Pharmaceutical combinations comprising anti-TIM-3 antibodies

Abstract

Provided is a pharmaceutical combination comprising an anti-TIM-3 antibody, which comprises an anti-TIM-3 antibody or an antigen-binding fragment thereof and an anti-PD-1 antibody or an antigen-binding fragment thereof; optionally, the pharmaceutical composition also comprises a chemotherapeutic drug. The invention further provides a kit for treating tumors. The kit comprises the medicine composition. In addition, the invention also provides application of the medicine composition in preparation of medicines for treating tumors and a method for treating tumors by using the medicine composition.

Description

Drug combinations containing anti-TIM-3 antibodies

[0001] This disclosure claims priority from the following:

[0002] CN202310201537.3, application date March 3, 2023;

[0003] CN202310407301.5, application date April 14, 2023;

[0004] CN202310399024.8, application date April 14, 2023. Technical Field

[0005] The present disclosure relates to the field of biopharmaceuticals, and specifically relates to a drug combination of an antibody that binds to TIM-3 and an antibody that binds to PD-1. Background Art

[0006] T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), also known as hepatitis A virus cellular receptor 2 (HAVCR2), is a member of the TIM family of immunoregulatory proteins (the human TIM family includes TIM-1, 3, and 4). TIM-3 is selectively expressed on the surface of activated Th1 cells and is also expressed on myeloid cells, dendritic cells, natural killer (NK) cells, macrophages, and various tumor cells. TIM-3 has multiple ligands, including galectin-9, phosphatidylserine (PtdSer), high mobility group protein B1 (HMGB1), and carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1). As an immune checkpoint, TIM-3 negatively regulates the body's immune response, preventing damage from excessive immune or autoimmune responses. Increasing evidence indicates that TIM-3 protein and / or mRNA is upregulated in a variety of tumor tissues and tumor-associated immune cells, participating in tumor immune escape and immune response, and promoting tumor development.

[0007] PD-1 (Programmed death-1) is a key immune checkpoint receptor expressed by activated T and B lymphocytes and mediates immunosuppression. Its ligands include PD-L1 and PD-L2. Chinese patent document CN106977602A discloses an anti-PD-1 monoclonal antibody, 14C12H1L1, which effectively blocks the binding of PD-1 to PD-L1 and exhibits significant anti-tumor activity.

[0008] Head and neck cancer is a group of malignant tumors that arise widely in the epithelial cells of the paranasal sinuses, nasal cavity, mouth, and throat. Over 90% of these tumors are head and neck squamous cell carcinomas (HNSCC). The mortality rate from head and neck cancer in my country is much higher than in other countries. Approximately 70%-80% of patients present with locally advanced disease (stage III or IV) at initial diagnosis. Even after radical treatment in these advanced stages, approximately 55% of patients will experience recurrence or metastasis. Therefore, there is an urgent need to explore alternative treatment options for head and neck cancer patients and improve treatment outcomes.

[0009] Esophageal cancer is a common digestive system malignancy, with over 90% of cases being squamous cell carcinoma. Although standard treatments can improve clinical outcomes for patients, most patients still develop acquired drug resistance. Therefore, there is an urgent need to explore alternative treatment options for esophageal cancer patients and improve their efficacy.

[0010] SUMMARY OF THE INVENTION

[0011] In one aspect, the present disclosure provides a drug combination comprising an anti-TIM-3 antibody or antigen-binding fragment thereof and an anti-PD-1 antibody or antigen-binding fragment thereof; optionally, further comprising a chemotherapeutic agent. In some embodiments, the chemotherapeutic agent is a platinum-based anti-tumor agent and / or a taxane-based anti-tumor agent. In some embodiments, the chemotherapeutic agent is cisplatin and paclitaxel. In some embodiments, the chemotherapeutic agent is carboplatin and paclitaxel.

[0012] In some embodiments, the drug combination comprises a unit dose of 60-1800 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof and a unit dose of 10-500 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof. In some embodiments, the drug combination comprises a unit dose of 60-1800 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, a unit dose of 10-500 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof and a chemotherapy drug. In some embodiments, the drug combination comprises a unit dose of 60-1800 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, a unit dose of 10-500 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, a unit dose of 2.5-100 mg of cisplatin and a unit dose of 30-150 mg of paclitaxel. In some embodiments, the drug combination comprises an anti-TIM-3 antibody or an antigen-binding fragment thereof at a unit dose of 60-1800 mg, an anti-PD-1 antibody or an antigen-binding fragment thereof at a unit dose of 10-500 mg, carboplatin at a unit dose of 50-450 mg, and paclitaxel at a unit dose of 30-150 mg.

[0013] In some embodiments, the drug combination comprises 100-1800 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof and 10-800 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof. In some embodiments, the drug combination comprises 100-1800 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, 10-800 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, and a chemotherapeutic drug. In some embodiments, the drug combination comprises 100-1800 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, 10-800 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, and 30-100 mg / m 2 Cisplatin, and 75-175 mg / m 2 In some embodiments, the drug combination comprises 100-1800 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, 10-800 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, 2.5-5 mg / (mL / min) AUC of carboplatin, and 75-175 mg / m 2 of paclitaxel.

[0014] In some embodiments, the drug combination is suitable for administration within a single treatment cycle, comprising 100-1800 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof and 10-800 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof. In some embodiments, the drug combination is suitable for administration within a single treatment cycle, comprising 100-1800 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, 10-800 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof and a chemotherapy drug. In some embodiments, the drug combination is suitable for administration within a single treatment cycle, comprising 100-1800 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, 10-800 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, and a chemotherapy drug. 2 Cisplatin, and 75-175 mg / m 2 In some embodiments, the drug combination is suitable for administration in a single treatment cycle and comprises 100-1800 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, 10-800 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, 2.5-5 mg / (mL / min) AUC of carboplatin, and 75-175 mg / m 2 of paclitaxel.

[0015] In some embodiments, the drug combination is used to treat a tumor.

[0016] On the other hand, the present disclosure also provides a method for treating a tumor in a subject, comprising administering to the subject a therapeutically effective amount of a drug combination of the present disclosure. The present disclosure also provides a method for treating a tumor in a subject as a first-line treatment, comprising administering to the subject a therapeutically effective amount of a drug combination of the present disclosure. The present disclosure also provides a method for treating a tumor in a subject, comprising administering to the subject a therapeutically effective amount of a drug combination of the present disclosure in a first treatment phase, and administering to the subject a therapeutically effective amount of a drug combination of the present disclosure in a second treatment phase. In some specific embodiments, the present disclosure provides a method for treating a tumor in a subject as a first-line treatment, comprising administering to the subject a therapeutically effective amount of a drug combination of the present disclosure in a first treatment phase, and administering to the subject a therapeutically effective amount of a drug combination of the present disclosure in a second treatment phase.

[0017] On the other hand, the present disclosure also provides the use of the drug combination of the present disclosure in the preparation of a medicament for treating a tumor in a subject. The present disclosure also provides the use of the drug combination of the present disclosure in the preparation of a medicament for first-line treatment of a tumor in a subject. In addition, the present disclosure also provides the use of the drug combination of the present disclosure in treating a tumor in a subject. The present disclosure also provides the use of the drug combination of the present disclosure in first-line treatment of a tumor in a subject. In some embodiments, the use comprises administering a therapeutically effective amount of the drug combination of the present disclosure to the subject. In some embodiments, the use comprises administering a therapeutically effective amount of the drug combination of the present disclosure to the subject in a first treatment phase, and administering a therapeutically effective amount of the drug combination of the present disclosure to the subject in a second treatment phase.

[0018] On the other hand, the present disclosure also provides a method for treating tumors, comprising administering to a subject a therapeutically effective amount of an anti-TIM-3 antibody or antigen-binding fragment thereof and an anti-PD-1 antibody or antigen-binding fragment thereof. The present disclosure also provides a method for treating tumors, comprising administering to a subject a therapeutically effective amount of an anti-TIM-3 antibody or antigen-binding fragment thereof, an anti-PD-1 antibody or antigen-binding fragment thereof, and a chemotherapeutic drug. The present disclosure also provides a method for first-line treatment of tumors, comprising administering to a subject a therapeutically effective amount of an anti-TIM-3 antibody or antigen-binding fragment thereof and an anti-PD-1 antibody or antigen-binding fragment thereof. The present disclosure also provides a method for first-line treatment of tumors, comprising administering to a subject a therapeutically effective amount of an anti-TIM-3 antibody or antigen-binding fragment thereof, an anti-PD-1 antibody or antigen-binding fragment thereof, and a chemotherapeutic drug. In some specific embodiments, the present disclosure provides a method for first-line treatment of tumors in a subject, comprising administering to the subject a therapeutically effective amount of an anti-TIM-3 antibody or antigen-binding fragment thereof, an anti-PD-1 antibody or antigen-binding fragment thereof, and a chemotherapeutic agent in a first treatment phase, and administering to the subject a therapeutically effective amount of an anti-TIM-3 antibody or antigen-binding fragment thereof, an anti-PD-1 antibody or antigen-binding fragment thereof, and a chemotherapeutic agent in a second treatment phase. In addition, the present disclosure also provides the use of the anti-TIM-3 antibody or antigen-binding fragment thereof, and an anti-PD-1 antibody or antigen-binding fragment thereof in the preparation of a medicament for treating tumors. The present disclosure also provides the use of the anti-TIM-3 antibody or antigen-binding fragment thereof, an anti-PD-1 antibody or antigen-binding fragment thereof, and a chemotherapeutic agent in the preparation of a medicament for treating tumors. The present disclosure also provides the use of the anti-TIM-3 antibody or antigen-binding fragment thereof, an anti-PD-1 antibody or antigen-binding fragment thereof, and a chemotherapeutic agent in the preparation of a medicament for treating tumors. The present disclosure also provides the use of the anti-TIM-3 antibody or antigen-binding fragment thereof, an anti-PD-1 antibody or antigen-binding fragment thereof, and a chemotherapeutic agent in the preparation of a medicament for treating tumors. In some embodiments, the chemotherapy drug is a platinum anti-tumor drug and / or a taxane anti-tumor drug. In some embodiments, the chemotherapy drug is cisplatin and paclitaxel. In some embodiments, the chemotherapy drug is carboplatin and paclitaxel.

[0019] On the other hand, the present disclosure also provides the use of the anti-TIM-3 antibody or its antigen-binding fragment in the preparation of a medicament for treating a tumor in a subject, wherein the medicament is used in combination with the anti-PD-1 antibody or its antigen-binding fragment. The present disclosure also provides the use of the anti-TIM-3 antibody or its antigen-binding fragment in the preparation of a medicament for treating a tumor in a subject, wherein the medicament is used in combination with the anti-PD-1 antibody or its antigen-binding fragment and a chemotherapeutic agent. The present disclosure also provides the use of the anti-TIM-3 antibody or its antigen-binding fragment in the preparation of a medicament for first-line treatment of a tumor in a subject, wherein the medicament is used in combination with the anti-PD-1 antibody or its antigen-binding fragment. The present disclosure also provides the use of the anti-TIM-3 antibody or its antigen-binding fragment in the preparation of a medicament for first-line treatment of a tumor in a subject, wherein the medicament is used in combination with the anti-PD-1 antibody or its antigen-binding fragment and a chemotherapeutic agent. In some embodiments, the chemotherapeutic agent is a platinum-based anti-tumor drug and / or a taxane-based anti-tumor drug. In some embodiments, the chemotherapeutic agent is cisplatin and paclitaxel. In some embodiments, the chemotherapy drugs are carboplatin and paclitaxel.

[0020] On the other hand, the present disclosure also provides the use of the anti-PD-1 antibody or its antigen-binding fragment of the present disclosure in the preparation of a medicament for treating a tumor in a subject, wherein the medicament is used in combination with the anti-TIM-3 antibody or its antigen-binding fragment of the present disclosure. The present disclosure also provides the use of the anti-PD-1 antibody or its antigen-binding fragment of the present disclosure in the preparation of a medicament for treating a tumor in a subject, wherein the medicament is used in combination with the anti-TIM-3 antibody or its antigen-binding fragment of the present disclosure and a chemotherapeutic agent. The present disclosure also provides the use of the anti-PD-1 antibody or its antigen-binding fragment of the present disclosure in the preparation of a medicament for first-line treatment of a tumor in a subject, wherein the medicament is used in combination with the anti-TIM-3 antibody or its antigen-binding fragment of the present disclosure. The present disclosure also provides the use of the anti-PD-1 antibody or its antigen-binding fragment of the present disclosure in the preparation of a medicament for first-line treatment of a tumor in a subject, wherein the medicament is used in combination with the anti-TIM-3 antibody or its antigen-binding fragment of the present disclosure and a chemotherapeutic agent. In some embodiments, the chemotherapeutic agent is a platinum-based anti-tumor drug and / or a taxane-based anti-tumor drug. In some embodiments, the chemotherapeutic agent is cisplatin and paclitaxel. In some embodiments, the chemotherapy drugs are carboplatin and paclitaxel.

[0021] On the other hand, the present disclosure also provides a method for treating a tumor in a subject, comprising administering to the subject a therapeutically effective amount of a combination drug combination of the present disclosure. In some specific embodiments, the present disclosure provides a method for first-line treatment of a tumor in a subject, comprising administering to the subject a therapeutically effective amount of a combination drug combination of the present disclosure. In addition, the present disclosure also provides the use of the combination drug combination of the present disclosure in the preparation of a medicament for treating a tumor in a subject. The present disclosure also provides the use of the combination drug combination of the present disclosure in the preparation of a medicament for first-line treatment of a tumor in a subject. In addition, the present disclosure also provides the use of the combination drug combination of the present disclosure in the treatment of a tumor in a subject. The present disclosure also provides the use of the combination drug combination of the present disclosure in the first-line treatment of a tumor in a subject.

[0022] In some embodiments, the anti-TIM-3 antibody or antigen-binding fragment thereof and the anti-PD-1 antibody or antigen-binding fragment thereof can be administered simultaneously, sequentially and / or alternately.

[0023] In some embodiments, the anti-TIM-3 antibody or antigen-binding fragment thereof, the anti-PD-1 antibody or antigen-binding fragment thereof, and the chemotherapeutic agent can be administered simultaneously, sequentially, and / or alternately. In some embodiments, the chemotherapeutic agent is a platinum-based antitumor agent and / or a taxane-based antitumor agent. In some embodiments, the chemotherapeutic agent is cisplatin and paclitaxel. In some embodiments, the chemotherapeutic agent is carboplatin and paclitaxel.

[0024] In some embodiments, the anti-TIM-3 antibody or antigen-binding fragment thereof is administered once every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks. In some embodiments, the anti-TIM-3 antibody or antigen-binding fragment thereof is administered at a dose of 100-1800 mg, 600-1800 mg, 600-1500 mg, or 1200-1500 mg each time.

[0025] In some embodiments, the anti-PD-1 antibody or antigen-binding fragment thereof is administered once every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks. In some embodiments, the anti-PD-1 antibody or antigen-binding fragment thereof is administered at a dose of 10-800 mg, 50-500 mg, or 100-200 mg each time.

[0026] In some embodiments, the cisplatin is administered once every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks. In some embodiments, the cisplatin is administered at a dose of 30-100 mg / m 2 30-75 mg / m 2 48-75 mg / m 2 or 60–75 mg / m 2 Dosage administration.

[0027] In some embodiments, the carboplatin is administered once every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks. In some embodiments, the carboplatin is administered at a dose of 2.5-5 mg / (mL / min) AUC or 3.2-5 mg / (mL / min) AUC each time.

[0028] In some embodiments, the paclitaxel is administered once every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks. In some embodiments, the paclitaxel is administered at a dose of 75-175 mg / m 2 100-175 mg / m 2 112-175 mg / m 2 or 135–175 mg / m 2 Dosage administration.

[0029] In another aspect, the present disclosure provides a kit for treating tumors, comprising the drug combination of the present disclosure. In some embodiments, the kit comprises an anti-TIM-3 antibody or antigen-binding fragment thereof and an anti-PD-1 antibody or antigen-binding fragment thereof; optionally, a chemotherapeutic agent. In some embodiments, the chemotherapeutic agent is a platinum-based anti-tumor agent and / or a taxane-based anti-tumor agent. In some embodiments, the chemotherapeutic agent is cisplatin and paclitaxel. In some embodiments, the chemotherapeutic agent is carboplatin and paclitaxel.

[0030] In addition, the present disclosure provides a method for treating a tumor in a subject, comprising administering to the subject a therapeutically effective amount of an anti-TIM-3 antibody or antigen-binding fragment thereof of the present disclosure. The present disclosure also provides a method for first-line treatment of a tumor in a subject, comprising administering to the subject a therapeutically effective amount of an anti-TIM-3 antibody or antigen-binding fragment thereof of the present disclosure. The present disclosure also provides the use of an anti-TIM-3 antibody or antigen-binding fragment thereof in the preparation of a medicament for treating a tumor in a subject. The present disclosure also provides the use of an anti-TIM-3 antibody or antigen-binding fragment thereof in treating a tumor.

[0031] In addition, the present disclosure also provides a method for treating a tumor in a subject, comprising administering to the subject a therapeutically effective amount of an anti-PD-1 antibody or its antigen-binding fragment of the present disclosure and a chemotherapy drug. The present disclosure also provides a method for first-line treatment of a tumor in a subject, comprising administering to the subject a therapeutically effective amount of an anti-PD-1 antibody or its antigen-binding fragment of the present disclosure and a chemotherapy drug. The present disclosure also provides the use of an anti-PD-1 antibody or its antigen-binding fragment and a chemotherapy drug in the preparation of a medicament for treating a tumor in a subject. The present disclosure also provides the use of an anti-PD-1 antibody or its antigen-binding fragment and a chemotherapy drug in the treatment of a tumor. In some embodiments, the chemotherapy drug is a platinum anti-tumor drug and / or a taxane anti-tumor drug. In some embodiments, the chemotherapy drug is cisplatin and paclitaxel. In some embodiments, the chemotherapy drug is carboplatin and paclitaxel.

[0032] In some embodiments, the tumor is a solid tumor. In some embodiments, the tumor is head and neck cancer. In some embodiments, the tumor is esophageal cancer.

[0033] Detailed Description of the Invention

[0034] Drug combinations

[0035] In one aspect, the present disclosure provides a drug combination comprising an anti-TIM-3 antibody or an antigen-binding fragment thereof and an anti-PD-1 antibody or an antigen-binding fragment thereof; optionally, further comprising a chemotherapeutic drug.

[0036] In some embodiments, the chemotherapy drugs include, but are not limited to, one or more of platinum-based antitumor drugs, taxane-based antitumor drugs, antimetabolite-based antitumor drugs, camptothecin-based antitumor drugs, nitrogen mustard-based antitumor drugs, anthracycline-based antitumor drugs, vinca alkaloid-based antitumor drugs, podophylloalkaloid-based antitumor drugs, and hormonal antitumor drugs. In some embodiments, the chemotherapy drugs are platinum-based antitumor drugs and / or taxane-based antitumor drugs. In some embodiments, the chemotherapy drugs are platinum-based antitumor drugs and taxane-based antitumor drugs. In some specific embodiments, the chemotherapy drugs are cisplatin and paclitaxel. In other specific embodiments, the chemotherapy drugs are carboplatin and paclitaxel.

[0037] In some embodiments, the drug combination comprises an anti-TIM-3 antibody or an antigen-binding fragment thereof and an anti-PD-1 antibody or an antigen-binding fragment thereof. In some embodiments, the drug combination comprises an anti-TIM-3 antibody or an antigen-binding fragment thereof, an anti-PD-1 antibody or an antigen-binding fragment thereof, and a chemotherapy drug. In some embodiments, the drug combination comprises an anti-TIM-3 antibody or an antigen-binding fragment thereof, an anti-PD-1 antibody or an antigen-binding fragment thereof, a platinum-based anti-tumor drug, and a taxane-based anti-tumor drug. In some embodiments, the drug combination comprises an anti-TIM-3 antibody or an antigen-binding fragment thereof, an anti-PD-1 antibody or an antigen-binding fragment thereof, cisplatin, and paclitaxel. In other embodiments, the drug combination comprises an anti-TIM-3 antibody or an antigen-binding fragment thereof, an anti-PD-1 antibody or an antigen-binding fragment thereof, carboplatin, and paclitaxel.

[0038] In addition, the present disclosure also provides a combined drug combination comprising:

[0039] (a) a pharmaceutical combination of the present disclosure, prepared so as to be suitable for administration to a subject during a first treatment phase; and

[0040] (b) A pharmaceutical combination of the present disclosure, formulated to be suitable for administration to a subject during the second treatment phase.

[0041] In some embodiments, the combination drug comprises:

[0042] (a) a pharmaceutical combination comprising an anti-TIM-3 antibody or an antigen-binding fragment thereof, an anti-PD-1 antibody or an antigen-binding fragment thereof, and a chemotherapeutic drug, which is prepared to be suitable for administration to a subject in a first treatment phase; and

[0043] (b) a pharmaceutical combination comprising an anti-TIM-3 antibody or an antigen-binding fragment thereof and an anti-PD-1 antibody or an antigen-binding fragment thereof, which is prepared and suitable for administration to the subject in the second treatment phase.

[0044] In some embodiments, the combination drug comprises:

[0045] (a) a drug combination comprising an anti-TIM-3 antibody or an antigen-binding fragment thereof, an anti-PD-1 antibody or an antigen-binding fragment thereof, a platinum anti-tumor drug, and a taxane anti-tumor drug, which is prepared to be suitable for administration to a subject in a first treatment phase; and

[0046] (b) a pharmaceutical combination comprising an anti-TIM-3 antibody or an antigen-binding fragment thereof and an anti-PD-1 antibody or an antigen-binding fragment thereof, which is prepared and suitable for administration to the subject in the second treatment phase.

[0047] In some embodiments, the combination drug comprises:

[0048] (a) a pharmaceutical combination comprising an anti-TIM-3 antibody or an antigen-binding fragment thereof, an anti-PD-1 antibody or an antigen-binding fragment thereof, cisplatin, and paclitaxel, which is prepared to be suitable for administration to a subject in a first treatment phase; and

[0049] (b) a pharmaceutical combination comprising an anti-TIM-3 antibody or an antigen-binding fragment thereof and an anti-PD-1 antibody or an antigen-binding fragment thereof, which is prepared and suitable for administration to the subject in the second treatment phase.

[0050] In some embodiments, the combination drug comprises:

[0051] (a) a pharmaceutical combination comprising an anti-TIM-3 antibody or an antigen-binding fragment thereof, an anti-PD-1 antibody or an antigen-binding fragment thereof, carboplatin, and paclitaxel, which is prepared to be suitable for administration to a subject in a first treatment phase; and

[0052] (b) a pharmaceutical combination comprising an anti-TIM-3 antibody or an antigen-binding fragment thereof and an anti-PD-1 antibody or an antigen-binding fragment thereof, which is prepared and suitable for administration to the subject in the second treatment phase.

[0053] In some embodiments, the first treatment phase comprises 1-14 treatment cycles, preferably 2-12 treatment cycles, 2-10 treatment cycles, more preferably 2-8 treatment cycles, for example, 2-8 treatment cycles, 3-8 treatment cycles, 4-8 treatment cycles, 2-7 treatment cycles, 3-7 treatment cycles, 4-7 treatment cycles, 2-6 treatment cycles, 3-6 treatment cycles, or 4-6 treatment cycles; most preferably 4-6 treatment cycles, for example, 4 treatment cycles, 5 treatment cycles, and / or 6 treatment cycles. In some embodiments, the first treatment phase comprises 4 treatment cycles. In some embodiments, the first treatment phase comprises 6 treatment cycles.

[0054] In some embodiments, one treatment cycle is every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks. In some embodiments, one treatment cycle is every 3 weeks.

[0055] In some embodiments, the second treatment period is after the first treatment period. In some embodiments, the second treatment period continues from the end of the first treatment period until the patient loses clinical benefit, has unacceptable toxicity, is evaluated as disease progression (PD), and / or the investigator deems it inappropriate to continue the medication.

[0056] In some embodiments, the drug combination is packaged in the same kit, which further includes instructions for using the anti-TIM-3 antibody or its antigen-binding fragment and the anti-PD-1 antibody or its antigen-binding fragment in combination to treat tumors. In other embodiments, the anti-TIM-3 antibody or its antigen-binding fragment and the anti-PD-1 antibody or its antigen-binding fragment in the drug combination are separately packaged in separate kits, which further include instructions for using the anti-TIM-3 antibody or its antigen-binding fragment and the anti-PD-1 antibody or its antigen-binding fragment in combination to treat tumors.

[0057] In some embodiments, the drug combination is packaged in the same kit, which further includes instructions for using the anti-TIM-3 antibody or its antigen-binding fragment, the anti-PD-1 antibody or its antigen-binding fragment, and the chemotherapy drug (e.g., cisplatin and paclitaxel, or carboplatin and paclitaxel) in combination to treat tumors. In other embodiments, the anti-TIM-3 antibody or its antigen-binding fragment, the anti-PD-1 antibody or its antigen-binding fragment, and the chemotherapy drug (e.g., cisplatin and paclitaxel, or carboplatin and paclitaxel) in the drug combination are separately packaged in separate medicine boxes, which further include instructions for using the anti-TIM-3 antibody or its antigen-binding fragment, the anti-PD-1 antibody or its antigen-binding fragment, and the chemotherapy drug (e.g., cisplatin and paclitaxel, or carboplatin and paclitaxel) in combination to treat tumors.

[0058] In some embodiments, the pharmaceutical combination is a fixed combination. In some embodiments, the anti-TIM-3 antibody or antigen-binding fragment thereof and the anti-PD-1 antibody or antigen-binding fragment thereof in the fixed combination are formulated in a single formulation. In some embodiments, in the fixed combination, the pharmaceutical composition containing the anti-TIM-3 antibody or antigen-binding fragment thereof and the anti-PD-1 antibody or antigen-binding fragment thereof is in the form of a liquid preparation or a solid preparation. In some specific embodiments, in the fixed combination, the pharmaceutical composition containing the anti-TIM-3 antibody or antigen-binding fragment thereof and the anti-PD-1 antibody or antigen-binding fragment thereof is an injectable solution. In some specific embodiments, in the fixed combination, the pharmaceutical composition containing the anti-TIM-3 antibody or antigen-binding fragment thereof and the anti-PD-1 antibody or antigen-binding fragment thereof is a lyophilized preparation.

[0059] In some embodiments, the drug combination is a non-fixed combination. In some embodiments, the anti-TIM-3 antibody or antigen-binding fragment thereof and the anti-PD-1 antibody or antigen-binding fragment thereof in the non-fixed combination are each in the form of a pharmaceutical composition. In some embodiments, the anti-TIM-3 antibody or antigen-binding fragment thereof, the anti-PD-1 antibody or antigen-binding fragment thereof, and the chemotherapy drug (e.g., cisplatin and paclitaxel, or carboplatin and paclitaxel) in the non-fixed combination are each in the form of a pharmaceutical composition.

[0060] In some embodiments, the pharmaceutical composition containing the anti-TIM-3 antibody or antigen-binding fragment thereof in the non-fixed combination is a liquid or solid formulation. In some specific embodiments, the pharmaceutical composition containing the anti-TIM-3 antibody or antigen-binding fragment thereof is an injectable solution. In some specific embodiments, the pharmaceutical composition containing the anti-TIM-3 antibody or antigen-binding fragment thereof is a lyophilized formulation.

[0061] In some embodiments, the pharmaceutical composition containing the anti-PD-1 antibody or antigen-binding fragment thereof in the non-fixed combination is a liquid or solid formulation. In some specific embodiments, the pharmaceutical composition containing the anti-PD-1 antibody or antigen-binding fragment thereof is an injectable solution. In some specific embodiments, the pharmaceutical composition containing the anti-PD-1 antibody or antigen-binding fragment thereof is a lyophilized formulation.

[0062] In some embodiments, in the non-fixed combination, the anti-TIM-3 antibody or antigen-binding fragment thereof and the anti-PD-1 antibody or antigen-binding fragment thereof are formulated in a single formulation. In some embodiments, in the non-fixed combination, the pharmaceutical composition comprising the anti-TIM-3 antibody or antigen-binding fragment thereof and the anti-PD-1 antibody or antigen-binding fragment thereof is a liquid formulation or a solid formulation. In some specific embodiments, the pharmaceutical composition comprising the anti-TIM-3 antibody or antigen-binding fragment thereof and the anti-PD-1 antibody or antigen-binding fragment thereof is an injectable solution. In some specific embodiments, the pharmaceutical composition comprising the anti-TIM-3 antibody or antigen-binding fragment thereof and the anti-PD-1 antibody or antigen-binding fragment thereof is a lyophilized formulation.

[0063] In some embodiments, in the non-fixed combination, the pharmaceutical composition containing the chemotherapeutic drug is a liquid or solid formulation. In some embodiments, the pharmaceutical composition containing cisplatin is a liquid formulation. In some specific embodiments, the pharmaceutical composition containing cisplatin is an injectable solution. In some embodiments, the pharmaceutical composition containing cisplatin is a solid formulation. In some specific embodiments, the pharmaceutical composition containing cisplatin is a lyophilized formulation. In some specific embodiments, the pharmaceutical composition containing cisplatin is a powder for injection. In some embodiments, the pharmaceutical composition containing carboplatin is a liquid formulation. In some specific embodiments, the pharmaceutical composition containing carboplatin is an injectable solution. In some embodiments, the pharmaceutical composition containing carboplatin is a solid formulation. In some specific embodiments, the pharmaceutical composition containing carboplatin is a lyophilized formulation. In some specific embodiments, the pharmaceutical composition containing carboplatin is a powder for injection. In some embodiments, the pharmaceutical composition containing paclitaxel is a liquid formulation. In some specific embodiments, the pharmaceutical composition containing paclitaxel is an injectable solution. In some embodiments, the pharmaceutical composition containing paclitaxel is a solid formulation. In some specific embodiments, the pharmaceutical composition containing paclitaxel is a lyophilized formulation. In some specific embodiments, the pharmaceutical composition containing paclitaxel is a powder injection preparation.

[0064] The present disclosure also aims to provide a drug package comprising single-packaged pharmaceutical compositions in separate containers, wherein the first container comprises a pharmaceutical composition containing an anti-TIM-3 antibody or an antigen-binding fragment thereof, and the second container comprises a pharmaceutical composition containing an anti-PD-1 antibody or an antigen-binding fragment thereof; optionally, the package further comprises one or more other containers, each of which comprises a pharmaceutical composition containing a chemotherapy drug (e.g., cisplatin and paclitaxel, or carboplatin and paclitaxel).

[0065] The present disclosure also aims to provide a drug pack comprising single-packaged pharmaceutical compositions in separate containers, wherein the first container comprises a pharmaceutical composition comprising an anti-TIM-3 antibody or an antigen-binding fragment thereof and an anti-PD-1 antibody or an antigen-binding fragment thereof; optionally, further comprising one or more other containers, each of which comprises a pharmaceutical composition comprising a chemotherapy drug (e.g., cisplatin and paclitaxel, or carboplatin and paclitaxel).

[0066] In some embodiments, the unit dose of the anti-TIM-3 antibody or antigen-binding fragment thereof in the pharmaceutical combination is 60-1800 mg, 100-1600 mg, 120-1600 mg, 180-1200 mg, or 240-600 mg. In some embodiments, the unit dose of the anti-TIM-3 antibody or antigen-binding fragment thereof in the pharmaceutical combination is about 60 mg, about 120 mg, about 160 mg, about 180 mg, about 200 mg, about 240 mg, about 280 mg, about 300 mg, about 320 mg, about 360 mg, about 400 mg, about 420 mg, about 440 mg, about 480 mg, about 520 mg, about 540 mg, about 560 mg, about 600 mg, about 640 mg, about 660 mg, about 680 mg, about 720 mg, about 760 mg, about 780 mg, about 800 mg, about 840 mg, about 880 mg, about 900 mg, about 920 mg, about 9 1600 mg, about 1620 mg, about 1640 mg, about 1680 mg, about 1720 mg, about 1740 mg, about 1760 mg and / or about 1800 mg, or a range formed by any of the foregoing values. In some embodiments, the unit dose of the anti-TIM-3 antibody or its antigen-binding fragment in the pharmaceutical combination is about 240 mg, about 300 mg, about 360 mg and / or about 600 mg. In some embodiments, the unit dose of the anti-TIM-3 antibody or its antigen-binding fragment in the pharmaceutical combination is about 240 mg and / or about 600 mg.

[0067] In some embodiments, the unit dose of the anti-PD-1 antibody or its antigen-binding fragment in the pharmaceutical combination is 10-500 mg, 50-500 mg, 50-200 mg, or 100-200 mg. In some embodiments, the unit dose of the anti-PD-1 antibody or its antigen-binding fragment in the pharmaceutical combination is about 10 mg, about 20 mg, about 30 mg, about 40 mg, about 50 mg, about 60 mg, about 70 mg, about 80 mg, about 90 mg, about 100 mg, about 110 mg, about 120 mg, about 130 mg, about 140 mg, about 150 mg, about 160 mg, about 170 mg, about 180 mg, about 190 mg, about 200 mg, about 210 mg, about 220 mg, about 230 mg, about 240 mg, about 250 mg, about 260 mg, about 270 mg, about 280 mg, about 290 mg, about 300 mg, about 310 mg, about 320 mg, about 330 mg, about 340 mg, about 350 mg, about 360 mg, about 370 mg, about 380 mg, about 390 mg, about 400 mg, about 410 mg, about 420 mg, about 430 mg, about 440 mg, about 450 mg, about 460 mg, about 470 mg, about 480 mg, about 490 mg, about 500 mg, about 510 mg, about 520 mg, about 530 mg, about 540 mg, about 550 mg, about 560 mg, about 570 mg, about 580 mg, about 590 mg, about 600 mg, about In some embodiments, the unit dose of the anti-PD-1 antibody or antigen-binding fragment thereof in the pharmaceutical combination is about 100 mg and / or about 200 mg. In some embodiments, the unit dose of the anti-PD-1 antibody or antigen-binding fragment thereof in the pharmaceutical combination is about 100 mg.

[0068] In some embodiments, the drug combination further comprises a chemotherapy drug. In some embodiments, the chemotherapy drug is cisplatin and paclitaxel. In other embodiments, the chemotherapy drug is carboplatin and paclitaxel. In some embodiments, the unit dose of cisplatin in the drug combination is 1-200 mg or 2.5-100 mg. In some embodiments, the unit dose of cisplatin in the drug combination is 2.5 mg, 5 mg, 10 mg, 20 mg, 25 mg, 30 mg, 50 mg and / or 100 mg. In some embodiments, the unit dose of cisplatin in the drug combination is 10 mg, 20 mg, 30 mg, 50 mg and / or 100 mg. In some embodiments, the unit dose of carboplatin in the drug combination is 10-500 mg or 50-450 mg. In some embodiments, the unit dose of carboplatin in the drug combination is 50 mg, 100 mg, 150 mg, 250 mg and / or 450 mg. In some embodiments, the unit dose of paclitaxel in the pharmaceutical combination is 10-300 mg or 30-150 mg. In some embodiments, the unit dose of paclitaxel in the pharmaceutical combination is 30 mg, 60 mg, 100 mg and / or 150 mg.

[0069] In some embodiments, the drug combination comprises an anti-TIM-3 antibody or an antigen-binding fragment thereof at a unit dose of 60-1800 mg, 100-1600 mg, 120-1600 mg, 180-1200 mg, or 240-600 mg, and an anti-PD-1 antibody or an antigen-binding fragment thereof at a unit dose of 10-500 mg, 50-500 mg, 50-200 mg, or 100-200 mg.In some embodiments, the pharmaceutical combination comprises a unit dose of about 60 mg, about 120 mg, about 160 mg, about 180 mg, about 200 mg, about 240 mg, about 280 mg, about 300 mg, about 320 mg, about 360 mg, about 400 mg, about 420 mg, about 440 mg, about 480 mg, about 520 mg, about 540 mg, about 560 mg, about 600 mg, about 640 mg, about 660 mg, about 680 mg, about 720 mg, about 760 mg, about 780 mg, about 800 mg, about 840 mg, about 880 mg, about 900 mg. g, about 920 mg, about 960 mg, about 1000 mg, about 1020 mg, about 1040 mg, about 1080 mg, about 1120 mg, about 1140 mg, about 1160 mg, about 1200 mg, about 1240 mg, about 1260 mg, about 1280 mg, about 1320 mg, about 1360 mg, about 1380 mg, about 1400 mg, about 1440 mg, about 1480 mg, about 1500 mg, about 1520 mg, about 1560 mg, about 1600 mg, about 1620 mg, about 1640 mg, about 1680 mg, about 1720 mg, about 1740 mg, about 1760 mg and / or about 1800 mg, or a range formed by any of the foregoing values, of an anti-TIM-3 antibody or antigen-binding fragment thereof, and a unit dose of about 10 mg, about 20 mg, about 30 mg, about 40 mg, about 50 mg, about 60 mg, about 70 mg, about 80 mg, about 90 mg, about 100 mg, about 110 mg, about 120 mg, about 130 mg, about 140 mg, about 150 mg, about 160 mg, about 170 mg, about 180 mg, about 190 mg, about 200 mg, about 210 mg, about 220 mg, about 230 mg, about 240 mg, about 250 mg, about 260 mg, about 270 mg, about 280 mg, about 290 mg, about 300 mg, about 310 mg, about 320 mg, about 330 mg, about 340 mg, about 350 mg, about 360 mg, about 370 mg, about 380 mg, about 390 mg, about 400 mg, about 410 mg, about 420 mg, about 430 mg, about 440 mg, about 450 mg, about 460 mg, about 470 mg, about 480 mg, about 490 mg, about 500 mg, about 510 mg, about 520 mg, about 530 mg, about 540 mg, about 550 mg, about 560 mg, about 570 mg, about 580 mg, about 590 mg, about 600 mg, about 610 mg, about 620 mg, about 630 mg, about 640 mg, about 650 mg 470 mg, about 480 mg, about 490 mg and / or about 500 mg, or a range formed by any of the foregoing values. In some embodiments, the drug combination comprises an anti-TIM-3 antibody or an antigen-binding fragment thereof at a unit dose of about 240 mg, about 300 mg, about 360 mg and / or about 600 mg, and an anti-PD-1 antibody or an antigen-binding fragment thereof at a unit dose of about 100 mg and / or about 200 mg.In some embodiments, the pharmaceutical combination comprises an anti-TIM-3 antibody or an antigen-binding fragment thereof at a unit dose of about 240 mg and / or about 600 mg, and an anti-PD-1 antibody or an antigen-binding fragment thereof at a unit dose of about 100 mg.

[0070] In some embodiments, the pharmaceutical combination further comprises cisplatin in a unit dose of 1-200 mg or 2.5-100 mg, and paclitaxel in a unit dose of 10-300 mg or 30-150 mg. In some embodiments, the pharmaceutical combination further comprises cisplatin in a unit dose of 2.5 mg, 5 mg, 10 mg, 20 mg, 25 mg, 30 mg, 50 mg and / or 100 mg, and paclitaxel in a unit dose of 30 mg, 60 mg, 100 mg and / or 150 mg. In some embodiments, the pharmaceutical combination further comprises cisplatin in a unit dose of 10 mg, 20 mg, 30 mg, 50 mg and / or 100 mg, and paclitaxel in a unit dose of 30 mg, 60 mg, 100 mg and / or 150 mg.

[0071] In other embodiments, the pharmaceutical combination further comprises carboplatin in a unit dose of 10-500 mg or 50-450 mg, and paclitaxel in a unit dose of 10-300 mg or 30-150 mg. In other embodiments, the pharmaceutical combination further comprises carboplatin in a unit dose of 50 mg, 100 mg, 150 mg, 250 mg and / or 450 mg, and paclitaxel in a unit dose of 30 mg, 60 mg, 100 mg and / or 150 mg.

[0072] In some specific embodiments, the drug combination comprises an anti-TIM-3 antibody or an antigen-binding fragment thereof at a unit dose of about 240 mg, about 300 mg, about 360 mg and / or about 600 mg, an anti-PD-1 antibody or an antigen-binding fragment thereof at a unit dose of about 100 mg and / or about 200 mg, cisplatin at a unit dose of 10 mg, 20 mg, 30 mg, 50 mg and / or 100 mg, and paclitaxel at a unit dose of 30 mg, 60 mg, 100 mg and / or 150 mg. In some specific embodiments, the drug combination comprises an anti-TIM-3 antibody or an antigen-binding fragment thereof at a unit dose of about 240 mg and / or about 600 mg, an anti-PD-1 antibody or an antigen-binding fragment thereof at a unit dose of about 100 mg, cisplatin at a unit dose of 10 mg, 20 mg, 30 mg, 50 mg and / or 100 mg, and paclitaxel at a unit dose of 30 mg, 60 mg, 100 mg and / or 150 mg.

[0073] In other specific embodiments, the drug combination comprises an anti-TIM-3 antibody or an antigen-binding fragment thereof at a unit dose of about 240 mg, about 300 mg, about 360 mg and / or about 600 mg, an anti-PD-1 antibody or an antigen-binding fragment thereof at a unit dose of about 100 mg and / or about 200 mg, a carboplatin at a unit dose of 50 mg, 100 mg, 150 mg, 250 mg and / or 450 mg, and paclitaxel at a unit dose of 30 mg, 60 mg, 100 mg and / or 150 mg. In other specific embodiments, the drug combination comprises an anti-TIM-3 antibody or an antigen-binding fragment thereof at a unit dose of about 240 mg and / or about 600 mg, an anti-PD-1 antibody or an antigen-binding fragment thereof at a unit dose of about 100 mg, carboplatin at a unit dose of 50 mg, 100 mg, 150 mg, 250 mg and / or 450 mg, and paclitaxel at a unit dose of 30 mg, 60 mg, 100 mg and / or 150 mg.

[0074] In some embodiments, the pharmaceutical composition comprises 100-1800 mg, 600-1800 mg, 600-1500 mg, or 1200-1500 mg of an anti-TIM-3 antibody or antigen-binding fragment thereof. In some embodiments, the pharmaceutical composition comprises about 100 mg, about 200 mg, about 300 mg, about 400 mg, about 500 mg, about 600 mg, about 700 mg, about 800 mg, about 900 mg, about 1000 mg, about 1100 mg, about 1200 mg, about 1300 mg, about 1400 mg, about 1500 mg, about 1600 mg, about 1700 mg, or about 1800 mg of an anti-TIM-3 antibody or antigen-binding fragment thereof, or a range formed by any of the foregoing values. In some embodiments, the pharmaceutical composition comprises about 1200 mg or about 1500 mg of an anti-TIM-3 antibody or antigen-binding fragment thereof. In some embodiments, the pharmaceutical combination comprises about 1200 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof.

[0075] In some embodiments, the pharmaceutical composition comprises 10-800 mg, 50-500 mg, or 100-200 mg of an anti-PD-1 antibody or antigen-binding fragment thereof. In some embodiments, the pharmaceutical composition comprises about 10 mg, about 50 mg, about 100 mg, about 120 mg, about 140 mg, about 160 mg, about 180 mg, about 200 mg, about 220 mg, about 240 mg, about 260 mg, about 280 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, or about 800 mg, or a range formed by any of the above values ​​of an anti-PD-1 antibody or antigen-binding fragment thereof. In some embodiments, the pharmaceutical composition comprises about 200 mg of an anti-PD-1 antibody or antigen-binding fragment thereof.

[0076] In some embodiments, the drug combination further comprises a chemotherapy drug. In some embodiments, the chemotherapy drug is cisplatin and paclitaxel. In other embodiments, the chemotherapy drug is carboplatin and paclitaxel. In some embodiments, the drug combination further comprises 30-100 mg / m 2 30-75 mg / m 2 48-75 mg / m 2 or 60–75 mg / m 2 In some embodiments, the drug combination further comprises about 30 mg / min of cisplatin, or 2.5-5 mg / (mL / min) AUC or 3.2-5 mg / (mL / min) AUC of carboplatin. 2 , about 32mg / m 2 , about 35mg / m 2 , about 37mg / m 2 , about 40mg / m 2 , about 45mg / m 2 , about 48mg / m 2 , about 50mg / m 2 , about 52mg / m 2 , about 54mg / m 2 , about 56mg / m 2 , about 60mg / m 2 , about 65mg / m 2 , about 70mg / m 2 , about 75mg / m 2 , about 80mg / m 2 , about 90mg / m 2 or about 100 mg / m 2, or any range formed by the foregoing values, or about 2.5 mg / (mL / min) AUC, about 3 mg / (mL / min) AUC, about 3.2 mg / (mL / min) AUC, about 3.5 mg / (mL / min) AUC, about 3.75 mg / (mL / min) AUC, about 4 mg / (mL / min) AUC, about 4.5 mg / (mL / min) AUC, or about 5 mg / (mL / min) AUC, or any range formed by the foregoing values, of cisplatin; or about 2.5 mg / (mL / min) AUC, about 3 mg / (mL / min) AUC, about 3.2 mg / (mL / min) AUC, about 3.5 mg / (mL / min) AUC, about 3.75 mg / (mL / min) AUC, about 4 mg / (mL / min) AUC, about 4.5 mg / (mL / min) AUC, or about 5 mg / (mL / min) AUC, or any range formed by the foregoing values, of carboplatin. In some embodiments, the drug combination further comprises 48-75 mg / m 2 In some embodiments, the drug combination further comprises about 48 mg / min of cisplatin or 3.2-5 mg / (mL / min) AUC of carboplatin. 2 , about 60mg / m 2 or about 75 mg / m 2 In some embodiments, the drug combination further comprises about 75 mg / min of cisplatin, or about 3.2 mg / (mL / min) AUC, about 4 mg / (mL / min) AUC, or about 5 mg / (mL / min) AUC of carboplatin. 2 In some embodiments, the drug combination further comprises 30-75 mg / m 2 In some embodiments, the drug combination further comprises 60-75 mg / m 2 In some embodiments, the drug combination further comprises about 60 mg / m 2 In some embodiments, the drug combination further comprises about 75 mg / m 2 In some embodiments, the drug combination further comprises 75-175 mg / m 2 100-175 mg / m 2 112-175 mg / m 2 or 135–175 mg / m 2 In some embodiments, the drug combination further comprises about 75 mg / m 2 , about 90mg / m 2 , about 100mg / m 2 , about 105mg / m 2 , about 109mg / m 2 , about 112mg / m 2 , about 135mg / m 2 , about 140mg / m 2 , about 145mg / m 2 , about 150mg / m 2 or about 175 mg / m2 , or paclitaxel in the range of any of the above values. In some embodiments, the drug combination further comprises 112-175 mg / m 2 In some embodiments, the drug combination further comprises about 112 mg / m 2 , about 135mg / m 2 , about 140mg / m 2 , about 150mg / m 2 or about 175 mg / m 2 In some embodiments, the drug combination further comprises about 175 mg / m 2 In some embodiments, the drug combination further comprises 67.5-150 mg / m 2 In some embodiments, the drug combination further comprises 135-150 mg / m 2 In some embodiments, the drug combination further comprises about 135 mg / m 2 In some embodiments, the drug combination further comprises about 150 mg / m 2 of paclitaxel.

[0077] In some embodiments, the drug combination comprises 100-1800 mg, 600-1800 mg, 600-1500 mg, or 1200-1500 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, and 10-800 mg, 50-500 mg, or 100-200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof. In some embodiments, the drug combination comprises about 100 mg, about 200 mg, about 300 mg, about 400 mg, about 500 mg, about 600 mg, about 700 mg, about 800 mg, about 900 mg, about 1000 mg, about 1100 mg, about 1200 mg, about 1300 mg, about 1400 mg, about 1500 mg, about 1600 mg, about 1700 mg, or about 1800 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, and about 1 In some embodiments, the pharmaceutical composition comprises about 1200 mg or about 1500 mg of an anti-TIM-3 antibody or antigen-binding fragment thereof and about 200 mg of an anti-PD-1 antibody or antigen-binding fragment thereof. In some embodiments, the drug combination comprises about 1200 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof and about 200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof.

[0078] In some embodiments, the drug combination further comprises 30-100 mg / m 2 30-75 mg / m 2 48-75 mg / m 2 or 60–75 mg / m 2 Cisplatin, and 75-175 mg / m 2 100-175 mg / m 2 112-175 mg / m 2 or 135–175 mg / m 2 In some embodiments, the drug combination further comprises about 30 mg / m 2 , about 32mg / m 2 , about 35mg / m 2 , about 37mg / m 2 , about 40mg / m 2, about 45mg / m 2 , about 48mg / m 2 , about 50mg / m 2 , about 52mg / m 2 , about 54mg / m 2 , about 56mg / m 2 , about 60mg / m 2 , about 65mg / m 2 , about 70mg / m 2 , about 75mg / m 2 , about 80mg / m 2 , about 90mg / m 2 or about 100 mg / m 2 , or cisplatin in a range of any of the above values, and about 75 mg / m 2 , about 90mg / m 2 , about 100mg / m 2 , about 105mg / m 2 , about 109mg / m 2 , about 112mg / m 2 , about 135mg / m 2 , about 140mg / m 2 , about 145mg / m 2 , about 150mg / m 2 or about 175 mg / m 2 , or paclitaxel in a range of any of the above values. In some embodiments, the drug combination further comprises 48-75 mg / m 2 Cisplatin, and 112-175 mg / m 2 In some embodiments, the drug combination further comprises about 75 mg / m 2 of cisplatin, and about 175 mg / m 2 In some embodiments, the drug combination further comprises 30-75 mg / m 2 Cisplatin, and 67.5-150mg / m 2 In some embodiments, the drug combination further comprises 60-75 mg / m 2 Cisplatin, and 135-175 mg / m 2 In some embodiments, the drug combination further comprises 60-75 mg / m 2 Cisplatin, and 135-150 mg / m 2 In some embodiments, the drug combination further comprises about 60 mg / m 2 or about 75 mg / m 2 of cisplatin, and about 135 mg / m 2or about 150 mg / m 2 of paclitaxel.

[0079] In other embodiments, the drug combination further comprises 2.5-5 mg / (mL / min) AUC or 3.2-5 mg / (mL / min) AUC of carboplatin and 75-175 mg / m 2 100-175 mg / m 2 112-175 mg / m 2 or 135–175 mg / m 2 In other embodiments, the drug combination further comprises about 2.5 mg / (mL / min) AUC, about 3 mg / (mL / min) AUC, about 3.2 mg / (mL / min) AUC, about 3.5 mg / (mL / min) AUC, about 3.75 mg / (mL / min) AUC, about 4 mg / (mL / min) AUC, about 4.5 mg / (mL / min) AUC or about 5 mg / (mL / min) AUC, or a range formed by any of the foregoing values ​​of carboplatin, and about 75 mg / (mL / min) AUC. 2 , about 90mg / m 2 , about 100mg / m 2 , about 105mg / m 2 , about 109mg / m 2 , about 112mg / m 2 , about 135mg / m 2 , about 140mg / m 2 , about 145mg / m 2 , about 150mg / m 2 or about 175 mg / m 2 In some other embodiments, the drug combination further comprises 3.2-5 mg / (mL / min) AUC of carboplatin and 112-175 mg / m 2 In other embodiments, the drug combination further comprises about 5 mg / (mL / min) AUC of carboplatin and about 175 mg / m 2 of paclitaxel.

[0080] In some embodiments, the drug combination further comprises cisplatin and paclitaxel. In some specific embodiments, the drug combination comprises 100-1800 mg, 600-1800 mg, 600-1500 mg, or 1200-1500 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, 10-800 mg, 50-500 mg, or 100-200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, 30-100 mg / m 230-75 mg / m 2 48-75 mg / m 2 or 60–75 mg / m 2 Cisplatin, and 75-175 mg / m 2 100-175 mg / m 2 112-175 mg / m 2 or 135–175 mg / m 2 In some specific embodiments, the drug combination includes about 1200 mg or about 1500 mg of anti-TIM-3 antibody or its antigen-binding fragment, about 200 mg of anti-PD-1 antibody or its antigen-binding fragment, 48-75 mg / m 2 Cisplatin, and 112-175 mg / m 2 In some specific embodiments, the drug combination includes about 1200 mg of anti-TIM-3 antibody or antigen-binding fragment thereof, about 200 mg of anti-PD-1 antibody or antigen-binding fragment thereof, and about 75 mg / m 2 of cisplatin, and about 175 mg / m 2 In some specific embodiments, the drug combination includes about 1200 mg or about 1500 mg of anti-TIM-3 antibody or its antigen-binding fragment, about 200 mg of anti-PD-1 antibody or its antigen-binding fragment, 30-75 mg / m 2 Cisplatin, and 67.5-150mg / m 2 In some specific embodiments, the drug combination includes about 1200 mg or about 1500 mg of anti-TIM-3 antibody or antigen-binding fragment thereof, about 200 mg of anti-PD-1 antibody or antigen-binding fragment thereof, 60-75 mg / m 2 Cisplatin, and 135-175 mg / m 2 In some specific embodiments, the drug combination includes about 1200 mg or about 1500 mg of anti-TIM-3 antibody or antigen-binding fragment thereof, about 200 mg of anti-PD-1 antibody or antigen-binding fragment thereof, 60-75 mg / m 2 Cisplatin, and 135-150 mg / m 2 In some specific embodiments, the drug combination includes about 1200 mg of anti-TIM-3 antibody or antigen-binding fragment thereof, about 200 mg of anti-PD-1 antibody or antigen-binding fragment thereof, 60-75 mg / m 2 Cisplatin, and 135-150 mg / m 2In some specific embodiments, the drug combination includes about 1200 mg of anti-TIM-3 antibody or antigen-binding fragment thereof, about 200 mg of anti-PD-1 antibody or antigen-binding fragment thereof, and about 60 mg / m 2 or about 75 mg / m 2 of cisplatin, and about 135 mg / m 2 or about 150 mg / m 2 of paclitaxel.

[0081] In other embodiments, the drug combination further comprises carboplatin and paclitaxel. In other specific embodiments, the drug combination comprises 100-1800 mg, 600-1800 mg, 600-1500 mg, or 1200-1500 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, 10-800 mg, 50-500 mg, or 100-200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, 2.5-5 mg / (mL / min) AUC or 3.2-5 mg / (mL / min) AUC of carboplatin, and 75-175 mg / m 2 100-175 mg / m 2 112-175 mg / m 2 or 135–175 mg / m 2 In other specific embodiments, the drug combination comprises about 1200 mg or about 1500 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, about 200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, 3.2-5 mg / (mL / min) AUC of carboplatin, and 112-175 mg / m 2 In other specific embodiments, the drug combination comprises about 1200 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, about 200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, about 5 mg / (mL / min) AUC of carboplatin, and about 175 mg / m 2 of paclitaxel.

[0082] In some embodiments, the amount of the anti-TIM-3 antibody or antigen-binding fragment thereof in the pharmaceutical combination is a daily dose. In some embodiments, the amount of the anti-TIM-3 antibody or antigen-binding fragment thereof in the pharmaceutical combination is a once-daily dose.

[0083] In some embodiments, the anti-TIM-3 antibody or antigen-binding fragment thereof in the pharmaceutical combination is present in a uniform dose.

[0084] In some embodiments, the anti-TIM-3 antibody or antigen-binding fragment thereof in the drug combination is contained in a dosage for one treatment cycle, and each treatment cycle is 3 weeks.

[0085] In some embodiments, the amount of the anti-PD-1 antibody or antigen-binding fragment thereof in the pharmaceutical combination is a daily dose. In some embodiments, the amount of the anti-PD-1 antibody or antigen-binding fragment thereof in the pharmaceutical combination is a once-daily dose.

[0086] In some embodiments, the anti-PD-1 antibody or antigen-binding fragment thereof in the pharmaceutical combination is present in a uniform dose.

[0087] In some embodiments, the anti-PD-1 antibody or antigen-binding fragment thereof in the drug combination is contained in a dosage for one treatment cycle, and each treatment cycle is 3 weeks.

[0088] In some embodiments, the amount of cisplatin in the pharmaceutical combination is a daily dose. In some embodiments, the amount of cisplatin in the pharmaceutical combination is a once-a-day dose.

[0089] In some embodiments, the content of cisplatin in the drug combination is a dose for one treatment cycle, and each treatment cycle is 3 weeks.

[0090] In some embodiments, the amount of carboplatin in the pharmaceutical combination is a daily dose. In some embodiments, the amount of carboplatin in the pharmaceutical combination is a once-daily dose.

[0091] In some embodiments, the content of carboplatin in the drug combination is a dose for one treatment cycle, and each treatment cycle is 3 weeks.

[0092] In some embodiments, the amount of paclitaxel in the pharmaceutical combination is a daily dose. In some embodiments, the amount of paclitaxel in the pharmaceutical combination is a once-daily dose.

[0093] In some embodiments, the content of paclitaxel in the drug combination is a dose for one treatment cycle, and each treatment cycle is 3 weeks.

[0094] In some embodiments, the drug combination is suitable for administration within a single treatment cycle and includes 100-1800 mg, 600-1800 mg, 600-1500 mg, or 1200-1500 mg of an anti-TIM-3 antibody or antigen-binding fragment thereof. In some embodiments, the drug combination is suitable for administration within a single treatment cycle and includes about 100 mg, about 200 mg, about 300 mg, about 400 mg, about 500 mg, about 600 mg, about 700 mg, about 800 mg, about 900 mg, about 1000 mg, about 1100 mg, about 1200 mg, about 1300 mg, about 1400 mg, about 1500 mg, about 1600 mg, about 1700 mg or about 1800 mg, or a range formed by any of the above values ​​of an anti-TIM-3 antibody or antigen-binding fragment thereof. In some embodiments, the pharmaceutical combination is suitable for administration in a single treatment cycle and includes about 1200 mg or about 1500 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof. In some embodiments, the pharmaceutical combination is suitable for administration in a single treatment cycle and includes about 1200 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof.

[0095] In some embodiments, the drug combination is suitable for administration in a single treatment cycle and includes 10-800 mg, 50-500 mg, or 100-200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof. In some embodiments, the drug combination is suitable for administration in a single treatment cycle and includes about 10 mg, about 50 mg, about 100 mg, about 120 mg, about 140 mg, about 160 mg, about 180 mg, about 200 mg, about 220 mg, about 240 mg, about 260 mg, about 280 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg or about 800 mg, or a range formed by any of the above values ​​of an anti-PD-1 antibody or an antigen-binding fragment thereof. In some embodiments, the pharmaceutical combination is suitable for administration in a single treatment cycle and includes about 200 mg of the anti-PD-1 antibody or antigen-binding fragment thereof.

[0096] In some embodiments, the drug combination is suitable for administration within a single treatment cycle and further comprises a chemotherapeutic agent. In some embodiments, the chemotherapeutic agents are cisplatin and paclitaxel. In other embodiments, the chemotherapeutic agents are carboplatin and paclitaxel. In some embodiments, the drug combination is suitable for administration within a single treatment cycle and further comprises 30-100 mg / m 2 30-75 mg / m 2 48-75 mg / m 2or 60–75 mg / m 2 In some embodiments, the drug combination is suitable for administration in a single treatment cycle and further comprises about 30 mg / m 2 , about 32mg / m 2 , about 35mg / m 2 , about 37mg / m 2 , about 40mg / m 2 , about 45mg / m 2 , about 48mg / m 2 , about 50mg / m 2 , about 52mg / m 2 , about 54mg / m 2 , about 56mg / m 2 , about 60mg / m 2 , about 65mg / m 2 , about 70mg / m 2 , about 75mg / m 2 , about 80mg / m 2 , about 90mg / m 2 or about 100 mg / m 2 , or a range formed by any of the above values ​​of cisplatin, or about 2.5 mg / (mL / min) AUC, about 3 mg / (mL / min) AUC, about 3.2 mg / (mL / min) AUC, about 3.5 mg / (mL / min) AUC, about 3.75 mg / (mL / min) AUC, about 4 mg / (mL / min) AUC, about 4.5 mg / (mL / min) AUC or about 5 mg / (mL / min) AUC, or a range formed by any of the above values ​​of carboplatin. In some embodiments, the drug combination is suitable for administration in a single treatment cycle and further includes 48-75 mg / m 2 In some embodiments, the drug combination is suitable for administration in a single treatment cycle and further comprises 48 mg / m 2 , about 60mg / m 2 or about 75 mg / m 2 In some embodiments, the drug combination is suitable for administration in a single treatment cycle and further comprises about 75 mg / m 2In some embodiments, the drug combination is suitable for administration in a single treatment cycle and further comprises 30-75 mg / m 2 In some embodiments, the drug combination is suitable for administration in a single treatment cycle and further comprises 60-75 mg / m 2 In some embodiments, the drug combination is suitable for administration in a single treatment cycle and further comprises about 60 mg / m 2 In some embodiments, the drug combination is suitable for administration in a single treatment cycle and further comprises about 75 mg / m 2 In some embodiments, the drug combination is suitable for administration in a single treatment cycle and further comprises 75-175 mg / m 2 100-175 mg / m 2 112-175 mg / m 2 or 135–175 mg / m 2 In some embodiments, the drug combination is suitable for administration in a single treatment cycle and further comprises about 75 mg / m 2 , about 90mg / m 2 , about 100mg / m 2 , about 105mg / m 2 , about 109mg / m 2 , about 112mg / m 2 , about 135mg / m 2 , about 140mg / m 2 , about 145mg / m 2 , about 150mg / m 2 or about 175 mg / m 2 , or paclitaxel in a range formed by any of the above values. In some embodiments, the drug combination is suitable for administration in a single treatment cycle and further comprises 112-175 mg / m 2 In some embodiments, the drug combination is suitable for administration in a single treatment cycle and further comprises about 112 mg / m 2 , about 135mg / m 2 , about 140mg / m 2 , 150mg / m 2 or about 175 mg / m 2 In some embodiments, the drug combination is suitable for administration in a single treatment cycle and further comprises about 175 mg / m 2 In some embodiments, the drug combination is suitable for administration in a single treatment cycle and further comprises 67.5-150 mg / m 2In some embodiments, the drug combination is suitable for administration in a single treatment cycle and further comprises 135-150 mg / m 2 In some embodiments, the drug combination is suitable for administration in a single treatment cycle and further comprises about 135 mg / m 2 In some embodiments, the drug combination is suitable for administration in a single treatment cycle and further comprises about 150 mg / m 2 of paclitaxel.

[0097] In some embodiments, the drug combination is suitable for administration within a single treatment cycle, comprising an anti-TIM-3 antibody or an antigen-binding fragment thereof and an anti-PD-1 antibody or an antigen-binding fragment thereof. In some embodiments, the drug combination is suitable for administration within a single treatment cycle, comprising 100-1800 mg, 600-1800 mg, 600-1500 mg, or 1200-1500 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, and 10-800 mg, 50-500 mg, or 100-200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof. In some embodiments, the pharmaceutical combination is suitable for administration in a single treatment cycle and comprises about 100 mg, about 200 mg, about 300 mg, about 400 mg, about 500 mg, about 600 mg, about 700 mg, about 800 mg, about 900 mg, about 1000 mg, about 1100 mg, about 1200 mg, about 1300 mg, about 1400 mg, about 1500 mg, about 1600 mg, about 1700 mg or about 1800 mg, or a range of any of the foregoing values, of an anti-TIM-3 antibody or its antigen binding site. In some embodiments, the drug combination comprises about 1200 mg or about 1500 mg of an anti-TIM-3 antibody or antigen-binding fragment thereof and about 200 mg of an anti-PD-1 antibody or antigen-binding fragment thereof, or a range thereof. In some embodiments, the drug combination is suitable for administration in a single treatment cycle and includes about 1200 mg of the anti-TIM-3 antibody or antigen-binding fragment thereof and about 200 mg of the anti-PD-1 antibody or antigen-binding fragment thereof.

[0098] In some embodiments, the drug combination is suitable for administration in a single treatment cycle and further comprises 30-100 mg / m 2 30-75 mg / m 2 48-75 mg / m 2 or 60–75 mg / m 2 Cisplatin, and 75-175 mg / m 2 100-175 mg / m 2 112-175 mg / m 2 or 135–175 mg / m 2 In some embodiments, the drug combination is suitable for administration in a single treatment cycle and further comprises about 30 mg / m 2 , about 32mg / m 2 , about 35mg / m 2 , about 37mg / m 2 , about 40mg / m 2 , about 45mg / m 2 , about 48mg / m 2 , about 50mg / m 2 , about 52mg / m 2 , about 54mg / m 2 , about 56mg / m 2 , about 60mg / m 2 , about 65mg / m 2 , about 70mg / m 2 , about 75mg / m 2 , about 80mg / m 2 , about 90mg / m 2 or about 100 mg / m 2 , or cisplatin in a range of any of the above values, and about 75 mg / m 2 , about 90mg / m 2 , about 100mg / m 2 , about 105mg / m 2 , about 109mg / m 2 , about 112mg / m 2 , about 135mg / m 2 , about 140mg / m 2 , about 145mg / m 2 , about 150mg / m 2 or about 175 mg / m 2 , or paclitaxel in a range formed by any of the above values. In some embodiments, the drug combination is suitable for administration in a single treatment cycle and further comprises 48-75 mg / m 2 Cisplatin, and 112-175 mg / m 2In some embodiments, the drug combination is suitable for administration in a single treatment cycle and further comprises 75 mg / m 2 Cisplatin, and 175mg / m 2 In some embodiments, the drug combination is suitable for administration in a single treatment cycle and further comprises 30-75 mg / m 2 Cisplatin, and 67.5-150mg / m 2 In some embodiments, the drug combination is suitable for administration in a single treatment cycle and further comprises 60-75 mg / m 2 Cisplatin, and 135-175 mg / m 2 In some embodiments, the drug combination is suitable for administration in a single treatment cycle and further comprises 60-75 mg / m 2 Cisplatin, and 135-150mg / m 2 In some embodiments, the drug combination is suitable for administration in a single treatment cycle and further comprises about 60 mg / m 2 or about 75 mg / m 2 Cisplatin, and about 135mg / m 2 or about 150 mg / m 2 of paclitaxel.

[0099] In some embodiments, the drug combination is suitable for administration in a single treatment cycle and further comprises 2.5-5 mg / (mL / min) AUC or 3.2-5 mg / (mL / min) AUC of carboplatin and 75-175 mg / m 2 100-175 mg / m 2 112-175 mg / m 2 or 135–175 mg / m 2 In some embodiments, the drug combination is suitable for administration in a single treatment cycle and further comprises carboplatin at about 2.5 mg / (mL / min) AUC, about 3 mg / (mL / min) AUC, about 3.2 mg / (mL / min) AUC, about 3.5 mg / (mL / min) AUC, about 3.75 mg / (mL / min) AUC, about 4 mg / (mL / min) AUC, about 4.5 mg / (mL / min) AUC, or about 5 mg / (mL / min) AUC, or a range formed by any of the foregoing values, and about 75 mg / (mL / min) AUC. 2 , about 90mg / m 2 , about 100mg / m 2 , about 105mg / m 2 , about 109mg / m 2 , about 112mg / m2 , about 135mg / m 2 , about 140mg / m 2 , about 145mg / m 2 , about 150mg / m 2 or about 175 mg / m 2 , or paclitaxel in a range formed by any of the above values. In some embodiments, the drug combination is suitable for administration in a single treatment cycle and further comprises 3.2-5 mg / (mL / min) AUC of carboplatin and 112-175 mg / m 2 In some embodiments, the drug combination is suitable for administration in a single treatment cycle and further comprises 5 mg / (mL / min) AUC of carboplatin and 175 mg / m 2 of paclitaxel.

[0100] In some embodiments, the drug combination is suitable for administration in a single treatment cycle, comprising an anti-TIM-3 antibody or an antigen-binding fragment thereof, an anti-PD-1 antibody or an antigen-binding fragment thereof, cisplatin, and paclitaxel. In some specific embodiments, the drug combination is suitable for administration in a single treatment cycle, comprising 100-1800 mg, 600-1800 mg, 600-1500 mg, or 1200-1500 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, 10-800 mg, 50-500 mg, or 100-200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, 30-100 mg / m 2 30-75 mg / m 2 48-75 mg / m 2 or 60–75 mg / m 2 Cisplatin, and 75-175 mg / m 2 100-175 mg / m 2 112-175 mg / m 2 or 135–175 mg / m 2 In some specific embodiments, the drug combination is suitable for administration in a single treatment cycle, which includes about 1200 mg or about 1500 mg of anti-TIM-3 antibody or antigen-binding fragment thereof, about 200 mg of anti-PD-1 antibody or antigen-binding fragment thereof, 48-75 mg / m 2 Cisplatin, and 112-175 mg / m 2 In some specific embodiments, the drug combination is suitable for administration in a single treatment cycle, which includes about 1200 mg of anti-TIM-3 antibody or antigen-binding fragment thereof, about 200 mg of anti-PD-1 antibody or antigen-binding fragment thereof, 75 mg / m 2Cisplatin, and 175 mg / m 2 In some specific embodiments, the drug combination is suitable for administration in a single treatment cycle, which includes about 1200 mg or about 1500 mg of anti-TIM-3 antibody or its antigen-binding fragment, about 200 mg of anti-PD-1 antibody or its antigen-binding fragment, 30-75 mg / m 2 Cisplatin, and 67.5-150mg / m 2 In some specific embodiments, the drug combination is suitable for administration in a single treatment cycle, which includes about 1200 mg or about 1500 mg of anti-TIM-3 antibody or antigen-binding fragment thereof, about 200 mg of anti-PD-1 antibody or antigen-binding fragment thereof, 60-75 mg / m 2 Cisplatin, and 135-175 mg / m 2 In some specific embodiments, the drug combination is suitable for administration in a single treatment cycle, which includes about 1200 mg or about 1500 mg of anti-TIM-3 antibody or its antigen-binding fragment, about 200 mg of anti-PD-1 antibody or its antigen-binding fragment, 60-75 mg / m 2 Cisplatin, and 135-150 mg / m 2 In some specific embodiments, the drug combination is suitable for administration in a single treatment cycle, which includes about 1200 mg of anti-TIM-3 antibody or antigen-binding fragment thereof, about 200 mg of anti-PD-1 antibody or antigen-binding fragment thereof, 60-75 mg / m 2 Cisplatin, and 135-150 mg / m 2 In other specific embodiments, the drug combination is suitable for administration in a single treatment cycle, which includes about 1200 mg of anti-TIM-3 antibody or antigen-binding fragment thereof, about 200 mg of anti-PD-1 antibody or antigen-binding fragment thereof, and about 60 mg / m 2 or about 75 mg / m 2 of cisplatin, and about 135 mg / m 2 or about 150 mg / m 2 of paclitaxel.

[0101] In other embodiments, the drug combination is suitable for administration within a single treatment cycle, comprising an anti-TIM-3 antibody or an antigen-binding fragment thereof, an anti-PD-1 antibody or an antigen-binding fragment thereof, carboplatin, and paclitaxel. In other specific embodiments, the drug combination is suitable for administration within a single treatment cycle, comprising 100-1800 mg, 600-1800 mg, 600-1500 mg, or 1200-1500 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, 10-800 mg, 50-500 mg, or 100-200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, 2.5-5 mg / (mL / min) AUC or 3.2-5 mg / (mL / min) AUC of carboplatin, and 75-175 mg / m 2 100-175 mg / m 2 112-175 mg / m 2 or 135–175 mg / m 2 In other specific embodiments, the drug combination is suitable for administration in a single treatment cycle, which includes about 1200 mg or about 1500 mg of anti-TIM-3 antibody or its antigen-binding fragment, about 200 mg of anti-PD-1 antibody or its antigen-binding fragment, 3.2-5 mg / (mL / min) AUC of carboplatin, and 112-175 mg / m 2 In other specific embodiments, the drug combination is suitable for administration in a single treatment cycle, which includes about 1200 mg of anti-TIM-3 antibody or antigen-binding fragment thereof, about 200 mg of anti-PD-1 antibody or antigen-binding fragment thereof, 5 mg / (mL / min) AUC of carboplatin, and 175 mg / m 2 of paclitaxel.

[0102] In some embodiments, the present disclosure provides a combination drug combination comprising:

[0103] (a) comprising 100-1800 mg, 600-1800 mg, 600-1500 mg, or 1200-1500 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, 10-800 mg, 50-500 mg, or 100-200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, 30-100 mg / m 2 30-75 mg / m 2 48-75 mg / m 2 or 60–75 mg / m 2 Cisplatin, and 75-175 mg / m 2 100-175 mg / m 2 112-175 mg / m 2or 135–175 mg / m 2 a drug combination comprising paclitaxel, formulated to be suitable for administration to the subject in a single treatment cycle during the first treatment phase; and

[0104] (b) a pharmaceutical combination comprising 100-1800 mg, 600-1800 mg, 600-1500 mg, or 1200-1500 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, and 10-800 mg, 50-500 mg, or 100-200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, prepared for administration to the subject in a single treatment cycle during the second treatment phase.

[0105] In some embodiments, the present disclosure provides a combination drug combination comprising:

[0106] (a) an anti-TIM-3 antibody or antigen-binding fragment thereof comprising about 100 mg, about 200 mg, about 300 mg, about 400 mg, about 500 mg, about 600 mg, about 700 mg, about 800 mg, about 900 mg, about 1000 mg, about 1100 mg, about 1200 mg, about 1300 mg, about 1400 mg, about 1500 mg, about 1600 mg, about 1700 mg or about 1800 mg, or a range formed by any of the foregoing values, about 10 mg, about 50 mg, about 60 mg, about 80 mg, about 900 mg, about 1000 mg, about 1100 mg, about 1200 mg, about 1300 mg, about 1400 mg, about 1500 mg, about 1600 mg, about 1700 mg or about 1800 mg, or a range formed by any of the foregoing values; about 100 mg, about 120 mg, about 140 mg, about 160 mg, about 180 mg, about 200 mg, about 220 mg, about 240 mg, about 260 mg, about 280 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg or about 800 mg, or a range formed by any of the foregoing values, of an anti-PD-1 antibody or antigen-binding fragment thereof, about 30 mg / m 2 , about 32mg / m 2 , about 35mg / m 2 , about 37mg / m 2 , about 40mg / m 2 , about 45mg / m 2 , about 48mg / m 2 , about 50mg / m 2 , about 52mg / m 2 , about 54mg / m 2 , about 56mg / m 2 , about 60mg / m 2 , about 65mg / m 2 , about 70mg / m 2 , about 75mg / m 2 , about 80mg / m2 , about 90mg / m 2 or about 100 mg / m 2 , or cisplatin in a range of any of the above values, and about 75 mg / m 2 , about 90mg / m 2 , about 100mg / m 2 , about 105mg / m 2 , about 109mg / m 2 , about 112mg / m 2 , about 135mg / m 2 , about 140mg / m 2 , about 145mg / m 2 , about 150mg / m 2 or about 175 mg / m 2 , or a range of any of the above values, which is prepared to be administered to a subject in a single treatment cycle in a first treatment phase; and

[0107] (b) an anti-TIM-3 antibody or antigen-binding fragment thereof comprising about 100 mg, about 200 mg, about 300 mg, about 400 mg, about 500 mg, about 600 mg, about 700 mg, about 800 mg, about 900 mg, about 1000 mg, about 1100 mg, about 1200 mg, about 1300 mg, about 1400 mg, about 1500 mg, about 1600 mg, about 1700 mg or about 1800 mg, or a range formed by any of the foregoing values, and about 10 mg, about 50 mg, about 100 mg, about 120 mg , about 140 mg, about 160 mg, about 180 mg, about 200 mg, about 220 mg, about 240 mg, about 260 mg, about 280 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg or about 800 mg, or a range formed by any of the foregoing values, which is prepared for administration to the subject in a single treatment cycle during the second treatment period.

[0108] In some embodiments, the present disclosure provides a combination drug combination comprising:

[0109] (a) comprising about 1200 mg or about 1500 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, about 200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, and 48-75 mg / m 2 Cisplatin, and 112-175 mg / m 2a drug combination comprising paclitaxel, formulated to be suitable for administration to the subject in a single treatment cycle during the first treatment phase; and

[0110] (b) a pharmaceutical combination comprising about 1200 mg or about 1500 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof and about 200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, prepared for administration to the subject in a single treatment cycle during the second treatment phase.

[0111] In some embodiments, the present disclosure provides a combination drug combination comprising:

[0112] (a) comprising approximately 1200 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, approximately 200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, and 75 mg / m 2 Cisplatin, and 175 mg / m 2 a drug combination comprising paclitaxel, formulated to be suitable for administration to the subject in a single treatment cycle during the first treatment phase; and

[0113] (b) a pharmaceutical combination comprising about 1200 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof and about 200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, prepared for administration to the subject in a single treatment cycle during the second treatment phase.

[0114] In some embodiments, the present disclosure provides a combination drug combination comprising:

[0115] (a) comprising about 1200 mg or about 1500 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, about 200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, and 30-75 mg / m 2 Cisplatin, and 67.5-150mg / m 2 a drug combination comprising paclitaxel, formulated to be suitable for administration to the subject in a single treatment cycle during the first treatment phase; and

[0116] (b) a pharmaceutical combination comprising about 1200 mg or about 1500 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof and about 200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, prepared for administration to the subject in a single treatment cycle during the second treatment phase.

[0117] In some embodiments, the present disclosure provides a combination drug combination comprising:

[0118] (a) comprising about 1200 mg or about 1500 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, about 200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, and 60-75 mg / m 2Cisplatin, and 135-175 mg / m 2 a drug combination comprising paclitaxel, formulated to be suitable for administration to the subject in a single treatment cycle during the first treatment phase; and

[0119] (b) a pharmaceutical combination comprising about 1200 mg or about 1500 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof and about 200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, prepared for administration to the subject in a single treatment cycle during the second treatment phase.

[0120] In some embodiments, the present disclosure provides a combination drug combination comprising:

[0121] (a) comprising about 1200 mg or about 1500 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, about 200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, and 60-75 mg / m 2 Cisplatin, and 135-150 mg / m 2 a drug combination comprising paclitaxel, formulated to be suitable for administration to the subject in a single treatment cycle during the first treatment phase; and

[0122] (b) a pharmaceutical combination comprising about 1200 mg or about 1500 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof and about 200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, prepared for administration to the subject in a single treatment cycle during the second treatment phase.

[0123] In some embodiments, the present disclosure provides a combination drug combination comprising:

[0124] (a) comprising approximately 1200 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, approximately 200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, and 60-75 mg / m 2 Cisplatin, and 135-150 mg / m 2 a drug combination comprising paclitaxel, formulated to be suitable for administration to the subject in a single treatment cycle during the first treatment phase; and

[0125] (b) a pharmaceutical combination comprising about 1200 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof and about 200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, prepared for administration to the subject in a single treatment cycle during the second treatment phase.

[0126] In some embodiments, the present disclosure provides a combination drug combination comprising:

[0127] (a) comprising about 1200 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, about 200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, and about 60 mg / m 2 or about 75 mg / m 2 of cisplatin, and about 135 mg / m 2 or about 150 mg / m 2 a drug combination comprising paclitaxel, formulated to be suitable for administration to the subject in a single treatment cycle during the first treatment phase; and

[0128] (b) a pharmaceutical combination comprising about 1200 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof and about 200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, prepared for administration to the subject in a single treatment cycle during the second treatment phase.

[0129] In some embodiments, the present disclosure provides a combination drug combination comprising:

[0130] (a) comprising 100-1800 mg, 600-1800 mg, 600-1500 mg, or 1200-1500 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, 10-800 mg, 50-500 mg, or 100-200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, 2.5-5 mg / (mL / min) AUC or 3.2-5 mg / (mL / min) AUC of carboplatin, and 75-175 mg / m 2 100-175 mg / m 2 112-175 mg / m 2 or 135–175 mg / m 2 a drug combination comprising paclitaxel, formulated to be suitable for administration to the subject in a single treatment cycle during the first treatment phase; and

[0131] (b) a pharmaceutical combination comprising 100-1800 mg, 600-1800 mg, 600-1500 mg, or 1200-1500 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, and 10-800 mg, 50-500 mg, or 100-200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, prepared for administration to the subject in a single treatment cycle during the second treatment phase.

[0132] In some embodiments, the present disclosure provides a combination drug combination comprising:

[0133] (a) an anti-TIM-3 antibody or antigen-binding fragment thereof comprising about 100 mg, about 200 mg, about 300 mg, about 400 mg, about 500 mg, about 600 mg, about 700 mg, about 800 mg, about 900 mg, about 1000 mg, about 1100 mg, about 1200 mg, about 1300 mg, about 1400 mg, about 1500 mg, about 1600 mg, about 1700 mg or about 1800 mg, or a range thereof, about 10 mg, about 50 mg, about 100 mg, about 120 mg, about 140 mg, about 160 mg, about 180 mg, about 200 mg, about 220 mg, about 240 mg, about 260 mg, about 280 mg, about 300 mg, about 350 mg g, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, or about 800 mg, or an anti-PD-1 antibody or antigen-binding fragment thereof, or a range formed by any of the foregoing values, about 2.5 mg / (mL / min) AUC, about 3 mg / (mL / min) AUC, about 3.2 mg / (mL / min) AUC, about 3.5 mg / (mL / min) AUC, about 3.75 mg / (mL / min) AUC, about 4 mg / (mL / min) AUC, about 4.5 mg / (mL / min) AUC, or about 5 mg / (mL / min) AUC, or a range formed by any of the foregoing values ​​of carboplatin, and about 75 mg / (mL / min) 2 , about 90mg / m 2 , about 100mg / m 2 , about 105mg / m 2 , about 109mg / m 2 , about 112mg / m 2 , about 135mg / m 2 , about 140mg / m 2 , about 145mg / m 2 , about 150mg / m 2 or about 175 mg / m 2 , or a range of any of the above values, which is prepared to be administered to a subject in a single treatment cycle in a first treatment phase; and

[0134] (b) about 100 mg, about 200 mg, about 300 mg, about 400 mg, about 500 mg, about 600 mg, about 700 mg, about 800 mg, about 900 mg, about 1000 mg, about 1100 mg, about 1200 mg, about 1300 mg, about 1400 mg, about 1500 mg, about 1600 mg, about 1700 mg, about 1800 mg, about 1900 mg, about 2000 mg, about 2100 mg, about 2200 mg, about 2300 mg, about 2400 mg, about 2500 mg, about 2600 mg, about 2700 mg, about 2800 mg, about 2900 mg, about 3000 mg, about 3100 mg, about 3200 mg, about 330 The present invention also provides a pharmaceutical combination of about 100 mg, about 1700 mg, or about 1800 mg of an anti-TIM-3 antibody, or an antigen-binding fragment thereof, or a range formed by any of the foregoing values, and about 10 mg, about 50 mg, about 100 mg, about 120 mg, about 140 mg, about 160 mg, about 180 mg, about 200 mg, about 220 mg, about 240 mg, about 260 mg, about 280 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, or about 800 mg of an anti-PD-1 antibody, or an antigen-binding fragment thereof, or a range formed by any of the foregoing values, which is prepared for administration to the subject in a single treatment cycle during the second treatment period.

[0135] In some embodiments, the present disclosure provides a combination drug combination comprising:

[0136] (a) comprising about 1200 mg or about 1500 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, about 200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, 3.2-5 mg / (mL / min) AUC of carboplatin, and 112-175 mg / m 2 a drug combination comprising paclitaxel, formulated to be suitable for administration to the subject in a single treatment cycle during the first treatment phase; and

[0137] (b) a pharmaceutical combination comprising about 1200 mg or about 1500 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof and about 200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, prepared for administration to the subject in a single treatment cycle during the second treatment phase.

[0138] In some embodiments, the present disclosure provides a combination drug combination comprising:

[0139] (a) comprising about 1200 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, about 200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, 5 mg / (mL / min) AUC of carboplatin, and 175 mg / m 2 a drug combination comprising paclitaxel, formulated to be suitable for administration to the subject in a single treatment cycle during the first treatment phase; and

[0140] (b) a pharmaceutical combination comprising about 1200 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof and about 200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, prepared for administration to the subject in a single treatment cycle during the second treatment phase.

[0141] In some embodiments, the first treatment phase comprises 1-14 treatment cycles, preferably 2-12 treatment cycles, 2-10 treatment cycles, more preferably 2-8 treatment cycles, for example, 2-8 treatment cycles, 3-8 treatment cycles, 4-8 treatment cycles, 2-7 treatment cycles, 3-7 treatment cycles, 4-7 treatment cycles, 2-6 treatment cycles, 3-6 treatment cycles, or 4-6 treatment cycles; most preferably 4-6 treatment cycles, for example, 4 treatment cycles, 5 treatment cycles, and / or 6 treatment cycles. In some embodiments, the first treatment phase comprises 4 treatment cycles. In some embodiments, the first treatment phase comprises 6 treatment cycles.

[0142] In some embodiments, one treatment cycle is every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks. In some embodiments, one treatment cycle is every 3 weeks.

[0143] In some embodiments, the second treatment period is after the first treatment period. In some embodiments, the second treatment period continues from the end of the first treatment period until the patient loses clinical benefit, has unacceptable toxicity, is evaluated as PD, and / or the investigator deems it inappropriate to continue the medication.

[0144] In some embodiments, the anti-TIM-3 antibody or antigen-binding fragment thereof can be a pharmaceutical composition comprising the anti-TIM-3 antibody or antigen-binding fragment thereof. The pharmaceutical composition comprising the anti-TIM-3 antibody or antigen-binding fragment thereof is a single dose or multiple doses, preferably multiple doses. In some embodiments, the multiple doses can consist of a single dose of a pharmaceutical composition containing approximately 240 mg, approximately 300 mg, approximately 360 mg, and / or approximately 600 mg of the anti-TIM-3 antibody or antigen-binding fragment thereof. In some embodiments, the multiple doses can consist of a single dose of a pharmaceutical composition containing approximately 240 mg and / or approximately 600 mg of the anti-TIM-3 antibody or antigen-binding fragment thereof.

[0145] In some embodiments, the anti-PD-1 antibody or antigen-binding fragment thereof may be a pharmaceutical composition comprising the anti-PD-1 antibody or antigen-binding fragment thereof. The pharmaceutical composition comprising the anti-PD-1 antibody or antigen-binding fragment thereof is a single dose or multiple doses, preferably multiple doses. In some embodiments, the multiple doses may consist of a single dose of a pharmaceutical composition containing about 100 mg and / or about 200 mg of the anti-PD-1 antibody or antigen-binding fragment thereof. In some embodiments, the multiple doses may consist of a single dose of a pharmaceutical composition containing about 100 mg of the anti-PD-1 antibody or antigen-binding fragment thereof.

[0146] In some embodiments, the chemotherapeutic agent can be a pharmaceutical composition comprising the chemotherapeutic agent. The pharmaceutical composition comprising the chemotherapeutic agent is administered in a single dose or multiple doses, preferably multiple doses. In some embodiments, the chemotherapeutic agent is cisplatin and paclitaxel. In other embodiments, the chemotherapeutic agent is carboplatin and paclitaxel.

[0147] In some embodiments, the cisplatin may be a pharmaceutical composition containing cisplatin. The pharmaceutical composition containing cisplatin is a single dose or multiple doses, preferably multiple doses. In some embodiments, the multiple doses may consist of a single dose of a pharmaceutical composition containing 2.5 mg, 5 mg, 10 mg, 20 mg, 25 mg, 30 mg, 50 mg, and / or 100 mg of cisplatin. In some embodiments, the multiple doses may consist of a single dose of a pharmaceutical composition containing 10 mg, 20 mg, 30 mg, 50 mg, and / or 100 mg of cisplatin.

[0148] In some embodiments, the carboplatin can be a pharmaceutical composition comprising carboplatin. The pharmaceutical composition comprising carboplatin is a single dose or multiple doses, preferably multiple doses. In some embodiments, the multiple doses can consist of a single dose of a pharmaceutical composition comprising 50 mg, 100 mg, 150 mg, 250 mg, and / or 450 mg of carboplatin.

[0149] In some embodiments, the paclitaxel may be a pharmaceutical composition comprising paclitaxel. The pharmaceutical composition comprising paclitaxel is a single dose or multiple doses, preferably multiple doses. In some embodiments, the multiple doses may consist of a single dose of a pharmaceutical composition comprising 30 mg, 60 mg, 100 mg, and / or 150 mg of paclitaxel.

[0150] In some embodiments, in the pharmaceutical combination, the mass ratio of the anti-TIM-3 antibody or its antigen-binding fragment: the anti-PD-1 antibody or its antigen-binding fragment is (0.1-180):1, (0.2-50):1, (0.5-9):1, (3-7.5):1, (4-7.5):1, or (6-7.5):1; wherein the anti-TIM-3 antibody or its antigen-binding fragment and the anti-PD-1 antibody or its antigen-binding fragment can be packaged separately or together. In some embodiments, the anti-TIM-3 antibody or its antigen-binding fragment and the anti-PD-1 antibody or its antigen-binding fragment are packaged separately, wherein the anti-TIM-3 antibody or its antigen-binding fragment can be packaged in a single portion or in multiple portions, and the anti-PD-1 antibody or its antigen-binding fragment can be packaged in a single portion or in multiple portions. In some embodiments, the anti-TIM-3 antibody or its antigen-binding fragment can be packaged in a single portion or multiple aliquots (e.g., 2 aliquots, 3 aliquots, 4 aliquots, 5 aliquots, 6 aliquots, 7 aliquots, 8 aliquots or more), and the anti-PD-1 antibody or its antigen-binding fragment can be packaged in a single portion or multiple aliquots (e.g., 2 aliquots or other aliquots).

[0151] In some embodiments, the pharmaceutical combination comprises a pharmaceutical composition comprising an anti-TIM-3 antibody or an antigen-binding fragment thereof and a pharmaceutical composition comprising an anti-PD-1 antibody or an antigen-binding fragment thereof, wherein the pharmaceutical composition comprising the anti-TIM-3 antibody or an antigen-binding fragment thereof is prepared as a single dose or multiple doses suitable for administering to a patient 100-1800 mg, 600-1800 mg, 600-1500 mg, or 1200-1500 mg of the anti-TIM-3 antibody or an antigen-binding fragment thereof, and the pharmaceutical composition comprising the anti-PD-1 antibody or an antigen-binding fragment thereof is prepared as a single dose or multiple doses suitable for administering to a patient 10-800 mg, 50-500 mg, or 100-200 mg of the anti-PD-1 antibody or an antigen-binding fragment thereof. In some embodiments, the pharmaceutical combination comprises a pharmaceutical composition comprising an anti-TIM-3 antibody or an antigen-binding fragment thereof and a pharmaceutical composition comprising an anti-PD-1 antibody or an antigen-binding fragment thereof, wherein the pharmaceutical composition comprising the anti-TIM-3 antibody or an antigen-binding fragment thereof is prepared to be suitable for administering to a patient about 100 mg, about 200 mg, about 300 mg, about 400 mg, about 500 mg, about 600 mg, about 700 mg, about 800 mg, about 900 mg, about 1000 mg, about 1100 mg, about 1200 mg, about 1300 mg, about 1400 mg, about 1500 mg, about 1600 mg, about 1700 mg or about 1800 mg of anti-TIM-3 antibody, or a range formed by any of the foregoing values. A single dose or multiple doses of M-3 antibody or its antigen-binding fragment, a pharmaceutical composition containing an anti-PD-1 antibody or its antigen-binding fragment is prepared to be suitable for administering to a patient a single dose or multiple doses of about 10 mg, about 50 mg, about 100 mg, about 120 mg, about 140 mg, about 160 mg, about 180 mg, about 200 mg, about 220 mg, about 240 mg, about 260 mg, about 280 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg or about 800 mg, or a range formed by any of the foregoing values, of an anti-PD-1 antibody or its antigen-binding fragment. In some embodiments, the pharmaceutical combination comprises a pharmaceutical composition comprising an anti-TIM-3 antibody or an antigen-binding fragment thereof and a pharmaceutical composition comprising an anti-PD-1 antibody or an antigen-binding fragment thereof, wherein the pharmaceutical composition comprising the anti-TIM-3 antibody or an antigen-binding fragment thereof is prepared as a single dose or multiple doses suitable for administering to a patient about 1200 mg or about 1500 mg of the anti-TIM-3 antibody or an antigen-binding fragment thereof, and the pharmaceutical composition comprising the anti-PD-1 antibody or an antigen-binding fragment thereof is prepared as a single dose or multiple doses suitable for administering to a patient about 200 mg of the anti-PD-1 antibody or an antigen-binding fragment thereof.In some embodiments, the pharmaceutical combination comprises a pharmaceutical composition comprising an anti-TIM-3 antibody or an antigen-binding fragment thereof and a pharmaceutical composition comprising an anti-PD-1 antibody or an antigen-binding fragment thereof, wherein the pharmaceutical composition comprising the anti-TIM-3 antibody or an antigen-binding fragment thereof is prepared as a single dose or multiple doses suitable for administering to a patient approximately 1200 mg of the anti-TIM-3 antibody or an antigen-binding fragment thereof, and the pharmaceutical composition comprising the anti-PD-1 antibody or an antigen-binding fragment thereof is prepared as a single dose or multiple doses suitable for administering to a patient approximately 200 mg of the anti-PD-1 antibody or an antigen-binding fragment thereof.

[0152] In some embodiments, the drug combination further comprises a chemotherapeutic agent. In some embodiments, the chemotherapeutic agents are cisplatin and paclitaxel. In other embodiments, the chemotherapeutic agents are carboplatin and paclitaxel. In some embodiments, the drug combination further comprises a pharmaceutical composition containing cisplatin and a pharmaceutical composition containing paclitaxel, wherein the pharmaceutical composition containing cisplatin is prepared to be suitable for administration to a patient at a dose of 30-100 mg / m 2 30-75 mg / m 2 48-75 mg / m 2 or 60–75 mg / m 2 A single dose or multiple doses of cisplatin, containing paclitaxel, is prepared to be suitable for administering to a patient 75-175 mg / m 2 100-175 mg / m 2 112-175 mg / m 2 or 135–175 mg / m 2 In some embodiments, the pharmaceutical combination further comprises a pharmaceutical composition comprising cisplatin and a pharmaceutical composition comprising paclitaxel, wherein the pharmaceutical composition comprising cisplatin is prepared to be suitable for administration to a patient at about 30 mg / m 2 , about 32mg / m 2 , about 35mg / m 2 , about 37mg / m 2 , about 40mg / m 2 , about 45mg / m 2 , about 48mg / m 2 , about 50mg / m 2 , about 52mg / m 2 , about 54mg / m 2 , about 56mg / m 2 , about 60mg / m 2 , about 65mg / m 2 , about 70mg / m 2 , about 75mg / m 2 , about 80mg / m 2 , about 90mg / m 2or about 100 mg / m 2 , or a single dose or multiple doses of cisplatin in a range of any of the above values, the pharmaceutical composition containing paclitaxel is prepared to be suitable for administering to a patient about 75 mg / m 2 , about 90mg / m 2 , about 100mg / m 2 , about 105mg / m 2 , about 109mg / m 2 , about 112mg / m 2 , about 135mg / m 2 , about 140mg / m 2 , about 145mg / m 2 , about 150mg / m 2 or about 175 mg / m 2 , or a single dose or multiple doses of paclitaxel in a range of 48-75 mg / m2 or any of the above values. In some embodiments, the pharmaceutical combination further comprises a pharmaceutical composition containing cisplatin and a pharmaceutical composition containing paclitaxel, wherein the pharmaceutical composition containing cisplatin is prepared to be suitable for administering 48-75 mg / m2 to a patient. 2 A single dose or multiple doses of cisplatin, containing paclitaxel, is prepared to be suitable for administering to a patient 112-175 mg / m 2 In some embodiments, the pharmaceutical combination further comprises a pharmaceutical composition containing cisplatin and a pharmaceutical composition containing paclitaxel, wherein the pharmaceutical composition containing cisplatin is prepared to be suitable for administration to a patient at 75 mg / m 2 A single dose or multiple doses of cisplatin, a pharmaceutical composition containing paclitaxel is prepared to be suitable for administering to a patient 175 mg / m 2 In some embodiments, the pharmaceutical combination further comprises a pharmaceutical composition containing cisplatin and a pharmaceutical composition containing paclitaxel, wherein the pharmaceutical composition containing cisplatin is prepared to be suitable for administration to a patient at a dose of 30-75 mg / m 2 A single dose or multiple doses of cisplatin, containing paclitaxel, is prepared to be suitable for administering to a patient 67.5-150 mg / m 2 In some embodiments, the pharmaceutical combination further comprises a pharmaceutical composition containing cisplatin and a pharmaceutical composition containing paclitaxel, wherein the pharmaceutical composition containing cisplatin is prepared to be suitable for administering 60-75 mg / m 2 A single dose or multiple doses of cisplatin, and a pharmaceutical composition containing paclitaxel are prepared to be suitable for administering to a patient 135-175 mg / m 2 In some embodiments, the pharmaceutical combination further comprises a pharmaceutical composition containing cisplatin and a pharmaceutical composition containing paclitaxel, wherein the pharmaceutical composition containing cisplatin is prepared to be suitable for administering 60-75 mg / m2 A single dose or multiple doses of cisplatin, containing paclitaxel, is prepared to be suitable for administering to a patient 135-150 mg / m 2 In some embodiments, the pharmaceutical combination further comprises a pharmaceutical composition comprising cisplatin and a pharmaceutical composition comprising paclitaxel, wherein the pharmaceutical composition comprising cisplatin is prepared to be suitable for administration to a patient at about 60 mg / m 2 or about 75 mg / m 2 A single dose or multiple doses of cisplatin, and a pharmaceutical composition containing paclitaxel are prepared to be administered to a patient at a dose of about 135 mg / m 2 or about 150 mg / m 2 Single or multiple doses of paclitaxel.

[0153] In other embodiments, the pharmaceutical combination further comprises a pharmaceutical composition comprising carboplatin and a pharmaceutical composition comprising paclitaxel, wherein the pharmaceutical composition comprising carboplatin is prepared as a single dose or multiple doses suitable for administering to a patient 2.5-5 mg / (mL / min) AUC or 3.2-5 mg / (mL / min) AUC of carboplatin, and the pharmaceutical composition comprising paclitaxel is prepared as a single dose or multiple doses suitable for administering to a patient 75-175 mg / (mL / min) AUC of carboplatin. 2 100-175 mg / m 2 112-175 mg / m 2 or 135–175 mg / m 2 In other embodiments, the pharmaceutical combination further comprises a pharmaceutical composition comprising carboplatin and a pharmaceutical composition comprising paclitaxel, wherein the pharmaceutical composition comprising carboplatin is prepared to be suitable for administering to a patient a single dose or multiple doses of carboplatin of about 2.5 mg / (mL / min) AUC, about 3 mg / (mL / min) AUC, about 3.2 mg / (mL / min) AUC, about 3.5 mg / (mL / min) AUC, about 3.75 mg / (mL / min) AUC, about 4 mg / (mL / min) AUC, about 4.5 mg / (mL / min) AUC, or about 5 mg / (mL / min) AUC, or a range formed by any of the foregoing values, and the pharmaceutical composition comprising paclitaxel is prepared to be suitable for administering to a patient about 75 mg / (mL / min) AUC. 2 , about 90mg / m 2 , about 100mg / m 2 , about 105mg / m 2 , about 109mg / m 2 , about 112mg / m 2 , about 135mg / m 2 , about 140mg / m 2 , about 145mg / m 2 , about 150mg / m2 or about 175 mg / m 2 , or a single dose or multiple doses of paclitaxel in a range formed by any of the above values. In some embodiments, the pharmaceutical combination further comprises a pharmaceutical composition containing carboplatin and a pharmaceutical composition containing paclitaxel, wherein the pharmaceutical composition containing carboplatin is prepared as a single dose or multiple doses suitable for administering to a patient a carboplatin AUC of 3.2-5 mg / (mL / min), and the pharmaceutical composition containing paclitaxel is prepared as a single dose or multiple doses suitable for administering to a patient a carboplatin AUC of 112-175 mg / m 2 In some embodiments, the pharmaceutical combination further comprises a pharmaceutical composition comprising carboplatin and a pharmaceutical composition comprising paclitaxel, wherein the pharmaceutical composition comprising carboplatin is prepared as a single dose or multiple doses suitable for administering to a patient a carboplatin AUC of 5 mg / (mL / min) and the pharmaceutical composition comprising paclitaxel is prepared as a single dose or multiple doses suitable for administering to a patient a carboplatin AUC of 175 mg / (mL / min). 2 Single or multiple doses of paclitaxel.

[0154] In some embodiments, the pharmaceutical combination comprises a pharmaceutical composition comprising an anti-TIM-3 antibody or an antigen-binding fragment thereof, a pharmaceutical composition comprising an anti-PD-1 antibody or an antigen-binding fragment thereof, a pharmaceutical composition comprising cisplatin, and a pharmaceutical composition comprising paclitaxel. In some specific embodiments, in the pharmaceutical combination, the pharmaceutical composition comprising the anti-TIM-3 antibody or an antigen-binding fragment thereof is prepared as a single dose or multiple doses suitable for administering to a patient 100-1800 mg, 600-1800 mg, 600-1500 mg, or 1200-1500 mg of the anti-TIM-3 antibody or an antigen-binding fragment thereof, the pharmaceutical composition comprising the anti-PD-1 antibody or an antigen-binding fragment thereof is prepared as a single dose or multiple doses suitable for administering to a patient 10-800 mg, 50-500 mg, or 100-200 mg of the anti-PD-1 antibody or an antigen-binding fragment thereof, and the pharmaceutical composition comprising cisplatin is prepared as a single dose or multiple doses suitable for administering to a patient 30-100 mg / m 2 30-75 mg / m 2 48-75 mg / m 2 or 60–75 mg / m 2 A single dose or multiple doses of cisplatin, containing paclitaxel, is prepared to be suitable for administering to a patient 75-175 mg / m 2 100-175 mg / m 2 112-175 mg / m 2 or 135–175 mg / m 2In some specific embodiments, the pharmaceutical composition comprising the anti-TIM-3 antibody or its antigen-binding fragment is prepared as a single dose or multiple doses suitable for administering to a patient about 1200 mg or about 1500 mg of the anti-TIM-3 antibody or its antigen-binding fragment, the pharmaceutical composition comprising the anti-PD-1 antibody or its antigen-binding fragment is prepared as a single dose or multiple doses suitable for administering to a patient about 200 mg of the anti-PD-1 antibody or its antigen-binding fragment, and the pharmaceutical composition comprising cisplatin is prepared as a single dose or multiple doses suitable for administering to a patient 48-75 mg / m 2 A single dose or multiple doses of cisplatin, containing paclitaxel, is prepared to be suitable for administering to a patient 112-175 mg / m 2 In some specific embodiments, the pharmaceutical composition comprising the anti-TIM-3 antibody or its antigen-binding fragment is prepared as a single dose or multiple doses suitable for administering to a patient about 1200 mg of the anti-TIM-3 antibody or its antigen-binding fragment, the pharmaceutical composition comprising the anti-PD-1 antibody or its antigen-binding fragment is prepared as a single dose or multiple doses suitable for administering to a patient about 200 mg of the anti-PD-1 antibody or its antigen-binding fragment, and the pharmaceutical composition comprising cisplatin is prepared as a single dose or multiple doses suitable for administering to a patient 75 mg / m 2 A single dose or multiple doses of cisplatin, a pharmaceutical composition containing paclitaxel is prepared to be suitable for administering to a patient 175 mg / m 2 In some specific embodiments, in the pharmaceutical combination, the pharmaceutical composition containing the anti-TIM-3 antibody or its antigen-binding fragment is prepared as a single dose or multiple doses suitable for administering to the patient about 1200 mg or about 1500 mg of the anti-TIM-3 antibody or its antigen-binding fragment, the pharmaceutical composition containing the anti-PD-1 antibody or its antigen-binding fragment is prepared as a single dose or multiple doses suitable for administering to the patient about 200 mg of the anti-PD-1 antibody or its antigen-binding fragment, and the pharmaceutical composition containing cisplatin is prepared as a single dose or multiple doses suitable for administering to the patient 30-75 mg / m 2 A single dose or multiple doses of cisplatin, containing paclitaxel, is prepared to be suitable for administering to a patient 67.5-150 mg / m 2 In some specific embodiments, the pharmaceutical composition comprising the anti-TIM-3 antibody or its antigen-binding fragment is prepared as a single dose or multiple doses suitable for administering to a patient about 1200 mg or about 1500 mg of the anti-TIM-3 antibody or its antigen-binding fragment, the pharmaceutical composition comprising the anti-PD-1 antibody or its antigen-binding fragment is prepared as a single dose or multiple doses suitable for administering to a patient about 200 mg of the anti-PD-1 antibody or its antigen-binding fragment, and the pharmaceutical composition comprising cisplatin is prepared as a single dose or multiple doses suitable for administering to a patient 60-75 mg / m 2A single dose or multiple doses of cisplatin, and a pharmaceutical composition containing paclitaxel are prepared to be suitable for administering to a patient 135-175 mg / m 2 In some specific embodiments, the pharmaceutical composition comprising the anti-TIM-3 antibody or its antigen-binding fragment is prepared as a single dose or multiple doses suitable for administering to a patient about 1200 mg or about 1500 mg of the anti-TIM-3 antibody or its antigen-binding fragment, the pharmaceutical composition comprising the anti-PD-1 antibody or its antigen-binding fragment is prepared as a single dose or multiple doses suitable for administering to a patient about 200 mg of the anti-PD-1 antibody or its antigen-binding fragment, and the pharmaceutical composition comprising cisplatin is prepared as a single dose or multiple doses suitable for administering to a patient 60-75 mg / m 2 A single dose or multiple doses of cisplatin, containing paclitaxel, is prepared to be suitable for administering to a patient 135-150 mg / m 2 In some specific embodiments, the pharmaceutical composition comprising the anti-TIM-3 antibody or its antigen-binding fragment is prepared as a single dose or multiple doses suitable for administering to a patient about 1200 mg of the anti-TIM-3 antibody or its antigen-binding fragment, the pharmaceutical composition comprising the anti-PD-1 antibody or its antigen-binding fragment is prepared as a single dose or multiple doses suitable for administering to a patient about 200 mg of the anti-PD-1 antibody or its antigen-binding fragment, and the pharmaceutical composition comprising cisplatin is prepared as a single dose or multiple doses suitable for administering to a patient 60-75 mg / m 2 A single dose or multiple doses of cisplatin, containing paclitaxel, is prepared to be suitable for administering to a patient 135-150 mg / m 2 In some specific embodiments, the pharmaceutical composition comprising the anti-TIM-3 antibody or its antigen-binding fragment is prepared as a single dose or multiple doses suitable for administering to a patient about 1200 mg of the anti-TIM-3 antibody or its antigen-binding fragment, the pharmaceutical composition comprising the anti-PD-1 antibody or its antigen-binding fragment is prepared as a single dose or multiple doses suitable for administering to a patient about 200 mg of the anti-PD-1 antibody or its antigen-binding fragment, and the pharmaceutical composition comprising cisplatin is prepared as a single dose or multiple doses suitable for administering to a patient about 60 mg / m 2 or about 75 mg / m 2 A single dose or multiple doses of cisplatin, and a pharmaceutical composition containing paclitaxel are prepared to be administered to a patient at a dose of about 135 mg / m 2 or about 150 mg / m 2 Single or multiple doses of paclitaxel.

[0155] In other embodiments, the drug combination includes a pharmaceutical composition comprising an anti-TIM-3 antibody or an antigen-binding fragment thereof, a pharmaceutical composition comprising an anti-PD-1 antibody or an antigen-binding fragment thereof, a pharmaceutical composition comprising carboplatin, and a pharmaceutical composition comprising paclitaxel. In other specific embodiments, in the pharmaceutical combination, the pharmaceutical composition containing the anti-TIM-3 antibody or its antigen-binding fragment is prepared as a single dose or multiple doses suitable for administering to the patient about 100-1800 mg, 600-1800 mg, 600-1500 mg, or 1200-1500 mg of the anti-TIM-3 antibody or its antigen-binding fragment, the pharmaceutical composition containing the anti-PD-1 antibody or its antigen-binding fragment is prepared as a single dose or multiple doses suitable for administering to the patient 10-800 mg, 50-500 mg, or 100-200 mg of the anti-PD-1 antibody or its antigen-binding fragment, the pharmaceutical composition containing carboplatin is prepared as a single dose or multiple doses suitable for administering to the patient 2.5-5 mg / (mL / min) AUC or 3.2-5 mg / (mL / min) AUC of carboplatin, and the pharmaceutical composition containing paclitaxel is prepared as a single dose or multiple doses suitable for administering to the patient 75-175 mg / m 2 100-175 mg / m 2 112-175 mg / m 2 or 135–175 mg / m 2 In other specific embodiments, in the pharmaceutical combination, the pharmaceutical composition containing the anti-TIM-3 antibody or its antigen-binding fragment is prepared as a single dose or multiple doses suitable for administering to the patient about 1200 mg or about 1500 mg of the anti-TIM-3 antibody or its antigen-binding fragment, the pharmaceutical composition containing the anti-PD-1 antibody or its antigen-binding fragment is prepared as a single dose or multiple doses suitable for administering to the patient about 200 mg of the anti-PD-1 antibody or its antigen-binding fragment, the pharmaceutical composition containing carboplatin is prepared as a single dose or multiple doses suitable for administering to the patient 3.2-5 mg / (mL / min) AUC of carboplatin, and the pharmaceutical composition containing paclitaxel is prepared as a single dose or multiple doses suitable for administering to the patient 112-175 mg / m 2 In other specific embodiments, in the pharmaceutical combination, the pharmaceutical composition containing the anti-TIM-3 antibody or its antigen-binding fragment is prepared as a single dose or multiple doses suitable for administering to the patient about 1200 mg of the anti-TIM-3 antibody or its antigen-binding fragment, the pharmaceutical composition containing the anti-PD-1 antibody or its antigen-binding fragment is prepared as a single dose or multiple doses suitable for administering to the patient about 200 mg of the anti-PD-1 antibody or its antigen-binding fragment, the pharmaceutical composition containing carboplatin is prepared as a single dose or multiple doses suitable for administering to the patient 5 mg / (mL / min) AUC of carboplatin, and the pharmaceutical composition containing paclitaxel is prepared as a single dose or multiple doses suitable for administering to the patient 175 mg / (mL / min) AUC of paclitaxel.2 Single or multiple doses of paclitaxel.

[0156] In another aspect, the present disclosure provides a kit for treating a tumor, comprising a pharmaceutical composition comprising an anti-TIM-3 antibody or an antigen-binding fragment thereof and a pharmaceutical composition comprising an anti-PD-1 antibody or an antigen-binding fragment thereof, and instructions for using the pharmaceutical composition comprising the anti-TIM-3 antibody or an antigen-binding fragment thereof and the pharmaceutical composition comprising the anti-PD-1 antibody or an antigen-binding fragment thereof in combination to treat the tumor.

[0157] In other embodiments, the kit includes a pharmaceutical composition comprising an anti-TIM-3 antibody or antigen-binding fragment thereof, a pharmaceutical composition comprising an anti-PD-1 antibody or antigen-binding fragment thereof, and a pharmaceutical composition comprising a chemotherapeutic agent, as well as instructions for using the pharmaceutical composition comprising an anti-TIM-3 antibody or antigen-binding fragment thereof, a pharmaceutical composition comprising an anti-PD-1 antibody or antigen-binding fragment thereof, and a pharmaceutical composition comprising a chemotherapeutic agent in combination to treat a tumor. In some embodiments, the chemotherapeutic agent is a platinum-based antitumor agent and / or a taxane-based antitumor agent. In some embodiments, the chemotherapeutic agent is cisplatin and paclitaxel. In other embodiments, the chemotherapeutic agent is carboplatin and paclitaxel. In some specific embodiments, the kit includes a pharmaceutical composition comprising an anti-TIM-3 antibody or an antigen-binding fragment thereof, a pharmaceutical composition comprising an anti-PD-1 antibody or an antigen-binding fragment thereof, a pharmaceutical composition comprising cisplatin or carboplatin, and a pharmaceutical composition comprising paclitaxel, as well as instructions for using the pharmaceutical composition comprising an anti-TIM-3 antibody or an antigen-binding fragment thereof, the pharmaceutical composition comprising an anti-PD-1 antibody or an antigen-binding fragment thereof, the pharmaceutical composition comprising cisplatin or carboplatin, and the pharmaceutical composition comprising paclitaxel in combination to treat a tumor.

[0158] In another aspect, the present disclosure provides a kit for treating a tumor, comprising a pharmaceutical composition comprising an anti-TIM-3 antibody or an antigen-binding fragment thereof and an anti-PD-1 antibody or an antigen-binding fragment thereof, and instructions for using the pharmaceutical composition to treat a tumor.

[0159] In other embodiments, the kit includes a pharmaceutical composition comprising an anti-TIM-3 antibody or antigen-binding fragment thereof and an anti-PD-1 antibody or antigen-binding fragment thereof, a pharmaceutical composition comprising a chemotherapeutic agent, and instructions for using the pharmaceutical composition comprising the anti-TIM-3 antibody or antigen-binding fragment thereof and the anti-PD-1 antibody or antigen-binding fragment thereof in combination with the pharmaceutical composition comprising the chemotherapeutic agent to treat tumors. In some embodiments, the chemotherapeutic agent is a platinum-based anti-tumor agent and / or a taxane-based anti-tumor agent. In some embodiments, the chemotherapeutic agent is cisplatin and paclitaxel. In other embodiments, the chemotherapeutic agent is carboplatin and paclitaxel. In some specific embodiments, the kit includes a pharmaceutical composition comprising an anti-TIM-3 antibody or antigen-binding fragment thereof and an anti-PD-1 antibody or antigen-binding fragment thereof, a pharmaceutical composition comprising cisplatin or carboplatin, and a pharmaceutical composition comprising paclitaxel, and instructions for using the pharmaceutical composition comprising the anti-TIM-3 antibody or antigen-binding fragment thereof and the anti-PD-1 antibody or antigen-binding fragment thereof, a pharmaceutical composition comprising cisplatin or carboplatin, and a pharmaceutical composition comprising paclitaxel in combination with the pharmaceutical composition comprising the anti-TIM-3 antibody or antigen-binding fragment thereof and the anti-PD-1 antibody or antigen-binding fragment thereof, a pharmaceutical composition comprising cisplatin or carboplatin, and a pharmaceutical composition comprising paclitaxel to treat tumors.

[0160] In another aspect, the present disclosure further provides a drug package for treating tumors, which contains individually packaged pharmaceutical compositions in separate containers, wherein the first container contains a pharmaceutical composition containing an anti-TIM-3 antibody or an antigen-binding fragment thereof, and the second container contains a pharmaceutical composition containing an anti-PD-1 antibody or an antigen-binding fragment thereof; optionally, the drug package further comprises one or more additional containers, each containing a pharmaceutical composition containing a chemotherapeutic drug. In some embodiments, the chemotherapeutic drug is a platinum-based anti-tumor drug and / or a taxane-based anti-tumor drug. In some embodiments, the chemotherapeutic drug is cisplatin and paclitaxel. In other embodiments, the chemotherapeutic drug is carboplatin and paclitaxel. In some specific embodiments, the drug package contains individually packaged pharmaceutical compositions in separate containers, wherein the first container contains a pharmaceutical composition containing an anti-TIM-3 antibody or an antigen-binding fragment thereof, and the second container contains a pharmaceutical composition containing an anti-PD-1 antibody or an antigen-binding fragment thereof. In some specific embodiments, the drug pack contains single-packaged pharmaceutical compositions in separate containers, wherein the first container includes a pharmaceutical composition containing an anti-TIM-3 antibody or an antigen-binding fragment thereof, the second container includes a pharmaceutical composition containing an anti-PD-1 antibody or an antigen-binding fragment thereof, the third container includes a pharmaceutical composition containing cisplatin or carboplatin, and the fourth container includes a pharmaceutical composition containing paclitaxel.

[0161] In another aspect, the present disclosure further provides a drug package for treating tumors, which contains individually packaged pharmaceutical compositions in separate containers, wherein the first container contains a pharmaceutical composition containing an anti-TIM-3 antibody or an antigen-binding fragment thereof and an anti-PD-1 antibody or an antigen-binding fragment thereof; optionally, the package further comprises one or more additional containers, each containing a pharmaceutical composition containing a chemotherapeutic drug. In some embodiments, the chemotherapeutic drug is a platinum-based anti-tumor drug and / or a taxane-based anti-tumor drug. In some embodiments, the chemotherapeutic drug is cisplatin and paclitaxel. In other embodiments, the chemotherapeutic drug is carboplatin and paclitaxel. In some specific embodiments, the drug package contains individually packaged pharmaceutical compositions in separate containers, wherein the container contains a pharmaceutical composition containing an anti-TIM-3 antibody or an antigen-binding fragment thereof and an anti-PD-1 antibody or an antigen-binding fragment thereof. In some specific embodiments, the drug pack contains single-packaged pharmaceutical compositions in separate containers, wherein the first container includes a pharmaceutical composition containing an anti-TIM-3 antibody or an antigen-binding fragment thereof and an anti-PD-1 antibody or an antigen-binding fragment thereof, the second container includes a pharmaceutical composition containing cisplatin or carboplatin, and the third container includes a pharmaceutical composition containing paclitaxel.

[0162] In some embodiments, the pharmaceutical composition containing the anti-TIM-3 antibody or antigen-binding fragment thereof in the kit or pharmaceutical pack is a liquid or solid formulation. In some specific embodiments, the pharmaceutical composition containing the anti-TIM-3 antibody or antigen-binding fragment thereof is an injectable solution. In some specific embodiments, the pharmaceutical composition containing the anti-TIM-3 antibody or antigen-binding fragment thereof is a lyophilized formulation.

[0163] In some embodiments, the pharmaceutical composition containing the anti-PD-1 antibody or antigen-binding fragment thereof in the kit or pharmaceutical pack is a liquid preparation or a solid preparation. In some specific embodiments, the pharmaceutical composition containing the anti-PD-1 antibody or antigen-binding fragment thereof is an injection. In some specific embodiments, the pharmaceutical composition containing the anti-PD-1 antibody or antigen-binding fragment thereof is a lyophilized preparation.

[0164] In some embodiments, the pharmaceutical composition comprising the anti-TIM-3 antibody or antigen-binding fragment thereof and the anti-PD-1 antibody or antigen-binding fragment thereof in the kit or pharmaceutical pack is a liquid or solid formulation. In some specific embodiments, the pharmaceutical composition comprising the anti-TIM-3 antibody or antigen-binding fragment thereof and the anti-PD-1 antibody or antigen-binding fragment thereof is an injectable solution. In some specific embodiments, the pharmaceutical composition comprising the anti-TIM-3 antibody or antigen-binding fragment thereof and the anti-PD-1 antibody or antigen-binding fragment thereof is a lyophilized formulation.

[0165] In some embodiments, the pharmaceutical composition containing the chemotherapeutic drug in the kit or pharmaceutical pack is a liquid preparation or a solid preparation. In some specific embodiments, the pharmaceutical composition containing cisplatin in the kit or pharmaceutical pack is a liquid preparation. In some specific embodiments, the pharmaceutical composition containing cisplatin is an injectable solution. In some embodiments, the pharmaceutical composition containing cisplatin is a solid preparation. In some specific embodiments, the pharmaceutical composition containing cisplatin is a lyophilized preparation. In some specific embodiments, the pharmaceutical composition containing cisplatin is a powder preparation for injection. In some specific embodiments, the pharmaceutical composition containing carboplatin in the kit or pharmaceutical pack is a liquid preparation. In some specific embodiments, the pharmaceutical composition containing carboplatin is an injectable solution. In some embodiments, the pharmaceutical composition containing carboplatin is a solid preparation. In some specific embodiments, the pharmaceutical composition containing carboplatin is a lyophilized preparation. In some specific embodiments, the pharmaceutical composition containing carboplatin is a powder preparation for injection. In some specific embodiments, the pharmaceutical composition containing paclitaxel in the kit or pharmaceutical pack is a liquid preparation. In some specific embodiments, the pharmaceutical composition containing paclitaxel is an injectable solution. In some embodiments, the pharmaceutical composition containing paclitaxel is a solid preparation. In some embodiments, the pharmaceutical composition containing paclitaxel is a lyophilized preparation. In some embodiments, the pharmaceutical composition containing paclitaxel is a powder injection preparation.

[0166] In some embodiments, the tumor is a solid tumor. In some embodiments, the solid tumor is head and neck cancer. In some embodiments, the solid tumor is esophageal cancer.

[0167] use

[0168] The present disclosure also provides a method for treating a tumor in a subject, comprising administering a drug combination of the present disclosure to the subject. The present disclosure provides a method for treating a tumor in a subject as a first-line treatment, comprising administering a drug combination of the present disclosure to the subject. The present disclosure also provides a method for treating a tumor in a subject, comprising administering a drug combination of the present disclosure to the subject in a first treatment phase, and administering a drug combination of the present disclosure to the subject in a second treatment phase. In some specific embodiments, the present disclosure provides a method for treating a tumor in a subject as a first-line treatment, comprising administering a drug combination of the present disclosure to the subject. In some specific embodiments, the present disclosure provides a method for treating a tumor in a subject as a first-line treatment, comprising administering a drug combination of the present disclosure to the subject in a first treatment phase, and administering a drug combination of the present disclosure to the subject in a second treatment phase.

[0169] On the other hand, the present disclosure also provides the use of the drug combination of the present disclosure in the preparation of a medicament for treating a tumor in a subject. The present disclosure also provides the use of the drug combination of the present disclosure in the preparation of a medicament for first-line treatment of a tumor in a subject. In addition, the present disclosure also provides the use of the drug combination of the present disclosure in treating a tumor in a subject. The present disclosure also provides the use of the drug combination of the present disclosure in first-line treatment of a tumor in a subject. In some embodiments, the use comprises administering the drug combination of the present disclosure to a subject. In some embodiments, the use comprises administering the drug combination of the present disclosure to a subject in a first treatment phase, and administering the drug combination of the present disclosure to a subject in a second treatment phase.

[0170] On the other hand, the present disclosure also provides a method for treating tumors, comprising administering to a subject an anti-TIM-3 antibody or antigen-binding fragment thereof and an anti-PD-1 antibody or antigen-binding fragment thereof of the present disclosure. The present disclosure also provides a method for treating tumors, comprising administering to a subject an anti-TIM-3 antibody or antigen-binding fragment thereof, an anti-PD-1 antibody or antigen-binding fragment thereof, and a chemotherapeutic drug. The present disclosure also provides a method for first-line treatment of tumors, comprising administering to a subject an anti-TIM-3 antibody or antigen-binding fragment thereof and an anti-PD-1 antibody or antigen-binding fragment thereof of the present disclosure. The present disclosure also provides a method for first-line treatment of tumors, comprising administering to a subject an anti-TIM-3 antibody or antigen-binding fragment thereof, an anti-PD-1 antibody or antigen-binding fragment thereof, and a chemotherapeutic drug. In some specific embodiments, the present disclosure provides a method for first-line treatment of tumors in a subject, comprising administering to a subject an anti-TIM-3 antibody or antigen-binding fragment thereof, an anti-PD-1 antibody or antigen-binding fragment thereof of the present disclosure, and a chemotherapeutic drug in a first treatment phase, and administering to a subject an anti-TIM-3 antibody or antigen-binding fragment thereof and an anti-PD-1 antibody or antigen-binding fragment thereof of the present disclosure in a second treatment phase. In addition, the present disclosure also provides the use of the anti-TIM-3 antibody or antigen-binding fragment thereof and the anti-PD-1 antibody or antigen-binding fragment thereof in the preparation of a medicament for treating tumors. The present disclosure also provides the use of the anti-TIM-3 antibody or antigen-binding fragment thereof, the anti-PD-1 antibody or antigen-binding fragment thereof, and a chemotherapy drug in the preparation of a medicament for treating tumors. The present disclosure also provides the use of the anti-TIM-3 antibody or antigen-binding fragment thereof and the anti-PD-1 antibody or antigen-binding fragment thereof in the preparation of a medicament for first-line treatment of tumors. The present disclosure also provides the use of the anti-TIM-3 antibody or antigen-binding fragment thereof, the anti-PD-1 antibody or antigen-binding fragment thereof, and a chemotherapy drug in the preparation of a medicament for first-line treatment of tumors. In some embodiments, the chemotherapy drug is a platinum anti-tumor drug and / or a taxane anti-tumor drug. In some embodiments, the chemotherapy drug is cisplatin and paclitaxel. In some embodiments, the chemotherapy drug is carboplatin and paclitaxel.

[0171] On the other hand, the present disclosure also provides the use of the anti-TIM-3 antibody or its antigen-binding fragment in the preparation of a medicament for treating a tumor in a subject, wherein the medicament is used in combination with the anti-PD-1 antibody or its antigen-binding fragment. The present disclosure also provides the use of the anti-TIM-3 antibody or its antigen-binding fragment in the preparation of a medicament for treating a tumor in a subject, wherein the medicament is used in combination with the anti-PD-1 antibody or its antigen-binding fragment and a chemotherapeutic agent. The present disclosure also provides the use of the anti-TIM-3 antibody or its antigen-binding fragment in the preparation of a medicament for first-line treatment of a tumor in a subject, wherein the medicament is used in combination with the anti-PD-1 antibody or its antigen-binding fragment. The present disclosure also provides the use of the anti-TIM-3 antibody or its antigen-binding fragment in the preparation of a medicament for first-line treatment of a tumor in a subject, wherein the medicament is used in combination with the anti-PD-1 antibody or its antigen-binding fragment and a chemotherapeutic agent. In some embodiments, the chemotherapeutic agent is a platinum-based anti-tumor drug and / or a taxane-based anti-tumor drug. In some embodiments, the chemotherapeutic agent is cisplatin and paclitaxel. In some embodiments, the chemotherapy drugs are carboplatin and paclitaxel.

[0172] On the other hand, the present disclosure also provides the use of the anti-PD-1 antibody or its antigen-binding fragment of the present disclosure in the preparation of a medicament for treating a tumor in a subject, wherein the medicament is used in combination with the anti-TIM-3 antibody or its antigen-binding fragment of the present disclosure. The present disclosure also provides the use of the anti-PD-1 antibody or its antigen-binding fragment of the present disclosure in the preparation of a medicament for treating a tumor in a subject, wherein the medicament is used in combination with the anti-TIM-3 antibody or its antigen-binding fragment of the present disclosure and a chemotherapeutic agent. The present disclosure also provides the use of the anti-PD-1 antibody or its antigen-binding fragment of the present disclosure in the preparation of a medicament for first-line treatment of a tumor in a subject, wherein the medicament is used in combination with the anti-TIM-3 antibody or its antigen-binding fragment of the present disclosure. The present disclosure also provides the use of the anti-PD-1 antibody or its antigen-binding fragment of the present disclosure in the preparation of a medicament for first-line treatment of a tumor in a subject, wherein the medicament is used in combination with the anti-TIM-3 antibody or its antigen-binding fragment of the present disclosure and a chemotherapeutic agent. In some embodiments, the chemotherapeutic agent is a platinum-based anti-tumor drug and / or a taxane-based anti-tumor drug. In some embodiments, the chemotherapeutic agent is cisplatin and paclitaxel. In some embodiments, the chemotherapy drugs are carboplatin and paclitaxel.

[0173] In some embodiments, in the methods or uses, the drug combination comprises an anti-TIM-3 antibody or antigen-binding fragment thereof and an anti-PD-1 antibody or antigen-binding fragment thereof. In some embodiments, in the methods or uses, the drug combination comprises an anti-TIM-3 antibody or antigen-binding fragment thereof, an anti-PD-1 antibody or antigen-binding fragment thereof, and a chemotherapy drug. In some embodiments, the chemotherapy drug includes, but is not limited to, one or more of a platinum-based anti-tumor drug, a taxane-based anti-tumor drug, an antimetabolite-based anti-tumor drug, a camptothecin-based anti-tumor drug, a nitrogen mustard-based anti-tumor drug, an anthracycline-based anti-tumor drug, a vinblastine-based anti-tumor drug, a podophylloalkaloid-based anti-tumor drug, and a hormonal anti-tumor drug. In some embodiments, the chemotherapy drug is a platinum-based anti-tumor drug and / or a taxane-based anti-tumor drug. In some specific embodiments, the chemotherapy drug is cisplatin and paclitaxel. In other specific embodiments, the chemotherapy drug is carboplatin and paclitaxel.

[0174] In some embodiments, in the methods or uses, the drug combination comprises an anti-TIM-3 antibody or an antigen-binding fragment thereof, an anti-PD-1 antibody or an antigen-binding fragment thereof, a platinum anti-tumor drug, and a taxane anti-tumor drug. In some embodiments, in the methods or uses, the drug combination comprises an anti-TIM-3 antibody or an antigen-binding fragment thereof, an anti-PD-1 antibody or an antigen-binding fragment thereof, cisplatin, and paclitaxel. In other embodiments, in the methods or uses, the drug combination comprises an anti-TIM-3 antibody or an antigen-binding fragment thereof, an anti-PD-1 antibody or an antigen-binding fragment thereof, carboplatin, and paclitaxel.

[0175] In some embodiments, the method or use comprises administering to the subject a therapeutically effective amount of the pharmaceutical combination of the present disclosure in a first treatment phase, and administering to the subject a therapeutically effective amount of the pharmaceutical combination of the present disclosure in a second treatment phase.

[0176] In some embodiments, the method or use comprises administering to the subject in a first treatment phase a therapeutically effective amount of a drug combination comprising an anti-TIM-3 antibody or an antigen-binding fragment thereof, an anti-PD-1 antibody or an antigen-binding fragment thereof, and a chemotherapeutic drug; and

[0177] In the second treatment phase, the subject is administered a therapeutically effective amount of a drug combination comprising an anti-TIM-3 antibody or an antigen-binding fragment thereof and an anti-PD-1 antibody or an antigen-binding fragment thereof.

[0178] In some embodiments, the method or use comprises administering to the subject in a first treatment phase a therapeutically effective amount of a drug combination comprising an anti-TIM-3 antibody or an antigen-binding fragment thereof, an anti-PD-1 antibody or an antigen-binding fragment thereof, a platinum anti-tumor drug, and a taxane anti-tumor drug; and

[0179] In the second treatment phase, the subject is administered a therapeutically effective amount of a drug combination comprising an anti-TIM-3 antibody or an antigen-binding fragment thereof and an anti-PD-1 antibody or an antigen-binding fragment thereof.

[0180] In some embodiments, the method or use comprises administering to the subject in a first treatment phase a therapeutically effective amount of a drug combination comprising an anti-TIM-3 antibody or an antigen-binding fragment thereof, an anti-PD-1 antibody or an antigen-binding fragment thereof, cisplatin, and paclitaxel; and

[0181] In the second treatment phase, the subject is administered a therapeutically effective amount of a drug combination comprising an anti-TIM-3 antibody or an antigen-binding fragment thereof and an anti-PD-1 antibody or an antigen-binding fragment thereof.

[0182] In some embodiments, the method or use comprises administering to the subject in a first treatment phase a therapeutically effective amount of a drug combination comprising an anti-TIM-3 antibody or an antigen-binding fragment thereof, an anti-PD-1 antibody or an antigen-binding fragment thereof, carboplatin, and paclitaxel; and

[0183] In the second treatment phase, the subject is administered a therapeutically effective amount of a drug combination comprising an anti-TIM-3 antibody or an antigen-binding fragment thereof and an anti-PD-1 antibody or an antigen-binding fragment thereof.

[0184] In some embodiments, the first treatment phase comprises 1-14 treatment cycles, preferably 2-12 treatment cycles, 2-10 treatment cycles, more preferably 2-8 treatment cycles, for example, 2-8 treatment cycles, 3-8 treatment cycles, 4-8 treatment cycles, 2-7 treatment cycles, 3-7 treatment cycles, 4-7 treatment cycles, 2-6 treatment cycles, 3-6 treatment cycles, or 4-6 treatment cycles; most preferably 4-6 treatment cycles, for example, 4 treatment cycles, 5 treatment cycles, and / or 6 treatment cycles. In some embodiments, the first treatment phase comprises 4 treatment cycles. In some embodiments, the first treatment phase comprises 6 treatment cycles.

[0185] In some embodiments, one treatment cycle is every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks. In some embodiments, one treatment cycle is every 3 weeks.

[0186] In some embodiments, the second treatment phase is after the first treatment phase. In some embodiments, the second treatment phase continues from the end of the first treatment phase until the patient loses clinical benefit, has unacceptable toxicity, is evaluated as PD, or the investigator deems it inappropriate to continue the medication.

[0187] In some embodiments, in the methods or uses, the anti-TIM-3 antibody or antigen-binding fragment thereof and the anti-PD-1 antibody or antigen-binding fragment thereof can be administered simultaneously, sequentially, and / or alternately. In some embodiments, in the methods or uses, the anti-TIM-3 antibody or antigen-binding fragment thereof and the anti-PD-1 antibody or antigen-binding fragment thereof are administered sequentially. In some embodiments, in the methods or uses, the anti-TIM-3 antibody or antigen-binding fragment thereof and the anti-PD-1 antibody or antigen-binding fragment thereof are administered simultaneously. In some embodiments, in the methods or uses, the anti-TIM-3 antibody or antigen-binding fragment thereof and the anti-PD-1 antibody or antigen-binding fragment thereof are each in the form of a pharmaceutical composition and can be administered simultaneously, sequentially, and / or alternately. In some embodiments, in the methods or uses, the anti-TIM-3 antibody or antigen-binding fragment thereof and the anti-PD-1 antibody or antigen-binding fragment thereof are each in the form of a pharmaceutical composition and can be administered sequentially. In some embodiments, in the methods or uses, the anti-PD-1 antibody or antigen-binding fragment thereof is administered first, followed by the anti-TIM-3 antibody or antigen-binding fragment thereof. In some embodiments, in the methods or uses, the anti-TIM-3 antibody or antigen-binding fragment thereof and the anti-PD-1 antibody or antigen-binding fragment thereof are each in the form of a pharmaceutical composition, and the pharmaceutical composition containing the anti-PD-1 antibody or antigen-binding fragment thereof is administered first, followed by the pharmaceutical composition containing the anti-TIM-3 antibody or antigen-binding fragment thereof. In some embodiments, in the methods or uses, the anti-TIM-3 antibody or antigen-binding fragment thereof and the anti-PD-1 antibody or antigen-binding fragment thereof are formulated in a single formulation and administered simultaneously.

[0188] In some embodiments, in the methods or uses, the anti-TIM-3 antibody or antigen-binding fragment thereof, the anti-PD-1 antibody or antigen-binding fragment thereof, and the chemotherapeutic drug can be administered simultaneously, sequentially, and / or alternately. In some embodiments, in the methods or uses, the anti-TIM-3 antibody or antigen-binding fragment thereof, the anti-PD-1 antibody or antigen-binding fragment thereof, and the chemotherapeutic drug are each in the form of a pharmaceutical composition and can be administered simultaneously, sequentially, and / or alternately. In some embodiments, in the methods or uses, the anti-TIM-3 antibody or antigen-binding fragment thereof, the anti-PD-1 antibody or antigen-binding fragment thereof, cisplatin, and paclitaxel can be administered simultaneously, sequentially, and / or alternately. In some embodiments, in the methods or uses, the anti-TIM-3 antibody or antigen-binding fragment thereof, the anti-PD-1 antibody or antigen-binding fragment thereof, cisplatin, and paclitaxel are administered sequentially. In some embodiments, in the methods or uses, the anti-TIM-3 antibody or antigen-binding fragment thereof, the anti-PD-1 antibody or antigen-binding fragment thereof, cisplatin, and paclitaxel are each in the form of a pharmaceutical composition and can be administered simultaneously, sequentially, and / or alternately. In some embodiments, in the methods or uses, the anti-TIM-3 antibody or antigen-binding fragment thereof, the anti-PD-1 antibody or antigen-binding fragment thereof, cisplatin, and paclitaxel are each in the form of a pharmaceutical composition and are administered sequentially. In some embodiments, in the methods or uses, the anti-TIM-3 antibody or antigen-binding fragment thereof and the anti-PD-1 antibody or antigen-binding fragment thereof are formulated in a single formulation, and the single formulation, cisplatin, and paclitaxel are each in the form of a pharmaceutical composition and can be administered simultaneously, sequentially, and / or alternatingly. In some embodiments, in the methods or uses, the anti-TIM-3 antibody or antigen-binding fragment thereof and the anti-PD-1 antibody or antigen-binding fragment thereof are formulated in a single formulation, and the single formulation, cisplatin, and paclitaxel are each in the form of a pharmaceutical composition and are administered sequentially. In some embodiments, in the methods or uses, the anti-TIM-3 antibody or antigen-binding fragment thereof, the anti-PD-1 antibody or antigen-binding fragment thereof, carboplatin, and paclitaxel can be administered simultaneously, sequentially, and / or alternatingly. In some embodiments, in the methods or uses, the anti-TIM-3 antibody or antigen-binding fragment thereof, the anti-PD-1 antibody or antigen-binding fragment thereof, carboplatin, and paclitaxel are administered sequentially. In some embodiments, in the methods or uses, the anti-TIM-3 antibody or antigen-binding fragment thereof, the anti-PD-1 antibody or antigen-binding fragment thereof, carboplatin, and paclitaxel are each in the form of a pharmaceutical composition and can be administered simultaneously, sequentially, and / or alternately. In some embodiments, in the methods or uses, the anti-TIM-3 antibody or antigen-binding fragment thereof, the anti-PD-1 antibody or antigen-binding fragment thereof, carboplatin, and paclitaxel are each in the form of a pharmaceutical composition and are administered sequentially.In some embodiments, in the methods or uses, the anti-TIM-3 antibody or antigen-binding fragment thereof and the anti-PD-1 antibody or antigen-binding fragment thereof are formulated in a single formulation, and the single formulation, carboplatin, and paclitaxel are each in the form of a pharmaceutical composition and can be administered simultaneously, sequentially, and / or alternately. In some embodiments, in the methods or uses, the anti-TIM-3 antibody or antigen-binding fragment thereof and the anti-PD-1 antibody or antigen-binding fragment thereof are formulated in a single formulation, and the single formulation, carboplatin, and paclitaxel are each in the form of a pharmaceutical composition and can be administered sequentially.

[0189] In some embodiments, in the methods or uses, the anti-TIM-3 antibody or antigen-binding fragment thereof and the anti-PD-1 antibody or antigen-binding fragment thereof are administered using the same or different dosing regimens. In some embodiments, in the methods or uses, the anti-TIM-3 antibody or antigen-binding fragment thereof and the anti-PD-1 antibody or antigen-binding fragment thereof are administered using different dosing regimens.

[0190] In some embodiments, in the methods or uses, the anti-TIM-3 antibody or antigen-binding fragment thereof, the anti-PD-1 antibody or antigen-binding fragment thereof, and the chemotherapeutic agent are administered at the same or different dosing schedules. In some embodiments, in the methods or uses, the anti-TIM-3 antibody or antigen-binding fragment thereof, the anti-PD-1 antibody or antigen-binding fragment thereof, cisplatin, and paclitaxel are administered at the same or different dosing schedules. In some specific embodiments, in the methods or uses, the anti-TIM-3 antibody or antigen-binding fragment thereof, the anti-PD-1 antibody or antigen-binding fragment thereof, cisplatin, and paclitaxel are administered at different dosing schedules. In some embodiments, in the methods or uses, the anti-TIM-3 antibody or antigen-binding fragment thereof, the anti-PD-1 antibody or antigen-binding fragment thereof, carboplatin, and paclitaxel are administered at the same or different dosing schedules. In some specific embodiments, in the methods or uses, the anti-TIM-3 antibody or antigen-binding fragment thereof, the anti-PD-1 antibody or antigen-binding fragment thereof, carboplatin, and paclitaxel are administered at different dosing schedules.

[0191] In some embodiments, in the methods or uses, the anti-TIM-3 antibody or antigen-binding fragment thereof is administered once every 1 week (q1w), every 2 weeks (q2w), every 3 weeks (q3w), or every 4 weeks (q4w). In a specific embodiment, the anti-TIM-3 antibody or antigen-binding fragment thereof is administered once every 3 weeks. In some embodiments, the anti-TIM-3 antibody or antigen-binding fragment thereof is administered at a dose of 100-1800 mg, 600-1800 mg, 600-1500 mg, or 1200-1500 mg each time. In some embodiments, the anti-TIM-3 antibody or antigen-binding fragment thereof is administered at a dose of about 100 mg, about 200 mg, about 300 mg, about 400 mg, about 500 mg, about 600 mg, about 700 mg, about 800 mg, about 900 mg, about 1000 mg, about 1100 mg, about 1200 mg, about 1300 mg, about 1400 mg, about 1500 mg, about 1600 mg, about 1700 mg, or about 1800 mg, or a range thereof. In some embodiments, the anti-TIM-3 antibody or antigen-binding fragment thereof is administered at a dose of about 1200 mg or about 1500 mg. In some embodiments, the anti-TIM-3 antibody or antigen-binding fragment thereof is administered at a dose of about 1200 mg. In some embodiments, the anti-TIM-3 antibody or antigen-binding fragment thereof is administered once every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks, each time at a dose of 100-1800 mg, 600-1800 mg, 600-1500 mg, or 1200-1500 mg of the anti-TIM-3 antibody or antigen-binding fragment thereof. In some embodiments, the anti-TIM-3 antibody or antigen-binding fragment thereof is administered once every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks, each time at a dose of 1200-1500 mg of the anti-TIM-3 antibody or antigen-binding fragment thereof. In some embodiments, the anti-TIM-3 antibody or antigen-binding fragment thereof is administered once every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks, each time at a dose of about 1200 mg or about 1500 mg of the anti-TIM-3 antibody or antigen-binding fragment thereof. In some embodiments, the anti-TIM-3 antibody or antigen-binding fragment thereof is administered once every 3 weeks at a dose of about 1200 mg or about 1500 mg of the anti-TIM-3 antibody or antigen-binding fragment thereof. In some embodiments, the anti-TIM-3 antibody or antigen-binding fragment thereof is administered once every 3 weeks at a dose of about 1200 mg of the anti-TIM-3 antibody or antigen-binding fragment thereof.

[0192] In some embodiments, in the methods or uses, the anti-PD-1 antibody or antigen-binding fragment thereof is administered once every 1 week (q1w), every 2 weeks (q2w), every 3 weeks (q3w), or every 4 weeks (q4w). In a specific embodiment, the anti-PD-1 antibody or antigen-binding fragment thereof is administered once every 3 weeks. In some embodiments, the anti-PD-1 antibody or antigen-binding fragment thereof is administered at a dose of 10-800 mg, 50-500 mg, or 100-200 mg each time. In some embodiments, the anti-PD-1 antibody or antigen-binding fragment thereof is administered at a dose of about 10 mg, about 50 mg, about 100 mg, about 120 mg, about 140 mg, about 160 mg, about 180 mg, about 200 mg, about 220 mg, about 240 mg, about 260 mg, about 280 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, or about 800 mg, or a range formed by any of the above values. In some embodiments, the anti-PD-1 antibody or antigen-binding fragment thereof is administered at a dose of about 200 mg. In some embodiments, the anti-PD-1 antibody or antigen-binding fragment thereof is administered once every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks, each time at a dose of 10-800 mg, 50-500 mg, or 100-200 mg of the anti-PD-1 antibody or antigen-binding fragment thereof. In some embodiments, the anti-PD-1 antibody or antigen-binding fragment thereof is administered once every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks, each time at a dose of about 200 mg of the anti-PD-1 antibody or antigen-binding fragment thereof. In some embodiments, the anti-PD-1 antibody or antigen-binding fragment thereof is administered once every 3 weeks, each time at a dose of about 200 mg of the anti-PD-1 antibody or antigen-binding fragment thereof.

[0193] In some embodiments, in the methods or uses, the cisplatin is administered once every 1 week (q1w), every 2 weeks (q2w), every 3 weeks (q3w), or every 4 weeks (q4w). In some embodiments, in the methods or uses, the cisplatin is administered once every 3 weeks (q3w). In some embodiments, the cisplatin is administered at a dose of 30-100 mg / m 2 30-75 mg / m 2 48-75 mg / m 2 or 60–75 mg / m 2 In some embodiments, the cisplatin is administered at a dose of about 30 mg / m 2 , about 32mg / m 2 , about 35mg / m 2 , about 37mg / m 2, about 40mg / m 2 , about 45mg / m 2 , about 48mg / m 2 , about 50mg / m 2 , about 52mg / m 2 , about 54mg / m 2 , about 56mg / m 2 , about 60mg / m 2 , about 65mg / m 2 , about 70mg / m 2 , about 75mg / m 2 , about 80mg / m 2 , about 90mg / m 2 or about 100 mg / m 2 , or a dose within the range of any of the above values. In some embodiments, the cisplatin is administered at a dose of 48-75 mg / m 2 In some embodiments, the cisplatin is administered at a dose of 30-75 mg / m 2 In some embodiments, the cisplatin is administered at a dose of 60-75 mg / m 2 In some embodiments, the cisplatin is administered once every 3 weeks at a dose of 48-75 mg / m 2 In some embodiments, the cisplatin is administered once every 3 weeks at a dose of 30-75 mg / m 2 In some embodiments, the cisplatin is administered once every 3 weeks at a dose of 60-75 mg / m 2 In some embodiments, the cisplatin is administered once every 3 weeks at a dose of about 75 mg / m 2 In some embodiments, the cisplatin is administered once every 3 weeks at a dose of about 60 mg / m 2 or about 75 mg / m 2 Dosage administration of cisplatin.

[0194] In some embodiments, in the methods or uses, the carboplatin is administered once every 1 week (q1w), every 2 weeks (q2w), every 3 weeks (q3w), or every 4 weeks (q4w). In some embodiments, in the methods or uses, the carboplatin is administered once every 3 weeks (q3w). In some embodiments, the carboplatin is administered at a dose of 2.5-5 mg / (mL / min) AUC or 3.2-5 mg / (mL / min) AUC each time. In some embodiments, the carboplatin is administered at a dose of about 2.5 mg / (mL / min) AUC, about 3 mg / (mL / min) AUC, about 3.2 mg / (mL / min) AUC, about 3.5 mg / (mL / min) AUC, about 3.75 mg / (mL / min) AUC, about 4 mg / (mL / min) AUC, about 4.5 mg / (mL / min) AUC, or about 5 mg / (mL / min) AUC, or a range of any of the above values. In some embodiments, the carboplatin is administered at a dose of 3.2-5 mg / (mL / min) AUC each time. In some embodiments, the carboplatin is administered at a dose of 5 mg / (mL / min) AUC each time. In some embodiments, the carboplatin is administered once every 3 weeks at a dose of 3.2-5 mg / (mL / min) AUC each time. In some embodiments, the carboplatin is administered once every 3 weeks at a dose of 5 mg / (mL / min) AUC each time.

[0195] In some embodiments, in the methods or uses, the paclitaxel is administered once every 1 week (q1w), every 2 weeks (q2w), every 3 weeks (q3w), or every 4 weeks (q4w). In some embodiments, in the methods or uses, the paclitaxel is administered once every 3 weeks (q3w). In some embodiments, the paclitaxel is administered at a dose of 75-175 mg / m 2 100-175 mg / m 2 112-175 mg / m 2 or 135–175 mg / m 2 In some embodiments, the paclitaxel is administered at a dose of about 75 mg / m 2 , about 90mg / m 2 , about 100mg / m 2 , about 105mg / m 2 , about 109mg / m 2 , about 112mg / m 2 , about 135mg / m 2 , about 140mg / m 2 , about 145mg / m 2 , about 150mg / m 2or about 175 mg / m 2 , or a dose within the range formed by any of the above values. In some embodiments, the paclitaxel is administered at a dose of 112-175 mg / m 2 In some embodiments, the paclitaxel is administered at a dose of 67.5-150 mg / m 2 In some embodiments, the paclitaxel is administered at a dose of 135-150 mg / m 2 In some embodiments, the paclitaxel is administered once every 3 weeks at a dose of 112-175 mg / m 2 In some embodiments, the paclitaxel is administered once every 3 weeks at a dose of 67.5-150 mg / m 2 In some embodiments, the paclitaxel is administered once every 3 weeks at a dose of 135-150 mg / m 2 In some embodiments, the paclitaxel is administered once every 3 weeks at a dose of about 175 mg / m 2 In some embodiments, the paclitaxel is administered once every 3 weeks at a dose of about 135 mg / m 2 or about 150 mg / m 2 Dosage of paclitaxel.

[0196] In some embodiments, in the methods or uses, the anti-TIM-3 antibody or antigen-binding fragment thereof and the anti-PD-1 antibody or antigen-binding fragment thereof have the same or different treatment cycles. In some specific embodiments, the anti-TIM-3 antibody or antigen-binding fragment thereof and the anti-PD-1 antibody or antigen-binding fragment thereof have the same treatment cycle, for example, every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks is a treatment cycle. In some specific embodiments, the anti-TIM-3 antibody or antigen-binding fragment thereof and the anti-PD-1 antibody or antigen-binding fragment thereof have the same treatment cycle, for example, every 3 weeks is a treatment cycle.

[0197] In some embodiments, in the methods or uses, the anti-TIM-3 antibody or antigen-binding fragment thereof, the anti-PD-1 antibody or antigen-binding fragment thereof, and the chemotherapy drug have the same or different treatment cycles. In some embodiments, in the methods or uses, the anti-TIM-3 antibody or antigen-binding fragment thereof, the anti-PD-1 antibody or antigen-binding fragment thereof, cisplatin, and paclitaxel have the same or different treatment cycles. In some specific embodiments, the anti-TIM-3 antibody or antigen-binding fragment thereof, the anti-PD-1 antibody or antigen-binding fragment thereof, cisplatin, and paclitaxel have the same treatment cycle, for example, every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks is a treatment cycle. In some specific embodiments, the anti-TIM-3 antibody or antigen-binding fragment thereof, the anti-PD-1 antibody or antigen-binding fragment thereof, cisplatin, and paclitaxel have the same treatment cycle, for example, every 3 weeks is a treatment cycle. In some embodiments, in the methods or uses, the anti-TIM-3 antibody or antigen-binding fragment thereof, the anti-PD-1 antibody or antigen-binding fragment thereof, carboplatin, and paclitaxel have the same or different treatment cycles. In some specific embodiments, the anti-TIM-3 antibody or antigen-binding fragment thereof, the anti-PD-1 antibody or antigen-binding fragment thereof, carboplatin, and paclitaxel have the same treatment cycle, for example, every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks is a treatment cycle. In some specific embodiments, the anti-TIM-3 antibody or antigen-binding fragment thereof, the anti-PD-1 antibody or antigen-binding fragment thereof, carboplatin, and paclitaxel have the same treatment cycle, for example, every 3 weeks is a treatment cycle.

[0198] In some embodiments, in the methods or uses, every 3 weeks is a treatment cycle, and the anti-TIM-3 antibody or its antigen-binding fragment and the anti-PD-1 antibody or its antigen-binding fragment are administered in each treatment cycle. In some embodiments, in the methods or uses, every 3 weeks is a treatment cycle, and the anti-TIM-3 antibody or its antigen-binding fragment and the anti-PD-1 antibody or its antigen-binding fragment are administered once in each treatment cycle. In some embodiments, in the methods or uses, every 3 weeks is a treatment cycle, and the anti-TIM-3 antibody or its antigen-binding fragment is administered on day 1 of each treatment cycle, and the anti-PD-1 antibody or its antigen-binding fragment is administered on day 1 of each treatment cycle. In some embodiments, in the methods or uses, every 3 weeks is a treatment cycle, and the anti-TIM-3 antibody or its antigen-binding fragment is administered once on day 1 of each treatment cycle, and the anti-PD-1 antibody or its antigen-binding fragment is administered once on day 1 of each treatment cycle.

[0199] In some embodiments, in the methods or uses, the anti-TIM-3 antibody or antigen-binding fragment thereof and the anti-PD-1 antibody or antigen-binding fragment thereof are formulated in a single formulation. In these embodiments, the single formulation is administered every 3 weeks as a treatment cycle. Alternatively, in these embodiments, the single formulation is administered once every 3 weeks as a treatment cycle. Alternatively, in these embodiments, the single formulation is administered on day 1 of each treatment cycle every 3 weeks as a treatment cycle. Alternatively, in these embodiments, the single formulation is administered on day 1 of each treatment cycle every 3 weeks as a treatment cycle.

[0200] In some specific embodiments, in the methods or uses, every 3 weeks is a treatment cycle, and about 1200 mg or about 1500 mg of the anti-TIM-3 antibody or its antigen-binding fragment is administered in each treatment cycle, and about 200 mg of the anti-PD-1 antibody or its antigen-binding fragment is administered in each treatment cycle. In some specific embodiments, in the methods or uses, every 3 weeks is a treatment cycle, and about 1200 mg of the anti-TIM-3 antibody or its antigen-binding fragment is administered in each treatment cycle, and about 200 mg of the anti-PD-1 antibody or its antigen-binding fragment is administered in each treatment cycle. In some specific embodiments, in the methods or uses, every 3 weeks is a treatment cycle, and about 1200 mg or about 1500 mg of the anti-TIM-3 antibody or its antigen-binding fragment is administered on day 1 of each treatment cycle, and about 200 mg of the anti-PD-1 antibody or its antigen-binding fragment is administered on day 1 of each treatment cycle. In some specific embodiments, in the method or use, one treatment cycle is 3 weeks, and about 1200 mg of anti-TIM-3 antibody or its antigen-binding fragment is administered on the first day of each treatment cycle, and about 200 mg of anti-PD-1 antibody or its antigen-binding fragment is administered on the first day of each treatment cycle.

[0201] In some embodiments, in the methods or uses, every 3 weeks is a treatment cycle, and the anti-TIM-3 antibody or its antigen-binding fragment, the anti-PD-1 antibody or its antigen-binding fragment, and the chemotherapy drug are administered in each treatment cycle. In some embodiments, in the methods or uses, every 3 weeks is a treatment cycle, and the anti-TIM-3 antibody or its antigen-binding fragment, the anti-PD-1 antibody or its antigen-binding fragment, cisplatin, and paclitaxel are administered in each treatment cycle. Alternatively, every 3 weeks is a treatment cycle, and the anti-TIM-3 antibody or its antigen-binding fragment, the anti-PD-1 antibody or its antigen-binding fragment, carboplatin, and paclitaxel are administered in each treatment cycle. In some embodiments, in the methods or uses, every 3 weeks is a treatment cycle, and the anti-TIM-3 antibody or its antigen-binding fragment, the anti-PD-1 antibody or its antigen-binding fragment, cisplatin, and paclitaxel are administered once each in each treatment cycle. Alternatively, every 3 weeks is a treatment cycle, and the anti-TIM-3 antibody or its antigen-binding fragment, the anti-PD-1 antibody or its antigen-binding fragment, carboplatin, and paclitaxel are administered once each in each treatment cycle. In some embodiments, in the methods or uses, one treatment cycle is 3 weeks, and the anti-TIM-3 antibody or its antigen-binding fragment is administered on day 1 of each treatment cycle, the anti-PD-1 antibody or its antigen-binding fragment is administered on day 1 of each treatment cycle, cisplatin or carboplatin is administered on day 1 of each treatment cycle, and paclitaxel is administered on day 1 of each treatment cycle. In some embodiments, in the methods or uses, one treatment cycle is 3 weeks, and the anti-TIM-3 antibody or its antigen-binding fragment is administered once on day 1 of each treatment cycle, the anti-PD-1 antibody or its antigen-binding fragment is administered once on day 1 of each treatment cycle, cisplatin or carboplatin is administered once on day 1 of each treatment cycle, and paclitaxel is administered once on day 1 of each treatment cycle.

[0202] In some embodiments, in the methods or uses, the anti-TIM-3 antibody or antigen-binding fragment thereof and the anti-PD-1 antibody or antigen-binding fragment thereof are formulated in a single formulation. In these embodiments, the single formulation and the chemotherapeutic agent are administered in each 3-week treatment cycle. Alternatively, in these embodiments, the single formulation, cisplatin, and paclitaxel are administered in each 3-week treatment cycle. Alternatively, in these embodiments, the single formulation, carboplatin, and paclitaxel are administered in each 3-week treatment cycle. Alternatively, in these embodiments, the single formulation, cisplatin, and paclitaxel are administered once in each 3-week treatment cycle. Alternatively, in these embodiments, the single formulation, carboplatin, and paclitaxel are administered once in each 3-week treatment cycle. Alternatively, in these embodiments, the single formulation, carboplatin, and paclitaxel are administered once in each 3-week treatment cycle. Alternatively, in these embodiments, the single formulation, cisplatin or carboplatin are administered on Day 1 of each 3-week treatment cycle, and paclitaxel is administered on Day 1 of each 3-week treatment cycle. Alternatively, in these embodiments, every 3 weeks is a treatment cycle, the single agent is administered once on day 1 of each treatment cycle, cisplatin or carboplatin is administered once on day 1 of each treatment cycle, and paclitaxel is administered once on day 1 of each treatment cycle.

[0203] In some specific embodiments, in the methods or uses, every 3 weeks is a treatment cycle, and 100-1800 mg, 600-1800 mg, 600-1500 mg, or 1200-1500 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof is administered in each treatment cycle, 10-800 mg, 50-500 mg, or 100-200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof is administered in each treatment cycle, and 30-100 mg / m2 is administered in each treatment cycle. 2 30-75 mg / m 2 48-75 mg / m 2 or 60–75 mg / m 2 Cisplatin, 75-175 mg / m2 per treatment cycle 2 100-175 mg / m 2 112-175 mg / m 2 or 135–175 mg / m 2 In some specific embodiments, in the methods or uses, every 3 weeks is a treatment cycle, and about 1200 mg or about 1500 mg of anti-TIM-3 antibody or its antigen-binding fragment is administered in each treatment cycle, about 200 mg of anti-PD-1 antibody or its antigen-binding fragment is administered in each treatment cycle, and 48-75 mg / m2 is administered in each treatment cycle. 2Cisplatin, 112-175 mg / m2 per treatment cycle 2 In some specific embodiments, in the methods or uses, every 3 weeks is a treatment cycle, and about 1200 mg of anti-TIM-3 antibody or its antigen-binding fragment is administered in each treatment cycle, about 200 mg of anti-PD-1 antibody or its antigen-binding fragment is administered in each treatment cycle, and 75 mg / m 2 Cisplatin, 175 mg / m2 per treatment cycle 2 In some specific embodiments, in the methods or uses, every 3 weeks is a treatment cycle, and about 1200 mg or about 1500 mg of anti-TIM-3 antibody or its antigen-binding fragment is administered in each treatment cycle, about 200 mg of anti-PD-1 antibody or its antigen-binding fragment is administered in each treatment cycle, and 30-75 mg / m2 is administered in each treatment cycle. 2 Cisplatin, 67.5-150 mg / m2 per treatment cycle 2 In some specific embodiments, in the methods or uses, every 3 weeks is a treatment cycle, and about 1200 mg or about 1500 mg of anti-TIM-3 antibody or its antigen-binding fragment is administered in each treatment cycle, about 200 mg of anti-PD-1 antibody or its antigen-binding fragment is administered in each treatment cycle, and 60-75 mg / m2 is administered in each treatment cycle. 2 Cisplatin, 135-150 mg / m2 per treatment cycle 2 In some specific embodiments, in the methods or uses, every 3 weeks is a treatment cycle, and about 1200 mg of anti-TIM-3 antibody or its antigen-binding fragment is administered in each treatment cycle, about 200 mg of anti-PD-1 antibody or its antigen-binding fragment is administered in each treatment cycle, and 60-75 mg / m2 is administered in each treatment cycle. 2 Cisplatin, 135-150 mg / m2 per treatment cycle 2 In some specific embodiments, in the methods or uses, every 3 weeks is a treatment cycle, and about 1200 mg or about 1500 mg of anti-TIM-3 antibody or its antigen-binding fragment is administered on the first day of each treatment cycle, about 200 mg of anti-PD-1 antibody or its antigen-binding fragment is administered on the first day of each treatment cycle, and 48-75 mg / m2 is administered on the first day of each treatment cycle. 2 Cisplatin, 112-175 mg / m2 on day 1 of each treatment cycle 2In some specific embodiments, in the methods or uses, every 3 weeks is a treatment cycle, and about 1200 mg of anti-TIM-3 antibody or its antigen-binding fragment is administered on the first day of each treatment cycle, about 200 mg of anti-PD-1 antibody or its antigen-binding fragment is administered on the first day of each treatment cycle, and 75 mg / m2 is administered on the first day of each treatment cycle. 2 Cisplatin, 175 mg / m2 on day 1 of each treatment cycle 2 In some specific embodiments, in the methods or uses, every 3 weeks is a treatment cycle, and about 1200 mg or about 1500 mg of anti-TIM-3 antibody or its antigen-binding fragment is administered on the first day of each treatment cycle, about 200 mg of anti-PD-1 antibody or its antigen-binding fragment is administered on the first day of each treatment cycle, and 60-75 mg / m2 is administered on the first day of each treatment cycle. 2 Cisplatin, 135-150 mg / m2 on day 1 of each treatment cycle 2 In some specific embodiments, in the methods or uses, one treatment cycle is 3 weeks, and about 1200 mg of anti-TIM-3 antibody or its antigen-binding fragment is administered on the first day of each treatment cycle, about 200 mg of anti-PD-1 antibody or its antigen-binding fragment is administered on the first day of each treatment cycle, and 60-75 mg / m2 is administered on the first day of each treatment cycle. 2 Cisplatin, 135-150 mg / m2 on day 1 of each treatment cycle 2 In some specific embodiments, in the methods or uses, every 3 weeks is a treatment cycle, and about 1200 mg of anti-TIM-3 antibody or its antigen-binding fragment is administered on the first day of each treatment cycle, about 200 mg of anti-PD-1 antibody or its antigen-binding fragment is administered on the first day of each treatment cycle, and about 60 mg / m2 is administered on the first day of each treatment cycle. 2 or about 75 mg / m 2 Cisplatin, approximately 135 mg / m2, was administered on day 1 of each treatment cycle. 2 or about 150 mg / m 2 of paclitaxel.

[0204] In some specific embodiments, in the methods or uses, every 3 weeks is a treatment cycle, 100-1800 mg, 600-1800 mg, 600-1500 mg, or 1200-1500 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof is administered in each treatment cycle, 10-800 mg, 50-500 mg, or 100-200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof is administered in each treatment cycle, 2.5-5 mg / (mL / min) AUC or 3.2-5 mg / (mL / min) AUC of carboplatin is administered in each treatment cycle, and 75-175 mg / m 2 100-175 mg / m 2 112-175 mg / m 2 or 135–175 mg / m 2 In some specific embodiments, in the methods or uses, every 3 weeks is a treatment cycle, and in each treatment cycle, about 1200 mg or about 1500 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof is administered, about 200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof is administered, 3.2-5 mg / (mL / min) AUC of carboplatin is administered in each treatment cycle, and 112-175 mg / m 2 In some specific embodiments, in the methods or uses, every 3 weeks is a treatment cycle, and in each treatment cycle, about 1200 mg of anti-TIM-3 antibody or its antigen-binding fragment is administered, about 200 mg of anti-PD-1 antibody or its antigen-binding fragment is administered, 5 mg / (mL / min) AUC of carboplatin is administered in each treatment cycle, and 175 mg / m 2 In some specific embodiments, in the methods or uses, every 3 weeks is a treatment cycle, and on the first day of each treatment cycle, about 1200 mg or about 1500 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof is administered, on the first day of each treatment cycle, about 200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof is administered, on the first day of each treatment cycle, 3.2-5 mg / (mL / min) AUC of carboplatin is administered, and on the first day of each treatment cycle, 112-175 mg / m 2In some specific embodiments, in the methods or uses, every 3 weeks is a treatment cycle, and on the first day of each treatment cycle, about 1200 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof is administered, on the first day of each treatment cycle, about 200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof is administered, on the first day of each treatment cycle, 5 mg / (mL / min) AUC of carboplatin is administered, and on the first day of each treatment cycle, 175 mg / (mL / min) AUC of dapoxetine is administered. 2 of paclitaxel.

[0205] In some embodiments, in each treatment cycle, the anti-TIM-3 antibody or its antigen-binding fragment and the anti-PD-1 antibody or its antigen-binding fragment are administered to the subject at a mass ratio of (0.1-180):1, (0.2-50):1, (0.5-9):1, (3-7.5):1, (4-7.5):1, or (6-7.5):1 of the anti-TIM-3 antibody or its antigen-binding fragment: the anti-PD-1 antibody or its antigen-binding fragment; optionally, the subject is further administered a chemotherapy drug. In some embodiments, the chemotherapy drug is a platinum anti-tumor drug and / or a taxane anti-tumor drug. In some specific embodiments, the chemotherapy drug is cisplatin and paclitaxel. In other specific embodiments, the chemotherapy drug is carboplatin and paclitaxel. In some embodiments, in each treatment cycle, the anti-TIM-3 antibody or its antigen-binding fragment and the anti-PD-1 antibody or its antigen-binding fragment are administered to the subject at a mass ratio of anti-TIM-3 antibody or its antigen-binding fragment: anti-PD-1 antibody or its antigen-binding fragment of (0.1-180):1, (0.2-50):1, (0.5-9):1, (3-7.5):1, (4-7.5):1, or (6-7.5):1; optionally, the subject is further administered cisplatin and paclitaxel. In some embodiments, in each treatment cycle, the anti-TIM-3 antibody or its antigen-binding fragment and the anti-PD-1 antibody or its antigen-binding fragment are administered to the subject at a mass ratio of anti-TIM-3 antibody or its antigen-binding fragment: anti-PD-1 antibody or its antigen-binding fragment of (0.1-180):1, (0.2-50):1, (0.5-9):1, (3-7.5):1, (4-7.5):1, or (6-7.5):1; optionally, the subject is further administered carboplatin and paclitaxel.

[0206] In some embodiments, the anti-TIM-3 antibody or antigen-binding fragment thereof and the anti-PD-1 antibody or antigen-binding fragment thereof are administered in multiple doses or a single dose in each treatment cycle. In some embodiments, the anti-TIM-3 antibody or antigen-binding fragment thereof and the anti-PD-1 antibody or antigen-binding fragment thereof are both administered in multiple doses in each treatment cycle. In some embodiments, the anti-TIM-3 antibody or antigen-binding fragment thereof, the anti-PD-1 antibody or antigen-binding fragment thereof and the chemotherapeutic drug are administered in multiple doses or a single dose in each treatment cycle. In some embodiments, the anti-TIM-3 antibody or antigen-binding fragment thereof, the anti-PD-1 antibody or antigen-binding fragment thereof, cisplatin and paclitaxel are administered in multiple doses or a single dose in each treatment cycle. In some embodiments, the anti-TIM-3 antibody or antigen-binding fragment thereof, the anti-PD-1 antibody or antigen-binding fragment thereof, cisplatin and paclitaxel are both administered in multiple doses in each treatment cycle. In some embodiments, the anti-TIM-3 antibody or antigen-binding fragment thereof, anti-PD-1 antibody or antigen-binding fragment thereof, carboplatin, and paclitaxel are administered in multiple doses or a single dose during each treatment cycle. In some embodiments, the anti-TIM-3 antibody or antigen-binding fragment thereof, anti-PD-1 antibody or antigen-binding fragment thereof, carboplatin, and paclitaxel are administered in multiple doses during each treatment cycle.

[0207] In some embodiments, in the methods or uses, the anti-TIM-3 antibody or antigen-binding fragment thereof can be selected from 0.01 to 50 mg / kg, 0.1 to 40 mg / kg, 0.1 to 35 mg / kg, 0.1 to 30 mg / kg, 0.1 to 25 mg / kg, 0.1 to 20 mg / kg, 0.1 to 15 mg / kg, 0.1 to 10 mg / kg, 1 to 40 mg / kg, 1 to 35 mg / kg, 1 to 30 mg / kg, 1 to 25 mg / kg, 1 to 20 mg / kg, 1 to 15 mg / kg, 1 to 10 mg / kg, 1 to 3 mg / kg, 3 to 40 mg / kg, 3 to 35 mg / kg, 3 to 30 mg / kg, 3 to 25 mg / kg, 3 to 20 mg / kg, 3 to 15 mg / kg, 3 to 10 mg / kg, 10 to 40 mg / kg, 10 to 30 mg / kg, 10 to 2 5 mg / kg, or 20 to 25 mg / kg; or 1-2400 mg, 20-1800 mg, 100-1800 mg, 300-1800 mg, 600-1600 mg, 700-1600 mg, 800-1600 mg, 900-1600 mg, 1000-1600 mg, 1100-1600 mg, 1200-1600 mg, 1300-1 A uniform dose of 600 mg, 1400-1600 mg, 1500-1600 mg, 600-1500 mg, 800-1500 mg, 1000-1500 mg, 1200-1500 mg, 600-1200 mg, 800-1200 mg, 1200 mg to 1800 mg, 800 mg, 1000 mg, 1200 mg, 1600 mg or 1800 mg is administered to the subject.

[0208] In some embodiments, in the methods or uses, the anti-PD-1 antibody or antigen-binding fragment thereof can be selected from 0.01 to 50 mg / kg, 0.1 to 40 mg / kg, 0.1 to 35 mg / kg, 0.1 to 30 mg / kg, 0.1 to 25 mg / kg, 0.1 to 20 mg / kg, 0.1 to 15 mg / kg, 0.1 to 10 mg / kg, 1 to 30 mg / kg, 1 to 25 mg / kg, 1 to 20 mg / kg, 1 to 15 mg / kg, 1 to 10 mg / kg, 1 to 8 mg / kg, 1 to 5 mg / kg, 1 to 3 mg / kg, 3 to 30 mg / kg, 3 to 25 mg / kg, 3 to 20 mg / kg, 3 to 15 mg / kg, 3 to 10 mg / kg, 3 to or administered to a subject at a uniform dose of 1-1000 mg, 10-1000 mg, 10-800 mg, 20-800 mg, 40-800 mg, 50-700 mg, 50-600 mg, 50-500 mg, 60-500 mg, 80-500 mg, 100-500 mg, 200-500 mg, 100-500 mg, 100-400 mg, 50-350 mg, 100-300 mg, 50-200 mg, 100-200 mg, 100 mg or 200 mg.

[0209] In some embodiments, in the methods or uses, the dosing regimen (e.g., dosing cycle, dosage, and dose adjustment) of the anti-TIM-3 antibody or antigen-binding fragment thereof, anti-PD-1 antibody or antigen-binding fragment thereof, and chemotherapy drug (e.g., cisplatin and paclitaxel, or carboplatin and paclitaxel) can be adjusted according to the severity of the disease, the response to the disease, any treatment-related toxicity, the patient's age and health status. For example, a treatment cycle of an anti-TIM-3 antibody or antigen-binding fragment thereof and / or an anti-PD-1 antibody or antigen-binding fragment thereof can be adjusted to 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, or 15 weeks. For example, the dosage of cisplatin, carboplatin, and / or paclitaxel can be adjusted to 80%, 75%, or 64% of the initial dosage. For example, a treatment cycle of cisplatin, carboplatin, and / or paclitaxel can be adjusted to 4 weeks.

[0210] Anti-TIM-3 antibodies or antigen-binding fragments thereof

[0211] In some embodiments, the anti-TIM-3 antibodies or antigen-binding fragments thereof described herein comprise: a heavy chain CDR1 (HCDR1) of the amino acid sequence set forth in SEQ ID NO: 1 or 21, a HCDR2 of the amino acid sequence set forth in SEQ ID NO: 2 or 22, a HCDR3 of the amino acid sequence set forth in SEQ ID NO: 3 or 23, a light chain CDR1 (LCDR1) of the amino acid sequence set forth in SEQ ID NO: 4 or 24, a LCDR2 of the amino acid sequence set forth in SEQ ID NO: 5 or 25, and a LCDR3 of the amino acid sequence set forth in SEQ ID NO: 6 or 26. In some embodiments, the anti-TIM-3 antibodies or antigen-binding fragments thereof described herein comprise: a HCDR1 of the amino acid sequence set forth in SEQ ID NO: 1, a HCDR2 of the amino acid sequence set forth in SEQ ID NO: 2, a HCDR3 of the amino acid sequence set forth in SEQ ID NO: 3, a LCDR1 of the amino acid sequence set forth in SEQ ID NO: 4, a LCDR2 of the amino acid sequence set forth in SEQ ID NO: 5, and a LCDR3 of the amino acid sequence set forth in SEQ ID NO: 6. In some embodiments, the anti-TIM-3 antibodies or antigen-binding fragments thereof described herein comprise: a HCDR1 having an amino acid sequence as set forth in SEQ ID NO: 21, a HCDR2 having an amino acid sequence as set forth in SEQ ID NO: 22, a HCDR3 having an amino acid sequence as set forth in SEQ ID NO: 23, a LCDR1 having an amino acid sequence as set forth in SEQ ID NO: 24, a LCDR2 having an amino acid sequence as set forth in SEQ ID NO: 25, and a LCDR3 having an amino acid sequence as set forth in SEQ ID NO: 26. The CDR sequences of the anti-TIM-3 antibodies or antigen-binding fragments thereof are shown in Table 1.

[0212] Table 1. CDR sequences of anti-TIM-3 antibodies or antigen-binding fragments thereof

[0213] It will be understood by those skilled in the art that, unless otherwise specified, the term "CDR" or "complementarity determining region" of a given antibody or region thereof (e.g., variable region) should be understood to encompass complementarity determining regions defined by any known scheme. Although Table 1 shows CDR sequences (wherein the CDR regions shown in SEQ ID NOs: 1-6 are defined by the AbM numbering system), when referring to antibodies defined by specific CDR sequences defined by certain divisions, the scope of the antibodies also encompasses antibodies defined by CDR sequences converted to other arbitrary numbering systems (e.g., one or more combinations of the definitions of Kabat, Chothia, IMGT, CCG, or Contact, which are well known in the art). For example, an anti-TIM-3 antibody or antigen-binding fragment thereof comprising the following amino acid sequence: HCDR1 of the amino acid sequence set forth in SEQ ID NO: 1, HCDR2 of the amino acid sequence set forth in SEQ ID NO: 2, HCDR3 of the amino acid sequence set forth in ARRYYGYDAMDY (SEQ ID NO: 31), LCDR1 of the amino acid sequence set forth in SEQ ID NO: 4, LCDR2 of the amino acid sequence set forth in SEQ ID NO: 5, and LCDR3 of the amino acid sequence set forth in SEQ ID NO: 6 is also encompassed within the scope of the anti-TIM-3 antibodies or antigen-binding fragments thereof of the present disclosure.

[0214] In some embodiments, the anti-TIM-3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 7 or 27. In some embodiments, the anti-TIM-3 antibody or antigen-binding fragment thereof comprises a light chain variable region having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 8 or 28. In some embodiments, the anti-TIM-3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region having the amino acid sequence set forth in SEQ ID NO: 7. In some embodiments, the anti-TIM-3 antibody or antigen-binding fragment thereof comprises a light chain variable region having the amino acid sequence set forth in SEQ ID NO: 8. In some embodiments, the anti-TIM-3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 7 or 27, and a light chain variable region having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 8 or 28. In some embodiments, the anti-TIM-3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region having the amino acid sequence of SEQ ID NO: 7 and a light chain variable region having the amino acid sequence of SEQ ID NO: 8. In some embodiments, the anti-TIM-3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region having the amino acid sequence of SEQ ID NO: 27 and a light chain variable region having the amino acid sequence of SEQ ID NO: 28. In some specific embodiments, the amino acid sequence of the heavy chain variable region of the anti-TIM-3 antibody or antigen-binding fragment thereof is as shown in SEQ ID NO: 7, and the amino acid sequence of the light chain variable region is as shown in SEQ ID NO: 8.In some specific embodiments, the amino acid sequence of the heavy chain variable region of the anti-TIM-3 antibody or antigen-binding fragment thereof is as shown in SEQ ID NO: 27, and the amino acid sequence of the light chain variable region is as shown in SEQ ID NO: 28.

[0215] In some embodiments, the anti-TIM-3 antibodies or antigen-binding fragments thereof described herein comprise a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises HCDR1, HCDR2, and HCDR3, and the light chain variable region comprises LCDR1, LCDR2, and LCDR3, wherein HCDR1 comprises the amino acid sequence of SEQ ID NO: 1, HCDR2 comprises the amino acid sequence of SEQ ID NO: 2, HCDR3 comprises the amino acid sequence of SEQ ID NO: 3, LCDR1 comprises the amino acid sequence of SEQ ID NO: 4, LCDR2 comprises the amino acid sequence of SEQ ID NO: 5, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 6, and the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 7. NO:7 having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical, and the light chain variable region comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO:8.

[0216] In some embodiments, the anti-TIM-3 antibody or its antigen-binding fragment may further comprise an immunoglobulin constant region, or a fragment, analog, variant, or derivative of the constant region. In some embodiments, the heavy chain constant region is derived from a human immunoglobulin heavy chain, such as IgG1, IgG2, IgG3, and IgG4 or other classes of immunoglobulin heavy chains, preferably IgG4 heavy chains. In some embodiments, the light chain constant region is derived from a human immunoglobulin light chain, such as a kappa light chain or a lambda light chain of a human immunoglobulin. In some embodiments, the constant region may comprise any modification described in the text, such as insertion, deletion, substitution, or chemical modification of amino acids. In some embodiments, the constant region comprises a mutation that alters effector function. In some embodiments, any amino acid residue in the constant region may be substituted with an amino acid residue of any allotype.

[0217] In some embodiments, the anti-TIM-3 antibody or antigen-binding fragment thereof comprises a heavy chain having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 9 or 29. In some embodiments, the anti-TIM-3 antibody or antigen-binding fragment thereof comprises a light chain having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 10 or 30. In some embodiments, the anti-TIM-3 antibody or antigen-binding fragment thereof comprises a heavy chain having the amino acid sequence of SEQ ID NO: 9. In some embodiments, the anti-TIM-3 antibody or antigen-binding fragment thereof comprises a light chain having the amino acid sequence of SEQ ID NO: 10. In some embodiments, the anti-TIM-3 antibody or antigen-binding fragment thereof comprises a heavy chain having an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 9 or 29, and a light chain having an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 10 or 30. In some embodiments, the anti-TIM-3 antibody or antigen-binding fragment thereof comprises a heavy chain having the amino acid sequence of SEQ ID NO: 9 and a light chain having the amino acid sequence of SEQ ID NO: 10. In some embodiments, the anti-TIM-3 antibody or antigen-binding fragment thereof comprises a heavy chain having the amino acid sequence of SEQ ID NO: 29 and a light chain having the amino acid sequence of SEQ ID NO: 30. In some specific embodiments, the amino acid sequence of the heavy chain of the anti-TIM-3 antibody or antigen-binding fragment thereof is as set forth in SEQ ID NO: 9, and the amino acid sequence of the light chain is as set forth in SEQ ID NO: 10. In some specific embodiments, the amino acid sequence of the heavy chain of the anti-TIM-3 antibody or antigen-binding fragment thereof is as set forth in SEQ ID NO: 29, and the amino acid sequence of the light chain is as set forth in SEQ ID NO: 30.

[0218] In some embodiments, the anti-TIM-3 antibody or antigen-binding fragment thereof of the present disclosure is mAb 50B5 or an antigen-binding fragment thereof described in the patent application document with publication number WO2020041520 or CN112566936, or a chimeric antibody or antigen-binding fragment thereof of mAb 50B5, or a humanized antibody or antigen-binding fragment thereof of mAb 50B5.

[0219] In other embodiments, the anti-TIM-3 antibody or antigen-binding fragment thereof disclosed herein is mAb 15B4 or an antigen-binding fragment thereof described in patent application documents with publication numbers WO2020041520 or CN112566936, or a chimeric antibody or an antigen-binding fragment thereof of mAb 15B4, or a humanized antibody or an antigen-binding fragment thereof of mAb 15B4.

[0220] In other embodiments, the anti-TIM-3 antibody or antigen-binding fragment thereof of the present disclosure is selected from Sabatolimab, Cobolimab, Surzebiclimab, Roche's Lomvastomig (RG-7769), Hengrui Medicine's SHR-1702, Agenus' Verzistobart (INCAGN-2390), WuXi Biologics' BC-3402, Weilizhibo's LBL-003, Jianxin Bio's LNL-005, or BMS's BMS-986258.

[0221] Anti-PD-1 antibodies or antigen-binding fragments thereof

[0222] In some embodiments, the anti-PD-1 antibodies or antigen-binding fragments thereof described herein comprise: a HCDR1 having an amino acid sequence as set forth in SEQ ID NO: 11, a HCDR2 having an amino acid sequence as set forth in SEQ ID NO: 12, a HCDR3 having an amino acid sequence as set forth in SEQ ID NO: 13, a LCDR1 having an amino acid sequence as set forth in SEQ ID NO: 14, a LCDR2 having an amino acid sequence as set forth in SEQ ID NO: 15, and a LCDR3 having an amino acid sequence as set forth in SEQ ID NO: 16. The CDR sequences of the anti-PD-1 antibodies or antigen-binding fragments thereof are shown in Table 2.

[0223] Table 2. CDR sequences of anti-PD-1 antibodies or antigen-binding fragments thereof

[0224] It will be understood by those skilled in the art that, unless otherwise specified, the term "CDR" or "complementarity determining region" of a given antibody or region thereof (e.g., variable region) should be understood to encompass complementarity determining regions defined by any known scheme. Although CDR regions are shown in Table 2, when referring to antibodies defined by specific CDR sequences defined by certain divisions, the scope of the antibodies also encompasses antibodies defined by CDR sequences converted to other arbitrary numbering systems (e.g., one or more combinations of AbM, Kabat, Chothia, IMGT, CCG, or Contact, etc., which are well known in the art).

[0225] In some embodiments, the anti-PD-1 antibody or antigen-binding fragment thereof comprises a heavy chain variable region having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 17. In some embodiments, the anti-PD-1 antibody or antigen-binding fragment thereof comprises a light chain variable region having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 18. In some embodiments, the anti-PD-1 antibody or antigen-binding fragment thereof comprises a heavy chain variable region having the amino acid sequence of SEQ ID NO: 17. In some embodiments, the anti-PD-1 antibody or antigen-binding fragment thereof comprises a light chain variable region having the amino acid sequence of SEQ ID NO: 18. In some embodiments, the anti-PD-1 antibody or antigen-binding fragment thereof comprises a heavy chain variable region having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 17, and a light chain variable region having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 18. In some embodiments, the anti-PD-1 antibody or antigen-binding fragment thereof comprises a heavy chain variable region having the amino acid sequence of SEQ ID NO: 17, and a light chain variable region having the amino acid sequence of SEQ ID NO: 18. In some specific embodiments, the amino acid sequence of the heavy chain variable region of the anti-PD-1 antibody or antigen-binding fragment thereof is as shown in SEQ ID NO: 17, and the amino acid sequence of the light chain variable region is as shown in SEQ ID NO: 18.

[0226] In some embodiments, the anti-PD-1 antibodies or antigen-binding fragments thereof described in the present disclosure comprise a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises HCDR1, HCDR2, and HCDR3, and the light chain variable region comprises LCDR1, LCDR2, and LCDR3, wherein HCDR1 comprises the amino acid sequence of SEQ ID NO: 11, HCDR2 comprises the amino acid sequence of SEQ ID NO: 12, HCDR3 comprises the amino acid sequence of SEQ ID NO: 13, LCDR1 comprises the amino acid sequence of SEQ ID NO: 14, LCDR2 comprises the amino acid sequence of SEQ ID NO: 15, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 16, and the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 17. NO:17 has an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical, and the light chain variable region comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO:18.

[0227] In some embodiments, the anti-PD-1 antibody or its antigen-binding fragment may further comprise an immunoglobulin constant region, or a fragment, analog, variant or derivative of the constant region. In some embodiments, the heavy chain constant region is from a human immunoglobulin heavy chain, such as IgG1, IgG2, IgG3 and IgG4 or the heavy chain of other classes of immunoglobulins, preferably a heavy chain of IgG1. In some embodiments, the light chain constant region is from a human immunoglobulin light chain, such as a kappa light chain or a lambda light chain of a human immunoglobulin. In some embodiments, the constant region may comprise any modification described in the text, such as insertion, deletion, substitution or chemical modification of amino acids. In some embodiments, the constant region comprises a mutation that alters effector function. In some embodiments, any amino acid residue in the constant region may be substituted with an amino acid residue of any allotype.

[0228] In some embodiments, the anti-PD-1 antibody or antigen-binding fragment thereof comprises a heavy chain having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 19. In some embodiments, the anti-PD-1 antibody or antigen-binding fragment thereof comprises a light chain having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 20. In some embodiments, the anti-PD-1 antibody or antigen-binding fragment thereof comprises a heavy chain having an amino acid sequence as shown in SEQ ID NO: 19. In some embodiments, the anti-PD-1 antibody or antigen-binding fragment thereof comprises a light chain having an amino acid sequence as shown in SEQ ID NO: 20. In some embodiments, the anti-PD-1 antibody or antigen-binding fragment thereof comprises a heavy chain having an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 19, and a light chain having an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 20. In some embodiments, the anti-PD-1 antibody or antigen-binding fragment thereof comprises a heavy chain having an amino acid sequence as shown in SEQ ID NO: 19, and a light chain having an amino acid sequence as shown in SEQ ID NO: 20. In some specific embodiments, the heavy chain amino acid sequence of the anti-PD-1 antibody or antigen-binding fragment thereof is as shown in SEQ ID NO: 19, and the light chain amino acid sequence is as shown in SEQ ID NO: 20.

[0229] In other embodiments, the anti-PD-1 antibodies or antigen-binding fragments thereof of the present disclosure are selected from nivolumab, pembrolizumab, toripalimab, sintilimab, camrelizumab, tislelizumab, zimberelimab, balstilimab, geptanolimab, Lipustobart (LZM-) of Livzon Pharmaceuticals, and the like. 009), Cemiplimab, Serplulimab, Prolgolimab, Pucotenlimab (HX008), Nofazinlimab, Finotonlimab, Dostarlimab, Cetrelimab, Qilu Pharmaceutical's QL1604, Spartalizumab, Retifanlimab, Sasanlimab, Shandong New Era Pharmaceutical's Rulonilimab (F520), or Shangjian Bio's Enlonstobart (SG001).

[0230] Pharmaceutical compositions containing antibodies or antigen-binding fragments thereof

[0231] In some embodiments, the anti-TIM-3 antibody or antigen-binding fragment thereof and / or the anti-PD-1 antibody or antigen-binding fragment thereof is formulated for parenteral administration. In some specific embodiments, the anti-TIM-3 antibody or antigen-binding fragment thereof and / or the anti-PD-1 antibody or antigen-binding fragment thereof is formulated for intravenous, intramuscular, subcutaneous or other parenteral administration, such as for injection or infusion. In some specific embodiments, the formulation is for intravenous, intramuscular or subcutaneous administration. In some specific embodiments, the formulation is for intravenous injection or infusion.

[0232] Anti-TIM-3 antibodies or antigen-binding fragments thereof and anti-PD-1 antibodies or antigen-binding fragments thereof can be formulated into suitable dosage forms, including but not limited to tablets, lozenges, pills, capsules (e.g., hard capsules, soft capsules, enteric-coated capsules, microcapsules), elixirs, granules, syrups, injections (i.e., formulations suitable for injection, such as formulations suitable for intramuscular, intravenous, intraperitoneal, or subcutaneous injection), granules, emulsions, suspensions, solutions, dispersions, and sustained-release formulations for oral or parenteral administration. In some specific embodiments, anti-TIM-3 antibodies or antigen-binding fragments thereof and anti-PD-1 antibodies or antigen-binding fragments thereof can be formulated into injections. In some specific embodiments, anti-TIM-3 antibodies or antigen-binding fragments thereof and anti-PD-1 antibodies or antigen-binding fragments thereof can be formulated into formulations suitable for intravenous injection.

[0233] In some embodiments, the anti-TIM-3 antibody or antigen-binding fragment thereof and the anti-PD-1 antibody or antigen-binding fragment thereof are formulated in a single formulation. In some embodiments, the anti-TIM-3 antibody or antigen-binding fragment thereof and the anti-PD-1 antibody or antigen-binding fragment thereof are formulated together with one or more pharmaceutically acceptable carriers to form a suitable pharmaceutical composition.

[0234] In some embodiments, the anti-TIM-3 antibody or antigen-binding fragment thereof and the anti-PD-1 antibody or antigen-binding fragment thereof are formulated separately (i.e., each in the form of a pharmaceutical composition). In some embodiments, the anti-TIM-3 antibody or antigen-binding fragment thereof is formulated together with one or more pharmaceutically acceptable carriers to form a suitable pharmaceutical composition. In some embodiments, the anti-PD-1 antibody or antigen-binding fragment thereof is formulated together with one or more pharmaceutically acceptable carriers to form a suitable pharmaceutical composition.

[0235] Pharmaceutically acceptable carriers include, for example, excipients, diluents, encapsulating materials, fillers, buffers or other agents.

[0236] In some embodiments, the unit dose of the pharmaceutical composition containing the anti-TIM-3 antibody or antigen-binding fragment thereof is 60-1800 mg, 100-1600 mg, 120-1600 mg, 180-1200 mg, or 240-600 mg of the anti-TIM-3 antibody or antigen-binding fragment thereof, for example, about 60 mg, about 120 mg, about 160 mg, about 180 mg, about 200 mg, about 240 mg, about 280 mg, about 300 mg, about 320 mg, about 360 mg, about 400 mg, about 420 mg, about 440 mg, about 480 mg, about 520 mg, about 540 mg, about 560 mg, about 600 mg, about 640 mg, about 660 mg, about 680 mg, about 720 mg, about 760 mg, about 780 mg, about 800 mg, about 8 or an anti-TIM-3 antibody or antigen-binding fragment thereof of about 40 mg, about 880 mg, about 900 mg, about 920 mg, about 960 mg, about 1000 mg, about 1020 mg, about 1040 mg, about 1080 mg, about 1120 mg, about 1140 mg, about 1160 mg, about 1200 mg, about 1240 mg, about 1260 mg, about 1280 mg, about 1320 mg, about 1360 mg, about 1380 mg, about 1400 mg, about 1440 mg, about 1480 mg, about 1500 mg, about 1520 mg, about 1560 mg, about 1600 mg, about 1620 mg, about 1640 mg, about 1680 mg, about 1720 mg, about 1740 mg, about 1760 mg, and / or about 1800 mg, or a range formed by any of the foregoing values.

[0237] In some embodiments, the unit dose of the pharmaceutical composition containing the anti-PD-1 antibody or antigen-binding fragment thereof is 10-500 mg, 50-500 mg, 50-200 mg, or 100-200 mg of the anti-PD-1 antibody or antigen-binding fragment thereof, for example, about 10 mg, about 20 mg, about 30 mg, about 40 mg, about 50 mg, about 60 mg, about 70 mg, about 80 mg, about 90 mg, about 100 mg, about 110 mg, about 120 mg, about 130 mg, about 140 mg, about 150 mg, about 160 mg, about 170 mg, about 180 mg, about 190 mg, about 200 mg, about 210 mg, about or about 500 mg, or a range of any of the foregoing values, of an anti-PD-1 antibody or antigen-binding fragment thereof.

[0238] In one embodiment, the pharmaceutical composition comprising an anti-TIM-3 antibody or antigen-binding fragment thereof is a water-soluble injection. In one embodiment, the pharmaceutical composition comprising an anti-PD-1 antibody or antigen-binding fragment thereof is a water-soluble injection. In one embodiment, the pharmaceutical composition comprising an anti-TIM-3 antibody or antigen-binding fragment thereof and an anti-PD-1 antibody or antigen-binding fragment thereof is a water-soluble injection. Such water-soluble injections include, but are not limited to, unlyophilized water-soluble formulations or water-soluble formulations reconstituted from lyophilized powders.

[0239] In other embodiments, the pharmaceutical composition containing an anti-TIM-3 antibody or an antigen-binding fragment thereof is a lyophilized formulation. In other embodiments, the pharmaceutical composition containing an anti-PD-1 antibody or an antigen-binding fragment thereof is a lyophilized formulation. In a specific embodiment, the pharmaceutical composition containing an anti-TIM-3 antibody or an antigen-binding fragment thereof and an anti-PD-1 antibody or an antigen-binding fragment thereof is a lyophilized formulation. The lyophilized formulation refers to a formulation prepared by a freeze-drying process of an aqueous solution, in which the substance is first frozen, and then the amount of solvent is reduced by sublimation (primary drying process), and then the amount of solvent is reduced by desorption (secondary drying process) until the amount of solvent is a value that no longer supports biological activity or chemical reaction. The lyophilized formulation of the present disclosure can also be dried by other methods known in the art, such as spray drying and bubble drying.

[0240] In some embodiments, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof in the pharmaceutical composition comprising the anti-PD-1 antibody or antigen-binding fragment thereof is 0.1-50 mg / mL, 0.5-30 mg / mL, 0.8-20 mg / mL, 1-15 mg / mL, 1-10 mg / mL, 1-5 mg / mL, 2-20 mg / mL, 2-15 mg / mL, 2-10 mg / mL, or 2-5 mg / mL. In some specific embodiments, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is about 0.8 mg / mL, about 1 mg / mL, about 2 mg / mL, about 3 mg / mL, about 4 mg / mL, about 5 mg / mL, about 6 mg / mL, about 7 mg / mL, about 8 mg / mL, about 9 mg / mL, about 10 mg / mL, about 15 mg / mL, or about 20 mg / mL. In some embodiments, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is about 1 mg / mL. In some embodiments, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is about 2 mg / mL. In some embodiments, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is about 5 mg / mL. In some embodiments, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is about 10 mg / mL.

[0241] In some embodiments, the anti-PD-1 antibody or antigen-binding fragment thereof is in the form of a pharmaceutical composition comprising the anti-PD-1 antibody or antigen-binding fragment thereof, a buffer, an isotonicity regulator / stabilizer, and a surfactant. In a specific embodiment, the anti-PD-1 antibody or antigen-binding fragment thereof is in the form of a liquid preparation (e.g., an injection) comprising the anti-PD-1 antibody or antigen-binding fragment thereof, sodium acetate trihydrate, glacial acetic acid, sorbitol, and polysorbate 80.

[0242] chemotherapy drugs

[0243] In some embodiments of the present disclosure, the chemotherapy drugs include but are not limited to platinum anti-tumor drugs (including but not limited to oxaliplatin, cisplatin, carboplatin, nedaplatin, dicycloplatin, miplatin, lobaplatin, picoplatin, lebaplatin, triplatin tetranitrate, phenanthreneplatin, satraplatin), camptothecin anti-tumor drugs (including but not limited to camptothecin, hydroxycamptothecin, aminocamptothecin, irinotecan, topotecan, exitecan, rubitecan, lurtotecan, gimatecan, karenitecin, 7-ethyl Camptothecin), taxane anti-tumor drugs (including but not limited to paclitaxel and docetaxel), nitrogen mustard anti-tumor drugs (including but not limited to cyclophosphamide, ifosfamide, chlorambucil, carmustine, melphalan, bendamustine), antimetabolite anti-tumor drugs (including but not limited to fluorouracil anti-tumor drugs (including but not limited to carmofur, 5-fluorouracil, tegafur, capecitabine, S-1, fufuroxidine, doxifluridine, trifluridine), cytosine anti-tumor drugs (including but not limited to cytarabine, gemcitabine, azacitidine, ancitabine), purine anti-tumor drugs Antitumor drugs (including but not limited to mercaptopurine, fludarabine), antifolate antitumor drugs (including but not limited to methotrexate, pemetrexed)), anthracycline antitumor drugs (including but not limited to doxorubicin, epirubicin, pirarubicin, amrubicin, aclarubicin, idarubicin, daunorubicin, mitoxantrone, idarubicin, valrubicin, zorubicin, pixantrone, liposomal doxorubicin), vinca alkaloid antitumor drugs (including but not limited to vinblastine, vincristine, vindesine, vinflunine and vinorelbine), podophyllotoxin antitumor drugs ( Including but not limited to etoposide, teniposide), hormonal anti-tumor drugs (including but not limited to prednisone, prednisolone, dexamethasone, methylprednisolone sodium succinate), methylprocarbazine, hexamethasone, dacarbazine, mitomycin, actinomycin D (dactinomycin), bleomycin, bleomycin, temozolomide, decarbazine, peplomycin, eribulin, plinabulin, sapacitabine, treosulfan, 153Sm-EDTMP, and one or more of encequidar.

[0244] In some embodiments, the chemotherapy drug is selected from one or more of a platinum-based anti-tumor drug, a taxane-based anti-tumor drug, and an antimetabolite-based anti-tumor drug. In some embodiments, the chemotherapy drug is a platinum-based anti-tumor drug and / or a taxane-based anti-tumor drug. In some embodiments, the chemotherapy drug is a platinum-based anti-tumor drug and a taxane-based anti-tumor drug.

[0245] Furthermore, the platinum anti-tumor drug is selected from one or more of cisplatin, carboplatin, nedaplatin, dicycloplatin, picoplatin, oxaliplatin, miplatin, lobaplatin, levoplatin, triplatin tetranitrate, phenoplatin and satraplatin, preferably carboplatin and / or cisplatin, more preferably cisplatin.

[0246] In some embodiments, the taxane anti-tumor drugs include various components having a taxane skeleton isolated from Taxus brevifolia or their semi-synthetic products, or pure synthetic products having a taxane skeleton. Specifically, they include paclitaxel, cabazitaxel, docetaxel, etc., with paclitaxel being preferred. Paclitaxel includes but is not limited to paclitaxel injection, paclitaxel lyophilized powder, paclitaxel liposomes, and albumin-bound paclitaxel.

[0247] In some specific embodiments, the chemotherapy drugs are cisplatin and paclitaxel. In some specific embodiments, the chemotherapy drugs are carboplatin and paclitaxel.

[0248] In some embodiments, the chemotherapy drug is administered according to a known administration regimen (including administration cycle, administration dosage and dosage adjustment, and administration route).

[0249] Pharmaceutical compositions containing chemotherapy drugs

[0250] In some embodiments of the present disclosure, the unit dose of the pharmaceutical composition containing cisplatin is 2.5 mg, 5 mg, 10 mg, 20 mg, 25 mg, 30 mg, 50 mg and / or 100 mg of cisplatin. In some embodiments, the unit dose of the pharmaceutical composition containing cisplatin is 10 mg, 20 mg, 30 mg, 50 mg and / or 100 mg of cisplatin.

[0251] In some embodiments of the present disclosure, the unit dose of the pharmaceutical composition containing carboplatin is 50 mg, 100 mg, 150 mg, 250 mg and / or 450 mg.

[0252] In some embodiments of the present disclosure, the unit dose of the paclitaxel-containing pharmaceutical composition is 30 mg, 60 mg, 100 mg, and / or 150 mg of paclitaxel.

[0253] In some embodiments, the pharmaceutical composition containing cisplatin is a formulation suitable for injection. In some embodiments, the pharmaceutical composition containing cisplatin is a liquid formulation. In some embodiments, the pharmaceutical composition containing cisplatin is a liquid formulation suitable for injection. In some embodiments, the pharmaceutical composition containing cisplatin is a liquid formulation suitable for intravenous injection. In some embodiments, the pharmaceutical composition containing cisplatin is a solid formulation. In some embodiments, the pharmaceutical composition containing cisplatin is a lyophilized formulation. In some specific embodiments, the pharmaceutical composition containing cisplatin is a powder injection formulation. Suitable formulations can be prepared by conventional methods using pharmaceutically acceptable carriers known in the art. In a specific embodiment, the pharmaceutically acceptable carrier of the liquid formulation containing cisplatin suitable for injection includes polyethylene glycol 400 and sodium chloride.

[0254] In some embodiments, the pharmaceutical composition containing carboplatin is a formulation suitable for injection. In some embodiments, the pharmaceutical composition containing carboplatin is a liquid formulation. In some embodiments, the pharmaceutical composition containing carboplatin is a liquid formulation suitable for injection. In some embodiments, the pharmaceutical composition containing carboplatin is a liquid formulation suitable for intravenous injection. In some embodiments, the pharmaceutical composition containing carboplatin is a solid formulation. In some embodiments, the pharmaceutical composition containing carboplatin is a lyophilized formulation. In some specific embodiments, the pharmaceutical composition containing carboplatin is a powder formulation for injection. Suitable formulations can be prepared by conventional methods using pharmaceutically acceptable carriers known in the art. In a specific embodiment, the pharmaceutically acceptable carrier for the liquid formulation containing carboplatin suitable for injection includes water for injection. In a specific embodiment, the pharmaceutically acceptable carrier for the solid formulation containing carboplatin suitable for injection includes mannitol.

[0255] In some embodiments, the pharmaceutical composition containing paclitaxel is a formulation suitable for injection. In some embodiments, the pharmaceutical composition containing paclitaxel is a liquid formulation. In some embodiments, the pharmaceutical composition containing paclitaxel is a liquid formulation suitable for injection. In some embodiments, the pharmaceutical composition containing paclitaxel is a liquid formulation suitable for intravenous injection. In some embodiments, the pharmaceutical composition containing paclitaxel is a solid formulation. In some embodiments, the pharmaceutical composition containing paclitaxel is a lyophilized formulation. In some specific embodiments, the pharmaceutical composition containing paclitaxel is a powder formulation for injection. Suitable formulations can be prepared by conventional methods using pharmaceutically acceptable carriers known in the art. In a specific embodiment, pharmaceutically acceptable carriers for liquid formulations containing paclitaxel suitable for injection include polyoxyethylene castor oil and anhydrous ethanol.

[0256] Administration

[0257] The following does not limit the mode of administration of the pharmaceutical combination of the present disclosure.

[0258] The components of the pharmaceutical combination of the present disclosure can be administered independently or partially or all thereof in combination by various suitable routes, including but not limited to parenteral (e.g., by intravenous, intramuscular, topical or subcutaneous routes). In some embodiments, the components of the pharmaceutical combination of the present disclosure can be administered independently or partially or all thereof in combination by injection, such as intravenous or subcutaneous injection.

[0259] The components in the pharmaceutical combination of the present disclosure can be each independently, or part or all of them can be formulated into a suitable dosage form together, including but not limited to, tablets, lozenges, pills, capsules (such as hard capsules, soft capsules, enteric-coated capsules, microcapsules), elixirs, granules, syrups, injections (i.e., preparations suitable for injection, such as preparations suitable for intramuscular, intravenous, intraperitoneal, subcutaneous injection), granules, emulsions, suspensions, solutions, dispersants and sustained-release preparations for oral or parenteral administration. In some embodiments, the components of the pharmaceutical combination of the present disclosure can each independently, or part or all of them can be formulated into an injection together.

[0260] The pharmaceutical combination of the present disclosure may further comprise an additional therapeutic agent. In one embodiment, the additional therapeutic agent may be a tumor therapeutic agent known in the art.

[0261] tumor

[0262] In certain aspects, the tumors described herein are malignant tumors (ie, cancer); malignant tumors refer to any malignant and / or invasive growth caused by abnormal cell growth.

[0263] In some embodiments, the tumor is a solid tumor. In some embodiments, the tumor is a treatment-naive, unresectable, refractory, advanced, recurrent and / or metastatic solid tumor. In some embodiments, the tumor is an unresectable solid tumor. In some embodiments, the tumor is an advanced solid tumor. In some embodiments, the tumor is a locally advanced solid tumor. In some embodiments, the tumor is a recurrent and / or metastatic solid tumor. In some embodiments, the tumor is a locally advanced, recurrent or metastatic solid tumor. In some embodiments, the tumor is an unresectable, recurrent or metastatic solid tumor.

[0264] In some embodiments, the tumor is head and neck cancer. In some embodiments, the tumor is head and neck cancer for which there is no local indication for radical treatment. In some embodiments, the tumor is treatment-naive, unresectable, refractory, advanced, recurrent and / or metastatic head and neck cancer. In some embodiments, the tumor is unresectable head and neck cancer. In some embodiments, the tumor is advanced head and neck cancer. In some embodiments, the tumor is locally advanced head and neck cancer. In some embodiments, the tumor is recurrent and / or metastatic head and neck cancer. In some embodiments, the tumor is locally advanced, recurrent or metastatic head and neck cancer for which there is no local indication for radical treatment. In some embodiments, the tumor is unresectable, recurrent or metastatic head and neck cancer for which there is no local indication for radical treatment.

[0265] The head and neck cancer described in the present disclosure is a type of cancer that mainly originates in the lips, oral cavity, salivary glands, pharynx, larynx, nasal cavity and paranasal sinuses, including but not limited to external nose-nasal cavity tumors, paranasal sinus tumors, lip and oral cavity tumors, oropharyngeal tumors, hypopharyngeal tumors, laryngeal tumors, cervical trachea, esophageal tumors, thyroid tumors, salivary gland tumors, cervical lymph node metastasis, skin and adnexal tumors. In some embodiments, the head and neck cancer includes but is not limited to oral cavity tumors, oropharyngeal tumors, hypopharyngeal tumors and laryngeal tumors. In some embodiments, the head and neck cancer includes but is not limited to nasal cavity tumors and paranasal sinus tumors.

[0266] The head and neck cancer described in the present disclosure encompasses squamous cell carcinoma (abbreviated as SCC), basal cell carcinoma, adenoid cystic carcinoma, papillary carcinoma, follicular carcinoma, medullary carcinoma, undifferentiated carcinoma, etc. In some embodiments, the head and neck cancer is head and neck squamous cell carcinoma (abbreviated as HNSCC).

[0267] In some embodiments, the tumor is a metastatic head and neck squamous cell carcinoma with a primary site in the lip, oral cavity, salivary gland, pharynx, larynx, nasal cavity, and paranasal sinuses. In some embodiments, the tumor is a metastatic head and neck squamous cell carcinoma with a primary site in the oral cavity, oropharynx, hypopharynx, and larynx. In some embodiments, the tumor is a metastatic head and neck squamous cell carcinoma with a primary site in the nasal cavity and paranasal sinuses.

[0268] In some embodiments, the head and neck cancer does not include nasopharyngeal carcinoma. In some embodiments, the head and neck squamous cell carcinoma does not include nasopharyngeal carcinoma.

[0269] In some embodiments, the tumor is a head and neck squamous cell carcinoma for which there is no indication for local radical treatment. In some embodiments, the tumor is a treatment-naive, unresectable, refractory, advanced, recurrent and / or metastatic head and neck squamous cell carcinoma. In some embodiments, the tumor is an unresectable head and neck squamous cell carcinoma. In some embodiments, the tumor is an advanced head and neck squamous cell carcinoma. In some embodiments, the tumor is a locally advanced head and neck squamous cell carcinoma. In some embodiments, the tumor is a recurrent and / or metastatic head and neck squamous cell carcinoma. In some embodiments, the tumor is a locally advanced, recurrent or metastatic head and neck squamous cell carcinoma. In some embodiments, the tumor is an unresectable, recurrent or metastatic head and neck squamous cell carcinoma. In some embodiments, the tumor is a recurrent or metastatic head and neck squamous cell carcinoma for which there is no indication for local radical treatment. In some embodiments, the tumor is a locally advanced, recurrent or metastatic head and neck squamous cell carcinoma for which there is no indication for local radical treatment. In some embodiments, the tumor is an unresectable, recurrent or metastatic head and neck squamous cell carcinoma for which there is no indication for local radical treatment.

[0270] In some embodiments, the subject of the head and neck squamous cell carcinoma has not been previously treated for head and neck squamous cell carcinoma (e.g., lack of an effective treatment regimen). In some embodiments, the subject of the head and neck squamous cell carcinoma has not previously received radiotherapy, chemotherapy, and / or immunotherapy to treat head and neck squamous cell carcinoma. In some embodiments, the subject of the head and neck squamous cell carcinoma has not previously received systemic treatment to treat head and neck squamous cell carcinoma. In some embodiments, the subject of the head and neck squamous cell carcinoma has not previously received immune checkpoint (e.g., PD-1, PD-L1, CTLA-4, or TIM-3) inhibitors to treat head and neck squamous cell carcinoma.

[0271] In some embodiments, the subject with head and neck squamous cell carcinoma for which there is no indication for local radical treatment has not previously received systemic treatment for head and neck squamous cell carcinoma. In some embodiments, the subject with treatment-naive, unresectable, refractory, advanced, recurrent and / or metastatic head and neck squamous cell carcinoma has not previously received systemic treatment for head and neck squamous cell carcinoma. In some embodiments, the subject with unresectable head and neck squamous cell carcinoma has not previously received systemic treatment for head and neck squamous cell carcinoma. In some embodiments, the subject with advanced head and neck squamous cell carcinoma has not previously received systemic treatment for head and neck squamous cell carcinoma. In some embodiments, the subject with locally advanced head and neck squamous cell carcinoma has not previously received systemic treatment for head and neck squamous cell carcinoma. In some embodiments, the subject with recurrent and / or metastatic head and neck squamous cell carcinoma has not previously received systemic treatment for head and neck squamous cell carcinoma. In some embodiments, the subject with recurrent or metastatic head and neck squamous cell carcinoma for which there is no indication for local radical treatment has not previously received systemic treatment for head and neck squamous cell carcinoma. In some embodiments, the subject with locally advanced, recurrent, or metastatic head and neck squamous cell carcinoma for which there is no indication for local radical treatment has not previously received systemic treatment for head and neck squamous cell carcinoma. In some embodiments, the subject with unresectable, recurrent, or metastatic head and neck squamous cell carcinoma for which there is no indication for local radical treatment has not previously received systemic treatment for head and neck squamous cell carcinoma.

[0272] In some embodiments, the subject of head and neck squamous cell carcinoma without local radical treatment indications has not previously received immune checkpoint (e.g., PD-1, PD-L1, CTLA-4 or TIM-3) inhibitors to treat head and neck squamous cell carcinoma. In some embodiments, the subject of the newly treated, unresectable, refractory, advanced, recurrent and / or metastatic head and neck squamous cell carcinoma has not previously received immune checkpoint (e.g., PD-1, PD-L1, CTLA-4 or TIM-3) inhibitors to treat head and neck squamous cell carcinoma. In some embodiments, the subject of the unresectable head and neck squamous cell carcinoma has not previously received immune checkpoint (e.g., PD-1, PD-L1, CTLA-4 or TIM-3) inhibitors to treat head and neck squamous cell carcinoma. In some embodiments, the subject of the late head and neck squamous cell carcinoma has not previously received immune checkpoint (e.g., PD-1, PD-L1, CTLA-4 or TIM-3) inhibitors to treat head and neck squamous cell carcinoma. In some embodiments, the subject of the locally advanced head and neck squamous cell carcinoma has not previously received immune checkpoint (e.g., PD-1, PD-L1, CTLA-4 or TIM-3) inhibitors to treat head and neck squamous cell carcinoma. In some embodiments, the subject of the recurrent and / or metastatic head and neck squamous cell carcinoma has not previously received immune checkpoint (e.g., PD-1, PD-L1, CTLA-4 or TIM-3) inhibitors to treat head and neck squamous cell carcinoma. In some embodiments, the subject of the recurrent or metastatic head and neck squamous cell carcinoma without local radical treatment indications has not previously received immune checkpoint (e.g., PD-1, PD-L1, CTLA-4 or TIM-3) inhibitors to treat head and neck squamous cell carcinoma. In some embodiments, the subject of the locally advanced, recurrent or metastatic head and neck squamous cell carcinoma without local radical treatment indications has not previously received immune checkpoint (e.g., PD-1, PD-L1, CTLA-4 or TIM-3) inhibitors to treat head and neck squamous cell carcinoma. In some embodiments, the subject with unresectable, recurrent, or metastatic head and neck squamous cell carcinoma who is not an indication for local curative treatment has not previously received an immune checkpoint (e.g., PD-1, PD-L1, CTLA-4, or TIM-3) inhibitor to treat head and neck squamous cell carcinoma.

[0273] In some embodiments, the subject of head and neck squamous cell carcinoma has previously been treated for head and neck squamous cell carcinoma with one or more different anti-tumor treatments. In some schemes, the subject of head and neck squamous cell carcinoma has previously received surgery, radiation therapy, induction chemotherapy, concurrent chemotherapy and / or adjuvant chemotherapy to treat head and neck squamous cell carcinoma. In some embodiments, the subject of head and neck squamous cell carcinoma has previously received neoadjuvant therapy, adjuvant therapy or radical concurrent chemoradiotherapy to treat head and neck squamous cell carcinoma. In some specific embodiments, the subject of head and neck squamous cell carcinoma has not previously received systemic chemotherapy, but has received surgery, radiation therapy, induction chemotherapy, concurrent chemotherapy and / or adjuvant chemotherapy to treat head and neck squamous cell carcinoma. In some specific embodiments, the subject of head and neck squamous cell carcinoma has not previously received systemic chemotherapy, but has received neoadjuvant therapy, adjuvant therapy or radical concurrent chemoradiotherapy to treat head and neck squamous cell carcinoma. In some specific embodiments, the subject of head and neck squamous cell carcinoma has not previously received systemic chemotherapy, but has received neoadjuvant therapy, adjuvant therapy or radical concurrent chemoradiotherapy to treat head and neck squamous cell carcinoma. In some specific embodiments, the subject of head and neck squamous cell carcinoma has achieved complete remission or partial remission after surgery, radiation therapy, induction chemotherapy, concurrent chemotherapy and / or adjuvant chemotherapy, and then the disease progresses again. In some embodiments, the subject of head and neck squamous cell carcinoma has undergone surgery, radiotherapy, induction chemotherapy, concurrent chemotherapy and / or adjuvant chemotherapy for the treatment of head and neck squamous cell carcinoma, and the disease progresses 6 months after stopping treatment (e.g., 6, 7, 8, 9 or 10 months). In some embodiments, the subject of head and neck squamous cell carcinoma has undergone surgery, radiotherapy, induction chemotherapy, concurrent chemotherapy and / or adjuvant chemotherapy for the treatment of head and neck squamous cell carcinoma, and the cancer metastasizes 6 months after stopping treatment (e.g., 6, 7, 8, 9 or 10 months).

[0274] In some embodiments, the subject with locally advanced, recurrent and / or metastatic head and neck squamous cell carcinoma for which there is no indication for local radical treatment has previously been treated for head and neck squamous cell carcinoma with one or more different anti-tumor treatments. In some embodiments, the subject with locally advanced, recurrent and / or metastatic head and neck squamous cell carcinoma for which there is no indication for local radical treatment has previously received surgery, radiotherapy, induction chemotherapy, concurrent chemotherapy and / or adjuvant chemotherapy to treat head and neck squamous cell carcinoma. In some specific embodiments, the subject with locally advanced, recurrent and / or metastatic head and neck squamous cell carcinoma for which there is no indication for local radical treatment has not previously received systemic chemotherapy, but has received surgery, radiotherapy, induction chemotherapy, concurrent chemotherapy and / or adjuvant chemotherapy to treat head and neck squamous cell carcinoma. In some specific embodiments, the subject with locally advanced, recurrent and / or metastatic head and neck squamous cell carcinoma for which there is no indication for local radical treatment has experienced disease progression again after achieving complete remission or partial remission after surgery, radiotherapy, induction chemotherapy, concurrent chemotherapy and / or adjuvant chemotherapy. In some embodiments, the subject of locally advanced, recurrent and / or metastatic head and neck squamous cell carcinoma without local radical treatment indications has undergone surgery, radiotherapy, induction chemotherapy, concurrent chemotherapy and / or adjuvant chemotherapy for the treatment of head and neck squamous cell carcinoma. In some embodiments, the subject of locally advanced, recurrent and / or metastatic head and neck squamous cell carcinoma without local radical treatment indications has previously received surgery, radiotherapy, induction chemotherapy, concurrent chemotherapy and / or adjuvant chemotherapy for the treatment of head and neck squamous cell carcinoma, and disease progression occurs 6 months after cessation of treatment (e.g., 6, 7, 8, 9 or 10 months). In some embodiments, the subject of locally advanced, recurrent and / or metastatic head and neck squamous cell carcinoma without local radical treatment indications has previously received surgery, radiotherapy, induction chemotherapy, concurrent chemotherapy and / or adjuvant chemotherapy for the treatment of head and neck squamous cell carcinoma, and cancer metastasis occurs 6 months after cessation of treatment (e.g., 6, 7, 8, 9 or 10 months).

[0275] In some embodiments, the tumor is esophageal cancer. In some embodiments, the tumor is treatment-naive, unresectable, refractory, recurrent, metastatic, and / or advanced esophageal cancer. In some embodiments, the tumor is treatment-naive esophageal cancer. In some embodiments, the tumor is unresectable esophageal cancer. In some embodiments, the tumor is advanced esophageal cancer. In some embodiments, the tumor is locally advanced esophageal cancer. In some embodiments, the tumor is recurrent and / or metastatic esophageal cancer. In some embodiments, the tumor is locally advanced, recurrent, or metastatic esophageal cancer. In some embodiments, the tumor is unresectable, locally advanced, recurrent, or metastatic esophageal cancer.

[0276] In some embodiments, the esophageal cancer is esophageal squamous cell carcinoma (i.e., esophageal squamous cell carcinoma), esophageal adenocarcinoma, squamous cell carcinoma across the esophagogastric junction, or esophagogastric junction adenocarcinoma. In some embodiments, the esophageal cancer is esophageal squamous cell carcinoma or esophageal adenocarcinoma. In some specific schemes, the esophageal cancer is a newly treated esophageal squamous cell carcinoma. In some embodiments, the tumor is unresectable esophageal squamous cell carcinoma. In some embodiments, the tumor is advanced esophageal squamous cell carcinoma. In some embodiments, the tumor is locally advanced esophageal squamous cell carcinoma. In some embodiments, the tumor is recurrent and / or metastatic esophageal squamous cell carcinoma. In some embodiments, the tumor is locally advanced, recurrent or metastatic esophageal squamous cell carcinoma. In some embodiments, the tumor is unresectable, locally advanced, recurrent or metastatic esophageal squamous cell carcinoma.

[0277] In some embodiments, the subject of the esophageal cancer has not been previously treated for esophageal cancer (e.g., lack of an effective treatment regimen). In some embodiments, the subject of the esophageal cancer has not previously received radiotherapy, chemotherapy, and / or immunotherapy to treat esophageal cancer. In some embodiments, the subject of the esophageal cancer has not previously received systemic therapy to treat esophageal cancer. In some embodiments, the subject of the esophageal cancer has not previously received immune checkpoint (e.g., PD-1, PD-L1, CTLA-4, or TIM-3) inhibitors to treat esophageal cancer.

[0278] In some embodiments, the subject with treatment-naive esophageal cancer has not previously received systemic treatment for esophageal cancer. In some embodiments, the subject with unresectable esophageal cancer has not previously received systemic treatment for esophageal cancer. In some embodiments, the subject with advanced esophageal cancer has not previously received systemic treatment for esophageal cancer. In some embodiments, the subject with locally advanced esophageal cancer has not previously received systemic treatment for esophageal cancer. In some embodiments, the subject with recurrent and / or metastatic esophageal cancer has not previously received systemic treatment for esophageal cancer. In some embodiments, the subject with locally advanced, recurrent or metastatic esophageal cancer has not previously received systemic treatment for esophageal cancer. In some embodiments, the subject with unresectable, locally advanced, recurrent or metastatic esophageal cancer has not previously received systemic treatment for esophageal cancer.

[0279] In some embodiments, the subject of the newly treated esophageal cancer has not previously received immune checkpoint (e.g., PD-1, PD-L1, CTLA-4, or TIM-3) inhibitors to treat esophageal cancer. In some embodiments, the subject of the unresectable esophageal cancer has not previously received immune checkpoint (e.g., PD-1, PD-L1, CTLA-4, or TIM-3) inhibitors to treat esophageal cancer. In some embodiments, the subject of the late esophageal cancer has not previously received immune checkpoint (e.g., PD-1, PD-L1, CTLA-4, or TIM-3) inhibitors to treat esophageal cancer. In some embodiments, the subject of the locally advanced esophageal cancer has not previously received immune checkpoint (e.g., PD-1, PD-L1, CTLA-4, or TIM-3) inhibitors to treat esophageal cancer. In some embodiments, the subject of the recurrent and / or metastatic esophageal cancer has not previously received immune checkpoint (e.g., PD-1, PD-L1, CTLA-4, or TIM-3) inhibitors to treat esophageal cancer. In some embodiments, the subject of the locally advanced, recurrent, or metastatic esophageal cancer has not previously received immune checkpoint (e.g., PD-1, PD-L1, CTLA-4, or TIM-3) inhibitors to treat esophageal cancer. In some embodiments, the subject of the unresectable, locally advanced, recurrent, or metastatic esophageal cancer has not previously received immune checkpoint (e.g., PD-1, PD-L1, CTLA-4, or TIM-3) inhibitors to treat esophageal cancer.

[0280] In some embodiments, the subject of esophageal squamous cell carcinoma has not been previously treated for esophageal squamous cell carcinoma (e.g., lack of an effective treatment regimen). In some embodiments, the subject of esophageal squamous cell carcinoma has not previously received radiotherapy, chemotherapy, and / or immunotherapy to treat esophageal squamous cell carcinoma. In some embodiments, the subject of esophageal squamous cell carcinoma has not previously received systemic treatment to treat esophageal squamous cell carcinoma. In some embodiments, the subject of esophageal squamous cell carcinoma has not previously received immune checkpoint (e.g., PD-1, PD-L1, CTLA-4, or TIM-3) inhibitors to treat esophageal squamous cell carcinoma.

[0281] In some embodiments, the subject with treatment-naive esophageal squamous cell carcinoma has not previously received systemic treatment for esophageal squamous cell carcinoma. In some embodiments, the subject with unresectable esophageal squamous cell carcinoma has not previously received systemic treatment for esophageal squamous cell carcinoma. In some embodiments, the subject with advanced esophageal squamous cell carcinoma has not previously received systemic treatment for esophageal squamous cell carcinoma. In some embodiments, the subject with locally advanced esophageal squamous cell carcinoma has not previously received systemic treatment for esophageal squamous cell carcinoma. In some embodiments, the subject with recurrent and / or metastatic esophageal squamous cell carcinoma has not previously received systemic treatment for esophageal squamous cell carcinoma. In some embodiments, the subject with locally advanced, recurrent or metastatic esophageal squamous cell carcinoma has not previously received systemic treatment for esophageal squamous cell carcinoma. In some embodiments, the subject with unresectable, locally advanced, recurrent or metastatic esophageal squamous cell carcinoma has not previously received systemic treatment for esophageal squamous cell carcinoma.

[0282] In some embodiments, the subject of the newly treated esophageal squamous cell carcinoma has not previously received immune checkpoint (e.g., PD-1, PD-L1, CTLA-4, or TIM-3) inhibitors to treat esophageal squamous cell carcinoma. In some embodiments, the subject of the unresectable esophageal squamous cell carcinoma has not previously received immune checkpoint (e.g., PD-1, PD-L1, CTLA-4, or TIM-3) inhibitors to treat esophageal squamous cell carcinoma. In some embodiments, the subject of the late esophageal squamous cell carcinoma has not previously received immune checkpoint (e.g., PD-1, PD-L1, CTLA-4, or TIM-3) inhibitors to treat esophageal squamous cell carcinoma. In some embodiments, the subject of the locally advanced esophageal squamous cell carcinoma has not previously received immune checkpoint (e.g., PD-1, PD-L1, CTLA-4, or TIM-3) inhibitors to treat esophageal squamous cell carcinoma. In some embodiments, the subject of the recurrent and / or metastatic esophageal squamous cell carcinoma has not previously received immune checkpoint (e.g., PD-1, PD-L1, CTLA-4, or TIM-3) inhibitors to treat esophageal squamous cell carcinoma. In some embodiments, the subject of the locally advanced, recurrent, or metastatic esophageal squamous cell carcinoma has not previously received immune checkpoint (e.g., PD-1, PD-L1, CTLA-4, or TIM-3) inhibitors to treat esophageal squamous cell carcinoma. In some embodiments, the subject of the unresectable, locally advanced, recurrent, or metastatic esophageal squamous cell carcinoma has not previously received immune checkpoint (e.g., PD-1, PD-L1, CTLA-4, or TIM-3) inhibitors to treat esophageal squamous cell carcinoma.

[0283] In some embodiments, the subject with esophageal cancer has previously been treated with one or more different anti-tumor therapies for esophageal cancer. In some embodiments, the subject with esophageal cancer has previously received surgery, radiation therapy, induction chemotherapy, concurrent chemotherapy, and / or adjuvant chemotherapy for esophageal cancer. In some embodiments, the subject with esophageal cancer has previously received neoadjuvant therapy, adjuvant therapy, or definitive concurrent chemoradiotherapy for esophageal cancer.

[0284] In some embodiments, the esophageal cancer is esophageal cancer that has failed neoadjuvant therapy, adjuvant therapy or radical concurrent chemoradiotherapy. In some embodiments, the esophageal cancer is esophageal cancer that has recurred after neoadjuvant therapy, adjuvant therapy or radical concurrent chemoradiotherapy. In some specific embodiments, the subject of the esophageal cancer has previously received neoadjuvant therapy, adjuvant therapy or radical concurrent chemoradiotherapy to treat esophageal cancer, and the disease relapsed 6 months after stopping treatment (e.g., 6, 7, 8, 9 or 10 months).

[0285] In some embodiments, the esophageal cancer is a locally advanced esophageal cancer that has failed neoadjuvant therapy, adjuvant therapy, or radical concurrent chemoradiotherapy. In some embodiments, the esophageal cancer is a locally advanced esophageal cancer that has recurred after neoadjuvant therapy, adjuvant therapy, or radical concurrent chemoradiotherapy. In some specific embodiments, the subject with locally advanced esophageal cancer has previously received neoadjuvant therapy, adjuvant therapy, or radical concurrent chemoradiotherapy to treat esophageal cancer, and the disease recurred 6 months (e.g., 6, 7, 8, 9, or 10 months) after stopping treatment.

[0286] In some embodiments, the esophageal cancer is recurrent and / or metastatic esophageal cancer that has failed neoadjuvant therapy, adjuvant therapy or radical concurrent chemoradiotherapy. In some embodiments, the esophageal cancer is recurrent and / or metastatic esophageal cancer that has relapsed after neoadjuvant therapy, adjuvant therapy or radical concurrent chemoradiotherapy. In some specific embodiments, the subject of the recurrent and / or metastatic esophageal cancer has previously received neoadjuvant therapy, adjuvant therapy or radical concurrent chemoradiotherapy to treat esophageal cancer, and the disease relapses 6 months after stopping treatment (e.g., 6, 7, 8, 9 or 10 months).

[0287] In some embodiments, the esophageal cancer is unresectable, locally advanced, recurrent or metastatic esophageal cancer that has failed neoadjuvant therapy, adjuvant therapy or radical concurrent chemoradiotherapy. In some embodiments, the esophageal cancer is unresectable, locally advanced, recurrent or metastatic esophageal cancer that has recurred after neoadjuvant therapy, adjuvant therapy or radical concurrent chemoradiotherapy. In some specific embodiments, the subject of the unresectable, locally advanced, recurrent or metastatic esophageal cancer has previously received neoadjuvant therapy, adjuvant therapy or radical concurrent chemoradiotherapy to treat esophageal cancer, and the disease relapses 6 months after stopping treatment (e.g., 6, 7, 8, 9 or 10 months).

[0288] In some embodiments, the subject with esophageal squamous cell carcinoma has previously been treated with one or more different anti-tumor therapies for esophageal squamous cell carcinoma. In some embodiments, the subject with esophageal squamous cell carcinoma has previously received neoadjuvant therapy, adjuvant therapy, or definitive concurrent chemoradiotherapy for esophageal squamous cell carcinoma.

[0289] In some embodiments, the esophageal squamous cell carcinoma is an esophageal squamous cell carcinoma that has failed neoadjuvant therapy, adjuvant therapy or radical concurrent chemoradiotherapy. In some embodiments, the esophageal squamous cell carcinoma is an esophageal squamous cell carcinoma that has recurred after neoadjuvant therapy, adjuvant therapy or radical concurrent chemoradiotherapy. In some specific embodiments, the subject of the esophageal squamous cell carcinoma has previously received neoadjuvant therapy, adjuvant therapy or radical concurrent chemoradiotherapy to treat esophageal squamous cell carcinoma, and the disease relapses 6 months after stopping treatment (e.g., 6, 7, 8, 9 or 10 months).

[0290] In some embodiments, the esophageal squamous cell carcinoma is a locally advanced esophageal squamous cell carcinoma that has failed neoadjuvant therapy, adjuvant therapy, or radical concurrent chemoradiotherapy. In some embodiments, the esophageal squamous cell carcinoma is a locally advanced esophageal squamous cell carcinoma that has recurred after neoadjuvant therapy, adjuvant therapy, or radical concurrent chemoradiotherapy. In some specific embodiments, the subject of the locally advanced esophageal squamous cell carcinoma has previously received neoadjuvant therapy, adjuvant therapy, or radical concurrent chemoradiotherapy to treat esophageal squamous cell carcinoma, and the disease recurred 6 months after stopping treatment (e.g., 6, 7, 8, 9, or 10 months).

[0291] In some embodiments, the esophageal squamous cell carcinoma is a recurrent and / or metastatic esophageal squamous cell carcinoma that has failed neoadjuvant therapy, adjuvant therapy or radical synchronous chemoradiotherapy. In some embodiments, the esophageal squamous cell carcinoma is a recurrent and / or metastatic esophageal squamous cell carcinoma that has relapsed after neoadjuvant therapy, adjuvant therapy or radical synchronous chemoradiotherapy. In some specific embodiments, the subject of the recurrent and / or metastatic esophageal squamous cell carcinoma has previously received neoadjuvant therapy, adjuvant therapy or radical synchronous chemoradiotherapy to treat esophageal squamous cell carcinoma, and the disease relapses 6 months after stopping treatment (e.g., 6, 7, 8, 9 or 10 months).

[0292] In some embodiments, the esophageal squamous cell carcinoma is unresectable, locally advanced, recurrent or metastatic esophageal squamous cell carcinoma that has failed neoadjuvant therapy, adjuvant therapy or radical synchronous chemoradiotherapy. In some embodiments, the esophageal squamous cell carcinoma is unresectable, locally advanced, recurrent or metastatic esophageal squamous cell carcinoma that has recurred after neoadjuvant therapy, adjuvant therapy or radical synchronous chemoradiotherapy. In some specific embodiments, the subject of the unresectable, locally advanced, recurrent or metastatic esophageal squamous cell carcinoma has previously received neoadjuvant therapy, adjuvant therapy or radical synchronous chemoradiotherapy to treat esophageal squamous cell carcinoma, and the disease recurs 6 months after stopping treatment (e.g., 6, 7, 8, 9 or 10 months).

[0293] The present disclosure also provides the following specific implementation schemes, but the protection scope of the present disclosure is not limited thereto:

[0294] Embodiment 1. A pharmaceutical combination comprising an anti-TIM-3 antibody or an antigen-binding fragment thereof and an anti-PD-1 antibody or an antigen-binding fragment thereof, wherein the anti-TIM-3 antibody or the antigen-binding fragment thereof comprises:

[0295] HCDR1 of the amino acid sequence set forth in SEQ ID NO:1, HCDR2 of the amino acid sequence set forth in SEQ ID NO:2, HCDR3 of the amino acid sequence set forth in SEQ ID NO:3, LCDR1 of the amino acid sequence set forth in SEQ ID NO:4, LCDR2 of the amino acid sequence set forth in SEQ ID NO:5, and LCDR3 of the amino acid sequence set forth in SEQ ID NO:6; or

[0296] HCDR1 of the amino acid sequence shown in SEQ ID NO:21, HCDR2 of the amino acid sequence shown in SEQ ID NO:22, HCDR3 of the amino acid sequence shown in SEQ ID NO:23, LCDR1 of the amino acid sequence shown in SEQ ID NO:24, LCDR2 of the amino acid sequence shown in SEQ ID NO:25, and LCDR3 of the amino acid sequence shown in SEQ ID NO:26.

[0297] Embodiment 2. The pharmaceutical combination according to embodiment 1, wherein the anti-TIM-3 antibody or antigen-binding fragment thereof comprises:

[0298] a heavy chain variable region having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 7, and a light chain variable region having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 8; or

[0299] A heavy chain variable region having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:27, and a light chain variable region having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:28.

[0300] Embodiment 3. The pharmaceutical combination according to embodiment 1 or 2, wherein the anti-TIM-3 antibody or antigen-binding fragment thereof comprises:

[0301] a heavy chain having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 9, and a light chain having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 10; or

[0302] A heavy chain having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:29, and a light chain having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:30.

[0303] Embodiment 4. The drug combination according to any one of Embodiments 1-3, wherein the anti-PD-1 antibody or antigen-binding fragment thereof comprises: a HCDR1 of the amino acid sequence shown in SEQ ID NO: 11, a HCDR2 of the amino acid sequence shown in SEQ ID NO: 12, a HCDR3 of the amino acid sequence shown in SEQ ID NO: 13, a LCDR1 of the amino acid sequence shown in SEQ ID NO: 14, a LCDR2 of the amino acid sequence shown in SEQ ID NO: 15, and a LCDR3 of the amino acid sequence shown in SEQ ID NO: 16.

[0304] Embodiment 5. The drug combination according to any one of Embodiments 1-4, wherein the anti-PD-1 antibody or antigen-binding fragment thereof comprises: a heavy chain variable region having an amino acid sequence that is at least 95% identical to the amino acid sequence shown in SEQ ID NO: 17, and a light chain variable region having an amino acid sequence that is at least 95% identical to the amino acid sequence shown in SEQ ID NO: 18.

[0305] Embodiment 6. The drug combination according to any one of Embodiments 1-5, wherein the anti-PD-1 antibody or antigen-binding fragment thereof comprises: a heavy chain having an amino acid sequence that is at least 95% identical to the amino acid sequence shown in SEQ ID NO: 19, and a light chain having an amino acid sequence that is at least 95% identical to the amino acid sequence shown in SEQ ID NO: 20.

[0306] Embodiment 7. The pharmaceutical combination according to any one of Embodiments 1-6, wherein the anti-TIM-3 antibody or antigen-binding fragment thereof and the anti-PD-1 antibody or antigen-binding fragment thereof are formulated as a preparation for parenteral administration, preferably, the anti-TIM-3 antibody or antigen-binding fragment thereof and the anti-PD-1 antibody or antigen-binding fragment thereof are formulated as a preparation for intravenous, intramuscular or subcutaneous administration.

[0307] Embodiment 8. The pharmaceutical combination according to any one of Embodiments 1-7, wherein the anti-TIM-3 antibody or antigen-binding fragment thereof and the anti-PD-1 antibody or antigen-binding fragment thereof are formulated in a single formulation.

[0308] Embodiment 9. The pharmaceutical combination according to any one of Embodiments 1-8, wherein the anti-TIM-3 antibody or antigen-binding fragment thereof and the anti-PD-1 antibody or antigen-binding fragment thereof are formulated separately.

[0309] Embodiment 10. The pharmaceutical combination according to any one of Embodiments 1-9, wherein the unit dose of the anti-TIM-3 antibody or antigen-binding fragment thereof is 60-1800 mg, 100-1600 mg, 120-1600 mg, 180-1200 mg, or 240-600 mg; preferably, the unit dose of the anti-TIM-3 antibody or antigen-binding fragment thereof is 240 mg, 300 mg, 360 mg and / or 600 mg.

[0310] Embodiment 11. The drug combination according to any one of Embodiments 1-10, wherein the unit dose of the anti-PD-1 antibody or its antigen-binding fragment is 10-500 mg, 50-500 mg, 50-200 mg, or 100-200 mg; preferably, the unit dose of the anti-PD-1 antibody or its antigen-binding fragment is 100 mg and / or 200 mg.

[0311] Embodiment 12. The drug combination according to any one of Embodiments 1-11, wherein the mass ratio of the anti-TIM-3 antibody or its antigen-binding fragment to the anti-PD-1 antibody or its antigen-binding fragment is (0.1-180):1, (0.2-50):1, (0.5-9):1, (3-7.5):1, (4-7.5):1 or (6-7.5):1.

[0312] Embodiment 13. The pharmaceutical combination according to any one of Embodiments 1-12, wherein the pharmaceutical combination is suitable for administration in a single treatment cycle, comprising 100-1800 mg, 600-1800 mg, 600-1500 mg, or 1200-1500 mg of the anti-TIM-3 antibody or antigen-binding fragment thereof, preferably 1200 mg or 1500 mg of the anti-TIM-3 antibody or antigen-binding fragment thereof; and / or

[0313] 10-800 mg, 50-500 mg, or 100-200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, preferably 200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof.

[0314] Embodiment 14. The drug combination according to any one of embodiments 1-13, further comprising a chemotherapy drug.

[0315] Embodiment 15. The pharmaceutical combination according to embodiment 14, wherein the chemotherapy drug is a platinum anti-tumor drug and / or a taxane anti-tumor drug;

[0316] Optionally, the platinum anti-tumor drug is selected from one or more of cisplatin, carboplatin, nedaplatin, dicycloplatin, picoplatin, oxaliplatin, miplatin, lobaplatin, levoplatin, triplatin tetranitrate, phenoplatin and satraplatin;

[0317] Optionally, the taxane anti-tumor drug is selected from one or more of paclitaxel, cabazitaxel and docetaxel.

[0318] Embodiment 16. The drug combination according to embodiment 14, wherein the chemotherapy drugs are cisplatin and paclitaxel, or the chemotherapy drugs are carboplatin and paclitaxel.

[0319] Embodiment 17. The pharmaceutical combination according to any one of Embodiments 14-16, wherein the pharmaceutical combination is suitable for administration in a single treatment cycle, comprising 100-1800 mg, 600-1800 mg, 600-1500 mg, or 1200-1500 mg of the anti-TIM-3 antibody or antigen-binding fragment thereof, preferably 1200 mg or 1500 mg of the anti-TIM-3 antibody or antigen-binding fragment thereof; and / or

[0320] 10-800 mg, 50-500 mg, or 100-200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, preferably 200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof.

[0321] Embodiment 18. The drug combination according to any one of Embodiments 14-16, wherein the drug combination is suitable for administration in a single treatment cycle, comprising 100-1800 mg, 600-1800 mg, 600-1500 mg, or 1200-1500 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, 10-800 mg, 50-500 mg, or 100-200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, 30-100 mg / m 2 30-75 mg / m 2 48-75 mg / m 2 or 60–75 mg / m 2 Cisplatin, and 75-175 mg / m 2 100-175 mg / m 2 112-175 mg / m 2 or 135–175 mg / m 2 or 100-1800 mg, 600-1800 mg, 600-1500 mg, or 1200-1500 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, 10-800 mg, 50-500 mg, or 100-200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, 2.5-5 mg / (mL / min) AUC or 3.2-5 mg / (mL / min) AUC of carboplatin, and 75-175 mg / m 2 100-175 mg / m 2 112-175 mg / m 2 or 135–175 mg / m 2 of paclitaxel.

[0322] Embodiment 19. Use of the pharmaceutical combination of any one of Embodiments 1-13 for the preparation of a medicament for treating a tumor in a subject.

[0323] Embodiment 20. The use according to Embodiment 19, wherein the anti-TIM-3 antibody or antigen-binding fragment thereof and the anti-PD-1 antibody or antigen-binding fragment thereof can be administered simultaneously, sequentially and / or alternately.

[0324] Embodiment 21. The use according to embodiment 19 or 20, wherein the anti-TIM-3 antibody or antigen-binding fragment thereof is administered once every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks. Preferably, the anti-TIM-3 antibody or antigen-binding fragment thereof is administered once every 3 weeks. Optionally, the anti-TIM-3 antibody or antigen-binding fragment thereof is administered at a dose of 100-1800 mg, 600-1800 mg, 600-1500 mg, or 1200-1500 mg each time. Preferably, the anti-TIM-3 antibody or antigen-binding fragment thereof is administered at a dose of 1200 mg each time.

[0325] Embodiment 22. The use according to any one of Embodiments 19-21, wherein the anti-PD-1 antibody or antigen-binding fragment thereof is administered once every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks. Preferably, the anti-PD-1 antibody or antigen-binding fragment thereof is administered once every 3 weeks. Optionally, the anti-PD-1 antibody or antigen-binding fragment thereof is administered at a dose of 10-800 mg, 50-500 mg, or 100-200 mg each time. Preferably, the anti-PD-1 antibody or antigen-binding fragment thereof is administered at a dose of 200 mg each time.

[0326] Embodiment 23. Use of the pharmaceutical combination of any one of Embodiments 14-18 for the preparation of a medicament for treating a tumor in a subject.

[0327] Embodiment 24. The use according to Embodiment 23, wherein the anti-TIM-3 antibody or antigen-binding fragment thereof, anti-PD-1 antibody or antigen-binding fragment thereof, cisplatin and paclitaxel can be administered simultaneously, sequentially and / or alternately; or the anti-TIM-3 antibody or antigen-binding fragment thereof, anti-PD-1 antibody or antigen-binding fragment thereof, carboplatin and paclitaxel can be administered simultaneously, sequentially and / or alternately.

[0328] Embodiment 25. The use according to embodiment 23 or 24, wherein the anti-TIM-3 antibody or antigen-binding fragment thereof is administered once every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks. Preferably, the anti-TIM-3 antibody or antigen-binding fragment thereof is administered once every 3 weeks. Optionally, the anti-TIM-3 antibody or antigen-binding fragment thereof is administered at a dose of 100-1800 mg, 600-1800 mg, 600-1500 mg, or 1200-1500 mg each time. Preferably, the anti-TIM-3 antibody or antigen-binding fragment thereof is administered at a dose of 1200 mg each time.

[0329] Embodiment 26. The use according to any one of Embodiments 23-25, wherein the anti-PD-1 antibody or antigen-binding fragment thereof is administered once every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks. Preferably, the anti-PD-1 antibody or antigen-binding fragment thereof is administered once every 3 weeks. Optionally, the anti-PD-1 antibody or antigen-binding fragment thereof is administered at a dose of 10-800 mg, 50-500 mg, or 100-200 mg each time. Preferably, the anti-PD-1 antibody or antigen-binding fragment thereof is administered at a dose of 200 mg each time.

[0330] Embodiment 27. The use according to any one of embodiments 23-26, wherein the cisplatin is administered once every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks. Preferably, the cisplatin is administered once every 3 weeks. Optionally, the cisplatin is administered at a dose of 30-100 mg / m 2 30-75 mg / m 2 48-75 mg / m 2 or 60–75 mg / m 2 Preferably, the cisplatin is administered at a dose of 60-75 mg / m 2 or the carboplatin is administered once every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks, preferably, the carboplatin is administered once every 3 weeks; optionally, the carboplatin is administered at a dose of 2.5-5 mg / (mL / min)AUC or 3.2-5 mg / (mL / min)AUC each time, preferably, the carboplatin is administered at a dose of 3.2-5 mg / (mL / min)AUC each time.

[0331] Embodiment 28. The use according to any one of embodiments 23-27, wherein the paclitaxel is administered once every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks, preferably, the paclitaxel is administered once every 3 weeks; optionally, the paclitaxel is administered at a dose of 75-175 mg / m 2 100-175 mg / m 2 112-175 mg / m 2 or 135–175 mg / m 2 Preferably, the paclitaxel is administered at a dose of 135-175 mg / m 2 Dosage administration.

[0332] Embodiment 29. The use according to any one of Embodiments 19-28, wherein the tumor is head and neck cancer; preferably, the tumor is head and neck squamous cell carcinoma; preferably, the tumor is locally advanced, recurrent or metastatic head and neck squamous cell carcinoma with no indication for local radical treatment.

[0333] Embodiment 30. The use according to embodiment 29, wherein the subject suffering from head and neck squamous cell carcinoma has not previously received systemic treatment for head and neck squamous cell carcinoma.

[0334] Embodiment 31. The use according to any one of embodiments 19-28, wherein the tumor is esophageal cancer; preferably, the tumor is esophageal squamous cell carcinoma; preferably, the tumor is unresectable, locally advanced, recurrent or metastatic esophageal squamous cell carcinoma.

[0335] Embodiment 32. The use according to embodiment 31, wherein the subject suffering from esophageal squamous cell carcinoma has not previously received systemic treatment for esophageal squamous cell carcinoma.

[0336] Embodiment 33. A method of treating a tumor in a subject, wherein the method comprises administering to the subject the pharmaceutical combination of any one of embodiments 1-18.

[0337] Embodiment 34. The method of embodiment 33, wherein the method comprises administering to the subject the drug combination of any one of embodiments 14-18 in a first treatment phase and administering to the subject the drug combination of any one of embodiments 1-13 in a second treatment phase.

[0338] Embodiment 35. The method according to embodiment 33 or 34, wherein the first treatment phase comprises 1-14 treatment cycles, 2-12 treatment cycles or 2-10 treatment cycles, preferably 2-8 treatment cycles, more preferably 4-6 treatment cycles.

[0339] Embodiment 36. The method according to embodiment 35, wherein one treatment cycle is every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks, preferably, one treatment cycle is every 3 weeks.

[0340] Embodiment 37. A method according to any one of Embodiments 33-36, wherein the tumor is head and neck cancer; preferably, the tumor is head and neck squamous cell carcinoma; preferably, the tumor is locally advanced, recurrent or metastatic head and neck squamous cell carcinoma with no indication for local radical treatment.

[0341] Embodiment 38. The use according to embodiment 37, wherein the subject suffering from head and neck squamous cell carcinoma has not previously received systemic treatment for head and neck squamous cell carcinoma.

[0342] Embodiment 39. The use according to any one of embodiments 33-36, wherein the tumor is esophageal cancer; preferably, the tumor is esophageal squamous cell carcinoma; preferably, the tumor is unresectable, locally advanced, recurrent or metastatic esophageal squamous cell carcinoma.

[0343] Embodiment 40. The use according to embodiment 39, wherein the subject suffering from esophageal squamous cell carcinoma has not previously received systemic treatment for esophageal squamous cell carcinoma.

[0344] Embodiment 41. A kit for treating tumors, comprising the pharmaceutical combination according to any one of embodiments 1-18.

[0345] Embodiment 42. A combination drug comprising:

[0346] a) The pharmaceutical combination according to any one of embodiments 14-18, which is formulated to be suitable for administration during the first treatment phase; and

[0347] b) The pharmaceutical combination according to any one of embodiments 1 to 13, which is formulated to be suitable for administration during the second treatment phase.

[0348] Embodiment 43. The combination drug combination according to embodiment 42, wherein the first treatment phase comprises 1-14 treatment cycles, 2-12 treatment cycles or 2-10 treatment cycles, preferably 2-8 treatment cycles, more preferably 4-6 treatment cycles.

[0349] Embodiment 44. The combination drug combination according to embodiment 43, wherein one treatment cycle is every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks, preferably, one treatment cycle is every 3 weeks.

[0350] Embodiment 45. Use of the combination drug combination of any one of Embodiments 42-44 in the preparation of a medicament for treating a tumor in a subject.

[0351] Embodiment 46. The use according to embodiment 45, wherein the tumor is head and neck cancer; preferably, the tumor is head and neck squamous cell carcinoma; preferably, the tumor is locally advanced, recurrent or metastatic head and neck squamous cell carcinoma with no indication for local radical treatment.

[0352] Embodiment 47. The use according to embodiment 46, wherein the subject with head and neck squamous cell carcinoma has not previously received systemic treatment for head and neck squamous cell carcinoma.

[0353] Embodiment 48. The use according to embodiment 45, wherein the tumor is esophageal cancer; preferably, the tumor is esophageal squamous cell carcinoma; preferably, the tumor is unresectable, locally advanced, recurrent or metastatic esophageal squamous cell carcinoma.

[0354] Embodiment 49. The use according to embodiment 48, wherein the subject suffering from esophageal squamous cell carcinoma has not previously received systemic treatment for esophageal squamous cell carcinoma.

[0355] Embodiment 50. Use of an anti-TIM-3 antibody or antigen-binding fragment thereof and an anti-PD-1 antibody or antigen-binding fragment thereof in the preparation of a medicament for treating a tumor in a subject, wherein the anti-TIM-3 antibody or antigen-binding fragment thereof comprises:

[0356] HCDR1 of the amino acid sequence set forth in SEQ ID NO:1, HCDR2 of the amino acid sequence set forth in SEQ ID NO:2, HCDR3 of the amino acid sequence set forth in SEQ ID NO:3, LCDR1 of the amino acid sequence set forth in SEQ ID NO:4, LCDR2 of the amino acid sequence set forth in SEQ ID NO:5, and LCDR3 of the amino acid sequence set forth in SEQ ID NO:6; or

[0357] HCDR1 of the amino acid sequence shown in SEQ ID NO:21, HCDR2 of the amino acid sequence shown in SEQ ID NO:22, HCDR3 of the amino acid sequence shown in SEQ ID NO:23, LCDR1 of the amino acid sequence shown in SEQ ID NO:24, LCDR2 of the amino acid sequence shown in SEQ ID NO:25, and LCDR3 of the amino acid sequence shown in SEQ ID NO:26.

[0358] Embodiment 51. Use of an anti-TIM-3 antibody or antigen-binding fragment thereof, an anti-PD-1 antibody or antigen-binding fragment thereof, and a chemotherapy drug in the preparation of a medicament for treating a tumor in a subject, wherein the anti-TIM-3 antibody or antigen-binding fragment thereof comprises:

[0359] HCDR1 of the amino acid sequence set forth in SEQ ID NO:1, HCDR2 of the amino acid sequence set forth in SEQ ID NO:2, HCDR3 of the amino acid sequence set forth in SEQ ID NO:3, LCDR1 of the amino acid sequence set forth in SEQ ID NO:4, LCDR2 of the amino acid sequence set forth in SEQ ID NO:5, and LCDR3 of the amino acid sequence set forth in SEQ ID NO:6; or

[0360] HCDR1 with the amino acid sequence set forth in SEQ ID NO:21, HCDR2 with the amino acid sequence set forth in SEQ ID NO:22, HCDR3 with the amino acid sequence set forth in SEQ ID NO:23, LCDR1 with the amino acid sequence set forth in SEQ ID NO:24, LCDR2 with the amino acid sequence set forth in SEQ ID NO:25, and LCDR3 with the amino acid sequence set forth in SEQ ID NO:26;

[0361] Optionally, the chemotherapy drug is a platinum anti-tumor drug and / or a taxane anti-tumor drug;

[0362] Optionally, the platinum anti-tumor drug is selected from one or more of cisplatin, carboplatin, nedaplatin, dicycloplatin, picoplatin, oxaliplatin, miplatin, lobaplatin, levoplatin, triplatin tetranitrate, phenoplatin and satraplatin;

[0363] Optionally, the taxane anti-tumor drug is selected from one or more of paclitaxel, cabazitaxel and docetaxel;

[0364] Optionally, the chemotherapy drugs are cisplatin and paclitaxel, or the chemotherapy drugs are carboplatin and paclitaxel.

[0365] Embodiment 52. The use according to embodiment 50 or 51, wherein the anti-TIM-3 antibody or antigen-binding fragment thereof comprises:

[0366] a heavy chain variable region having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 7, and a light chain variable region having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 8; or

[0367] A heavy chain variable region having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:27, and a light chain variable region having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:28.

[0368] Embodiment 53. The use according to any one of Embodiments 50-52, wherein the anti-TIM-3 antibody or antigen-binding fragment thereof comprises:

[0369] a heavy chain having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 9, and a light chain having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 10; or

[0370] A heavy chain having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:29, and a light chain having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:30.

[0371] Embodiment 54. The use according to any one of Embodiments 50-53, wherein the anti-PD-1 antibody or antigen-binding fragment thereof comprises: a HCDR1 of the amino acid sequence shown in SEQ ID NO: 11, a HCDR2 of the amino acid sequence shown in SEQ ID NO: 12, a HCDR3 of the amino acid sequence shown in SEQ ID NO: 13, a LCDR1 of the amino acid sequence shown in SEQ ID NO: 14, a LCDR2 of the amino acid sequence shown in SEQ ID NO: 15, and a LCDR3 of the amino acid sequence shown in SEQ ID NO: 16.

[0372] Embodiment 55. The use according to any one of Embodiments 50-54, wherein the anti-PD-1 antibody or antigen-binding fragment thereof comprises: a heavy chain variable region having an amino acid sequence that is at least 95% identical to the amino acid sequence shown in SEQ ID NO: 17, and a light chain variable region having an amino acid sequence that is at least 95% identical to the amino acid sequence shown in SEQ ID NO: 18.

[0373] Embodiment 56. The use according to any one of Embodiments 50-55, wherein the anti-PD-1 antibody or antigen-binding fragment thereof comprises: a heavy chain having an amino acid sequence that is at least 95% identical to the amino acid sequence shown in SEQ ID NO: 19, and a light chain having an amino acid sequence that is at least 95% identical to the amino acid sequence shown in SEQ ID NO: 20.

[0374] Embodiment 57. The use according to any one of Embodiments 50-56, wherein the anti-TIM-3 antibody or antigen-binding fragment thereof and the anti-PD-1 antibody or antigen-binding fragment thereof are formulated as a preparation for parenteral administration, preferably, the anti-TIM-3 antibody or antigen-binding fragment thereof and the anti-PD-1 antibody or antigen-binding fragment thereof are formulated as a preparation for intravenous, intramuscular or subcutaneous administration.

[0375] Embodiment 58. The use according to any one of Embodiments 50-57, wherein the anti-TIM-3 antibody or antigen-binding fragment thereof and the anti-PD-1 antibody or antigen-binding fragment thereof are formulated in a single formulation.

[0376] Embodiment 59. The use according to any one of Embodiments 50-58, wherein the anti-TIM-3 antibody or antigen-binding fragment thereof and the anti-PD-1 antibody or antigen-binding fragment thereof are formulated separately.

[0377] Embodiment 60. The use according to any one of Embodiments 50-59, wherein the unit dose of the anti-TIM-3 antibody or antigen-binding fragment thereof is 60-1800 mg, 100-1600 mg, 120-1600 mg, 180-1200 mg, or 240-600 mg; preferably, the unit dose of the anti-TIM-3 antibody or antigen-binding fragment thereof is 240 mg, 300 mg, 360 mg and / or 600 mg.

[0378] Embodiment 61. The use according to any one of Embodiments 50-60, wherein the unit dose of the anti-PD-1 antibody or antigen-binding fragment thereof is 10-500 mg, 50-500 mg, 50-200 mg, or 100-200 mg; preferably, the unit dose of the anti-PD-1 antibody or antigen-binding fragment thereof is 100 mg and / or 200 mg.

[0379] Embodiment 62. The use according to any one of Embodiments 50-61, wherein the mass ratio of the anti-TIM-3 antibody or its antigen-binding fragment to the anti-PD-1 antibody or its antigen-binding fragment is (0.1-180):1, (0.2-50):1, (0.5-9):1, (3-7.5):1, (4-7.5):1 or (6-7.5):1.

[0380] Embodiment 63. The use according to any one of Embodiments 50-62, wherein the anti-TIM-3 antibody or antigen-binding fragment thereof and the anti-PD-1 antibody or antigen-binding fragment thereof can be administered simultaneously, sequentially and / or alternately.

[0381] Embodiment 64. The use according to any one of Embodiments 50-62, wherein the anti-TIM-3 antibody or antigen-binding fragment thereof, anti-PD-1 antibody or antigen-binding fragment thereof, cisplatin and paclitaxel are administered simultaneously, sequentially and / or alternately; or the anti-TIM-3 antibody or antigen-binding fragment thereof, anti-PD-1 antibody or antigen-binding fragment thereof, carboplatin and paclitaxel are administered simultaneously, sequentially and / or alternately.

[0382] Embodiment 65. The use according to any one of Embodiments 50-64, wherein the anti-TIM-3 antibody or antigen-binding fragment thereof is administered once every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks, preferably, the anti-TIM-3 antibody or antigen-binding fragment thereof is administered once every 3 weeks; optionally, the anti-TIM-3 antibody or antigen-binding fragment thereof is administered at a dose of 100-1800 mg, 600-1800 mg, 600-1500 mg, or 1200-1500 mg each time, preferably, the anti-TIM-3 antibody or antigen-binding fragment thereof is administered at a dose of 1200 mg each time.

[0383] Embodiment 66. The use according to any one of Embodiments 50-65, wherein the anti-PD-1 antibody or antigen-binding fragment thereof is administered once every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks. Preferably, the anti-PD-1 antibody or antigen-binding fragment thereof is administered once every 3 weeks. Optionally, the anti-PD-1 antibody or antigen-binding fragment thereof is administered at a dose of 10-800 mg, 50-500 mg, or 100-200 mg each time. Preferably, the anti-PD-1 antibody or antigen-binding fragment thereof is administered at a dose of 200 mg each time.

[0384] Embodiment 67. The use according to any one of embodiments 50-66, wherein the cisplatin is administered once every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks, preferably, the cisplatin is administered once every 3 weeks; optionally, the cisplatin is administered at a dose of 30-100 mg / m 2 30-75 mg / m 2 48-75 mg / m 2 or 60–75 mg / m 2 Preferably, the cisplatin is administered at a dose of 60-75 mg / m 2 or the carboplatin is administered once every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks, preferably, the carboplatin is administered once every 3 weeks; optionally, the carboplatin is administered at a dose of 2.5-5 mg / (mL / min)AUC or 3.2-5 mg / (mL / min)AUC each time, preferably, the carboplatin is administered at a dose of 3.2-5 mg / (mL / min)AUC each time.

[0385] Embodiment 68. The use according to any one of embodiments 50-67, wherein the paclitaxel is administered once every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks, preferably, the paclitaxel is administered once every 3 weeks; optionally, the paclitaxel is administered at a dose of 75-175 mg / m 2 100-175 mg / m 2 112-175 mg / m 2or 135–175 mg / m 2 Preferably, the paclitaxel is administered at a dose of 135-175 mg / m 2 Dosage administration.

[0386] Embodiment 69. The use according to any one of Embodiments 50-68, wherein the tumor is head and neck cancer; preferably, the tumor is head and neck squamous cell carcinoma; preferably, the tumor is locally advanced, recurrent or metastatic head and neck squamous cell carcinoma with no indication for local radical treatment.

[0387] Embodiment 70. The use according to embodiment 69, wherein the subject with head and neck squamous cell carcinoma has not previously received systemic treatment for head and neck squamous cell carcinoma.

[0388] Embodiment 71. The use according to any one of embodiments 50-68, wherein the tumor is esophageal cancer; preferably, the tumor is esophageal squamous cell carcinoma; preferably, the tumor is unresectable, locally advanced, recurrent or metastatic esophageal squamous cell carcinoma.

[0389] Embodiment 72. The use according to embodiment 71, wherein the subject suffering from esophageal squamous cell carcinoma has not previously received systemic treatment for esophageal squamous cell carcinoma.

[0390] Technical Effects

[0391] In general, use of the above-described pharmaceutical combinations of the present disclosure will help:

[0392] (1) Produce a better therapeutic effect in reducing tumor growth or even eliminating tumors compared to administering either drug alone;

[0393] (2) provide for administration of a smaller amount of the drug than would be possible with either drug alone;

[0394] (3) provide a treatment that is well tolerated by patients and has fewer adverse effects and / or complications than either drug given alone;

[0395] (4) provide better disease control rates among treated patients;

[0396] (5) provide longer survival (e.g., median survival, progression-free survival, or overall survival) in treated patients;

[0397] (6) provide longer survival (e.g., median survival, progression-free survival, or overall survival) for treated patients compared to standard chemotherapy;

[0398] (7) provide a longer duration of disease remission (DOR); and / or

[0399] (8) Compared with the administration of any drug in the combination alone, it has good anti-tumor activity and shows a more excellent anti-tumor synergistic effect.

[0400] The drug combination and treatment regimen disclosed herein have excellent efficacy in treating head and neck cancer, particularly recurrent or metastatic head and neck squamous cell carcinoma. The combination and treatment regimen have beneficial effects on at least one of ORR, DCR, DOR, PFS, 9-month PFS rate, 6-month PFS rate, OS, tolerability, and side effects, for example, improving the 9-month PFS rate and / or 6-month PFS rate.

[0401] The drug combination and treatment regimen disclosed herein have excellent efficacy in treating esophageal cancer, especially unresectable locally advanced, recurrent, or metastatic esophageal squamous cell carcinoma. The combination and treatment regimen have beneficial effects on at least one of ORR, DCR, DOR, PFS, 9-month PFS rate, 6-month PFS rate, OS, tolerability, and side effects, for example, improving ORR, PFS, 9-month PFS rate, and / or 6-month PFS rate.

[0402] Definition and Description

[0403] Unless otherwise indicated, the following terms used in this disclosure have the following meanings. A particular term should not be construed as undefined or unclear unless specifically defined, but rather should be understood according to its ordinary meaning in the art. When a trade name appears in this disclosure, it is intended to refer to the corresponding commercial product or its active ingredient.

[0404] As used herein, the term "drug combination" refers to a combination of two or more active ingredients (including administration in the form of each active ingredient itself, or in the form of its own pharmaceutically acceptable salt or ester derivatives, prodrugs or compositions) administered simultaneously or sequentially. The active ingredients can be administered to a subject simultaneously as a single formulation, or sequentially in any order as a single formulation. Alternatively, all of the active ingredients are formulated in a single formulation and administered to a subject simultaneously. Alternatively, part of the active ingredients are formulated in a single formulation and the other parts of the active ingredients are each administered to a subject simultaneously or sequentially in any order as a single formulation.

[0405] The term "fixed combination" means that the active ingredients are administered to a subject simultaneously in a fixed total dose or dose ratio, or in the form of a single entity, pharmaceutical composition or formulation.

[0406] The term "non-fixed combination" refers to two or more active ingredients administered to a subject as separate entities (e.g., pharmaceutical compositions, formulations) simultaneously, concurrently or sequentially, wherein the active ingredients administered to the subject reach a therapeutically effective level. An example of a non-fixed combination is cocktail therapy, e.g., administration of three or more active ingredients. In a non-fixed combination, the individual active ingredients may be packaged, sold or administered as completely independent pharmaceutical compositions. The "non-fixed combination" also includes the combined use of "fixed combinations" with each other, or a "fixed combination" with any one or more independent entities of the active ingredients.

[0407] As used herein, the term "antibody" refers to an antigen-binding protein having at least one antigen-binding domain. The antibodies and fragments thereof disclosed herein may be whole antibodies or any fragment thereof. Therefore, the antibodies and fragments thereof disclosed herein include monoclonal antibodies or fragments thereof and antibody variants or fragments thereof. Examples of antibodies and antigen-binding fragments thereof include monospecific antibodies, bispecific antibodies, multispecific antibodies, Fab fragments, Fab' fragments, F(ab)'2 fragments, Fv fragments, isolated CDR regions, single-chain Fv molecules (scFv) and other antibody fragments known in the art. The anti-TIM-3 antibodies and anti-PD-1 antibodies and antigen-binding fragments thereof disclosed herein may be IgG1, IgG2, IgG3 or IgG4 isotypes. The term "isotype" refers to the class of antibodies encoded by the heavy chain constant region gene. The anti-TIM-3 antibodies and antigen-binding fragments thereof and anti-PD-1 antibodies and antigen-binding fragments thereof disclosed herein may be derived from any species, including but not limited to mice, rats, rabbits, primates, llamas and humans. The anti-TIM-3 antibodies and antigen-binding fragments thereof, as well as the anti-PD-1 antibodies and antigen-binding fragments thereof disclosed herein can be murine antibodies, chimeric antibodies, humanized antibodies, or fully human antibodies. Unless otherwise indicated, the "antibodies" disclosed herein include whole antibodies and any antigen-binding fragments (or "antigen-binding portions") or single chains thereof. Conventional "whole antibodies" are glycoproteins comprising two heavy (H) chains and two light (L) chains, the heavy chains and light chains being linked by disulfide bonds. Each heavy chain consists of a heavy chain variable region (VH) and a heavy chain constant region (CH). The heavy chain constant region consists of three domains, namely CH1, CH2, and CH3. Each light chain consists of a light chain variable region (VL) and a light chain constant region (CL). The light chain constant region consists of one domain, CL. The VH and VL regions can also be divided into hypervariable regions, namely complementarity determining regions (CDRs), and framework regions (FRs) whose sequences are relatively conserved. Each VH and VL is composed of three CDRs and four FRs, respectively, from the amino terminus to the carboxyl terminus: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4. The variable regions of the heavy and light chains contain binding domains that interact with antigens. The constant region of the antibody can mediate the binding of the immunoglobulin to host tissues or factors, including various cells of the immune system (e.g., effector cells) and the first component (C1q) of the classical complement system. At the same time, as will be appreciated by those skilled in the art, special "whole antibodies," such as nanobodies, have only heavy (H) chains and no light (L) chains.

[0408] An "antigen-binding fragment" or "antibody binding portion" of an antibody refers to one or more fragments of an antibody that retain the function of specifically binding to an antigen (e.g., TIM-3 or PD-1). It has been demonstrated that the antigen-binding function of an antibody can be performed by fragments of the entire antibody. Examples encompassed by the term "antigen-binding portion / fragment" of an antibody include: (i) Fab fragment: a fragment consisting of V L 、V H The invention relates to a monovalent fragment consisting of a single variable domain (VL), a monovalent fragment consisting of a CL and a CH1 domain; (ii) a F(ab')2 fragment, a bivalent fragment comprising two Fab fragments connected by a disulfide bridge at the hinge region; (iii) an Fd fragment consisting of the VH and CH1 domains; (iv) an Fv fragment consisting of the VL and VH domains of a single arm of an antibody; (v) a dAb fragment consisting of a VH domain (see Ward et al., Nature. 341:544-546 (1989)); (vi) an isolated complementarity determining region (CDR); and (vii) a nanobody, a heavy chain variable region comprising a single variable domain and two constant domains. In addition, although the two domains VL and VH of the Fv fragment are encoded by different genes, VH and VL can be connected into a single protein chain by a recombinant method through a synthetic linker, wherein VL and VH pair to form a monovalent molecule (called single-chain Fv (scFv); see, for example, Bird et al., Science. 242: 423-426 (1988); Huston et al., Proc. Natl. Acad. Sci. 85: 5879-5883 (1988)). These single-chain antibodies are also encompassed by the term antigen-binding portion / fragment. In addition, recombinant polypeptides, fusion proteins, and immunoconjugates comprising the antigen-binding portion / fragment are also encompassed by the term antigen-binding portion / fragment.

[0409] A "chimeric antibody" is an antibody having at least a portion of a heavy chain variable region and at least a portion of a light chain variable region derived from one species, and at least a portion of a constant region derived from another species. For example, in one embodiment, a chimeric antibody may comprise a murine variable region and a human constant region.

[0410] "Humanized antibodies" are antibodies that contain complementary determining regions (CDRs) derived from non-human antibodies and framework regions and constant regions derived from human antibodies. For example, anti-TIM-3 antibodies and anti-PD-1 antibodies may contain CDRs derived from one or more murine antibodies and human framework regions and human constant regions. Exemplary humanized antibodies are provided herein. Additional anti-TIM-3 antibodies or variants thereof comprising the HCDRs and LCDRs provided herein can be produced using any human framework sequence and are also included in the present disclosure. Additional anti-PD-1 antibodies or variants thereof comprising the HCDRs and LCDRs provided herein can be produced using any human framework sequence and are also included in the present disclosure. In one embodiment, framework sequences suitable for use in the present disclosure include those that are structurally similar to the framework sequences provided herein. Additional modifications may be made in the framework region to improve the properties of the antibodies provided herein. Such additional framework modifications may include chemical modifications; point mutations to reduce immunogenicity or remove T cell epitopes; or reverting mutations to residues in the original germline sequence. In some embodiments, such modifications include those corresponding to the mutations exemplified herein, including back mutations to the germline sequence. For example, in one embodiment, one or more amino acids in the human framework regions of the VH and / or VL of the humanized antibodies provided herein are backmutated to the corresponding amino acids in the parent murine antibody.

[0411] The term "identity" is also known as consistency. The "percentage (%) identity" of an amino acid sequence refers to the percentage of amino acid residues in the sequence to be aligned that are identical to the amino acid residues in the specific amino acid sequence shown in this article, after comparing the sequence to be aligned and, if necessary, introducing gaps to achieve maximum sequence identity, and not considering any conservative substitutions as part of sequence identity. The alignment of amino acid sequences for identity can be performed in a variety of ways within the scope of the art, such as BLAST, BLAST-2, ALIGN or Megalign (DNASTAR) software. Those skilled in the art can determine the appropriate parameters for aligning sequences, including any algorithm needed to obtain maximum alignment over the full length of the comparison sequence.

[0412] The term "treatment" generally refers to an operation to obtain a desired pharmacological and / or physiological effect. The effect can be preventive, in terms of completely or partially preventing a disease or its symptoms; and / or therapeutic, in terms of partially or completely stabilizing or curing a disease and / or side effects produced by the disease. As used herein, "treatment" encompasses any treatment of a patient's disease, including but...

Claims

1. A drug combination comprising an anti-TIM-3 antibody or an antigen-binding fragment thereof and an anti-PD-1 antibody or an antigen-binding fragment thereof, wherein: The anti-TIM-3 antibody or antigen-binding fragment thereof comprises: HCDR1 of the amino acid sequence shown in SEQ ID NO: 1, HCDR2 of the amino acid sequence shown in SEQ ID NO: 2, HCDR3 of the amino acid sequence shown in SEQ ID NO: 3, LCDR1 of the amino acid sequence shown in SEQ ID NO: 4, LCDR2 of the amino acid sequence shown in SEQ ID NO: 5, and LCDR3 of the amino acid sequence shown in SEQ ID NO: 6; or HCDR1 of the amino acid sequence shown in SEQ ID NO: 21, HCDR2 of the amino acid sequence shown in SEQ ID NO: 22, HCDR3 of the amino acid sequence shown in SEQ ID NO: 23, LCDR1 of the amino acid sequence shown in SEQ ID NO: 24, LCDR2 of the amino acid sequence shown in SEQ ID NO: 25, and LCDR3 of the amino acid sequence shown in SEQ ID NO: 26; The anti-PD-1 antibody or its antigen-binding fragment comprises: HCDR1 of the amino acid sequence shown in SEQ ID NO:11, HCDR2 of the amino acid sequence shown in SEQ ID NO:12, HCDR3 of the amino acid sequence shown in SEQ ID NO:13, LCDR1 of the amino acid sequence shown in SEQ ID NO:14, LCDR2 of the amino acid sequence shown in SEQ ID NO:15, and LCDR3 of the amino acid sequence shown in SEQ ID NO:

16.

2. The pharmaceutical combination according to claim 1, wherein The anti-TIM-3 antibody or its antigen-binding fragment and the anti-PD-1 antibody or its antigen-binding fragment are formulated as a preparation for parenteral administration. Preferably, the anti-TIM-3 antibody or its antigen-binding fragment and the anti-PD-1 antibody or its antigen-binding fragment are formulated as a preparation for intravenous, intramuscular or subcutaneous administration.

3. The pharmaceutical combination according to claim 1 or 2, wherein: The anti-TIM-3 antibody or antigen-binding fragment thereof and the anti-PD-1 antibody or antigen-binding fragment thereof are formulated in a single formulation or separately.

4. The pharmaceutical combination according to any one of claims 1 to 3, wherein: The unit dose of the anti-TIM-3 antibody or its antigen-binding fragment is 60-1800 mg, 100-1600 mg, 120-1600 mg, 180-1200 mg, or 240-600 mg; preferably, the unit dose of the anti-TIM-3 antibody or its antigen-binding fragment is 240 mg, 300 mg, 360 mg and / or 600 mg; and / or The unit dose of the anti-PD-1 antibody or antigen-binding fragment thereof is 10-500 mg, 50-500 mg, 50-200 mg, or 100-200 mg; Preferably, the unit dose of the anti-PD-1 antibody or antigen-binding fragment thereof is 100 mg and / or 200 mg.

5. The pharmaceutical combination according to any one of claims 1 to 4, wherein: The mass ratio of the anti-TIM-3 antibody or its antigen-binding fragment to the anti-PD-1 antibody or its antigen-binding fragment is (0.1-180):1, (0.2-50):1, (0.5-9):1, (3-7.5):1, (4-7.5):1 or (6-7.5):

1.

6. The pharmaceutical combination according to any one of claims 1 to 5, wherein: The drug combination further comprises a chemotherapeutic drug; preferably, the chemotherapeutic drug is a platinum anti-tumor drug and / or a taxane anti-tumor drug; Optionally, the platinum anti-tumor drug is selected from one or more of cisplatin, carboplatin, nedaplatin, dicycloplatin, picoplatin, oxaliplatin, miplatin, lobaplatin, levoplatin, triplatin tetranitrate, phenoplatin and satraplatin; Optionally, the taxane anti-tumor drug is selected from one or more of paclitaxel, cabazitaxel and docetaxel; Optionally, the chemotherapy drugs are cisplatin and paclitaxel, or the chemotherapy drugs are carboplatin and paclitaxel.

7. The pharmaceutical combination according to any one of claims 1 to 6, wherein: The drug combination is suitable for administration in a single treatment cycle, and includes 100-1800 mg, 600-1800 mg, 600-1500 mg, or 1200-1500 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof; and / or 10-800 mg, 50-500 mg, or 100-200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof.

8. Use of the pharmaceutical combination according to any one of claims 1 to 7 in the preparation of a medicament for treating a tumor in a subject.

9. Use of an anti-TIM-3 antibody or an antigen-binding fragment thereof and an anti-PD-1 antibody or an antigen-binding fragment thereof in the preparation of a medicament for treating a tumor in a subject, wherein: The anti-TIM-3 antibody or antigen-binding fragment thereof comprises: HCDR1 of the amino acid sequence shown in SEQ ID NO: 1, HCDR2 of the amino acid sequence shown in SEQ ID NO: 2, HCDR3 of the amino acid sequence shown in SEQ ID NO: 3, LCDR1 of the amino acid sequence shown in SEQ ID NO: 4, LCDR2 of the amino acid sequence shown in SEQ ID NO: 5, and LCDR3 of the amino acid sequence shown in SEQ ID NO: 6; or HCDR1 of the amino acid sequence shown in SEQ ID NO: 21, HCDR2 of the amino acid sequence shown in SEQ ID NO: 22, HCDR3 of the amino acid sequence shown in SEQ ID NO: 23, LCDR1 of the amino acid sequence shown in SEQ ID NO: 24, LCDR2 of the amino acid sequence shown in SEQ ID NO: 25, and LCDR3 of the amino acid sequence shown in SEQ ID NO: 26; The anti-PD-1 antibody or its antigen-binding fragment comprises: HCDR1 of the amino acid sequence shown in SEQ ID NO:11, HCDR2 of the amino acid sequence shown in SEQ ID NO:12, HCDR3 of the amino acid sequence shown in SEQ ID NO:13, LCDR1 of the amino acid sequence shown in SEQ ID NO:14, LCDR2 of the amino acid sequence shown in SEQ ID NO:15, and LCDR3 of the amino acid sequence shown in SEQ ID NO:

16.

10. Use of an anti-TIM-3 antibody or an antigen-binding fragment thereof, an anti-PD-1 antibody or an antigen-binding fragment thereof, and a chemotherapeutic drug in the preparation of a medicament for treating a tumor in a subject, wherein: The anti-TIM-3 antibody or antigen-binding fragment thereof comprises: HCDR1 of the amino acid sequence shown in SEQ ID NO: 1, HCDR2 of the amino acid sequence shown in SEQ ID NO: 2, HCDR3 of the amino acid sequence shown in SEQ ID NO: 3, LCDR1 of the amino acid sequence shown in SEQ ID NO: 4, LCDR2 of the amino acid sequence shown in SEQ ID NO: 5, and LCDR3 of the amino acid sequence shown in SEQ ID NO: 6; or HCDR1 of the amino acid sequence shown in SEQ ID NO: 21, HCDR2 of the amino acid sequence shown in SEQ ID NO: 22, HCDR3 of the amino acid sequence shown in SEQ ID NO: 23, LCDR1 of the amino acid sequence shown in SEQ ID NO: 24, LCDR2 of the amino acid sequence shown in SEQ ID NO: 25, and LCDR3 of the amino acid sequence shown in SEQ ID NO: 26; The anti-PD-1 antibody or antigen-binding fragment thereof comprises: HCDR1 of the amino acid sequence shown in SEQ ID NO: 11, HCDR2 of the amino acid sequence shown in SEQ ID NO: 12, HCDR3 of the amino acid sequence shown in SEQ ID NO: 13, LCDR1 of the amino acid sequence shown in SEQ ID NO: 14, LCDR2 of the amino acid sequence shown in SEQ ID NO: 15, and LCDR3 of the amino acid sequence shown in SEQ ID NO: 16; Preferably, the chemotherapy drug is a platinum anti-tumor drug and / or a taxane anti-tumor drug; Optionally, the platinum anti-tumor drug is selected from one or more of cisplatin, carboplatin, nedaplatin, dicycloplatin, picoplatin, oxaliplatin, miplatin, lobaplatin, levoplatin, triplatin tetranitrate, phenoplatin and satraplatin; Optionally, the taxane anti-tumor drug is selected from one or more of paclitaxel, cabazitaxel and docetaxel; Optionally, the chemotherapy drugs are cisplatin and paclitaxel, or the chemotherapy drugs are carboplatin and paclitaxel.

11. The use according to any one of claims 8 to 10, wherein The anti-TIM-3 antibody or its antigen-binding fragment and the anti-PD-1 antibody or its antigen-binding fragment can be administered simultaneously, sequentially and / or alternately; or the anti-TIM-3 antibody or its antigen-binding fragment, the anti-PD-1 antibody or its antigen-binding fragment, cisplatin and paclitaxel can be administered simultaneously, sequentially and / or alternately; or the anti-TIM-3 antibody or its antigen-binding fragment, the anti-PD-1 antibody or its antigen-binding fragment, carboplatin and paclitaxel can be administered simultaneously, sequentially and / or alternately.

12. The use according to any one of claims 8 to 11, wherein The anti-TIM-3 antibody or antigen-binding fragment thereof is administered once every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks. Preferably, the anti-TIM-3 antibody or antigen-binding fragment thereof is administered once every 3 weeks. Alternatively, the anti-TIM-3 antibody or antigen-binding fragment thereof is administered at a dose of 100-1800 mg, 600-1800 mg, 600-1500 mg, or 1200-1500 mg each time. Preferably, the anti-TIM-3 antibody or antigen-binding fragment thereof is administered at a dose of 1200 mg each time. And / or The anti-PD-1 antibody or antigen-binding fragment thereof is administered once every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks. Preferably, the anti-PD-1 antibody or antigen-binding fragment thereof is administered once every 3 weeks. Optionally, the anti-PD-1 antibody or antigen-binding fragment thereof is administered at a dose of 10-800 mg, 50-500 mg, or 100-200 mg each time. Preferably, the anti-PD-1 antibody or antigen-binding fragment thereof is administered at a dose of 200 mg each time.

13. The use according to any one of claims 8 to 12, wherein The tumor is head and neck cancer; preferably, the tumor is head and neck squamous cell carcinoma; preferably, the tumor is locally advanced, recurrent or metastatic head and neck squamous cell carcinoma without local radical treatment indication; Optionally, the subject with head and neck squamous cell carcinoma has not previously received systemic treatment for head and neck squamous cell carcinoma.

14. The use according to any one of claims 8 to 12, wherein The tumor is esophageal cancer; preferably, the tumor is esophageal squamous cell carcinoma; preferably, the tumor is unresectable, locally advanced, recurrent or metastatic esophageal squamous cell carcinoma; Optionally, the subject with esophageal squamous cell carcinoma has not previously received systemic treatment for esophageal squamous cell carcinoma.

15. The pharmaceutical combination according to any one of claims 1 to 7, or the use according to any one of claims 8 to 13, wherein: The anti-TIM-3 antibody or antigen-binding fragment thereof comprises: a heavy chain variable region having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 7, and a light chain variable region having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 8; a heavy chain variable region having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 27, and a light chain variable region having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 28; Optionally, the anti-TIM-3 antibody or antigen-binding fragment thereof comprises: a heavy chain having an amino acid sequence that is at least 95% identical to the amino acid sequence shown in SEQ ID NO: 9, and a light chain having an amino acid sequence that is at least 95% identical to the amino acid sequence shown in SEQ ID NO: 10; or a heavy chain having an amino acid sequence that is at least 95% identical to the amino acid sequence set forth in SEQ ID NO:29, and a light chain having an amino acid sequence that is at least 95% identical to the amino acid sequence set forth in SEQ ID NO:30; Optionally, the anti-PD-1 antibody or antigen-binding fragment thereof comprises: a heavy chain variable region having an amino acid sequence that is at least 95% identical to the amino acid sequence shown in SEQ ID NO: 17, and a light chain variable region having an amino acid sequence that is at least 95% identical to the amino acid sequence shown in SEQ ID NO: 18; Optionally, the anti-PD-1 antibody or antigen-binding fragment thereof comprises: a heavy chain having an amino acid sequence that is at least 95% identical to the amino acid sequence shown in SEQ ID NO: 19, and a light chain having an amino acid sequence that is at least 95% identical to the amino acid sequence shown in SEQ ID NO: 20.