks; d) Carboplatin administered at a dose (AUC) of approximately 1 mg / mL / min to approximately 20 mg / mL / min, administered once every 3 weeks;

[0552] a) The dosage of the anti-HER2 antibody drug conjugate is 1.0 mg / kg-8.0 mg / kg, administered once every 3 weeks; b1) The dosage of the anti-PD-L1 antibody is approximately 500 mg, 800 mg, 1000 mg, 1200 mg, 1500 mg, 1800 mg, or 2000 mg, administered once every 3 weeks; b2) The dosage of the anti-CTLA-4 antibody is approximately 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, or 7 mg / kg. 0 mg, approximately 80 mg, approximately 90 mg, approximately 100 mg, approximately 150 mg, approximately 200 mg, approximately 250 mg, approximately 280 mg, approximately 300 mg, approximately 350 mg, approximately 500 mg, or approximately 700 mg, administered once every 6 weeks or as a single dose; c) Anti-VEGF antibody administered at a dose of 10 mg / kg-20 mg / kg, administered once every 3 weeks; d) Carboplatin administered at a dose (AUC) of approximately 1 mg / mL / min to approximately 20 mg / mL / min, administered once every 3 weeks;

[0553] a) The dosage of anti-HER2 antibody-drug conjugate is 1.0 mg / kg-6.0 mg / kg, administered once every 3 weeks; b1) The dosage of anti-PD-L1 antibody is approximately 500 mg, 800 mg, 1000 mg, 1200 mg, 1500 mg, 1800 mg, or 2000 mg, administered once every 3 weeks; b2) The dosage of anti-CTLA-4 antibody is approximately 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, or 7 mg / kg. 0 mg, approximately 80 mg, approximately 90 mg, approximately 100 mg, approximately 150 mg, approximately 200 mg, approximately 250 mg, approximately 280 mg, approximately 300 mg, approximately 350 mg, approximately 500 mg, or approximately 700 mg, administered once every 6 weeks or as a single dose; c) Anti-VEGF antibody administered at a dose of 10 mg / kg-20 mg / kg, administered once every 3 weeks; d) Carboplatin administered at a dose (AUC) of approximately 1 mg / mL / min to approximately 20 mg / mL / min, administered once every 3 weeks;

[0554] a) The dosage of the anti-HER2 antibody-drug conjugate is 1.0 mg / kg-5.0 mg / kg, administered once every 3 weeks; b1) The dosage of the anti-PD-L1 antibody is approximately 500 mg, 800 mg, 1000 mg, 1200 mg, 1500 mg, 1800 mg, or 2000 mg, administered once every 3 weeks; b2) The dosage of the anti-CTLA-4 antibody is approximately 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, or 7 mg / kg. 0 mg, approximately 80 mg, approximately 90 mg, approximately 100 mg, approximately 150 mg, approximately 200 mg, approximately 250 mg, approximately 280 mg, approximately 300 mg, approximately 350 mg, approximately 500 mg, or approximately 700 mg, administered once every 6 weeks or as a single dose; c) Anti-VEGF antibody administered at a dose of 10 mg / kg-20 mg / kg, administered once every 3 weeks; d) Carboplatin administered at a dose (AUC) of approximately 1 mg / mL / min to approximately 20 mg / mL / min, administered once every 3 weeks;

[0555] a) The dosage of the anti-HER2 antibody-drug conjugate is 2.0 mg / kg-8.0 mg / kg, administered once every 3 weeks; b1) The dosage of the anti-PD-L1 antibody is approximately 500 mg, 800 mg, 1000 mg, 1200 mg, 1500 mg, 1800 mg, or 2000 mg, administered once every 3 weeks; b2) The dosage of the anti-CTLA-4 antibody is approximately 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, or 7 mg / kg. 0 mg, approximately 80 mg, approximately 90 mg, approximately 100 mg, approximately 150 mg, approximately 200 mg, approximately 250 mg, approximately 280 mg, approximately 300 mg, approximately 350 mg, approximately 500 mg, or approximately 700 mg, administered once every 6 weeks or as a single dose; c) Anti-VEGF antibody administered at a dose of 10 mg / kg-20 mg / kg, administered once every 3 weeks; d) Carboplatin administered at a dose (AUC) of approximately 1 mg / mL / min to approximately 20 mg / mL / min, administered once every 3 weeks;

[0556] a) The dosage of the anti-HER2 antibody-drug conjugate is 2.0 mg / kg-6.4 mg / kg, administered once every 3 weeks; b1) The dosage of the anti-PD-L1 antibody is approximately 500 mg, 800 mg, 1000 mg, 1200 mg, 1500 mg, 1800 mg, or 2000 mg, administered once every 3 weeks; b2) The dosage of the anti-CTLA-4 antibody is approximately 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, or 7 mg / kg. 0 mg, approximately 80 mg, approximately 90 mg, approximately 100 mg, approximately 150 mg, approximately 200 mg, approximately 250 mg, approximately 280 mg, approximately 300 mg, approximately 350 mg, approximately 500 mg, or approximately 700 mg, administered once every 6 weeks or as a single dose; c) Anti-VEGF antibody administered at a dose of 10 mg / kg-20 mg / kg, administered once every 3 weeks; d) Carboplatin administered at a dose (AUC) of approximately 1 mg / mL / min to approximately 20 mg / mL / min, administered once every 3 weeks;

[0557] a) The dosage of the anti-HER2 antibody-drug conjugate is 3.2 mg / kg-8.0 mg / kg, administered once every 3 weeks; b1) The dosage of the anti-PD-L1 antibody is approximately 500 mg, 800 mg, 1000 mg, 1200 mg, 1500 mg, 1800 mg, or 2000 mg, administered once every 3 weeks; b2) The dosage of the anti-CTLA-4 antibody is approximately 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, or 7 mg / kg. 0 mg, approximately 80 mg, approximately 90 mg, approximately 100 mg, approximately 150 mg, approximately 200 mg, approximately 250 mg, approximately 280 mg, approximately 300 mg, approximately 350 mg, approximately 500 mg, or approximately 700 mg, administered once every 6 weeks or as a single dose; c) Anti-VEGF antibody administered at a dose of 10 mg / kg-20 mg / kg, administered once every 3 weeks; d) Carboplatin administered at a dose (AUC) of approximately 1 mg / mL / min to approximately 20 mg / mL / min, administered once every 3 weeks;

[0558] a) The dosage of the anti-HER2 antibody-drug conjugate is 3.2 mg / kg-6.4 mg / kg, administered once every 3 weeks; b1) The dosage of the anti-PD-L1 antibody is approximately 500 mg, 800 mg, 1000 mg, 1200 mg, 1500 mg, 1800 mg, or 2000 mg, administered once every 3 weeks; b2) The dosage of the anti-CTLA-4 antibody is approximately 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, or 7 mg / kg. 0 mg, approximately 80 mg, approximately 90 mg, approximately 100 mg, approximately 150 mg, approximately 200 mg, approximately 250 mg, approximately 280 mg, approximately 300 mg, approximately 350 mg, approximately 500 mg, or approximately 700 mg, administered once every 6 weeks or as a single dose; c) Anti-VEGF antibody administered at a dose of 10 mg / kg-20 mg / kg, administered once every 3 weeks; d) Carboplatin administered at a dose (AUC) of approximately 1 mg / mL / min to approximately 20 mg / mL / min, administered once every 3 weeks;

[0559] a) The dosage of the anti-HER2 antibody-drug conjugate is approximately 1.0 mg / kg, approximately 2.0 mg / kg, approximately 3.0 mg / kg, approximately 3.2 mg / kg, approximately 4.0 mg / kg, approximately 4.5 mg / kg, approximately 4.8 mg / kg, approximately 5.0 mg / kg, approximately 5.5 mg / kg, approximately 5.6 mg / kg, approximately 6.0 mg / kg, approximately 6.4 mg / kg, approximately 7 mg / kg, approximately 8.0 mg / kg, approximately 9.0 mg / kg, or approximately 10 mg / kg; the frequency of administration is once every 3 weeks; b1) The dosage of the anti-PD-L1 antibody is approximately 500 mg / kg. a) The dosage of anti-CTLA-4 antibody is approximately 800 mg, 1000 mg, 1200 mg, 1500 mg, 1800 mg, or 2000 mg, administered once every 3 weeks; b2) 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, 250 mg, 280 mg, 300 mg, 350 mg, 500 mg, or 700 mg, administered once every 6 weeks or as a single dose; c) The dosage of anti-VEGF antibody is approximately 2.0 mg / kg, approximately 3.0 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 / kg, approximately 22.0 mg / kg, and approximately 23.0 mg / kg. / kg, approximately 24.0 mg / kg, or approximately 25.0 mg / kg, administered once every 3 weeks; d) Carboplatin dosage (AUC) 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, approximately 10 mg / mL / min, approximately 15 mg / mL / min, or approximately 20 mg / mL / min; administered once every 3 weeks;

[0560] a) The dosage of the anti-HER2 antibody-drug conjugate is approximately 1.0 mg / kg, approximately 2.0 mg / kg, approximately 3.0 mg / kg, approximately 3.2 mg / kg, approximately 4.0 mg / kg, approximately 4.5 mg / kg, approximately 4.8 mg / kg, approximately 5.0 mg / kg, approximately 5.5 mg / kg, approximately 5.6 mg / kg, approximately 6.0 mg / kg, approximately 6.4 mg / kg, approximately 7 mg / kg, approximately 8.0 mg / kg, approximately 9.0 mg / kg, or approximately 10 mg / kg, administered every 3 days. a) Once a week; b1) The dose of anti-PD-L1 antibody is approximately 1200 mg, administered once every 3 weeks; b2) The dose of anti-CTLA-4 antibody is a single dose of approximately 280 mg in week 1, with no administration from week 2 to week 12, and from week 13 onwards, the dose is approximately 70 mg, administered once every 6 weeks; c) The dose of anti-VEGF antibody is approximately 15 mg / kg, administered once every 3 weeks; d) The dose (AUC) of carboplatin is approximately 5 mg / mL / min, administered once every 3 weeks.

[0561] a) The dosage of the anti-HER2 antibody-drug conjugate is approximately 3.2 mg / kg, 4.0 mg / kg, or 4.8 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 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; c) The dosage of the anti-VEGF antibody is approximately 15 mg / kg, administered once every 3 weeks; d) The dosage (AUC) of carboplatin is approximately 5 mg / mL / min, administered once every 3 weeks.

[0562] The treatment strategy of combining anti-HER2 antibody-drug conjugates with immunotherapy agents, anti-VEGF antibodies, and / or platinum-based drugs disclosed in this paper has shown certain clinical benefits in cervical cancer, which can help patients achieve a higher pCR (complete response) rate and bring better clinical benefits, providing a safe and effective clinical treatment option for cervical cancer patients.

[0563] the term

[0564] To facilitate understanding of this disclosure, certain technical and scientific terms are specifically defined below. Unless otherwise expressly defined herein, all other technical and scientific terms used herein have the meanings commonly understood by one of ordinary skill in the art to which this disclosure pertains.

[0565] This disclosure incorporates the entire contents of application WO2020063676A.

[0566] Antibody-drug conjugates (ADCs) 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.

[0567] If 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.).

[0568] If the biological activity of an antibody-drug conjugate at a given time is within a predetermined range of the biological activity exhibited when the drug formulation is prepared, then the antibody-drug conjugate "retains its biological activity" in the drug formulation.

[0569] The term "drug loading" refers to the average number of cytotoxic drugs loaded onto each antibody or its antigen-binding fragment in a molecule of formula (I), and can also be expressed as the ratio of drug amount to antibody amount. The drug loading range can be 0-12 cytotoxic drugs (D) linked to each antibody or its antigen-binding fragment (Pc), preferably 1-10, more preferably 3-8, and most preferably 5.3-6.1. In embodiments of this disclosure, the drug loading is expressed as n, which can be an average of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, as exemplarily. The average number of drugs per ADC molecule after the coupling reaction can be identified using conventional methods such as UV / visible spectroscopy, mass spectrometry, ELISA, and HPLC characterization.

[0570] In one embodiment of this disclosure, a cytotoxic drug is coupled to the N-terminal amino group, the ε-amino group of a lysine residue, and / or the thiol group of an antibody or its antigen-binding fragment via a linker unit. Generally, the number of drug molecules that can be coupled to the antibody in the coupling reaction will be less than the theoretical maximum value.

[0571] The loading of cytotoxic drugs can be controlled using the following non-limiting methods, including:

[0572] (1) Control the molar ratio of the ligation reagent and the monoclonal antibody.

[0573] (2) Control the reaction time and temperature.

[0574] (3) Choose different reaction reagents.

[0575] For the preparation of conventional pharmaceutical compositions, please refer to the Chinese Pharmacopoeia.

[0576] When applied to animals, humans, experimental subjects, cells, tissues, organs, or biological fluids, "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. When applied to humans, veterinary, or research subjects, "treatment" refers to therapeutic treatment, preventative or prophylactic measures, research, and diagnostic applications.

[0577] "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. Typically, 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 (also referred to as a "therapeuticly effective amount") 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. Although 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.

[0578] 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.

[0579] In this disclosure of anti-HER2 antibody-drug conjugates, "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, and is the average amount of drug in each ADC molecule after the conjugation reaction is identified by hydrophobic chromatography (HIC) mass spectrometry. Detailed Implementation

[0580] The present disclosure is further described below with reference to embodiments, but these embodiments are not intended to limit the scope of the disclosure. Experimental methods in the embodiments of this disclosure that do not specify specific conditions are generally performed under conventional conditions, such as those described in Cold Spring Harbor Laboratory's *Antibody Technology Laboratory Manual* and *Molecular Cloning Handbook*; or under conditions recommended by the raw material or commercial manufacturer. Reagents whose specific source is not specified are commercially available, conventional reagents.

[0581] Example 1. Preparation of anti-HER2 antibody drug conjugate

[0582] Following the preparation method of ADC-32 described in WO2021190581A, an anti-HER2 antibody-drug conjugate with the structure shown below (FADC-4A) was prepared using Trastuzumab (anti-HER2 antibody) and an eczema analog. The average value calculated by the HIC method was n = 5.7-6.4.

[0583] The following is the sequence of Trastuzumab:

[0584] Light chain

[0585] Heavy chain

[0586] Example 2. Open-label, multicenter phase Ib / II clinical trial of anti-HER2 antibody-drug conjugate in combination therapy for recurrent or metastatic cervical cancer.

[0587] 1. Test drug

[0588] (1) The anti-HER2 antibody drug conjugate prepared in Example 1 is a lyophilized powder for injection, specification: 100mg / vial; route of administration: intravenous infusion.

[0589] (2) Anti-VEGF antibody, Bevacizumab injection: its heavy chain sequence is SEQ ID NO: 9, its light chain sequence is SEQ ID NO: 10, specification: 4mL: 100mg. Route of administration: intravenous infusion.

[0590] (3) Anti-PD-L1 antibody, Adebrelimab injection: its heavy chain sequence is SEQ ID NO: 29, its light chain sequence is SEQ ID NO: 30, specification: 600mg / 12mL / vial. Route of administration: intravenous infusion.

[0591] (4) Anti-CTLA-4 antibody, the heavy chain sequence of which is SEQ ID NO: 39 and the light chain sequence of which is SEQ ID NO: 40, specification: 50mg / 10mL / vial. Route of administration: intravenous infusion.

[0592] (5) Carboplatin, Carboplatin Injection, 0.1g (calculated as carboplatin) / vial, route of administration: intravenous infusion.

[0593] (6) Cisplatin, Cisplatin Injection, Specification: 6mL: 30mg, Route of administration: Intravenous infusion.

[0594] 2. Enrolled subjects

[0595] (1) Age between 18 and 75 years old (inclusive), female;

[0596] (2) Eastern Cooperative Oncology Group (ECOG) score of 0-1;

[0597] (3) Recurrent or metastatic cervical cancer (FIGO 2018 IVB stage) confirmed by histological or cytological pathology, with pathological type of squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma, and no longer suitable for radical surgery and / or radical radiotherapy or chemoradiotherapy:

[0598] ●Ib stage:

[0599] Cohort 1 and Cohort 2: Cervical cancer patients who had received ≤1 line of systemic therapy during the recurrence and metastasis stage;

[0600] Cohort 3: Cervical cancer patients in the recurrent or metastatic stage who have not received systemic treatment;

[0601] ●Phase II:

[0602] Cohort 1, Cohort 2 and Cohort 3: Cervical cancer patients in the recurrent and metastatic stage who have not received systemic treatment;

[0603] Note: If a patient receives platinum-based systemic therapy (excluding radiosensitizing chemotherapy) during neoadjuvant or adjuvant therapy and experiences disease relapse or progression within 6 months (183 days) after treatment (≥4 cycles), it is considered first-line systemic therapy.

[0604] (4) The subject is able to provide sufficient fresh or archived tumor tissue specimens for the third-party central laboratory designated by the sponsor to test the HER2 expression level and PD-L1 expression level; if the subject is unable to provide tumor tissue sections for PD-L1 expression level test for some reason, the investigator and the sponsor will jointly evaluate and decide whether to enroll the subject.

[0605] (5) There is at least one measurable lesion according to RECIST v1.1 criteria.

[0606] (6) Expected survival ≥ 12 weeks.

[0607] 3. Clinical protocol

[0608] 3.1 Research Design

[0609] This study was divided into two phases: dose exploration (Phase Ib) and efficacy expansion (Phase II).

[0610] ● Dosage exploration phase (Phase Ib):

[0611] Cohort 1: (1) Anti-HER2 antibody-drug conjugate, administered at a dose of 4.8 mg / kg or 4.0 mg / kg, once every 3 weeks (Q3W); (2) Anti-PD-L1 antibody, administered at a dose of 1200 mg, once every 3 weeks (Q3W); (3) Anti-VEGF antibody, administered at a dose of 15 mg / kg, once every 3 weeks (Q3W).

[0612] Cohort 2: (1) Anti-HER2 antibody-drug conjugate, administered at a dose of 4.8 mg / kg or 4.0 mg / kg, once every 3 weeks (Q3W); (2) Anti-PD-L1 antibody, administered at a dose of 1200 mg, once every 3 weeks (Q3W); (3) Anti-CTLA-4 antibody, administered as follows: C1D1 280 mg, C5D1 70 mg initially, Q6W (with a 21-day cycle, a single dose of 280 mg on the first day of the first cycle, no doses in cycles 2-4, and 70 mg starting from the first day of cycle 5, followed by doses once every 6 weeks); (4) Anti-VEGF antibody, administered at a dose of 15 mg / kg, once every 3 weeks (Q3W).

[0613] Cohort 3: (1) Anti-HER2 antibody-drug conjugate, dose of 3.2 mg / kg, once every 3 weeks (Q3W); (2) Anti-PD-L1 antibody, dose of 1200 mg, once every 3 weeks (Q3W); (3) Anti-CTLA-4 antibody, dosing regimen of C1D1 280 mg, C5D1 70 mg initially, Q6W (with 21 days as one cycle, a single dose of 280 mg on day 1 of the first cycle, no dosing in cycles 2-4, and 70 mg starting from day 1 of the fifth cycle, followed by dosing once every 6 weeks); (4) Anti-VEGF antibody, dose of 15 mg / kg, once every 3 weeks (Q3W); (5) Carboplatin, dose (AUC) of 5 mg / mL / min, once every 3 weeks (Q3W); or cisplatin, dose of 50 mg / mL / min. 2 Administer once every 3 weeks (Q3W).

[0614] After the last subject in each cohort has completed at least one cycle of observation, SMC will discuss and decide whether to use the above dosage level to enter Phase II or to continue exploring other dosage levels, such as downscaling the dosage of the anti-HER2 antibody drug conjugate to 4.0 mg / kg or 3.2 mg / kg Q3W, based on safety data (focusing on the incidence and severity of Grade 3 TRAE and TRSAE) and efficacy data.

[0615] ●Extended Therapy (Phase II):

[0616] Cohort 1: (1) Anti-HER2 antibody-drug conjugate, dose determined in phase Ib (e.g., 4.0 mg / kg), Q3W; (2) Anti-PD-L1 antibody, dose of 1200 mg, Q3W; (3) Anti-VEGF antibody, dose of 15 mg / kg, Q3W.

[0617] Cohort 2: (1) Anti-HER2 antibody-drug conjugate, dose determined in phase Ib (e.g., 4.0 mg / kg), Q3W; (2) Anti-PD-L1 antibody, dose of 1200 mg, Q3W; (3) Anti-CTLA-4 antibody, C1D1 280 mg, C5D1 70 mg initially, Q6W (with a 21-day cycle, a single dose of 280 mg on day 1 of the first cycle, no doses in cycles 2-4, and 70 mg starting from day 1 of the fifth cycle, followed by doses every 6 weeks); (4) Anti-VEGF antibody, dose of 15 mg / kg, Q3W.

[0618] Cohort 3: (1) Anti-HER2 antibody-drug conjugate, dose determined in phase Ib (e.g., 3.2 mg / kg), Q3W; (2) Anti-PD-L1 antibody, dose of 1200 mg, Q3W; (3) Anti-CTLA-4 antibody, C1D1 280 mg, C5D1 70 mg initially, Q6W (with a 21-day cycle, a single dose of 280 mg on day 1 of the first cycle, no doses in cycles 2-4, and 70 mg starting from day 1 of the fifth cycle, followed by doses every 6 weeks thereafter); (4) Anti-VEGF antibody, dose of 15 mg / kg, Q3W; (5) Carboplatin, dose (AUC) of 5 mg / mL / min, Q3W; or cisplatin, dose of 50 mg / mL / min. 2 , Q3W.

[0619] The enrolled subjects were randomly assigned to cohort 1 and cohort 2 in a 1:1 ratio. The randomization stratification factor was HER2 expression level (IHC < 1+ vs. IHC ≥ 1+).

[0620] 3.2 Administration method

[0621] (1) Anti-HER2 antibody drug conjugate, 3.2 mg / kg, 4.0 mg / kg, 4.8 mg / kg, Q3W, intravenous infusion; the first infusion time is 90±10 minutes (min). If no infusion-related reaction occurs after the first administration, the subsequent infusion time can be shortened to about 30 minutes.

[0622] (2) Anti-VEGF antibody: 15 mg / kg, Q3W, intravenous infusion. The first infusion time needs to last for 90 minutes. If the first infusion is well tolerated, the second infusion time can be shortened to 60 minutes. If the subject also tolerates the 60-minute infusion well, then all subsequent infusions can be completed in 30 minutes (including the flushing phase).

[0623] (3) Anti-PD-L1 antibody: 1200mg, Q3W, intravenous infusion. The infusion should be completed within 30-60 minutes. Each treatment cycle is 3 weeks, and the maximum cumulative treatment cycle is 35 cycles (2 years).

[0624] (4) Anti-CTLA-4 antibody: C1D1 280mg, starting from C5D1, 70mg, every 6 weeks (Q6W) (Note: C2-C4 do not require administration). Intravenous infusion, administration time is 30±10 minutes.

[0625] (5) Carboplatin injection: AUC 5mg / mL / min, Q3W, intravenous infusion, the infusion should be completed within 30 to 60 minutes (including the flushing phase), every 3 weeks is a treatment cycle, and carboplatin can be used for a maximum of 6 cycles.

[0626] (6) Cisplatin injection: 50 mg / m 2 Q3W, intravenous infusion, the infusion should be completed within 60 to 120 minutes, each 3 weeks is a treatment cycle, and a maximum of 6 cycles of medication.

[0627] 3.3 Order of administration:

[0628] The dosing sequence for Cohort 1 was as follows: on cycle D1, anti-HER2 antibody-drug conjugate, anti-PD-L1 antibody, and anti-VEGF antibody were administered sequentially.

[0629] The dosing sequence for Cohort 2 was as follows: on cycle D1, antiHER2 antibody-drug conjugate, antiPD-L1 antibody, antiCTLA-4 antibody, and antiVEGF antibody were administered sequentially.

[0630] The dosing sequence for Cohort 3 was as follows: on cycle D1, anti-HER2 antibody-drug conjugate, anti-PD-L1 antibody, anti-CTLA-4 antibody, cisplatin / carboplatin, and anti-VEGF antibody were administered sequentially.

[0631] The time interval between administration of the two drugs should be >30 minutes. Unless there are special circumstances, the administration should be completed on the same day. If required by local clinical practice, the administration can be divided into two days.

[0632] 3.4 Carboplatin Dosage Calculation Formula

[0633] The dosage of carboplatin injection needs to be calculated based on the area under the plasma concentration-time curve (AUC) and endogenous creatinine clearance. The maximum dose of carboplatin should not exceed 600 mg. If the calculated dose of carboplatin is greater than 600 mg, it should be administered at 600 mg.

[0634] Calvert formula for carboplatin dosage based on AUC: Carboplatin dose (mg) = set AUC (mg / mL / min) × [creatinine clearance (mL / min) + 25]

[0635] The endogenous creatinine clearance rate was calculated using the Cockcroft formula.

[0636] Serum creatinine concentration (mg / dL)

[0637] Serum creatinine concentration (mol / L):

[0638] 3.5 Formula for Body Surface Area: Body surface area (m²) 2 = 0.0061 × height (cm) + 0.0128 × weight (kg) - 0.1529

[0639] 4. Results Evaluation

[0640] (1) Validity:

[0641] 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 objective response rate (ORR), disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), and overall survival (OS).

[0642] The clinical trial is still ongoing. To date, 27 subjects have been enrolled, including 10 subjects enrolled in Phase Ib Cohort 1 (administered with anti-HER2 antibody-drug conjugate at 4.8 mg / kg), 1 subject enrolled in Phase II Cohort 1 (administered with anti-HER2 antibody-drug conjugate at 4.0 mg / kg), and a total of 16 subjects enrolled in Phase Ib and Phase II Cohort 2 (administered with anti-HER2 antibody-drug conjugate at 4.0 mg / kg). Among the subjects enrolled in Phase Ib Cohort 1, the HER2 expression level test results included 3 cases of IHC 2+, 2 cases of IHC 1+, and 4 cases of IHC <1+.

[0643] The efficacy evaluation results are as follows: In the Phase Ib cohort 1 subjects, one patient achieved complete remission (CR), the ORR of all subjects reached 80%, and the DCR reached 100%; In the Phase Ib and Phase II cohort 2 subjects, the ORR of the 8 patients who had received treatment evaluation reached 75%, and the DCR reached 100%.

[0644] Table 5. Efficacy Data

[0645] *uORR indicates that ORR has not been confirmed.

[0646] (2) Security:

[0647] After all subjects are enrolled in the study, a safety assessment will be conducted at each treatment cycle. This includes the incidence and grade of adverse events (AEs) and serious adverse events (SAEs) (judged according to the NCI-CTCAE v5.0 criteria), laboratory tests (complete blood count, blood biochemistry, coagulation function, thyroid function, urinalysis, fecal occult blood test, etc.), vital signs, physical examination, weight, ECOG score, echocardiography, and 12-lead electrocardiogram.

[0648] Safety evaluation of all 27 enrolled subjects showed that TRAEs with an incidence of ≥10% included decreased neutrophil count, decreased white blood cell count, and anemia. The proportion of subjects experiencing ≥3 grade TRAEs was 44.4% (50% in cohort 1 and 43.8% in cohort 2).

[0649] In summary, anti-HER2 antibody-drug conjugates used in combination with other drugs (including immunotherapeutic agents) have demonstrated tolerable and manageable safety profiles and show promising antitumor activity in the treatment of cervical cancer.

Claims

1. The use of anti-HER2 antibody drug conjugates in combination with other drugs in the preparation of antitumor drugs; the structure of the anti-HER2 antibody drug conjugate is shown in formula (I): in: n is between 3 and 8, where n is a decimal or an integer; Pc is the anti-HER2 antibody; The other drugs include immunotherapeutic agents; the tumor is cervical cancer.

2. The use according to claim 1, wherein the cervical cancer is recurrent or metastatic cervical cancer.

3. The use according to claim 1 or 2, wherein the cervical cancer includes cervical squamous cell carcinoma, cervical adenocarcinoma, and / or cervical adenosquamous carcinoma.

4. The use according to any one of claims 1-3, wherein the subject suffering from said cervical cancer has received or has not received systemic antitumor therapy during the recurrence or metastasis stage; preferably, the subject has received ≤1 line of systemic antitumor therapy during the recurrence or metastasis stage.

5. The use according to any one of claims 1-4, wherein the anti-HER2 antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2 and HCDR3 as shown in SEQ ID NO:11, SEQ ID NO:12 and SEQ ID NO:13 respectively, and the VL comprises LCDR1, LCDR2 and LCDR3 as shown in SEQ ID NO:14, SEQ ID NO:15 and SEQ ID NO:16 respectively; Preferably, the VH comprises an amino acid sequence as shown in SEQ ID NO: 17 or having at least 80% or 90% identity with it, and the VL comprises an amino acid sequence as shown in SEQ ID NO: 18 or having at least 80% or 90% identity with it; More preferably, the anti-HER2 antibody comprises a heavy chain and a light chain, the heavy chain comprising an amino acid sequence as shown in or having at least 80% or 90% identity with SEQ ID NO: 19, and the light chain comprising an amino acid sequence as shown in or having at least 80% or 90% identity with SEQ ID NO: 20; Most preferably, the anti-HER2 antibody is Trastuzumab.

6. The use according to any one of claims 1-5, wherein the anti-HER2 antibody drug conjugate has the structure shown in the following formula: in, n is between 3 and 8, where n is a decimal or an integer; preferably 5.3-6.

4.

7. The use according to any one of claims 1-6, wherein the anti-HER2 antibody drug conjugate is administered at a dose of about 0.1 mg / kg to about 20.0 mg / kg; preferably about 1.0 mg / kg to about 10.0 mg / kg, more preferably about 1.0 mg / kg, about 2.0 mg / kg, about 3.2 mg / kg, about 4.0 mg / kg, about 4.8 mg / kg, about 5.6 mg / kg, about 6.4 mg / kg, about 8.0 mg / kg, or about 10.0 mg / kg; and / or, The anti-HER2 antibody drug conjugate is administered once a 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; preferably once every three weeks. Preferably, the anti-HER2 antibody-drug conjugate is administered once every 3 weeks at a dose of approximately 1.0 mg / kg, approximately 2.0 mg / kg, approximately 3.2 mg / kg, approximately 4.0 mg / kg, approximately 4.8 mg / kg, approximately 5.6 mg / kg, approximately 6.4 mg / kg, approximately 8.0 mg / kg, or approximately 10.0 mg / kg. More preferably, the anti-HER2 antibody drug conjugate is administered once every 3 weeks at a dose of about 3.2 mg / kg, about 4.0 mg / kg, or about 4.8 mg / kg.

8. The use according to any one of claims 1-7, wherein, The immunotherapeutic agent is an anti-PD-L1 antibody and / or an anti-CTLA-4 antibody.

9. The use according to claim 8, wherein, 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 as shown in SEQ ID NO:21, SEQ ID NO:22 and SEQ ID NO:23 respectively, and the VL comprises LCDR1, LCDR2 and LCDR3 as shown in SEQ ID NO:24, SEQ ID NO:25 and SEQ ID NO:26 respectively; Preferably, the VH comprises an amino acid sequence as shown in SEQ ID NO: 27 or having at least 80% or 90% identity with it, and the VL comprises an amino acid sequence as shown in SEQ ID NO: 28 or having at least 80% or 90% identity with it; More preferably, the anti-PD-L1 antibody comprises a heavy chain and a light chain, the heavy chain comprising an amino acid sequence as shown in or having at least 80% or 90% identity with SEQ ID NO: 29, and the light chain comprising an amino acid sequence as shown in or having at least 80% or 90% identity with SEQ ID NO:

30.

10. The use according to claim 8 or 9, wherein, The anti-PD-L1 antibody is administered at a dose of about 5 mg to about 5000 mg, preferably about 100 mg, about 500 mg, about 800 mg, about 1000 mg, about 1200 mg, about 1500 mg, about 1800 mg, about 2000 mg, about 2200 mg, about 2500 mg, or about 3000 mg; and / or, 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, preferably once every 3 weeks; Preferably, the anti-PD-L1 antibody is administered once every 3 weeks, in doses of approximately 100 mg, approximately 500 mg, approximately 800 mg, approximately 1000 mg, approximately 1200 mg, approximately 1500 mg, approximately 1800 mg, approximately 2000 mg, approximately 2200 mg, approximately 2500 mg, or approximately 3000 mg. More preferably, the anti-PD-L1 antibody is administered once every 3 weeks, at a dose of approximately 1200 mg.

11. The use according to claim 8, wherein, 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 as shown in SEQ ID NO:31, SEQ ID NO:32 and SEQ ID NO:33 respectively, and the VL comprises LCDR1, LCDR2 and LCDR3 as shown in SEQ ID NO:34, SEQ ID NO:35 and SEQ ID NO:36 respectively; Preferably, the VH contains an amino acid sequence as shown in SEQ ID NO:37 or having at least 90% identity with it, and the VL contains an amino acid sequence as shown in SEQ ID NO:38 or having at least 90% identity with it. More preferably, 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:39 or having at least 80% or 90% identity with it, and the light chain comprises an amino acid sequence as shown in SEQ ID NO:40 or having at least 80% or 90% identity with it.

12. The use according to claim 8 or 11, wherein, The anti-CTLA-4 antibody is administered at doses of approximately 1 mg to approximately 1000 mg, preferably 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 250 mg, approximately 280 mg, approximately 300 mg, approximately 350 mg, approximately 500 mg, or approximately 700 mg; and / or The anti-CTLA-4 antibody is administered once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, once every 6 weeks, once every 7 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, preferably once every 6 weeks or as a single dose. Preferably, the anti-CTLA-4 antibody is administered at a dose of about 40 mg, about 50 mg, about 60 mg, about 70 mg, about 80 mg, about 90 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 280 mg, about 300 mg, or about 350 mg, and the anti-CTLA-4 antibody is administered once every 6 weeks or as a single dose; More preferably, the anti-CTLA-4 antibody is administered as a single dose of about 210 mg or 280 mg in week 1, and then every 6 weeks thereafter, starting from week 13, the dose is about 70 mg.

13. The use according to any one of claims 1-12, wherein the other drugs further comprise VEGF signaling pathway inhibitors; Preferably, the VEGF signaling pathway inhibitor is an anti-VEGF antibody; More preferably, the anti-VEGF antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1, HCDR2 and HCDR3 as shown in SEQ ID NO:1, SEQ ID NO:2 and SEQ ID NO:3 respectively, and the VL comprises LCDR1, LCDR2 and LCDR3 as shown in SEQ ID NO:4, SEQ ID NO:5 and SEQ ID NO:6 respectively; More preferably, the VH comprises an amino acid sequence as shown in or having at least 80% identity with SEQ ID NO: 7, and the VL comprises an amino acid sequence as shown in or having at least 80% identity with SEQ ID NO: 8; Most preferably, the anti-VEGF antibody comprises a heavy chain and a light chain, the heavy chain comprising an amino acid sequence as shown in or having at least 80% identity with SEQ ID NO: 9, and the light chain comprising an amino acid sequence as shown in or having at least 80% identity with SEQ ID NO:

10.

14. The use according to claim 13, wherein the anti-VEGF antibody is administered at a dose of about 1 mg / kg to about 30 mg / kg; preferably about 10 mg / kg to about 20 mg / kg; more preferably about 10 mg / kg, about 11 mg / kg, about 12 mg / kg, about 13 mg / kg, about 14 mg / kg, about 15 mg / kg, about 16 mg / kg, about 17 mg / kg, about 18 mg / kg, about 19 mg / kg, or about 20 mg / kg; and / or 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; preferably once every 3 weeks. Preferably, the anti-VEGF antibody is administered once every 3 weeks at a dose of 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, or approximately 20 mg / kg. More preferably, the anti-VEGF antibody is administered once every 3 weeks at a dose of approximately 15 mg / kg.

15. The use according to claim 13 or 14, wherein the other medicament further comprises a platinum-based drug; Preferably, the platinum-based drug is carboplatin and / or cisplatin.

16. The use according to claim 15, wherein, The carboplatin administration rate (based on AUC) is approximately 0.1 mg / mL / min to approximately 50 mg / mL / min; preferably approximately 1 mg / mL / min to approximately 20 mg / mL / min, more preferably approximately 1 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, approximately 10 mg / mL / min, approximately 15 mg / mL / min, or approximately 20 mg / mL / min; and / or 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; preferably once every 3 weeks. Preferably, the carboplatin is administered once every 3 weeks at a rate (based on AUC) of approximately 1 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, approximately 10 mg / mL / min, approximately 15 mg / mL / min, or approximately 20 mg / mL / min. More preferably, the carboplatin is administered once every 3 weeks at a dose of approximately 5 mg / mL / min (based on AUC).

17. The use according to claim 15, wherein, The cisplatin dosage was approximately 1 mg / m². 2 Approximately 500 mg / m 2 Preferably about 10 mg / m 2 Approximately 150 mg / m 2 More preferably about 10 mg / m 2 Approximately 20 mg / m 2 Approximately 30 mg / m 2 Approximately 40 mg / m 2 Approximately 45 mg / m 2 Approximately 50 mg / m 2 Approximately 55 mg / m 2 Approximately 60 mg / m 2 Approximately 65 mg / m 2 Approximately 70 mg / m 2 Approximately 75 mg / m 2 Approximately 80 mg / m 2 Approximately 85 mg / m 2 Approximately 90 mg / m 2 Approximately 100 mg / m 2 Approximately 150 mg / m 2 ; and / or 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, preferably once every 3 weeks; Preferably, the cisplatin is administered once every 3 weeks at a dose of approximately 10 mg / m². 2 Approximately 20 mg / m 2 Approximately 30 mg / m 2 Approximately 40 mg / m 2 Approximately 45 mg / m 2 Approximately 50 mg / m 2 Approximately 55 mg / m 2 Approximately 60 mg / m 2 Approximately 65 mg / m 2 Approximately 70 mg / m 2 Approximately 75 mg / m 2 Approximately 80 mg / m 2 Approximately 85 mg / m 2 Approximately 90 mg / m 2 Approximately 100 mg / m 2 Approximately 150 mg / m 2 ; More preferably, the cisplatin is administered once every 3 weeks at a dose of approximately 50 mg / m². 2 .

18. The use of any of the following combinations in the preparation of antitumor drugs: (1) Anti-HER2 antibody-drug conjugate combined with anti-PD-L1 antibody; (2) Anti-HER2 antibody-drug conjugate combined with anti-PD-L1 antibody and anti-CTLA-4 antibody; (3) Anti-HER2 antibody-drug conjugate combined with anti-PD-L1 antibody and anti-VEGF antibody; (4) Anti-HER2 antibody drug conjugate combined with anti-PD-L1 antibody, anti-CTLA-4 antibody and anti-VEGF antibody; (5) Anti-HER2 antibody-drug conjugate combined with anti-PD-L1 antibody, anti-VEGF antibody and carboplatin; (6) Anti-HER2 antibody-drug conjugate combined with anti-PD-L1 antibody, anti-VEGF antibody and cisplatin; (7) Anti-HER2 antibody drug conjugate combined with anti-PD-L1 antibody, anti-CTLA-4 antibody, anti-VEGF antibody and carboplatin; (8) Anti-HER2 antibody-drug conjugate combined with anti-PD-L1 antibody, anti-CTLA-4 antibody, anti-VEGF antibody and cisplatin; The tumor is cervical cancer; The anti-HER2 antibody-drug conjugate has the structure shown in the following formula: in, n is between 3 and 8, where n is a decimal or an integer; preferably 5.3-6.

4. The anti-PD-L1 antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence shown in SEQ ID NO: 29, and the light chain comprises the amino acid sequence shown in SEQ ID NO: 30; 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:39 and the light chain comprises an amino acid sequence as shown in SEQ ID NO:40; The anti-VEGF antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence shown in SEQ ID NO: 9, and the light chain comprises the amino acid sequence shown in SEQ ID NO: 10; The cervical cancer is as defined in any one of claims 2-4.

19. The use according to claim 18, wherein: (1) The dosing regimen of the anti-HER2 antibody-drug conjugate combined with the anti-PD-L1 antibody is as follows: (a) Anti-HER2 antibody-drug conjugates are administered once every 2 or 3 weeks at a dose of approximately 1.0 mg / kg to 10.0 mg / kg; (b1) Anti-PD-L1 antibody is administered once every 3 weeks at a dose of approximately 50 mg to 3000 mg; or, (a) Anti-HER2 antibody-drug conjugates administered every 2 or 3 weeks at doses of approximately 1.0 mg / kg, 2.0 mg / kg, 3.2 mg / kg, 4.0 mg / kg, 4.8 mg / kg, 5.6 mg / kg, 6.4 mg / kg, or 8.0 mg / kg; (b1) Anti-PD-L1 antibody administered every 3 weeks at doses ranging from approximately 50 mg to 3000 mg; or, (a) Anti-HER2 antibody-drug conjugate was administered once every 3 weeks at a dose of approximately 4.0 mg / kg, approximately 4.8 mg / kg, or approximately 3.2 mg / kg; (b1) Anti-PD-L1 antibody was administered once every 3 weeks at a dose of approximately 1200 mg. (2) The dosing regimen for the anti-HER2 antibody-drug conjugate combined with anti-PD-L1 antibody and anti-CTLA-4 antibody is as follows: (a) Anti-HER2 antibody-drug conjugates are administered once every 2 or 3 weeks, at a dose of approximately 1.0 mg / kg to 10.0 mg / kg; (b1) Anti-PD-L1 antibody is administered once every 3 weeks, at a dose of approximately 50 mg to 3000 mg; (b2) Anti-CTLA-4 antibody is administered once every 6 weeks or as a single dose, at a dose of approximately 1 mg to 1000 mg; or, (a) Anti-HER2 antibody-drug conjugates administered every 2 or 3 weeks at doses of approximately 1.0 mg / kg, 2.0 mg / kg, 3.2 mg / kg, 4.0 mg / kg, 4.8 mg / kg, 5.6 mg / kg, 6.4 mg / kg, or 8.0 mg / kg; (b1) Anti-PD-L1 antibody administered every 3 weeks at doses of approximately 50 mg to 3000 mg; (b2) Anti-CTLA-4 antibody administered every 6 weeks or as a single dose at doses of approximately 1 mg to 1000 mg; or, (a) Anti-HER2 antibody-drug conjugate was administered once every 3 weeks at approximately 4.0 mg / kg, approximately 4.8 mg / kg, or approximately 3.2 mg / kg; (b1) Anti-PD-L1 antibody was administered once every 3 weeks at approximately 1200 mg; (b2) Anti-CTLA-4 antibody was administered once in week 1 at approximately 210 mg or approximately 280 mg, and then once every 6 weeks from week 13 at approximately 70 mg. (3) The dosing regimen of the anti-HER2 antibody-drug conjugate combined with anti-PD-L1 antibody and anti-VEGF antibody is as follows: (a) Anti-HER2 antibody-drug conjugates are administered once every 2 or 3 weeks at a dose of approximately 1.0 mg / kg to 10.0 mg / kg; (b1) Anti-PD-L1 antibody is administered once every 3 weeks at a dose of approximately 50 mg to 3000 mg; (c) Anti-VEGF antibody is administered once every 3 weeks at a dose of approximately 1 mg / kg to approximately 30 mg / kg; or, (a) Anti-HER2 antibody-drug conjugates administered every 2 or 3 weeks at doses of approximately 1.0 mg / kg, 2.0 mg / kg, 3.2 mg / kg, 4.0 mg / kg, 4.8 mg / kg, 5.6 mg / kg, 6.4 mg / kg, or 8.0 mg / kg; (b1) Anti-PD-L1 antibody administered every 3 weeks at doses ranging from approximately 50 mg to 3000 mg; (c) Anti-VEGF antibody administered every 3 weeks at doses ranging from approximately 1 mg / kg to approximately 30 mg / kg; or, (a) Anti-HER2 antibody-drug conjugate was administered once every 3 weeks at a dose of approximately 4.0 mg / kg, approximately 4.8 mg / kg, or approximately 3.2 mg / kg; (b1) Anti-PD-L1 antibody was administered once every 3 weeks at a dose of approximately 1200 mg; (c) Anti-VEGF antibody was administered once every 3 weeks at a dose of approximately 15 mg / kg. (4) The dosing regimen of the anti-HER2 antibody-drug conjugate combined with anti-PD-L1 antibody, anti-CTLA-4 antibody and anti-VEGF antibody is as follows: (a) Anti-HER2 antibody-drug conjugates are administered once every 2 or 3 weeks, at a dose of approximately 1.0 mg / kg to 10.0 mg / kg; (b1) Anti-PD-L1 antibody is administered once every 3 weeks, at a dose of approximately 50 mg to 3000 mg; (b2) Anti-CTLA-4 antibody is administered once every 6 weeks or as a single dose, at a dose of approximately 1 mg to 1000 mg; (c) Anti-VEGF antibody is administered once every 3 weeks, at a dose of approximately 1 mg / kg to approximately 30 mg / kg; or, (a) Anti-HER2 antibody-drug conjugates administered every 2 or 3 weeks at doses of approximately 1.0 mg / kg, 2.0 mg / kg, 3.2 mg / kg, 4.0 mg / kg, 4.8 mg / kg, 5.6 mg / kg, 6.4 mg / kg, or 8.0 mg / kg; (b1) Anti-PD-L1 antibody administered every 3 weeks at doses of approximately 50 mg to 3000 mg; (b2) Anti-CTLA-4 antibody administered every 6 weeks or as a single dose at doses of approximately 1 mg to 1000 mg; (c) Anti-VEGF antibody administered every 3 weeks at doses of approximately 1 mg / kg to approximately 30 mg / kg; or, (a) Anti-HER2 antibody-drug conjugate, administered once every 3 weeks at approximately 4.0 mg / kg, approximately 4.8 mg / kg, or approximately 3.2 mg / kg; (b1) Anti-PD-L1 antibody, administered once every 3 weeks at approximately 1200 mg; (b2) Anti-CTLA-4 antibody, administered once in week 1 at approximately 210 mg or approximately 280 mg, and then every 6 weeks from week 13 at approximately 70 mg; (c) Anti-VEGF antibody, administered once every 3 weeks at approximately 15 mg / kg. (5) The dosing regimen of the anti-HER2 antibody-drug conjugate combined with anti-PD-L1 antibody, anti-VEGF antibody and carboplatin is as follows: (a) Anti-HER2 antibody-drug conjugates are administered once every 2 or 3 weeks at a dose of approximately 1.0 mg / kg to 10.0 mg / kg; (b1) Anti-PD-L1 antibody is administered once every 3 weeks at a dose of approximately 50 mg to 3000 mg; (c) Anti-VEGF antibody is administered once every 3 weeks at a dose of approximately 1 mg / kg to 30 mg / kg; (d) Carboplatin is administered once every 3 weeks at a dose of approximately 0.1 mg / mL / min to approximately 50 mg / mL / min; or, (a) Anti-HER2 antibody-drug conjugates administered every 2 or 3 weeks at doses of approximately 1.0 mg / kg, 2.0 mg / kg, 3.2 mg / kg, 4.0 mg / kg, 4.8 mg / kg, 5.6 mg / kg, 6.4 mg / kg, or 8.0 mg / kg; (b1) Anti-PD-L1 antibody administered every 3 weeks at doses of approximately 50 mg to 3000 mg; (c) Anti-VEGF antibody administered every 3 weeks at doses of approximately 1 mg / kg to 30 mg / kg; (d) Carboplatin administered every 3 weeks at doses of approximately 0.1 mg / mL / min to approximately 50 mg / mL / min; or, (a) Anti-HER2 antibody-drug conjugate, administered once every 3 weeks at approximately 4.0 mg / kg, 4.8 mg / kg, or 3.2 mg / kg; (b1) Anti-PD-L1 antibody, administered once every 3 weeks at approximately 1200 mg; (c) Anti-VEGF antibody, administered once every 3 weeks at approximately 15 mg / kg; (d) Carboplatin, administered once every 3 weeks at approximately 5 mg / mL / min. (6) The dosing regimen of the anti-HER2 antibody-drug conjugate combined with anti-PD-L1 antibody, anti-VEGF antibody and cisplatin is as follows: (a) Anti-HER2 antibody-drug conjugates are administered once every 2 or 3 weeks, at a dose of approximately 1.0 mg / kg to 10.0 mg / kg; (b1) Anti-PD-L1 antibody is administered once every 3 weeks, at a dose of approximately 50 mg to 3000 mg; (c) Anti-VEGF antibody is administered once every 3 weeks, at a dose of approximately 1 mg / kg to 30 mg / kg; (d) Cisplatin is administered once every 3 weeks, at a dose of approximately 1 mg / kg. 2- 500 mg / m 2 ;or, (a) Anti-HER2 antibody-drug conjugates are administered once every 2 or 3 weeks at doses of approximately 1.0 mg / kg, 2.0 mg / kg, 3.2 mg / kg, 4.0 mg / kg, 4.8 mg / kg, 5.6 mg / kg, 6.4 mg / kg, or 8.0 mg / kg; (b1) Anti-PD-L1 antibody is administered once every 3 weeks at doses ranging from approximately 50 mg to 3000 mg; (c) Anti-VEGF antibody is administered once every 3 weeks at doses ranging from approximately 1 mg / kg to 30 mg / kg; (d) Cisplatin is administered once every 3 weeks at doses ranging from approximately 1 mg / kg. 2- 500 mg / m 2 ;or, (a) Anti-HER2 antibody-drug conjugate, administered once every 3 weeks at approximately 4.0 mg / kg, 4.8 mg / kg, or 3.2 mg / kg; (b1) Anti-PD-L1 antibody, administered once every 3 weeks at approximately 1200 mg; (c) Anti-VEGF antibody, administered once every 3 weeks at approximately 15 mg / kg; (d) Cisplatin, administered once every 3 weeks at approximately 50 mg / kg. 2 ; (7) The dosing regimen of the anti-HER2 antibody-drug conjugate combined with anti-PD-L1 antibody, anti-CTLA-4 antibody, anti-VEGF antibody and carboplatin is as follows: (a) Anti-HER2 antibody-drug conjugates are administered once every 2 or 3 weeks at a dose of approximately 1.0 mg / kg to 10.0 mg / kg; (b1) Anti-PD-L1 antibody is administered once every 3 weeks at a dose of approximately 50 mg to 3000 mg; (b2) Anti-CTLA-4 antibody is administered once every 6 weeks or as a single dose at a dose of approximately 1 mg to 1000 mg; (c) Anti-VEGF antibody is administered once every 3 weeks at a dose of approximately 1 mg / kg to 30 mg / kg; (d) Carboplatin is administered once every 3 weeks at a dose of approximately 0.1 mg / mL / min to approximately 50 mg / mL / min; or, (a) Anti-HER2 antibody-drug conjugates administered every 2 or 3 weeks at doses of approximately 1.0 mg / kg, 2.0 mg / kg, 3.2 mg / kg, 4.0 mg / kg, 4.8 mg / kg, 5.6 mg / kg, 6.4 mg / kg, or 8.0 mg / kg; (b1) Anti-PD-L1 antibody administered every 3 weeks at doses of approximately 50 mg to 3000 mg; (b2) Anti-CTLA-4 antibody administered every 6 weeks or as a single dose at doses of approximately 1 mg to 1000 mg; (c) Anti-VEGF antibody administered every 3 weeks at doses of approximately 1 mg / kg to 30 mg / kg; (d) Carboplatin administered every 3 weeks at doses of approximately 0.1 mg / mL / min to approximately 50 mg / mL / min; or, (a) Anti-HER2 antibody-drug conjugate, administered once every 3 weeks at approximately 4.0 mg / kg, 4.8 mg / kg, or 3.2 mg / kg; (b1) Anti-PD-L1 antibody, administered once every 3 weeks at approximately 1200 mg; (b2) Anti-CTLA-4 antibody, administered once in week 1 at approximately 210 mg or 280 mg, and then every 6 weeks from week 13 at approximately 70 mg; (c) Anti-VEGF antibody, administered once every 3 weeks at approximately 15 mg / kg; (d) Carboplatin, administered once every 3 weeks at approximately 5 mg / mL / min. (8) The dosing regimen of the anti-HER2 antibody-drug conjugate combined with anti-PD-L1 antibody, anti-CTLA-4 antibody, anti-VEGF antibody and cisplatin is as follows: (a) Anti-HER2 antibody-drug conjugates are administered once every 2 or 3 weeks, at a dose of approximately 1.0 mg / kg to 10.0 mg / kg; (b1) Anti-PD-L1 antibody is administered once every 3 weeks, at a dose of approximately 50 mg to 3000 mg; (b2) Anti-CTLA-4 antibody is administered once every 6 weeks or as a single dose, at a dose of approximately 1 mg to 1000 mg; (c) Anti-VEGF antibody is administered once every 3 weeks, at a dose of approximately 1 mg / kg to 30 mg / kg; (d) Cisplatin is administered once every 3 weeks, at a dose of approximately 1 mg / kg. 2- 500 mg / m 2 ;or, (a) Anti-HER2 antibody-drug conjugates are administered every 2 or 3 weeks at doses of approximately 1.0 mg / kg, 2.0 mg / kg, 3.2 mg / kg, 4.0 mg / kg, 4.8 mg / kg, 5.6 mg / kg, 6.4 mg / kg, or 8.0 mg / kg, respectively; (b1) Anti-PD-L1 antibody is administered every 3 weeks at doses of approximately 50 mg to 3000 mg; (b2) Anti-CTLA-4 antibody is administered every 6 weeks or as a single dose at doses of approximately 1 mg to 1000 mg; (c) Anti-VEGF antibody is administered every 3 weeks at doses of approximately 1 mg / kg to 30 mg / kg; (d) Cisplatin is administered every 3 weeks at doses of approximately 1 mg / kg. 2- 500 mg / m 2 ;or, (a) Anti-HER2 antibody-drug conjugate, administered once every 3 weeks at approximately 4.0 mg / kg, 4.8 mg / kg, or 3.2 mg / kg; (b1) Anti-PD-L1 antibody, administered once every 3 weeks at approximately 1200 mg; (b2) Anti-CTLA-4 antibody, administered once in week 1 at approximately 210 mg or 280 mg, followed by once every 6 weeks at approximately 70 mg starting from week 13; (c) Anti-VEGF antibody, administered once every 3 weeks at approximately 15 mg / kg; (d) Cisplatin, administered once every 3 weeks at approximately 50 mg / kg. 2 .

20. A kit or article comprising an anti-HER2 antibody-drug conjugate as defined in any one of claims 1, 5-7, 18-19 and an immunotherapeutic agent as defined in any one of claims 8-12, 18-19; or; The kit or article comprises an anti-HER2 antibody-drug conjugate as defined in any one of claims 1, 5-7, 18-19, an immunotherapeutic agent as defined in any one of claims 8-12, 18-19, and a VEGF signaling pathway inhibitor as defined in any one of claims 13-14, 18-19; or; The kit or article comprises an anti-HER2 antibody-drug conjugate as defined in any one of claims 1, 5-7, 18-19, an immunotherapeutic agent as defined in any one of claims 8-12, 18-19, a VEGF signaling pathway inhibitor as defined in any one of claims 13-14, 18-19, and a platinum-based drug as defined in any one of claims 15-17, 18-19.

21. A pharmaceutical composition comprising an anti-HER2 antibody-drug conjugate as defined in any one of claims 1, 5-7, 18-19 and an immunotherapeutic agent as defined in any one of claims 8-12, 18-19; or; The pharmaceutical composition comprises an anti-HER2 antibody-drug conjugate as defined in any one of claims 1, 5-7, 18-19, an immunotherapeutic agent as defined in any one of claims 8-12, 18-19, and a VEGF signaling pathway inhibitor as defined in any one of claims 13-14, 18-19; or; The pharmaceutical composition comprises an anti-HER2 antibody-drug conjugate as defined in any one of claims 1, 5-7, 18-19, an immunotherapeutic agent as defined in any one of claims 8-12, 18-19, a VEGF signaling pathway inhibitor as defined in any one of claims 13-14, 18-19, and a platinum-based drug as defined in any one of claims 15-17, 18-19.

22. Use of the cassette or article of claim 20, or the pharmaceutical composition of claim 21, in the preparation of an antitumor drug; Preferably, the tumor is as defined in any one of claims 1-4.

23. The use according to any one of claims 1-19, 22, wherein the antitumor drug may be a neoadjuvant therapy drug before cervical cancer surgery and / or an adjuvant therapy drug after cervical cancer surgery.

24. A method for treating cervical cancer, comprising administering an anti-HER2 antibody-drug conjugate and other drugs to a subject in need, said antibody-drug conjugate being of formula (I), in: n is between 3 and 8, and n is a decimal or an integer; Pc is an anti-HER2 antibody; The other drugs include immunotherapeutic agents; Preferably, the anti-HER2 antibody drug conjugate is as defined in any one of claims 1, 5-7, 18-19; the immunotherapy agent is as defined in any one of claims 8-12, 18-19; and the cervical cancer is as defined in any one of claims 2-4.

25. The method of claim 24, wherein the other drug further comprises a VEGF signaling pathway inhibitor; Preferably, the VEGF signaling pathway inhibitor is as defined in any one of claims 13-14, 18-19.

26. The method of claim 25, wherein the other drugs further comprise platinum-based drugs; Preferably, the platinum-based drug is as defined in any one of claims 15-17, 18-19.

27. The method according to any one of claims 24-26, wherein the treatment of cervical cancer may be perioperative treatment of cervical cancer, including neoadjuvant therapy before cervical cancer surgery and / or adjuvant therapy after cervical cancer surgery.

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