WO2025242190A1 - Treatment of tumors by means of anti-tigit antibody in combination with anti-pd-1 antibody - Google Patents

Abstract

Disclosed in the present invention is the use of an anti-TIGIT antibody or an antigen-binding fragment and an anti-PD-1 antibody or an antigen-binding fragment in the preparation of drugs for treating tumors.

Description

Combination therapy of anti-TIGIT antibody and anti-PD-1 antibody for tumors Technical Field

This invention relates to the field of drug therapy, and more specifically to the use or method of using anti-TIGIT antibodies and anti-PD-1 antibodies to treat cancer patients.

Background Technology

Cancer is one of the most serious threats to human health and social development. For example, gastric cancer is one of the most common malignant tumors worldwide, the third leading cause of cancer death globally, and the fifth most common malignant tumor. Gastric cancer is the third leading cause of cancer death worldwide, with approximately 769,000 patients dying from it each year. The 5-year survival rate for advanced or metastatic gastric cancer is approximately 5% to 20%, and the median overall survival for patients receiving chemotherapy alone is only about one year. However, for a long time, first-line treatment for gastric cancer has mainly consisted of surgery or radiotherapy and chemotherapy, and patients with locally advanced or metastatic gastric cancer that cannot be surgically resected have a poor prognosis, indicating a significant unmet clinical need.

However, the development of drugs or treatments for cancer still faces enormous challenges. There is still a need in this field to develop clinically effective and safer drugs or treatments to treat or prolong the lives of cancer patients.

Summary of the Invention

The present invention provides a method or use for treating tumors, the method or use comprising: administering an effective amount of an anti-TIGIT antibody or antigen-binding fragment and an anti-PD-1 antibody or antigen-binding fragment to a patient in need.

On one hand, the present invention provides the use of anti-TIGIT antibodies or antigen-binding fragments and anti-PD-1 antibodies or antigen-binding fragments in the preparation of medicaments for treating tumors. On the other hand, the present invention provides the use of anti-TIGIT antibodies or antigen-binding fragments in the preparation of medicaments for treating tumors in combination with anti-PD-1 antibodies or antigen-binding fragments. Furthermore, the present invention provides the use of anti-PD-1 antibodies or antigen-binding fragments in the preparation of medicaments for treating tumors in combination with anti-TIGIT antibodies or antigen-binding fragments.

On one hand, the present invention provides the use of anti-TIGIT antibody or antigen-binding fragment and anti-PD-1 antibody or antigen-binding fragment in the treatment of tumors. On the other hand, the present invention provides the use of anti-TIGIT antibody or antigen-binding fragment and anti-PD-1 antibody or antigen-binding fragment in combination for the treatment of tumors. Furthermore, the present invention provides the use of anti-TIGIT antibody or antigen-binding fragment in combination with anti-PD-1 antibody or antigen-binding fragment for the treatment of tumors.

On one hand, the present invention provides a combination drug comprising an anti-TIGIT antibody or antigen-binding fragment and an anti-PD-1 antibody or antigen-binding fragment. On the other hand, the present invention provides a pharmaceutical composition comprising an anti-TIGIT antibody or antigen-binding fragment and an anti-PD-1 antibody or antigen-binding fragment.

On one hand, the present invention also provides a kit comprising an anti-TIGIT antibody or antigen-binding fragment and an anti-PD-1 antibody or antigen-binding fragment. In some embodiments, the kit further includes instructions for use.

In some embodiments, the tumor includes, but is not limited to, hematologic malignancies and solid tumors. In some embodiments, hematologic malignancies include, but are not limited to, leukemia, lymphoma, and myeloma. In some embodiments, leukemia includes acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), and myeloproliferative disorders/tumors (MPDS). In some embodiments, lymphoma includes Hodgkin lymphoma, painless and aggressive non-Hodgkin lymphoma, Burkitt lymphoma, and follicular lymphoma (small cell and large cell). In some embodiments, myeloma includes multiple myeloma (MM), giant cell myeloma, heavy chain myeloma, and light chain or Bens-Jones myeloma. In some implementations, solid tumors include breast cancer, ovarian cancer, pancreatic cancer, prostate cancer, melanoma, colorectal cancer, colon cancer, lung cancer (such as non-small cell lung cancer (NSCLC)), head and neck cancer, bladder cancer, esophageal cancer, liver cancer (such as hepatocellular carcinoma (HCC)), kidney cancer, and stomach cancer.

In some embodiments, the tumor is selected from acute lymphoblastic leukemia, acute myeloid leukemia, chronic lymphocytic leukemia, chronic myeloid leukemia, myeloproliferative disorders/tumors, Hodgkin lymphoma, painless and aggressive non-Hodgkin lymphoma, Burkitt lymphoma, follicular lymphoma, multiple myeloma, giant cell myeloma, heavy chain myeloma, light chain or Bens-Jones myeloma, breast cancer, ovarian cancer, pancreatic cancer, prostate cancer, melanoma, colorectal cancer, colon cancer, lung cancer, head and neck cancer, bladder cancer, esophageal cancer, liver cancer, kidney cancer, and stomach cancer.

In some implementations, the tumor is selected from gastric cancer, gastroesophageal junction cancer, esophageal cancer, non-small cell lung cancer, and hepatocellular carcinoma.

In some implementations, the tumor is an advanced solid tumor.

In some implementations, the tumor patients include those with advanced malignant tumors diagnosed by cytology or pathology who have failed standard treatment, have no standard treatment available, are intolerant to standard treatment, or refuse standard treatment. In some implementations, the standard treatment refers to the standard treatment regimens recommended by the NCCN and CSCO guidelines for the tumors.

In some implementations, the tumor patients include those with locally advanced, unresectable, or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal cancer who have not previously received systemic therapy. In some implementations, the patient has a combined PD-L1 positive score (CPS) ≥5 and the tumor tissue is HER2 negative.

In some implementations, the tumor patient includes a patient with histologically or cytologically confirmed locally advanced or metastatic (refer to the American Joint Committee on Cancer (AJCC) 8th Edition Staging Manual) non-small cell lung cancer. In some implementations, the patient may be:

a. Patients whose disease progressed after first-line treatment with PD-1/PD-L1 antibodies and platinum-based doublet chemotherapy, or who are unable to receive standard treatment; or

b. Individuals with driver gene mutations who have failed targeted therapy or chemotherapy, or who are unable to receive standard treatment.

In some implementations, the tumor patients include those with pathologically or clinically diagnosed advanced hepatocellular carcinoma who have experienced disease progression or are ineligible for standard treatment after systemic therapy with PD-1/PD-L1 antibodies and targeted therapies. In some implementations, the patients are those with a Child-Pugh liver function classification of A or a better B (≤7 points).

In some embodiments, the anti-TIGIT antibody or antigen-binding fragment is the anti-TIGIT antibody or antigen-binding fragment disclosed in WO2021/043206.

In some embodiments, the anti-TIGIT antibody or antigen-binding fragment comprises at least one or more of HCDR1 shown in SEQ ID NO:1, HCDR2 shown in SEQ ID NO:2, HCDR3 shown in SEQ ID NO:3, LCDR1 shown in SEQ ID NO:4, LCDR2 shown in SEQ ID NO:5, and LCDR3 shown in SEQ ID NO:6.

In some embodiments, the anti-TIGIT antibody or antigen-binding fragment comprises HCDR1 shown in SEQ ID NO:1, HCDR2 shown in SEQ ID NO:2, HCDR3 shown in SEQ ID NO:3, LCDR1 shown in SEQ ID NO:4, LCDR2 shown in SEQ ID NO:5, and LCDR3 shown in SEQ ID NO:6.

In some embodiments, the heavy chain variable region of the anti-TIGIT antibody or antigen-binding fragment comprises the amino acid sequence shown in SEQ ID NO:7, or an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with the sequence shown in SEQ ID NO:7, or an amino acid sequence having one or more conserved amino acid substitutions with the sequence shown in SEQ ID NO:7.

In some embodiments, the light chain variable region of the anti-TIGIT antibody or antigen-binding fragment comprises the amino acid sequence shown in SEQ ID NO:8, or an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with the sequence shown in SEQ ID NO:8, or an amino acid sequence having one or more conserved amino acid substitutions with the sequence shown in SEQ ID NO:8.

In some embodiments, the heavy chain variable region of the anti-TIGIT antibody or antigen-binding fragment contains the amino acid sequence shown in SEQ ID NO:7, and/or the light chain variable region of the anti-TIGIT antibody or antigen-binding fragment contains the amino acid sequence shown in SEQ ID NO:8.

In some embodiments, the heavy chain of the anti-TIGIT antibody comprises the amino acid sequence shown in SEQ ID NO:9, or an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with the sequence shown in SEQ ID NO:9, or an amino acid sequence having one or more conserved amino acid substitutions with the sequence shown in SEQ ID NO:9.

In some embodiments, the light chain of the anti-TIGIT antibody comprises the amino acid sequence shown in SEQ ID NO:10, or an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with the sequence shown in SEQ ID NO:10, or an amino acid sequence having one or more conserved amino acid substitutions with the sequence shown in SEQ ID NO:10.

In some embodiments, the heavy chain of the anti-TIGIT antibody comprises the amino acid sequence shown in SEQ ID NO:9, and/or the light chain of the antibody comprises the amino acid sequence shown in SEQ ID NO:10. In some embodiments, the anti-TIGIT antibody comprises two identical heavy chains and two identical light chains.

In some embodiments, the anti-TIGIT antibody is antibody h10D8OF.

In some embodiments, the anti-PD-1 antibody or antigen-binding fragment is nivolumab (such as Opdivo or OPDIVO or their biosimilars), pembrolizumab (such as Keytruda or their biosimilars), camrelizumab (such as Eryka or their biosimilars), or sintilimab (such as...). (or its biosimilars), toripalimab (e.g., Tuoyi or its biosimilars), or tislelizumab (e.g., ... (or its biosimilars).

In some embodiments, the anti-PD-1 antibody or antigen-binding fragment is the anti-PD-1 antibody or antigen-binding fragment disclosed in WO2020/207432.

In some embodiments, the anti-PD-1 antibody or antigen-binding fragment comprises one or more of HCDR1 shown in SEQ ID NO:11, HCDR2 shown in SEQ ID NO:12, HCDR3 shown in SEQ ID NO:13, LCDR1 shown in SEQ ID NO:14, LCDR2 shown in SEQ ID NO:15, and LCDR3 shown in SEQ ID NO:16.

In some embodiments, the anti-PD-1 antibody or antigen-binding fragment comprises HCDR1 shown in SEQ ID NO:11, HCDR2 shown in SEQ ID NO:12, HCDR3 shown in SEQ ID NO:13, LCDR1 shown in SEQ ID NO:14, LCDR2 shown in SEQ ID NO:15, and LCDR3 shown in SEQ ID NO:16.

In some embodiments, the heavy chain variable region of the anti-PD-1 antibody or antigen-binding fragment comprises the amino acid sequence shown in SEQ ID NO:17, or an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with the sequence shown in SEQ ID NO:17, or an amino acid sequence having one or more conserved amino acid substitutions with the sequence shown in SEQ ID NO:17.

In some embodiments, the light chain variable region of the anti-PD-1 antibody or antigen-binding fragment comprises the amino acid sequence shown in SEQ ID NO:18, or an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with the sequence shown in SEQ ID NO:18, or an amino acid sequence having one or more conserved amino acid substitutions with the sequence shown in SEQ ID NO:18.

In some embodiments, the heavy chain variable region of the anti-PD-1 antibody or antigen-binding fragment contains the amino acid sequence shown in SEQ ID NO:17, and/or the light chain variable region of the anti-PD-1 antibody or antigen-binding fragment contains the amino acid sequence shown in SEQ ID NO:18.

In some embodiments, the heavy chain of the anti-PD-1 antibody comprises an amino acid sequence as shown in SEQ ID NO:19, or an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with the sequence shown in SEQ ID NO:19, or an amino acid sequence having one or more conserved amino acid substitutions with the sequence shown in SEQ ID NO:19.

In some embodiments, the light chain of the anti-PD-1 antibody comprises an amino acid sequence as shown in SEQ ID NO:20, or an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with the sequence shown in SEQ ID NO:20, or an amino acid sequence having one or more conserved amino acid substitutions with the sequence shown in SEQ ID NO:20.

In some embodiments, the heavy chain of the anti-PD-1 antibody comprises the amino acid sequence shown in SEQ ID NO:19, and/or the light chain of the anti-PD-1 antibody comprises the amino acid sequence shown in SEQ ID NO:20. In some embodiments, the anti-PD-1 antibody comprises two identical heavy chains and two identical light chains.

In some implementations, the anti-PD-1 antibody is antibody A.

In some embodiments, the heavy chain of the anti-TIGIT antibody comprises the amino acid sequence shown in SEQ ID NO:9 and the light chain comprises the amino acid sequence shown in SEQ ID NO:10, the heavy chain of the anti-PD-1 antibody comprises the amino acid sequence shown in SEQ ID NO:19 and the light chain comprises the amino acid sequence shown in SEQ ID NO:20, and the tumor is selected from gastric cancer, gastroesophageal junction cancer, esophageal cancer, non-small cell lung cancer and hepatocellular carcinoma.

In some implementations, the effective amount refers to the amount of an active compound or agent that elicits a biological or pharmaceutical response in an tissue, system, animal, individual, or human that is being sought by a researcher, veterinarian, physician, or other clinician, including the treatment of a disease such as cancer.

In some embodiments, the anti-TIGIT antibody or antigen-binding fragment is administered at doses of about 0.01-1200 mg, about 0.01-1 mg, about 1-3 mg, about 1-5 mg, about 1-10 mg, about 3-10 mg, about 10-30 mg, about 10-50 mg, 10-100 mg, about 100-300 mg, about 100-500 mg, about 100-600 mg, about 300-600 mg, about 100-900 mg, about 600-900 mg, about 100-1000 mg, or about 1000-1200 mg per treatment cycle. In some embodiments, the anti-TIGIT antibody or antigen-binding fragment is administered at a dose of about 0.01 mg, about 1 mg, about 3 mg, about 5 mg, about 10 mg, about 30 mg, about 50 mg, about 100 mg, about 300 mg, about 500 mg, about 600 mg, about 900 mg, about 1000 mg, or about 1200 mg per treatment cycle, or a range (including endpoints) of any two of these values, or any value thereof. In some embodiments, the anti-TIGIT antibody or antigen-binding fragment is administered at a dose of about 600 mg or about 900 mg per treatment cycle.

In some embodiments, the anti-TIGIT antibody or antigen-binding fragment is administered at doses of about 0.01 mg/kg to 20 mg/kg, about 0.01 mg/kg to 0.05 mg/kg, about 0.01 mg/kg to 0.06 mg/kg, about 0.1 mg/kg to 0.2 mg/kg, about 0.1 mg/kg to 0.5 mg/kg, about 0.1 mg/kg to 0.6 mg/kg, about 1 mg/kg to 2 mg/kg, about 1 mg/kg to 5 mg/kg, about 1 mg/kg to 6 mg/kg, about 10 mg/kg to 12 mg/kg, about 12 mg/kg to 15 mg/kg, about 15 mg/kg to 18 mg/kg, or about 18 mg/kg to 20 mg/kg per treatment cycle. In some embodiments, the anti-TIGIT antibody or antigen-binding fragment is administered at a dose of about 0.01 mg/kg, about 0.05 mg/kg, about 0.06 mg/kg, about 0.1 mg/kg, about 0.2 mg/kg, about 0.5 mg/kg, about 0.6 mg/kg, about 1 mg/kg, about 2 mg/kg, about 5 mg/kg, about 6 mg/kg, about 10 mg/kg, about 12 mg/kg, about 15 mg/kg, about 18 mg/kg, or about 20 mg/kg per treatment cycle, or a range (including endpoints) of any two of these values, or any value therein. In some embodiments, the anti-TIGIT antibody or antigen-binding fragment is administered at a dose of about 12 mg/kg or about 18 mg/kg per treatment cycle.

In some embodiments, a treatment cycle is 1 week, 2 weeks, 3 weeks, 4 weeks, 1 month, 5 weeks, 6 weeks, 7 weeks, or a range (including endpoints) between any two of these values, or any value therein. In some embodiments, the anti-TIGIT antibody or antigen-binding fragment is administered once daily to once every 7 weeks. In some embodiments, the anti-TIGIT antibody or antigen-binding fragment is administered once weekly, once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, once every 6 weeks, or once every 7 weeks.

In some embodiments, the anti-TIGIT antibody or antigen-binding fragment is administered once daily to once every 7 weeks, with each dose being about 0.01-1200 mg, about 0.01-1 mg, about 1-3 mg, about 1-5 mg, about 1-10 mg, about 3-10 mg, about 10-30 mg, about 10-50 mg, 10-100 mg, about 100-300 mg, about 100-500 mg, about 100-600 mg, about 300-600 mg, about 100-900 mg, about 600-900 mg, about 100-1000 mg, or about 1000-1200 mg. In some embodiments, the anti-TIGIT antibody or antigen-binding fragment is administered once daily to once every 7 weeks, with each dose being about 0.01 mg, about 1 mg, about 3 mg, about 5 mg, about 10 mg, about 30 mg, about 50 mg, about 100 mg, about 300 mg, about 500 mg, about 600 mg, about 900 mg, about 1000 mg, or about 1200 mg, or a range (including endpoints) of any two of these values, or any value therein.

In some implementations, the anti-TIGIT antibody or antigen-binding fragment is administered approximately every 3 weeks, with each dose being approximately 0.01-1200 mg, approximately 0.01-1 mg, approximately 1-3 mg, approximately 1-5 mg, approximately 1-10 mg, approximately 3-10 mg, approximately 10-30 mg, approximately 10-50 mg, 10-100 mg, approximately 100-300 mg, approximately 100-500 mg, approximately 100-600 mg, approximately 300-600 mg, approximately 100-900 mg, approximately 600-900 mg, approximately 100-1000 mg, or approximately 1000-1200 mg. In some embodiments, the anti-TIGIT antibody or antigen-binding fragment is administered approximately every 3 weeks at a dose of approximately 0.01 mg, approximately 1 mg, approximately 3 mg, approximately 5 mg, approximately 10 mg, approximately 30 mg, approximately 50 mg, approximately 100 mg, approximately 300 mg, approximately 500 mg, approximately 600 mg, approximately 900 mg, approximately 1000 mg, or approximately 1200 mg, or a range (including endpoints) of any two of these values, or any value thereof. In some embodiments, the anti-TIGIT antibody or antigen-binding fragment is administered approximately every 3 weeks at a dose of approximately 600 mg or approximately 900 mg.

In some embodiments, the anti-TIGIT antibody or antigen-binding fragment is administered approximately every 3 weeks at doses of approximately 0.01 mg/kg-20 mg/kg, approximately 0.01 mg/kg-0.05 mg/kg, approximately 0.01 mg/kg-0.06 mg/kg, approximately 0.1 mg/kg-0.2 mg/kg, approximately 0.1 mg/kg-0.5 mg/kg, approximately 0.1 mg/kg-0.6 mg/kg, approximately 1 mg/kg-2 mg/kg, approximately 1 mg/kg-5 mg/kg, approximately 1 mg/kg-6 mg/kg, approximately 10 mg/kg-12 mg/kg, approximately 12 mg/kg-15 mg/kg, approximately 15 mg/kg-18 mg/kg, or approximately 18 mg/kg-20 mg/kg. In some embodiments, the anti-TIGIT antibody or antigen-binding fragment is administered approximately every 3 weeks at a dose of approximately 0.01 mg/kg, approximately 0.05 mg/kg, approximately 0.06 mg/kg, approximately 0.1 mg/kg, approximately 0.2 mg/kg, approximately 0.5 mg/kg, approximately 0.6 mg/kg, approximately 1 mg/kg, approximately 2 mg/kg, approximately 5 mg/kg, approximately 6 mg/kg, approximately 10 mg/kg, approximately 12 mg/kg, approximately 15 mg/kg, approximately 18 mg/kg, or approximately 20 mg/kg, or a range (including endpoints) of any two of these values, or any value thereof. In some embodiments, the anti-TIGIT antibody or antigen-binding fragment is administered approximately every 3 weeks at a dose of approximately 12 mg/kg or approximately 18 mg/kg.

In some embodiments, the anti-TIGIT antibody or antigen-binding fragment is administered approximately every 3 weeks, with each dose being approximately 600 mg or approximately 900 mg, wherein the anti-TIGIT antibody or antigen-binding fragment is antibody h10D8OF.

In some embodiments, the anti-PD-1 antibody or antigen-binding fragment is administered at doses of about 1-1000 mg, about 1-10 mg, about 1-50 mg, about 1-100 mg, about 1-200 mg, about 1-240 mg, about 1-300 mg, about 1-600 mg, about 100-300 mg, about 100-500 mg, about 100-600 mg, 100-900 mg, about 300-600 mg, about 300-900 mg, about 600-900 mg, or about 900-1000 mg per treatment cycle. In some embodiments, the anti-PD-1 antibody or antigen-binding fragment is administered at a dose of about 1 mg, about 10 mg, about 50 mg, about 100 mg, about 200 mg, about 240 mg, about 300 mg, about 500 mg, about 600 mg, about 900 mg, or about 1000 mg per treatment cycle, or a range (including endpoints) of any two of these values, or any value thereof. In some embodiments, the anti-PD-1 antibody or antigen-binding fragment is administered at a dose of about 300 mg per treatment cycle.

In some embodiments, the dosage of the anti-PD-1 antibody or antigen-binding fragment is about 0.01 mg/kg-20 mg/kg, about 0.01 mg/kg-1 mg/kg, about 1 mg/kg-2 mg/kg, about 1 mg/kg-3 mg/kg, about 1 mg/kg-5 mg/kg, about 1 mg/kg-6 mg/kg, about 1 mg/kg-10 mg/kg, about 2 mg/kg-6 mg/kg, about 6 mg/kg-12 mg/kg, about 10 mg/kg-12 mg/kg, about 12 mg/kg-15 mg/kg, or about 12 mg/kg-20 mg/kg per treatment cycle. In some embodiments, the anti-PD-1 antibody or antigen-binding fragment is administered at a dose of about 0.01 mg/kg, about 1 mg/kg, about 2 mg/kg, about 3 mg/kg, about 5 mg/kg, about 6 mg/kg, about 10 mg/kg, about 12 mg/kg, about 15 mg/kg, or about 20 mg/kg per treatment cycle, or a range (including endpoints) of any two of these values, or any value thereof. In some embodiments, the anti-PD-1 antibody or antigen-binding fragment is administered at a dose of about 6 mg/kg per treatment cycle.

In some embodiments, the anti-PD-1 antibody or antigen-binding fragment is administered once daily to once every 7 weeks. In some embodiments, the anti-PD-1 antibody or antigen-binding fragment is administered once weekly, once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, once every 6 weeks, or once every 7 weeks.

In some embodiments, the anti-PD-1 antibody or antigen-binding fragment is administered once daily to once every 7 weeks, with each dose being about 1-1000 mg, about 1-10 mg, about 1-50 mg, about 1-100 mg, about 1-200 mg, about 1-240 mg, about 1-300 mg, about 1-600 mg, about 100-300 mg, about 100-500 mg, about 100-600 mg, 100-900 mg, about 300-600 mg, about 300-900 mg, about 600-900 mg, or about 900-1000 mg. In some embodiments, the anti-PD-1 antibody or antigen-binding fragment is administered once daily to once every 7 weeks, with each dose being about 1 mg, about 10 mg, about 50 mg, about 100 mg, about 200 mg, about 240 mg, about 300 mg, about 500 mg, about 600 mg, about 900 mg, or about 1000 mg, or a range (including endpoints) of any two of these values, or any value therein.

In some implementations, the anti-PD-1 antibody or antigen-binding fragment is administered approximately every 3 weeks, with each dose being approximately 1-1000 mg, approximately 1-10 mg, approximately 1-50 mg, approximately 1-100 mg, approximately 1-200 mg, approximately 1-240 mg, approximately 1-300 mg, approximately 1-600 mg, approximately 100-300 mg, approximately 100-500 mg, approximately 100-600 mg, 100-900 mg, approximately 300-600 mg, approximately 300-900 mg, approximately 600-900 mg, or approximately 900-1000 mg. In some embodiments, the anti-PD-1 antibody or antigen-binding fragment is administered approximately every 3 weeks at a dose of approximately 1 mg, approximately 10 mg, approximately 50 mg, approximately 100 mg, approximately 200 mg, approximately 240 mg, approximately 300 mg, approximately 500 mg, approximately 600 mg, approximately 900 mg, or approximately 1000 mg, or a range (including endpoints) of any two of these values, or any value thereof. In some embodiments, the anti-PD-1 antibody or antigen-binding fragment is administered approximately every 3 weeks at a dose of approximately 300 mg.

In some embodiments, the anti-PD-1 antibody or antigen-binding fragment is administered approximately every 3 weeks at a dose of approximately 0.01 mg/kg-20 mg/kg, approximately 0.01 mg/kg-1 mg/kg, approximately 1 mg/kg-2 mg/kg, approximately 1 mg/kg-3 mg/kg, approximately 1 mg/kg-5 mg/kg, approximately 1 mg/kg-6 mg/kg, approximately 1 mg/kg-10 mg/kg, approximately 2 mg/kg-6 mg/kg, approximately 6 mg/kg-12 mg/kg, approximately 10 mg/kg-12 mg/kg, approximately 12 mg/kg-15 mg/kg, or approximately 12 mg/kg-20 mg/kg. In some embodiments, the anti-PD-1 antibody or antigen-binding fragment is administered approximately every 3 weeks at a dose of approximately 0.01 mg/kg, approximately 1 mg/kg, approximately 2 mg/kg, approximately 3 mg/kg, approximately 5 mg/kg, approximately 6 mg/kg, approximately 10 mg/kg, approximately 12 mg/kg, approximately 15 mg/kg, or approximately 20 mg/kg, or a range (including endpoints) of any two of these values, or any value thereof. In some embodiments, the anti-PD-1 antibody or antigen-binding fragment is administered approximately every 3 weeks at a dose of approximately 6 mg/kg.

In some embodiments, the anti-PD-1 antibody or antigen-binding fragment is administered approximately every 3 weeks, with each dose being approximately 300 mg, wherein the anti-PD-1 antibody or antigen-binding fragment is antibody A.

In some implementations, the antibody h10D8OF and antibody A are administered approximately every 3 weeks, with each dose of antibody h10D8OF being approximately 600 mg or approximately 900 mg and each dose of antibody A being approximately 300 mg. The tumor is selected from gastric cancer, gastroesophageal junction cancer, esophageal cancer, non-small cell lung cancer, and hepatocellular carcinoma.

In some implementations, the patient receives one treatment cycle. In some implementations, the patient receives multiple treatment cycles (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 or more, or a range between any two of these values (including endpoints) or any of these values). In some implementations, the patient receives treatment until the symptoms are relieved and treatment is no longer required.

The term "combination" as used herein refers to a route of administration that includes various situations in which two or more drugs are administered sequentially or simultaneously. In some embodiments, the anti-TIGIT antibody or antigen-binding fragment and the anti-PD-1 antibody or antigen-binding fragment are prepared as a single pharmaceutical composition and administered simultaneously to a patient in need. In some embodiments, the anti-TIGIT antibody or antigen-binding fragment and the anti-PD-1 antibody or antigen-binding fragment are prepared as separate pharmaceutical compositions and administered simultaneously to a patient in need, or administered at different times during treatment. For example, the anti-TIGIT antibody or antigen-binding fragment may be administered before, after, or in an alternating manner with the anti-PD-1 antibody or antigen-binding fragment. In this invention, the anti-TIGIT antibody or antigen-binding fragment and the anti-PD-1 antibody or antigen-binding fragment may be administered to patients in need in a single dose or multiple doses.

In some implementations, the anti-PD-1 antibody or antigen-binding fragment is administered after the patient in need has been given the anti-TIGIT antibody or antigen-binding fragment.

In some implementations, an anti-TIGIT antibody or antigen-binding fragment, wherein the anti-TIGIT antibody or antigen-binding fragment is antibody h10D8OF, is administered approximately every 3 weeks at a dose of approximately 600 mg or approximately 900 mg, and wherein the anti-PD-1 antibody or antigen-binding fragment is antibody A, is administered approximately every 3 weeks at a dose of approximately 300 mg.

In some embodiments, the anti-TIGIT antibody or antigen-binding fragment (or formulation) and/or anti-PD-1 antibody or antigen-binding fragment (or formulation) are administered by injection or infusion. In some embodiments, the anti-TIGIT antibody or antigen-binding fragment (or formulation) or anti-PD-1 antibody or antigen-binding fragment (or formulation) is administered via subcutaneous (s.c.) injection, intraperitoneal (i.p.) injection, parenteral injection, intra-arterial injection, or intravenous (i.v.) infusion (i.e., intravenous infusion). The dosage of the anti-TIGIT antibody or antigen-binding fragment and the anti-PD-1 antibody or antigen-binding fragment will depend on the nature of the drug, the extent to which cell surface triggers drug internalization, transport, and release, and the disease being treated and the patient's condition (e.g., age, sex, weight, etc.).

In some embodiments, the anti-TIGIT antibody or antigen-binding fragment (or formulation) and/or anti-PD-1 antibody or antigen-binding fragment (or formulation) are administered by intravenous infusion.

In some embodiments, the intravenous infusion duration of the anti-TIGIT antibody or antigen-binding fragment (or formulation) is approximately 30 to 120 minutes, for example, approximately 30 minutes, approximately 35 minutes, approximately 40 minutes, approximately 45 minutes, approximately 50 minutes, approximately 55 minutes, approximately 60 minutes, approximately 65 minutes, approximately 70 minutes, approximately 75 minutes, approximately 80 minutes, approximately 85 minutes, approximately 90 minutes, approximately 95 minutes, approximately 100 minutes, approximately 105 minutes, approximately 110 minutes, approximately 105 minutes, approximately 120 minutes, or a range (including endpoints) of any two of these values, or any value thereof. In some embodiments, the intravenous infusion time of the anti-TIGIT antibody or antigen-binding fragment (or formulation) is approximately 30 to 60 minutes. In some embodiments, the intravenous infusion time of the anti-TIGIT antibody or antigen-binding fragment (or formulation) is 60 (±10) minutes.

In some embodiments, the intravenous infusion duration of the anti-PD-1 antibody or antigen-binding fragment (or formulation) is approximately 30 to 120 minutes, for example, approximately 30 minutes, approximately 35 minutes, approximately 40 minutes, approximately 45 minutes, approximately 50 minutes, approximately 55 minutes, approximately 60 minutes, approximately 65 minutes, approximately 70 minutes, approximately 75 minutes, approximately 80 minutes, approximately 85 minutes, approximately 90 minutes, approximately 95 minutes, approximately 100 minutes, approximately 105 minutes, approximately 110 minutes, approximately 105 minutes, or approximately 120 minutes, or a range (including endpoints) between any two of these values, or any value therein. In some embodiments, the intravenous infusion time of the anti-PD-1 antibody or antigen-binding fragment (or formulation) is approximately 30 to 60 minutes. In some embodiments, the intravenous infusion time of the anti-PD-1 antibody or antigen-binding fragment (or formulation) is 60 (±10) minutes.

In some implementations, the anti-TIGIT antibody or antigen-binding fragment, or the anti-PD-1 antibody or antigen-binding fragment, can be further used in combination with other treatment methods for treating tumors, such as chemotherapy, radiotherapy, and surgery.

In some embodiments, the anti-TIGIT antibody or antigen-binding fragment, or the anti-PD-1 antibody or antigen-binding fragment, may be further used in combination with one or more chemotherapeutic agents for the treatment of tumors.

In some embodiments, the tumor is a hematologic cancer or a solid tumor; or, the tumor is selected from acute lymphoblastic leukemia, acute myeloid leukemia, chronic lymphocytic leukemia, chronic myeloid leukemia, myeloproliferative disorders/tumors, Hodgkin lymphoma, painless and aggressive non-Hodgkin lymphoma, Burkitt lymphoma, follicular lymphoma, multiple myeloma, giant cell myeloma, heavy chain myeloma, light chain or Bens-Jones myeloma, breast cancer, ovarian cancer, pancreatic cancer, prostate cancer, melanoma, colorectal cancer, colon cancer, lung cancer, head and neck cancer, bladder cancer, esophageal cancer, liver cancer, kidney cancer, and stomach cancer.

In some implementations, the tumor is selected from gastric cancer, gastroesophageal junction cancer, esophageal cancer, non-small cell lung cancer, and hepatocellular carcinoma.

In some embodiments, the chemotherapeutic agent includes capecitabine, taxane, or platinum-based drugs or combinations thereof. In some embodiments, the platinum-based drug is cisplatin, carboplatin, oxaliplatin, nedaplatin, triplatinum tetranitrate, phenanthreneplatin, pyridine, lipopyram, or saxaplatin.

In some implementations, the chemotherapeutic agent is a combination of platinum-based drugs and capecitabine.

In some implementations, the chemotherapeutic agent is oxaliplatin in combination with capecitabine.

In some implementations, the chemotherapeutic agent is capecitabine.

In some embodiments, the antibody h10D8OF and antibody A are further combined with oxaliplatin and capecitabine for the treatment of tumors. In some embodiments, the tumor is selected from gastric cancer, gastroesophageal junction cancer, esophageal cancer, non-small cell lung cancer, and hepatocellular carcinoma.

In some embodiments, the antibody h10D8OF and antibody A are further combined with capecitabine for the treatment of tumors. In some embodiments, the tumor is selected from gastric cancer, gastroesophageal junction cancer, esophageal cancer, non-small cell lung cancer, and hepatocellular carcinoma.

In some implementations, patients receive the first 6 cycles of treatment with antibody h10D8OF and antibody A plus oxaliplatin and capecitabine. In some implementations, after the first 6 cycles of treatment with antibody h10D8OF and antibody A plus oxaliplatin and capecitabine, patients receive antibody h10D8OF and antibody A treatment, or receive capecitabine treatment alone.

In some embodiments, oxaliplatin is administered at a dose of approximately 50-300 mg/ ^m² of body surface area. In some embodiments, oxaliplatin is administered at a dose of approximately 85-130 mg/ ^m² of body surface area. In some embodiments, oxaliplatin is administered at a dose of approximately 50 mg/ ^m² , approximately 85 mg/ ^m² , approximately 100 mg/ ^m² , approximately 130 mg/ ^m² , approximately 150 mg/ ^m² , approximately 175 mg/ ^m² , approximately 200 mg/ ^m² , approximately 250 mg/ ^m² , or approximately 300 mg/ ^m² of body surface area, or a range (including endpoints) or any of these values. In some embodiments, oxaliplatin is administered at a dose of approximately 130 mg/ ^m² of body surface area. In some embodiments, oxaliplatin is administered once weekly, every 2 weeks, every 3 weeks, or every 4 weeks. In some implementations, oxaliplatin is administered once every 3 weeks. In some implementations, oxaliplatin is administered at a dose of approximately 130 mg/ ^m² per body surface area, once every 3 weeks.

In some implementations, oxaliplatin is administered intravenously at a dose of approximately 130 mg/ ^m² per body surface area, once every 3 weeks.

In some embodiments, capecitabine is administered at a dose of approximately 100-2000 mg/ ^m² of body surface area. In some embodiments, capecitabine is administered at a dose of approximately 100 mg/ ^m² , approximately 500 mg/ ^m² , approximately 1000 mg/ ^m² , approximately 1250 mg/ ^m² , approximately 1500 mg/ ^m² , approximately 1750 mg/ ^m² , or approximately 2000 mg/ ^m² of body surface area, or a range (including endpoints) or any of these values. In some embodiments, capecitabine is administered at a dose of approximately 1000 mg/ ^m² of body surface area. In some embodiments, capecitabine is administered once daily for 1 week; once daily for 2 weeks; or once daily for 3 weeks. In some embodiments, capecitabine is administered twice daily for 2 weeks; twice daily for 2 weeks; or twice daily for 3 weeks. In some implementations, a treatment cycle consists of 3 weeks, with capecitabine administered twice daily for 2 weeks, followed by a 1-week rest period. In other implementations, a treatment cycle consists of 3 weeks, with capecitabine administered at a dose of approximately 1000 mg/ ^m² per body surface area, twice daily for 2 weeks, followed by a 1-week rest period.

In some embodiments, capecitabine is administered orally at a dose of approximately 1000 mg/ ^m² per body surface area, with each treatment cycle lasting 3 weeks, administered twice daily on days 1-14 of each cycle.

In some embodiments, the method or use of treating tumors includes administering to a patient one or more treatment cycles of the anti-TIGIT antibody or antigen-binding fragment and the anti-PD-1 antibody or antigen-binding fragment, wherein:

(1) At least one treatment cycle, the patient is administered a combination of: the anti-TIGIT antibody or antigen-binding fragment and the anti-PD-1 antibody or antigen-binding fragment; and/or

(2) Administration to the patient for at least one treatment cycle of the following: the anti-TIGIT antibody or antigen-binding fragment, the anti-PD-1 antibody or antigen-binding fragment, oxaliplatin, and capecitabine; and/or

(3) The patient is given at least one treatment cycle the following: the anti-TIGIT antibody or antigen-binding fragment, the anti-PD-1 antibody or antigen-binding fragment, and capecitabine.

In some embodiments, the method or use of treating tumors includes administering to a patient one or more treatment cycles of the anti-TIGIT antibody or antigen-binding fragment and the anti-PD-1 antibody or antigen-binding fragment, wherein:

(1) During treatment cycles 1, 1–2, 1–3, 1–4, 1–5, 1–6, 1–7, 1–8, or 1–9, the patient is administered a combination of: the anti-TIGIT antibody or antigen-binding fragment, the anti-PD-1 antibody or antigen-binding fragment, oxaliplatin, and capecitabine; and/or

(2) During the 2nd, 3rd, 4th, 5th, 6th, 7th, 8th, 9th, and subsequent treatment cycles, the patient is administered a combination of: the anti-TIGIT antibody or antigen-binding fragment, the anti-PD-1 antibody or antigen-binding fragment, and capecitabine; or

In the 2nd, 3rd, 4th, 5th, 6th, 7th, 8th, 9th, and subsequent treatment cycles, the patient is administered an anti-TIGIT antibody or antigen-binding fragment and an anti-PD-1 antibody or antigen-binding fragment.

In some embodiments, the method or use of treating tumors includes administering to a patient one or more treatment cycles of the anti-TIGIT antibody or antigen-binding fragment and the anti-PD-1 antibody or antigen-binding fragment, with each treatment cycle consisting of 3 weeks, wherein:

(1) Administration to the patient for at least one treatment cycle of the following: administration of the anti-TIGIT antibody or antigen-binding fragment approximately every 3 weeks at a dose of approximately 600 mg or approximately 900 mg; administration of the anti-PD-1 antibody or antigen-binding fragment approximately every 3 weeks at a dose of approximately 300 mg; and/or

(2) Administration to the patient for at least one treatment cycle of the following: administration of the anti-TIGIT antibody or antigen-binding fragment approximately every 3 weeks at a dose of approximately 600 mg or approximately 900 mg; administration of the anti-PD-1 antibody or antigen-binding fragment approximately every 3 weeks at a dose of approximately 300 mg; administration of oxaliplatin at a dose of approximately 130 mg/ ^m² of body surface area every 3 weeks; administration of capecitabine at a dose of approximately 1000 mg/ ^m² of body surface area twice daily from day 1 to day 14 of each cycle; and/or

(3) The patient is given the following medications for at least one treatment cycle: the anti-TIGIT antibody or antigen-binding fragment is administered approximately every 3 weeks at a dose of approximately 600 mg or approximately 900 mg; the anti-PD-1 antibody or antigen-binding fragment is administered approximately every 3 weeks at a dose of approximately 300 mg; and capecitabine is administered at a dose of approximately 1000 mg/ ^m² per body surface area, twice daily on days 1-14 of each cycle.

In some embodiments, the method or use of treating tumors includes administering to a patient one or more treatment cycles of the anti-TIGIT antibody or antigen-binding fragment and the anti-PD-1 antibody or antigen-binding fragment, with each treatment cycle consisting of 3 weeks, wherein:

(1) During treatment cycles 1, 1–2, 1–3, 1–4, 1–5, 1–6, 1–7, 1–8, or 1–9, the patient is given the following: the anti-TIGIT antibody or antigen-binding fragment is administered approximately every 3 weeks at a dose of approximately 600 mg or approximately 900 mg; the anti-PD-1 antibody or antigen-binding fragment is administered approximately every 3 weeks at a dose of approximately 300 mg; oxaliplatin is administered at a dose of approximately 130 mg/ ^m² of body surface area every 3 weeks; capecitabine is administered at a dose of approximately 1000 mg/ ^m² of body surface area twice daily on days 1–14 of each cycle; and/or

(2) During the 2nd, 3rd, 4th, 5th, 6th, 7th, 8th, 9th, or 10th treatment cycles and subsequent cycles, the patient shall be administered the following: the anti-TIGIT antibody or antigen-binding fragment approximately every 3 weeks at a dose of approximately 600 mg or approximately 900 mg; the anti-PD-1 antibody or antigen-binding fragment approximately every 3 weeks at a dose of approximately 300 mg; capecitabine at a dose of approximately 1000 mg/ ^m² of body surface area, administered twice daily on days 1-14 of each cycle; or

In the 2nd, 3rd, 4th, 5th, 6th, 7th, 8th, 9th, or 10th and subsequent treatment cycles, the patient is given the following: the anti-TIGIT antibody or antigen-binding fragment is administered approximately every 3 weeks at a dose of approximately 600 mg or approximately 900 mg; the anti-PD-1 antibody or antigen-binding fragment is administered approximately every 3 weeks at a dose of approximately 300 mg.

In some embodiments, the method or use of treating tumors includes administering one or more treatment cycles of the antibody h10D8OF and antibody A to a patient, with each treatment cycle consisting of 3 weeks, wherein:

(1) During treatment cycles 1, 1–2, 1–3, 1–4, 1–5, 1–6, 1–7, 1–8, or 1–9, the patient is given the following: the antibody h10D8OF is administered approximately every 3 weeks at a dose of approximately 600 mg or approximately 900 mg; the antibody A is administered approximately every 3 weeks at a dose of approximately 300 mg; oxaliplatin is administered at a dose of approximately 130 mg/ ^m² of body surface area every 3 weeks; capecitabine is administered at a dose of approximately 1000 mg/ ^m² of body surface area twice daily on days 1–14 of each cycle; and/or

(2) During the 2nd, 3rd, 4th, 5th, 6th, 7th, 8th, 9th, or 10th treatment cycles and subsequent cycles, the patient shall be administered the following: the antibody h10D8OF, administered approximately every 3 weeks at a dose of approximately 600 mg or approximately 900 mg; the antibody A, administered approximately every 3 weeks at a dose of approximately 300 mg; ^capecitabine , administered at a dose of approximately 1000 mg/m² per body surface area, twice daily on days 1-14 of each cycle; or

In the 2nd, 3rd, 4th, 5th, 6th, 7th, 8th, 9th or 10th and subsequent treatment cycles, the patient is given the following: the antibody h10D8OF is administered approximately every 3 weeks at a dose of approximately 600 mg or approximately 900 mg; the antibody A is administered approximately every 3 weeks at a dose of approximately 300 mg.

In some embodiments, the method or use of treating tumors includes administering one or more treatment cycles of antibody h10D8OF and antibody A to a patient, with each treatment cycle consisting of 3 weeks, wherein:

(1) During treatment cycles 1–6, the patient is administered the following: the antibody h10D8OF is administered approximately every 3 weeks at a dose of approximately 600 mg or approximately 900 mg; the antibody A is administered approximately every 3 weeks at a dose of approximately 300 mg; oxaliplatin is administered at a dose of approximately 130 mg/ ^m² of body surface area every 3 weeks; capecitabine is administered at a dose of approximately 1000 mg/ ^m² of body surface area twice daily on days 1–14 of each cycle; and/or

(2) In the 7th and subsequent treatment cycles, the patient is administered the following: the antibody h10D8OF is administered approximately every 3 weeks at a dose of approximately 600 mg or approximately 900 mg; the antibody A is administered approximately every 3 weeks at a dose of approximately 300 mg; capecitabine is administered at a dose of approximately 1000 mg/ ^m² of body surface area, twice daily on days 1-14 of each cycle; or

In the 7th and subsequent treatment cycles, the patient is administered the following: the antibody h10D8OF is administered approximately every 3 weeks at a dose of approximately 600 mg or approximately 900 mg; the antibody A is administered approximately every 3 weeks at a dose of approximately 300 mg.

The tumor is selected from gastric cancer, gastroesophageal junction cancer, esophageal cancer, non-small cell lung cancer, and hepatocellular carcinoma.

the term

Unless otherwise stated, each of the following terms shall have the meaning described below.

It should be noted that an entity “a” refers to one or more of the same entity. For example, “an antibody” should be understood as one or more antibodies. Therefore, the terms “a” (or “an”), “one or more” and “at least one” can be used interchangeably in this document.

As used herein, “comprising” or “including” means that compositions and methods include the listed elements, such as components or steps, but do not exclude others. “consistently composed of” means that compositions and methods exclude other elements that have a fundamental effect on the characteristics of the composition, but do not exclude elements that do not substantially affect the composition or method. “composed of” means excluding elements not specifically listed.

"Approximately" refers to a typical error range for a given value that is readily known to those skilled in the art. In some embodiments, "approximately" as used herein refers to the described value and its range of ±10%, ±5%, or ±1%.

TIGIT (T cell immunoreceptor with Ig and ITIM domains) is a T cell immune receptor with immunoglobulin (Ig) and tyrosine inhibitor motif (ITIM) domains, primarily expressed on activated T cells and NK cells. TIGIT is an immune receptor inhibitory checkpoint and plays an important role in tumor immune surveillance.

PD-1 (Programmed death 1), also known as programmed death receptor 1, is an immunosuppressive receptor expressed on activated T cells, B cells, and myeloid cells, and is a member of the CD28 immunoglobulin superfamily. The interaction between PD-1 and its ligand PD-L1 negatively regulates antigen receptor signaling and weakens T cell responses. Numerous studies to date have shown that the interaction between PD-1 and PD-L1 leads to a reduction in lymphocytes infiltrating tumors, a decrease in T cell receptor-mediated proliferation, and immune evasion by cancer cells. Blocking the interaction between PD-1 and PD-L1 has been shown to increase T cell proliferation and cytokine production, enhance the immunity of tumor-specific CD8+ T cells, and thus help the immune system clear tumor cells.

"Antibody" or "antigen-binding fragment" refers to a polypeptide or polypeptide complex that specifically recognizes and binds to an antigen. An antibody can be a complete antibody, any antigen-binding fragment, or a single chain thereof. Therefore, the term "antibody" includes any protein or peptide containing at least a portion of an immunoglobulin molecule that has biological activity of binding to an antigen. Antibody and antigen-binding fragments include, but are not limited to, the complementarity-determining region (CDR), heavy chain variable region (VH), light chain variable region (VL), heavy chain constant region (CH), light chain constant region (CL), framework region (FR), or any portion thereof of the heavy chain or light chain or its ligand-binding moiety, or at least a portion of the binding protein. The CDR region includes the CDR regions of the light chain (LCDR1-3) and the CDR regions of the heavy chain (HCDR1-3).

The antibodies, antigen-binding fragments or derivatives described herein include, but are not limited to, polyclonal, monoclonal, multispecific, fully human, humanized, primate-derived, chimeric antibodies, single-chain antibodies (scFv), and epitope-binding fragments (e.g., Fab, Fab', and F(ab') ₂ ).

DNA encoding the antibody can be designed and synthesized according to the antibody amino acid sequence described herein using conventional methods. This DNA can then be placed into an expression vector, transfected into host cells, and cultured in a culture medium to produce monoclonal antibodies. In some embodiments, the antibody expression vector includes at least one promoter element, an antibody-coding sequence, a transcription termination signal, and a polyA tail. Other elements include an enhancer, a Kozak sequence, and donor and acceptor sites for RNA splicing flanking the insert sequence. Efficient transcription can be achieved using early and late promoters of SV40, early promoters from long terminal repeat sequences of retroviruses such as RSV, HTLV1, HIV, and cytomegalovirus, or other cellular promoters such as the actin promoter. Suitable expression vectors may include pIRES1neo, pRetro-Off, pRetro-On, PLXSN, or Plncx, pcDNA3.1(+/-), pcDNA3.1/Zeo(+/-), pcDNA3.1/Hygro(+/-), pcDNA3.1/G418(+/-), PSVL, PMSG, pRSVcat, pSV2dhfr, pBC12MI, and pCS2, etc. Commonly used mammalian cell lines include HEK293 cells, Cos1 cells, Cos7 cells, CV1 cells, mouse L cells, and CHO cells, etc.

"Treatment" refers to therapeutic treatments and preventative or preventative measures aimed at preventing, mitigating, improving, and stopping adverse physiological changes or disorders, such as disease progression, including but not limited to the following, whether detectable or undetectable: symptom relief, reduction in disease severity, stabilization of the disease state (i.e., no worsening), delay or slowing of disease progression, improvement or mitigation of the disease state, reduction or disappearance (whether partial or complete), and prolongation of expected survival without treatment. Patients requiring treatment include those already suffering from the condition or disorder, those susceptible to the condition or disorder, or those needing prevention of the condition or disorder, as well as those who can or are expected to benefit from the application of the antibodies or compositions of the present invention for detection, diagnostic procedures, and/or treatment.

"Need" means that the patient has been identified as requiring a specific method or treatment. In some embodiments, this identification can be made through any diagnostic approach. The patient may require any of the methods and treatments described herein.

"Patient" refers to any mammal requiring diagnosis, prognosis, or treatment, including humans, dogs, cats, guinea pigs, rabbits, rats, mice, horses, cattle, etc. In some implementations, the patient is a human.

"Combination therapy" includes two or more drugs, which may form independent dosing units or together form a combined dosing unit. In some embodiments, combination therapy includes separate anti-TIGIT antibody or antigen-binding fragments and anti-PD-1 or antigen-binding fragments. In some embodiments, combination therapy includes a composition of anti-TIGIT antibody or antigen-binding fragments and anti-PD-1 or antigen-binding fragments. In some embodiments, combination therapy includes separate anti-TIGIT antibody or antigen-binding fragments, anti-PD-1 or antigen-binding fragments, and a chemotherapeutic agent. In some embodiments, combination therapy includes separate anti-TIGIT antibody or antigen-binding fragments, anti-PD-1 or antigen-binding fragments, oxaliplatin, and capecitabine. In some embodiments, when administering combination therapy, the different drugs may be administered simultaneously or separately.

"Effective dose" or "therapeutic effective dose" refers to the amount of a drug, such as an anti-TIGIT antibody or antigen-binding fragment or an anti-PD-1 antibody or antigen-binding fragment, sufficient to reduce or improve the severity and/or duration of a condition (e.g., cancer) or one or more of its symptoms; prevent disease progression; induce disease remission; prevent recurrence, development, onset, or progression of one or more symptoms associated with the condition; detect the condition; or enhance or improve the preventive or therapeutic effect of another therapy (e.g., a prophylactic or therapeutic agent). For example, an effective dose of an anti-TIGIT antibody or antigen-binding fragment or an anti-PD-1 antibody or antigen-binding fragment can inhibit tumor growth (e.g., inhibit the increase in tumor volume); reduce tumor growth (e.g., reduce tumor volume); reduce the number of cancer cells; and/or alleviate one or more symptoms associated with the cancer to some extent. For example, an effective dose can improve progression-free survival (PFS), improve overall survival (OS), improve objective response rate (ORR), improve duration of response (DoR), improve disease control rate (DCR), or reduce the likelihood of relapse.

"Administration" or "application" refers to the application of a substance to achieve a therapeutic purpose (e.g., treating a tumor). Administration can be parenteral, intravenous, or local. Parenteral administration is typically via injection, including but not limited to intravenous, intramuscular, intra-arterial, intrathecal, intracapsular, intra-bursal, intraorbital, intracardiac, intradermal, intraperitoneal, tracheal, subcutaneous, subepidermal, intra-articular, subcapsular, subarachnoid, intraspinal, and intrasternal injections and infusions.

The evaluation of antitumor efficacy can be carried out by imaging assessment (CT/MRI), physical examination and survival assessment; the indicators of antitumor efficacy include: objective response rate (ORR), duration of response (DoR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS) based on imaging efficacy assessment using CT/MRI as the main evaluation means, according to RECIST 1.1 evaluation criteria (Eisenhauer, EA et al., Eur J Cancer. 2009; 45(2):228-247).

Objective response rate (ORR): This refers to the proportion of patients whose tumors shrink to a certain extent and remain so for a certain period of time, including cases of complete response (CR) and partial response (PR). In some implementation plans, the objective response rate is the proportion of patients who achieve PR or CR at the end of a certain treatment period, such as the first 6 cycles of treatment. In some implementation plans, the objective response rate is the proportion of patients who achieve PR or CR with the best response throughout the study period.

Duration of Response (DoR): DoR is defined as the time from the first assessment of objective response to the first assessment of disease progression (PD) or death from any cause prior to PD, reflecting the duration of ORR.

Disease control rate (DCR): The proportion of patients whose tumors shrink or stabilize and remain so for a certain period of time, including cases of CR, PR, and disease-stable (SD).

Progression-free survival (PFS): the time from the first dose to the occurrence of objective tumor progression or all-cause death (whichever comes first).

Overall survival (OS): The time from the date of first administration to death from any cause. For patients still alive at the time of analysis, the cutoff date is the date of their last contact.

MTD Definition: MTD (Maximum Tolerated Dose) is defined as the highest dose level of DLT observed in ≤1/6 of patients within a dose group during the dose-limiting toxicity (DLT) assessment period.

The Eastern Cooperative Oncology Group (ECOG) has developed a simplified activity status scoring system that classifies patients’ activity status into 6 levels from 0 to 5. The ECOG activity status scoring system is scored as 0, 1, 2, 3, 4, and 5.

The PK (pharmacokinetic) parameters used in this article are defined as follows:

Single-dose pharmacokinetic parameters: _Cmax , _Tmax , T1 _/2 , CL, Vd, Ke, MRT, AUC _(0-τ) , AUC _(0-∞) :

Multiple-dose pharmacokinetic parameters: _Cmax,ss , Cavg _,ss , Cmin _,ss , AUC _(0-τ)ss , AUC _(0-∞)ss , _Tmax,ss , _T1/2,ss , CL, _Vss , Ke, MRT, accumulation index ( _Rac ), volatility index DF.

All publications, patents and patent applications cited in this document are incorporated herein by reference for all purposes.

Detailed Implementation

The following specific embodiments further illustrate the technical solution of the present invention. These specific embodiments do not represent a limitation on the scope of protection of the present invention. Non-essential modifications and adjustments made by others based on the concept of the present invention still fall within the scope of protection of the present invention.

Unless otherwise specified, all materials and reagents used in the following examples are commercially available.

Example 1: Method for preparing antibodies

The DNA sequences encoding the heavy and light chains of the antibody are cloned into an expression vector, then transformed into host cells, cultured, and purified to obtain the antibody.

The amino acid sequences of antibody h10D8OF and antibody A are shown in Tables 1 and 2, respectively. The heavy chain of antibody h10D8OF is shown in SEQ ID NO:9, and the light chain in SEQ ID NO:10; the heavy chain of antibody A is shown in SEQ ID NO:19, and the light chain in SEQ ID NO:20. Both antibody h10D8OF and antibody A were expressed using CHO cells during preparation.

Table 1. Amino acid sequence of antibody h10D8OF

Table 2. Amino acid sequence of antibody A

Example 2: A multicenter, open-label phase Ib/IIa clinical study of the safety, tolerability, pharmacokinetic characteristics, and preliminary clinical efficacy of antibody A injection combined with antibody h10D8OF injection in patients with locally advanced or metastatic solid tumors.

1. Clinical investigation drugs:

Phase Ib medication and dosage: Antibody A (300mg) + Antibody h10D8OF (600mg or 900mg).

Antibody A injection is administered at a fixed dose of 300 mg. Antibody h10D8OF injection is administered in two dose groups: Group A (600 mg) and Group B (900 mg).

Phase II drugs and dosages:

Antibody A (300mg) + Antibody h10D8OF (600mg or 900mg) + Oxaliplatin + Capecitabine.

Table 3. Dosage and administration of oxaliplatin and capecitabine

Among them, patients with gastric cancer, gastroesophageal junction cancer, and esophageal cancer received antibody A injection combined with antibody h10D8OF injection plus chemotherapy (oxaliplatin [130mg/m2 IV Q3W] and oral capecitabine [1000mg/ ^m2 BID, days 1-14, Q3W]) for the first 6 cycles. Subsequent treatment cycles received antibody A injection combined with antibody h10D8OF injection ± capecitabine. Whether capecitabine was used after the 6th cycle was adjusted according to the actual situation.

Antibody A injection administration regimen: Intravenous infusion, once every 3 weeks (Q3W). In phase Ib studies, the infusion time is 60 (±10) minutes; in phase II studies, chemotherapy should be administered first before infusion, and the recommended infusion time is 30–60 minutes.

Dosage regimen for antibody h10D8OF injection: Intravenous infusion should begin 30 (±10) minutes after the completion of antibody A injection, administered once every 3 weeks (Q3W). In Phase Ib studies, the infusion duration was 60 (±10) minutes; in Phase II studies, an infusion duration of 30–60 minutes is recommended. If no infusion-related reactions are observed, subsequent infusion times can be adjusted to 30 minutes to 2 hours based on clinical circumstances.

2. Study population

2.1 Inclusion criteria

1) Age ≥ 18 years;

2) For different stages or queues, the following requirements must be met accordingly:

Stage Ib: Patients with advanced malignant tumors diagnosed by cytology or pathology who have failed standard treatment, have no standard treatment available, are intolerant to standard treatment, or refuse standard treatment;

Phase II Cohort 1: Locally advanced unresectable or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal cancer that have not previously received systemic therapy: PD-L1 CPS ≥ 5 and HER2 negative tumor tissue test;

Phase II Cohort 2: Patients with histologically or cytologically confirmed locally advanced or metastatic (refer to AJCC 8th Edition Manual of Tumor Staging) NSCLC:

a. Patients whose disease progressed after first-line treatment with PD-1/PD-L1 antibodies and platinum-based doublet chemotherapy or who are unable to receive standard treatment;

b. Individuals with driver gene mutations who have failed targeted therapy or chemotherapy, or who are unable to receive standard treatment;

Phase II Cohort 3: Patients with advanced HCC diagnosed by pathology or clinical diagnosis who have experienced disease progression or are unable to receive standard treatment after systemic therapy with PD-1/PD-L1 antibodies and targeted drugs, and whose Child-Pugh liver function is grade A or better grade B (≤7 points).

4) Eastern Cooperative Oncology Group (ECOG) performance status score is 0 or 1;

5) Assess expected survival of ≥12 weeks;

6) Possess sufficient organ and bone marrow function.

2.2 Exclusion Criteria

1) Currently receiving or expected to receive other anti-tumor treatments during the study period, including but not limited to chemotherapy, radiotherapy, immunotherapy, endocrine therapy (excluding replacement therapy), targeted therapy, biotherapy, and traditional Chinese medicines with anti-tumor effects;

2) The first study dose is given within 4 weeks or 5 half-lives (whichever is longer) of the previous anti-tumor treatment (chemotherapy, endocrine therapy, targeted therapy), or within 4 weeks of the last large-area radiotherapy (2 weeks for palliative radiotherapy for bone metastases), or within 2 weeks of the last treatment with traditional Chinese medicine/immunomodulatory drugs with anti-tumor indications (including thymopeptide, interferon, interleukin, etc.), or within 8 weeks of the last radiotherapy.

3) Received other unmarketed investigational drugs or treatments within 4 weeks prior to the first use of the investigational drug;

4) Those who have been vaccinated or plan to be vaccinated with a live/attenuated or mRNA vaccine within 4 weeks prior to screening, during the study period;

5) Pregnant or breastfeeding women;

6) Patients with primary central nervous system tumors, those with meningeal metastases, or those with symptomatic central nervous system metastases must be excluded. Asymptomatic patients with clinically controlled central nervous system metastases, or those with symptomatic but stable conditions, may be included, provided they meet the following criteria: a. Disease stability ≥4 weeks prior to first administration; b. No evidence of central nervous system disease progression on plain/enhanced MRI within 4 weeks prior to first administration; c. Discontinuation of antiepileptic drugs and prednisone dosage ≤10 mg/day or equivalent dose of hormones ≥2 weeks prior to first administration.

7) Patients who have undergone major organ surgery (excluding biopsy) within 4 weeks prior to the first use of the study drug, or who have not yet recovered post-surgery, or who require elective surgery during the trial; patients with a history of gastrointestinal perforation or gastrointestinal fistula within 6 months prior to the first dose in the extended cohort are not eligible. If the perforation or fistula has been treated with resection or repair, and the disease is judged to have resolved or been alleviated, enrollment may be permitted;

8) Individuals with a history of tissue or organ transplantation surgery;

9) Patients who have had a serious infection within 4 weeks prior to the first dose or patients with an active infection within 2 weeks prior to the first dose;

10) Known history of human immunodeficiency virus (HIV) infection;

11) Untreated active hepatitis B must be excluded; Note: Hepatitis B virus (HBV) viral load <2000 IU/ml or <104 copies/ml before the first dose may not be excluded, but anti-HBV therapy should be considered during the study; For patients with anti-HBc(+), HBsAg(-), anti-HBs(-) and HBV viral load(-), routine prophylactic anti-HBV therapy is not required, but close monitoring for viral reactivation is necessary;

12) Patients with active hepatitis C virus (HCV) infection (defined as: HCV antibody positive and HCV-RNA level above the detection limit);

13) Patients with tuberculosis who are either untreated or under treatment, including but not limited to pulmonary tuberculosis; those who have undergone standard anti-tuberculosis treatment and have been confirmed to be cured may be included;

14) Patients with a known history of severe allergies, or patients with a known history of grade ≥3 allergic reactions to macromolecular protein preparations/antibodies;

15) Patients with a history of autoimmune diseases (excluding vitiligo and thyroid diseases that can be treated with hormone replacement therapy, and type I diabetes);

16) Received systemic glucocorticoids (prednisone >10 mg/day or equivalent dose of the same drug) or other immunosuppressants within 14 days prior to the first use of the study drug; except for the following: use of topical, ocular, intra-articular, intranasal and inhaled glucocorticoids, short-term use of glucocorticoids for prophylactic treatment (e.g., prevention of contrast agent allergy).

17) Patients who have previously experienced ≥ grade 3 immune-related adverse events (irAEs), or who have previously experienced ≥ grade 2 irAEs that require permanent discontinuation of immunotherapy as stipulated in the "Guidelines for the Management of Immune Checkpoint Inhibitor-Related Toxicity" (CSCO Guidelines) (2023 version or later);

18) Severe cardiovascular disease: New York Heart Association (NYHA) class III or higher heart failure, left ventricular ejection fraction (LVEF) <50%, unstable angina, uncontrolled hypertension (defined in this protocol as systolic blood pressure >160 mmHg and/or diastolic blood pressure >100 mmHg after optimal antihypertensive treatment), history of myocardial infarction within the past 6 months, or severe arrhythmia requiring medication (atrial fibrillation or supraventricular tachycardia will be determined by the investigator for inclusion).

19) Patients with a known history of psychotropic substance abuse or drug use, who are considered to have a negative impact on their adherence to this study;

20) In addition to the tumors they had at the time of enrollment in the study, other active malignancies, excluding adequately treated cervical carcinoma in situ, basal cell or squamous cell skin cancer, localized prostate cancer after radical mastectomy, and ductal carcinoma in situ after radical mastectomy, were present within 5 years prior to the first dose of the drug.

21) Patients with effusion in the pericardial cavity, pleural cavity, abdominal cavity, pelvic cavity, or other serous cavities who require puncture or drainage in the near future (those whose effusion has stabilized after recent puncture and drainage may be included).

3. Research Objectives and Endpoints

3.1 Primary and Secondary Objectives of the Study

The primary objective of the Phase Ib study was to evaluate the safety and tolerability of the combined administration of antibody A injection and antibody h10D8OF injection in patients with locally advanced or metastatic solid tumors, providing recommended dosages for subsequent clinical trials. Secondary objectives included: preliminary evaluation of the antitumor efficacy of antibody A injection and antibody h10D8OF injection in the combined administration regimen; evaluation of the pharmacokinetic (PK) characteristics of single-dose and multiple-dose administration of antibody A injection and antibody h10D8OF injection in patients with advanced solid tumors in the combined administration regimen; and evaluation of the immunogenicity of BA1308 and antibody h10D8OF injection in the combined administration regimen.

The primary objective of the Phase II study was to evaluate the safety and preliminary antitumor efficacy of antibody A injection and antibody h10D8OF injection in combination with chemotherapy in advanced gastric cancer, gastroesophageal junction cancer, and esophageal cancer, as well as the safety and preliminary efficacy of antibody A injection and antibody h10D8OF injection in advanced non-small cell lung cancer (NSCLC) and hepatocellular carcinoma (HCC), and to provide recommended dosages for subsequent clinical trials.

The secondary objective was to evaluate the pharmacokinetic (PK) characteristics of single-dose and multiple-dose administration of antibody A injection and antibody h10D8OF injection in combination with chemotherapy in patients with advanced gastric cancer, gastroesophageal junction cancer, and esophageal cancer, as well as in patients with advanced non-small cell lung cancer (NSCLC) and hepatocellular carcinoma (HCC); and to evaluate the immunogenicity of antibody A injection and antibody h10D8OF injection in combination with chemotherapy in patients with advanced gastric cancer, gastroesophageal junction cancer, and esophageal cancer, as well as in patients with advanced non-small cell lung cancer (NSCLC) and hepatocellular carcinoma (HCC).

3.2 Primary and Secondary Endpoints of the Study

The primary endpoint was a safety endpoint: vital signs and physical examination, adverse events (AEs), clinical laboratory tests, and clinical ancillary tests (such as electrocardiogram).

Secondary endpoint indicators:

1) Preliminary efficacy evaluation based on the RECIST V1.1 criteria for evaluating the efficacy of treatment in solid tumors. Key endpoints include: objective response rate (ORR), duration of response (DoR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS).

2) Pharmacokinetic parameters of antibody A injection and antibody h10D8OF injection under single and multiple doses, including:

Single dose: _Cmax , _Tmax , T1 _/2 , CL, Vd, Ke, MRT, AUC(0-τ), AUC(0-∞);

Multiple administrations: _Cmax,ss , Cavg _,ss , Cmin _,ss , AUC _(0-τ)ss , AUC _(0-∞)ss , _Tmax,ss , _T1/2,ss , CL, _Vss , Ke, MRT, accumulation index ( _Rac ), volatility index DF.

3) Antidrug-resistant antibodies (ADA) / neutralizing antibodies (NAb)

The combined administration regimen of antibody A injection and antibody h10D8OF injection of the present invention is expected to have good safety and tolerability, or result in improvements selected from at least one of the following: objective response rate (ORR), duration of response (DoR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS).

Claims (31)

A method for treating tumors, comprising: administering to a patient in need an effective amount of an anti-TIGIT antibody or antigen-binding fragment and an anti-PD-1 antibody or antigen-binding fragment; The anti-TIGIT antibody or antigen-binding fragment comprises HCDR1 shown in SEQ ID NO:1, HCDR2 shown in SEQ ID NO:2, HCDR3 shown in SEQ ID NO:3, LCDR1 shown in SEQ ID NO:4, LCDR2 shown in SEQ ID NO:5, and LCDR3 shown in SEQ ID NO:6; The tumor is a hematologic cancer or a solid tumor; or, the tumor is selected from acute lymphoblastic leukemia, acute myeloid leukemia, chronic lymphocytic leukemia, chronic myeloid leukemia, myeloproliferative disorders/tumors, Hodgkin lymphoma, painless and aggressive non-Hodgkin lymphoma, Burkitt lymphoma, follicular lymphoma, multiple myeloma, giant cell myeloma, heavy chain myeloma, light chain or Bens-Jones myeloma, breast cancer, ovarian cancer, pancreatic cancer, prostate cancer, melanoma, colorectal cancer, colon cancer, lung cancer, head and neck cancer, bladder cancer, esophageal cancer, liver cancer, kidney cancer, and stomach cancer; Alternatively, the tumor may be selected from gastric cancer, gastroesophageal junction cancer, esophageal cancer, non-small cell lung cancer, and hepatocellular carcinoma. A method for treating tumors, comprising administering to a patient in need an effective amount of an anti-TIGIT antibody or antigen-binding fragment, an anti-PD-1 antibody or antigen-binding fragment, and one or more chemotherapeutic agents; The anti-TIGIT antibody or antigen-binding fragment therein comprises HCDR1 shown in SEQ ID NO:1, HCDR2 shown in SEQ ID NO:2, HCDR3 shown in SEQ ID NO:3, LCDR1 shown in SEQ ID NO:4, LCDR2 shown in SEQ ID NO:5, and LCDR3 shown in SEQ ID NO:6. The method of claim 2, wherein the chemotherapeutic agent comprises capecitabine, taxane, or platinum-based drugs or combinations thereof. The method of claim 3, wherein the chemotherapeutic agent is oxaliplatin combined with capecitabine. The method of claim 3, wherein the chemotherapeutic agent is capecitabine. The method of claim 4, wherein oxaliplatin is administered at a dose of approximately 50-300 mg/ ^m² per body surface area. The method according to any one of claims 4-6, wherein capecitabine is administered at a dose of about 100-2000 mg/ ^m² per body surface area. The method of claim 4 or any one of 6-7, wherein oxaliplatin is administered at a dose of approximately 130 mg/ ^m² per body surface area. The method according to any one of claims 4-8, wherein capecitabine is administered at a dose of approximately 1000 mg/ ^m² per body surface area. As described in any one of claims 4 or 6-9, oxaliplatin is administered intravenously at a dose of approximately 130 mg/ ^m² per body surface area, once every 3 weeks. As described in any one of claims 4-10, capecitabine is administered orally at a dose of approximately 1000 mg/ ^m² per body surface area, with each treatment cycle lasting 3 weeks, and the medication is administered twice daily on days 1-14 of each cycle. The method according to any one of claims 2-11, wherein the tumor is a hematologic cancer or a solid tumor. The method according to any one of claims 2-12, wherein the tumor is selected from acute lymphoblastic leukemia, acute myeloid leukemia, chronic lymphoblastic leukemia, chronic myeloid leukemia, myeloproliferative disorders/tumors, Hodgkin lymphoma, painless and aggressive non-Hodgkin lymphoma, Burkitt lymphoma, follicular lymphoma, multiple myeloma, giant cell myeloma, heavy chain myeloma, light chain or Bens-Jones myeloma, breast cancer, ovarian cancer, pancreatic cancer, prostate cancer, melanoma, colorectal cancer, colon cancer, lung cancer, head and neck cancer, bladder cancer, esophageal cancer, liver cancer, kidney cancer, and stomach cancer. The method according to any one of claims 2-13, wherein the tumor is selected from gastric cancer, gastroesophageal junction cancer, esophageal cancer, non-small cell lung cancer, and hepatocellular carcinoma. The method according to any one of claims 1-14, wherein the anti-TIGIT antibody or antigen-binding fragment comprises a heavy chain variable region and a light chain variable region, wherein: the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:7, or an amino acid sequence having at least 80% identity with the sequence shown in SEQ ID NO:7, or an amino acid sequence having one or more conserved amino acid substitutions compared to the sequence shown in SEQ ID NO:7; and/or The light chain variable region comprises the amino acid sequence shown in SEQ ID NO:8, or an amino acid sequence having at least 80% identity with the sequence shown in SEQ ID NO:8, or an amino acid sequence having one or more conserved amino acid substitutions compared to the sequence shown in SEQ ID NO:8. The method according to any one of claims 1-15, wherein the anti-TIGIT antibody or antigen-binding fragment comprises a heavy chain and a light chain, wherein: the heavy chain of the anti-TIGIT antibody comprises the amino acid sequence shown in SEQ ID NO:9, or an amino acid sequence having at least 80% identity with the sequence shown in SEQ ID NO:9, or an amino acid sequence having one or more conserved amino acid substitutions compared to the sequence shown in SEQ ID NO:9; and/or The light chain of the anti-TIGIT antibody comprises the amino acid sequence shown in SEQ ID NO:10, or an amino acid sequence having at least 80% identity with the sequence shown in SEQ ID NO:10, or an amino acid sequence having one or more conserved amino acid substitutions compared to the sequence shown in SEQ ID NO:10. The method according to any one of claims 1-16, wherein the anti-PD-1 antibody or antigen-binding fragment comprises nivolumab, pembrolizumab, camrelizumab, sintilimab, toripalimab, or tislelizumab. The method according to any one of claims 1-16, wherein the anti-PD-1 antibody or antigen-binding fragment comprises HCDR1 shown in SEQ ID NO:11, HCDR2 shown in SEQ ID NO:12, HCDR3 shown in SEQ ID NO:13, LCDR1 shown in SEQ ID NO:14, LCDR2 shown in SEQ ID NO:15, and LCDR3 shown in SEQ ID NO:16. The method according to any one of claims 1-16 or 18, wherein the anti-PD-1 antibody or antigen-binding fragment comprises a heavy chain variable region and a light chain variable region, wherein: the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:17, or an amino acid sequence having at least 80% identity with the sequence shown in SEQ ID NO:17, or an amino acid sequence having one or more conserved amino acid substitutions compared to the sequence shown in SEQ ID NO:17; and/or The light chain variable region comprises the amino acid sequence shown in SEQ ID NO:18, or an amino acid sequence having at least 80% identity with the sequence shown in SEQ ID NO:18, or an amino acid sequence having one or more conserved amino acid substitutions compared to the sequence shown in SEQ ID NO:18. The method according to any one of claims 1-16 or 18-19, wherein the anti-PD-1 antibody or antigen-binding fragment comprises a heavy chain and a light chain, wherein: the heavy chain of the anti-PD-1 antibody comprises the amino acid sequence shown in SEQ ID NO:19, or an amino acid sequence having at least 80% identity with the sequence shown in SEQ ID NO:19, or an amino acid sequence having one or more conserved amino acid substitutions compared to the sequence shown in SEQ ID NO:19; and/or The light chain of the anti-PD-1 antibody comprises the amino acid sequence shown in SEQ ID NO:20, or an amino acid sequence having at least 80% identity with the sequence shown in SEQ ID NO:20, or an amino acid sequence having one or more conserved amino acid substitutions compared to the sequence shown in SEQ ID NO:20. The method according to any one of claims 1-20, wherein the dose of the anti-TIGIT antibody or antigen-binding fragment is about 0.01 mg, about 1 mg, about 3 mg, about 5 mg, about 10 mg, about 30 mg, about 50 mg, about 100 mg, about 300 mg, about 500 mg, about 600 mg, about 900 mg, about 1000 mg, or about 1200 mg per treatment cycle, or a range (including endpoints) between any two of these values, or any value therein. The method according to any one of claims 1-21, wherein the dose of the anti-TIGIT antibody or antigen-binding fragment is about 600 mg or about 900 mg per treatment cycle. The method according to any one of claims 1-22, wherein the dose of the anti-PD-1 antibody or antigen-binding fragment is about 1 mg, about 10 mg, about 50 mg, about 100 mg, about 200 mg, about 240 mg, about 300 mg, about 500 mg, about 600 mg, about 900 mg, or about 1000 mg per treatment cycle, or a range (including endpoints) between any two of these values, or any value therein. The method according to any one of claims 1-23, wherein the dose of the anti-PD-1 antibody or antigen-binding fragment is about 300 mg per treatment cycle. The method according to any one of claims 1-24, wherein the anti-TIGIT antibody or antigen-binding fragment and the anti-PD-1 antibody or antigen-binding fragment are administered separately or simultaneously. The method according to any one of claims 1-25, wherein the anti-PD-1 antibody or antigen-binding fragment is administered after administration of the anti-TIGIT antibody or antigen-binding fragment. The method according to any one of claims 1-26, wherein the anti-TIGIT antibody or antigen-binding fragment is administered once daily to once every 7 weeks, at a dose of about 600 mg or about 900 mg per administration; and/or The anti-PD-1 antibody or antigen-binding fragment is administered once daily to once every 7 weeks, with each dose being approximately 300 mg. The method according to any one of claims 1-27, wherein the anti-TIGIT antibody or antigen-binding fragment is administered approximately every 3 weeks at a dose of approximately 600 mg or approximately 900 mg; and/or The anti-PD-1 antibody or antigen-binding fragment is administered approximately every 3 weeks, with each dose being approximately 300 mg. The method according to any one of claims 1-28, the method comprising administering to a patient one or more treatment cycles of an anti-TIGIT antibody or antigen-binding fragment and an anti-PD-1 antibody or antigen-binding fragment. The method of any one of claims 1-29, the method comprising administering to a patient one or more treatment cycles of an anti-TIGIT antibody or antigen-binding fragment and an anti-PD-1 antibody or antigen-binding fragment, wherein: (1) At least one treatment cycle, the patient is administered a combination of: the anti-TIGIT antibody or antigen-binding fragment and the anti-PD-1 antibody or antigen-binding fragment; and/or (2) Administration to the patient for at least one treatment cycle of the following: the anti-TIGIT antibody or antigen-binding fragment, the anti-PD-1 antibody or antigen-binding fragment, oxaliplatin, and capecitabine; and/or (3) The patient is given at least one treatment cycle the following: the anti-TIGIT antibody or antigen-binding fragment, the anti-PD-1 antibody or antigen-binding fragment, and capecitabine. Use of anti-TIGIT antibody or antigen-binding fragment and anti-PD-1 antibody or antigen-binding fragment in the preparation of a medicament for treating tumors, wherein the treatment is the method according to any one of claims 1-30.