Therapeutic combination, and use and therapeutic method thereof

Abstract

Provided are a therapeutic combination, and a use and therapeutic method thereof. Specifically provided are a therapeutic combination comprising an anti-Trop-2 antibody-drug conjugate, one or both of a VEGF inhibitor and an EGFR inhibitor, and optionally other active therapeutic agents, a method for preventing and / or treating tumors or cancers using same, and a use thereof in the preparation of drugs for preventing and / or treating tumors or cancers.

Description

Treatment combinations, their uses, and treatment methods

[0001] This application is based on and claims priority to Chinese Patent Application No. 202411813920.5, filed on December 10, 2024, and Chinese Patent Application No. 202511759121.9, filed on November 27, 2025, the disclosures of which are incorporated herein by reference in their entirety. Technical Field

[0002] This application belongs to the field of biomedicine and relates to therapeutic combinations, their uses, and methods of treatment. Specifically, it relates to combinations of antibody-drug conjugates, EGFR inhibitors, and VEGF inhibitors, their methods for preventing and / or treating cancer, and their use in the preparation of medicaments for the prevention and / or treatment of cancer. Background Technology

[0003] Malignant tumors have become a common and prevalent disease in my country, seriously threatening human life and health. Chemotherapy remains the primary treatment for advanced malignant tumors; however, chemotherapy drugs not only kill tumor cells but also indiscriminately attack normal human cells, causing severe side effects.

[0004] Trop-2 is a glycoprotein aberrantly expressed in various tumors. Trop-2 is closely related to cell proliferation and invasion, and its role extends beyond tumor cell proliferation and migration to include the regulation of the tumor microenvironment and tumor angiogenesis. Trop-2 expression levels are elevated in various tumors, including breast cancer, gastric cancer, and ovarian cancer, and are associated with tumor invasiveness and metastasis. Considering Trop-2 expression patterns and associated adverse prognostic outcomes, it is a plausible prognostic biomarker and therapeutic target. Targeting Trop-2 with antibody-drug conjugates (ADCs) is a highly efficient and precise anti-tumor therapeutic strategy. By binding to the surface of target cells, it achieves targeting while simultaneously generating a bystander effect, killing surrounding cancer cells. However, due to the heterogeneity of tumor cells and individual variability, exploring the combination of ADCs may offer opportunities to improve efficacy, reduce side effects on multiple organs, and mitigate drug resistance.

[0005] VEGF is a crucial factor in angiogenesis and is also overexpressed in tumor endothelial cells. VEGF, by binding to its receptor VEGFR, promotes the proliferation and migration of vascular endothelial cells, increases vascular permeability, and inhibits apoptosis. Anti-tumor cell angiogenesis holds promise as a targeted therapeutic strategy. Drugs that specifically bind to VEGF and prevent its interaction with its receptor inhibit tumor angiogenesis, thereby sustainably suppressing tumor cell growth and metastasis. Anti-VEGF antibodies can specifically bind to VEGF, blocking its binding to receptors on vascular endothelial cells, thus inhibiting tumor cell proliferation or metastasis and exhibiting good anti-tumor therapeutic effects.

[0006] Cetuximab is a targeted drug against the epidermal growth factor receptor EGFR; it is a monoclonal antibody that acts on EGFR. EGFR is an important cellular protein that can bind to epidermal growth factor (EGF), inhibiting the secretion of angiogenesis factors by tumor cells and reducing tumor angiogenesis and metastasis.

[0007] This application demonstrates through extensive research that the combination of Trop-2-targeting ADCs with EGFR inhibitors and / or VEGF inhibitors has good safety and clinical benefits in various tumor types, and has great potential for anti-tumor or anti-cancer treatment. Summary of the Invention

[0008] The treatment combination, pharmaceutical composition, and kit provided in this application are for treating tumors or cancer, exhibiting significant anti-tumor effects and good tolerability.

[0009] In the first aspect, this application provides a treatment combination comprising:

[0010] (1) Antibody-drug conjugates;

[0011] (2) Selected from one or both of EGFR inhibitors and VEGF inhibitors; and

[0012] (3) Other optional active therapeutic agents.

[0013] In some embodiments, the antibody-drug conjugate is selected from anti-Trop-2 antibody-drug conjugates.

[0014] In some embodiments, the treatment combination includes an anti-Trop-2 antibody-drug conjugate and a VEGF inhibitor, and optionally includes other active therapeutic agents.

[0015] In some embodiments, the treatment combination includes an anti-Trop-2 antibody-drug conjugate and an EGFR inhibitor, and optionally includes other active therapeutic agents.

[0016] In some implementations, the treatment combination includes an anti-Trop-2 antibody-drug conjugate, an EGFR inhibitor, and a VEGF inhibitor.

[0017] In some implementations, the treatment combination includes an anti-Trop-2 antibody-drug conjugate and an EGFR inhibitor.

[0018] In some implementations, the treatment combination includes an anti-Trop-2 antibody-drug conjugate and a VEGF inhibitor.

[0019] In some embodiments, the VEGF inhibitor is selected from anti-VEGF antibodies and / or their antigen-binding fragments.

[0020] In some embodiments, the EGFR inhibitor is selected from anti-EGFR antibodies and / or antigen-binding fragments.

[0021] In some embodiments, the VEGF inhibitor is selected from anti-VEGF antibodies and / or their antigen-binding fragments, and the EGFR inhibitor is selected from anti-EGFR antibodies and / or their antigen-binding fragments.

[0022] In some embodiments, the treatment combination includes an anti-Trop-2 antibody-drug conjugate and an anti-VEGF antibody and / or its antigen-binding fragment.

[0023] In some embodiments, the anti-VEGF antibody and / or its antigen-binding fragment is selected from one or more of bevacizumab, ramucirumab, ranibizumab, and faricimab or their biosimilars.

[0024] In some embodiments, the anti-VEGF antibody and / or its antigen-binding fragment is bevacizumab or a biosimilar thereof.

[0025] In some implementations, the anti-VEGF antibody is bevacizumab or a biosimilar thereof.

[0026] In some embodiments, the anti-VEGF antibody and / or its antigen-binding fragment in the treatment combination includes sequences having at least 90%, 95%, 98%, and 99% identity with the heavy chain variable regions of bevacizumab, ramucirumab, ranibizumab, and faricimab, and / or sequences having at least 90%, 95%, 98%, and 99% identity with the light chain variable regions of bevacizumab, ramucirumab, ranibizumab, and faricimab.

[0027] In some embodiments, the bevacizumab biosimilar is selected from: MVASI, Zirabev, Bevax, Lumiere, Bambevi, Equidacent, Avegra, BP 01, BCD500, Krabeva, BAT1706, BXT-2316, Bevalo, BI 695502, CT-P16, CHS-5217, DRZ BZ, Cizumab, Byvasda, MIL60, MYL 1402O, ONS1045, HD204, Ankeda, Bevaciler, Aybintio, Onbevzi, HLX04, TX16, MB02, and Oyavas.

[0028] In some implementations, the anti-EGFR antibody and its biosimilar are selected from one or more of cetuximab, panitumumab, nexituzumab, nimotuzumab, Rybrevant, and Amivantamab.

[0029] In some implementations, the anti-EGFR antibody and its biosimilar are selected from cetuximab.

[0030] In some embodiments, the anti-Trop-2 antibody-drug conjugate, as well as one or both of EGFR inhibitors and VEGF inhibitors, and optionally other active therapeutic agents, can be administered simultaneously, separately, sequentially, or in sequence.

[0031] In some implementations, the anti-Trop-2 antibody-drug conjugate is administered simultaneously with one or both of an EGFR inhibitor and a VEGF inhibitor.

[0032] In some implementations, the anti-Trop-2 antibody-drug conjugate, along with one or both of an EGFR inhibitor and a VEGF inhibitor, are administered separately.

[0033] In some embodiments, the anti-Trop-2 antibody-drug conjugate, along with one or both of an EGFR inhibitor and a VEGF inhibitor, is administered sequentially.

[0034] In some embodiments, the anti-Trop-2 antibody-drug conjugate is administered sequentially with one or both of an EGFR inhibitor and a VEGF inhibitor.

[0035] In some implementations, the anti-Trop-2 antibody-drug conjugate and the EGFR inhibitor are administered simultaneously.

[0036] In some implementations, the anti-Trop-2 antibody-drug conjugate and the EGFR inhibitor are administered separately.

[0037] In some implementations, the anti-Trop-2 antibody-drug conjugate and the EGFR inhibitor are administered sequentially.

[0038] In some implementations, the anti-Trop-2 antibody-drug conjugate and the EGFR inhibitor are administered sequentially.

[0039] In some implementations, the anti-Trop-2 antibody-drug conjugate and the VEGF inhibitor are administered simultaneously.

[0040] In some implementations, the anti-Trop-2 antibody-drug conjugate and the VEGF inhibitor are administered separately.

[0041] In some implementations, the anti-Trop-2 antibody-drug conjugate and the VEGF inhibitor are administered sequentially.

[0042] In some implementations, the anti-Trop-2 antibody-drug conjugate and the VEGF inhibitor are administered sequentially.

[0043] In some embodiments, the dosing period of the anti-Trop-2 antibody-drug conjugate is 1-42 days. In some embodiments, the dosing period of the anti-Trop-2 antibody-drug conjugate is 7-42 days. In some embodiments, the dosing period of the anti-Trop-2 antibody-drug conjugate is 14-42 days. In some embodiments, the dosing period of the anti-Trop-2 antibody-drug conjugate is 1 day. In some embodiments, the dosing period of the anti-Trop-2 antibody-drug conjugate is 3 days. In some embodiments, the dosing period of the anti-Trop-2 antibody-drug conjugate is 7 days. In some embodiments, the dosing period of the anti-Trop-2 antibody-drug conjugate is 14 days. In some embodiments, the dosing period of the anti-Trop-2 antibody-drug conjugate is 21 days. In some embodiments, the dosing period of the anti-Trop-2 antibody-drug conjugate is 28 days.

[0044] In some embodiments, the anti-Trop-2 antibody drug conjugate, VEGF inhibitor, and / or EGFR inhibitor may be administered simultaneously, within one day, or at intervals of at least 1 day, 2 days, 3 days, 5 days, 6 days, 7 days, 10 days, 15 days, 21 days, 30 days, 45 days, 2 months, 75 days, 3 months, or 6 months.

[0045] In some implementations, the anti-Trop-2 antibody-drug conjugate and the VEGF inhibitor can be administered simultaneously, within one day, or at intervals of at least 1 day, 2 days, 3 days, 5 days, 6 days, 7 days, 10 days, 15 days, 21 days, 30 days, 45 days, 2 months, 75 days, 3 months, or 6 months.

[0046] In some implementations, the anti-Trop-2 antibody-drug conjugate and the EGFR inhibitor can be administered simultaneously, within one day, or at intervals of at least 1 day, 2 days, 3 days, 5 days, 6 days, 7 days, 10 days, 15 days, 21 days, 30 days, 45 days, 2 months, 75 days, 3 months, or 6 months.

[0047] In some implementations, the treatment combination or any component of the treatment combination may be repeatedly applied, with the applications spaced at least 1 day, 2 days, 3 days, 5 days, 6 days, 7 days, 10 days, 15 days, 21 days, 30 days, 45 days, 2 months, 75 days, 3 months, or 6 months apart.

[0048] In some implementations, the treatment combination or individual components of the treatment combination may be repeatedly applied, with the applications spaced at least 1 day, 2 days, 3 days, 5 days, 6 days, 7 days, 10 days, 15 days, 21 days, 30 days, 45 days, 2 months, 75 days, 3 months, or 6 months apart.

[0049] In some embodiments, the anti-Trop-2 antibody-drug conjugate is administered 1 to 8 times over a period of 1 to 4 weeks.

[0050] In some implementations, the anti-Trop-2 antibody-drug conjugate is administered once a week, twice a week, once every two weeks, or once every three weeks.

[0051] In some implementations, the dose of the anti-Trop-2 antibody-drug conjugate administered per dose is selected from 0.1-20 mg / kg or more, based on the subject's weight.

[0052] In some embodiments, the dose of the anti-Trop-2 antibody-drug conjugate administered per administration is selected from 0.5-10 mg / kg, based on the subject's weight. In some embodiments, the dose of the anti-Trop-2 antibody-drug conjugate administered per administration is selected from 0.5-5 mg / kg, based on the subject's weight.

[0053] In some implementations, the dose of the anti-Trop-2 antibody-drug conjugate administered per dose, based on the subject's weight, is selected from 0.5 mg / kg, 1 mg / kg, 2 mg / kg, 2.5 mg / kg, 3 mg / kg, 3.5 mg / kg, 4 mg / kg, 4.5 mg / kg, 5 mg / kg, 5.5 mg / kg, 6 mg / kg, 6.5 mg / kg, 7 mg / kg, 7.5 mg / kg, 8 mg / kg, 8.5 mg / kg, 9 mg / kg, 9.5 mg / kg, or 10 mg / kg.

[0054] In some implementations, the dose of the anti-Trop-2 antibody-drug conjugate administered per dose is 0.5 mg / kg, 1 mg / kg, 2 mg / kg, 3 mg / kg, 4 mg / kg, or 5 mg / kg, depending on the subject's weight.

[0055] In some implementations, the dose of the anti-Trop-2 antibody-drug conjugate is 0.5 mg / kg per administration, based on the subject's weight.

[0056] In some implementations, the dose of the anti-Trop-2 antibody-drug conjugate is 1 mg / kg per administration, based on the subject's weight.

[0057] In some implementations, the dose of the anti-Trop-2 antibody-drug conjugate is 2 mg / kg per administration, based on the subject's weight.

[0058] In some implementations, the dose of the anti-Trop-2 antibody-drug conjugate is 3 mg / kg per administration, based on the subject's weight.

[0059] In some implementations, the dose of the anti-Trop-2 antibody-drug conjugate is 4 mg / kg per administration, based on the subject's weight.

[0060] In some implementations, the dose of the anti-Trop-2 antibody-drug conjugate is 5 mg / kg per administration, based on the subject's weight.

[0061] In some embodiments, the dose of the anti-Trop-2 antibody-drug conjugate administered at a time is selected from 0.1-20 mg / kg or more.

[0062] In some embodiments, the dose of the anti-Trop-2 antibody-drug conjugate administered at a time is selected from 0.5-10 mg / kg.

[0063] In some embodiments, the dose of the anti-Trop-2 antibody-drug conjugate administered at a time is selected from 0.5-5 mg / kg.

[0064] In some embodiments, the dose of the anti-Trop-2 antibody-drug conjugate administered at each dose is selected from 0.5 mg / kg, 1 mg / kg, 2 mg / kg, 2.5 mg / kg, 3 mg / kg, 3.5 mg / kg, 4 mg / kg, 4.5 mg / kg, 5 mg / kg, 5.5 mg / kg, 6 mg / kg, 6.5 mg / kg, 7 mg / kg, 7.5 mg / kg, 8 mg / kg, 8.5 mg / kg, 9 mg / kg, 9.5 mg / kg, or 10 mg / kg.

[0065] In some embodiments, the dose of the anti-Trop-2 antibody-drug conjugate administered at a time is 0.5 mg / kg, 1 mg / kg, 2 mg / kg, 3 mg / kg, 4 mg / kg, or 5 mg / kg.

[0066] In some embodiments, the dose of the anti-Trop-2 antibody-drug conjugate is 0.5 mg / kg per administration.

[0067] In some embodiments, the dose of the anti-Trop-2 antibody-drug conjugate is 1 mg / kg per administration.

[0068] In some embodiments, the dose of the anti-Trop-2 antibody-drug conjugate is 2 mg / kg per administration.

[0069] In some embodiments, the dose of the anti-Trop-2 antibody-drug conjugate is 3 mg / kg per administration.

[0070] In some embodiments, the dose of the anti-Trop-2 antibody-drug conjugate is 4 mg / kg per administration.

[0071] In some embodiments, the dose of the anti-Trop-2 antibody-drug conjugate is 5 mg / kg per administration.

[0072] In some embodiments, the dose concentration of the anti-Trop-2 antibody-drug conjugate administered per dose is selected from 0.01-50 mg / ml.

[0073] In some embodiments, the dose concentration of the anti-Trop-2 antibody-drug conjugate administered per dose is selected from 0.01-40 mg / ml, 0.01-30 mg / ml, 0.01-20 mg / ml, or 0.01-10 mg / ml.

[0074] In some embodiments, the dose concentration of the anti-Trop-2 antibody-drug conjugate administered per dose is selected from 0.01 mg / ml, 0.03 mg / ml, 0.05 mg / ml, 0.06 mg / ml, 0.1 mg / ml, 0.3 mg / ml, 0.5 mg / ml, 0.6 mg / ml, 0.7 mg / ml, 0.8 mg / ml, 0.9 mg / ml, 1.0 mg / ml, 2.0 mg / ml, 3.0 mg / ml, 4.0 mg / ml, 5.0 mg / ml, 6.0 mg / ml, 7.0 mg / ml, 8.0 mg / ml, 9.0 mg / ml, 10.0 mg / ml, 15.0 mg / ml, 20.0 mg / ml, 25 mg / ml, 30 mg / ml, 35 mg / ml, 40 mg / ml, 45 mg / ml, and 50 mg / ml.

[0075] In some embodiments, the dose of the anti-Trop-2 antibody drug conjugate (e.g., a single-dose dose or a unit dose) is selected from 0.1-1000 mg.

[0076] In some embodiments, the dose of the anti-Trop-2 antibody-drug conjugate (e.g., a single-dose dose or a unit dose) is selected from 0.1-900 mg, 0.1-800 mg, 0.1-700 mg, 0.1-600 mg, 0.1-500 mg, 0.1-400 mg, 0.1-300 mg, 0.1-200 mg, 0.1-100 mg, 0.1-50 mg, 0.1-30 mg, 0.1-20 mg, and 0.1-10 mg.

[0077] In some embodiments, the dose of the anti-Trop-2 antibody-drug conjugate (e.g., a single-dose dose or a unit dose) is selected from 0.1 mg, 1.0 mg, 2.0 mg, 3.0 mg, 4.0 mg, 5.0 mg, 6.0 mg, 7.0 mg, 8.0 mg, 9.0 mg, 10.0 mg, 15.0 mg, 20.0 mg, 25 mg, 30 mg, 35 mg, 40 mg, 45 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, 400 mg, 450 mg, and 500 mg.

[0078] In some embodiments, the dose of the anti-Trop-2 antibody drug conjugate is a single dose or a total dose for each dosing cycle.

[0079] In some embodiments, the dosing period of the VEGF inhibitor is 1-42 days. In some embodiments, the dosing period of the VEGF inhibitor is 7-42 days. In some embodiments, the dosing period of the VEGF inhibitor is 1 day, 7 days, 14 days, 21 days, 28 days, or 42 days. In some embodiments, the dosing period of the VEGF inhibitor is 1 day. In some embodiments, the dosing period of the VEGF inhibitor is 3 days. In some embodiments, the dosing period of the VEGF inhibitor is 7 days. In some embodiments, the dosing period of the VEGF inhibitor is 14 days. In some embodiments, the dosing period of the VEGF inhibitor is 21 days. In some embodiments, the dosing period of the VEGF inhibitor is 28 days.

[0080] In some embodiments, the VEGF inhibitor is administered 1 to 8 times over a period of 1 to 4 weeks.

[0081] In some implementations, the VEGF inhibitor is administered once a week, twice a week, once every two weeks, or once every three weeks.

[0082] In some implementations, the dose of the VEGF inhibitor administered per dose is selected from 0.5-50 mg / kg, based on the subject's weight.

[0083] In some implementations, the dose of the VEGF inhibitor administered per dose, based on the subject's weight, is selected from 0.5-40 mg / kg, 0.5-30 mg / kg, 0.5-20 mg / kg, 0.5-10 mg / kg, and 0.5-5 mg / kg.

[0084] In some implementations, the dose of the VEGF inhibitor administered per administration, based on the subject's weight, is selected from 0.5 mg / kg, 1 mg / kg, 1.5 mg / kg, 2 mg / kg, 2.5 mg / kg, 3 mg / kg, 3.5 mg / kg, 4 mg / kg, 4.5 mg / kg, 5 mg / kg, 5.5 mg / kg, 6 mg / kg, 6.5 mg / kg, 7 mg / kg, 7.5 mg / kg, 8 mg / kg, 8.5 mg / kg, 9 mg / kg, 9.5 mg / kg, 10 mg / kg, 15 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 35 mg / kg, 40 mg / kg, 45 mg / kg, or 50 mg / kg.

[0085] In some embodiments, the VEGF inhibitor is administered at a dose of 0.5 mg / kg, 1 mg / kg, 1.5 mg / kg, 2 mg / kg, 2.5 mg / kg, 3 mg / kg, 3.5 mg / kg, 4 mg / kg, 4.5 mg / kg, or 5 mg / kg, based on the subject's weight. In some embodiments, the VEGF inhibitor is administered at a dose of 1.0 mg / kg, based on the subject's weight. In some embodiments, the VEGF inhibitor is administered at a dose of 1.5 mg / kg, based on the subject's weight. In some embodiments, the VEGF inhibitor is administered at a dose of 2 mg / kg, based on the subject's weight. In some embodiments, the VEGF inhibitor is administered at a dose of 2.5 mg / kg, based on the subject's weight. In some embodiments, the VEGF inhibitor is administered at a dose of 3 mg / kg, based on the subject's weight. In some embodiments, the VEGF inhibitor is administered at a dose of 4 mg / kg, based on the subject's weight. In some embodiments, the VEGF inhibitor is administered at a dose of 5 mg / kg, based on the subject's weight. In some embodiments, the VEGF inhibitor is administered at a dose of 10 mg / kg per administration, based on the subject's weight. In some embodiments, the VEGF inhibitor is administered at a dose of 20 mg / kg per administration, based on the subject's weight.

[0086] In some embodiments, the dose of the VEGF inhibitor administered each time is selected from 0.5-50 mg / kg.

[0087] In some embodiments, the dose of the VEGF inhibitor administered per administration is selected from 0.5-40 mg / kg, 0.5-30 mg / kg, 0.5-20 mg / kg, 0.5-10 mg / kg, and 0.5-5 mg / kg.

[0088] In some embodiments, the dose of the VEGF inhibitor administered per administration is selected from 0.5 mg / kg, 1 mg / kg, 1.5 mg / kg, 2 mg / kg, 2.5 mg / kg, 3 mg / kg, 3.5 mg / kg, 4 mg / kg, 4.5 mg / kg, 5 mg / kg, 5.5 mg / kg, 6 mg / kg, 6.5 mg / kg, 7 mg / kg, 7.5 mg / kg, 8 mg / kg, 8.5 mg / kg, 9 mg / kg, 9.5 mg / kg, 10 mg / kg, 15 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 35 mg / kg, 40 mg / kg, 45 mg / kg, or 50 mg / kg.

[0089] In some embodiments, the VEGF inhibitor is administered at a dose of 0.5 mg / kg, 1 mg / kg, 1.5 mg / kg, 2 mg / kg, 2.5 mg / kg, 3 mg / kg, 3.5 mg / kg, 4 mg / kg, 4.5 mg / kg, or 5 mg / kg. In some embodiments, the VEGF inhibitor is administered at a dose of 1.0 mg / kg. In some embodiments, the VEGF inhibitor is administered at a dose of 1.5 mg / kg. In some embodiments, the VEGF inhibitor is administered at a dose of 2 mg / kg. In some embodiments, the VEGF inhibitor is administered at a dose of 2.5 mg / kg. In some embodiments, the VEGF inhibitor is administered at a dose of 3 mg / kg. In some embodiments, the VEGF inhibitor is administered at a dose of 4 mg / kg. In some embodiments, the VEGF inhibitor is administered at a dose of 5 mg / kg. In some embodiments, the VEGF inhibitor is administered at a dose of 10 mg / kg. In some embodiments, the VEGF inhibitor is administered at a dose of 20 mg / kg.

[0090] In some embodiments, the VEGF inhibitor is administered at a concentration selected from 0.05-50 mg / ml per dose.

[0091] In some embodiments, the VEGF inhibitor is administered at a concentration selected from 0.05-40 mg / ml, 0.05-30 mg / ml, 0.1-20 mg / ml, or 0.1-10 mg / ml.

[0092] In some embodiments, the dose concentration of the VEGF inhibitor administered per dose is selected from 0.05 mg / ml, 0.1 mg / ml, 0.15 mg / ml, 0.2 mg / ml, 0.3 mg / ml, 0.4 mg / ml, 0.5 mg / ml, 0.6 mg / ml, 0.7 mg / ml, 0.8 mg / ml, 0.9 mg / ml, 1.0 mg / ml, 2.0 mg / ml, 3.0 mg / ml, 4.0 mg / ml, 5.0 mg / ml, 6.0 mg / ml, 7.0 mg / ml, 8.0 mg / ml, 9.0 mg / ml, 10.0 mg / ml, 15.0 mg / ml, 20.0 mg / ml, 25 mg / ml, 30 mg / ml, 35 mg / ml, 40 mg / ml, 45 mg / ml, and 50 mg / ml.

[0093] In some embodiments, the dose of the VEGF inhibitor (e.g., a single-dose dose or a unit dose) is selected from 0.1-1000 mg.

[0094] In some embodiments, the dose of the VEGF inhibitor (e.g., a single-dose dose or a unit dose) is selected from 0.1-900 mg, 0.1-800 mg, 0.1-700 mg, 0.1-600 mg, 0.1-500 mg, 0.1-400 mg, 0.1-300 mg, 0.1-200 mg, 0.1-100 mg, 0.1-50 mg, 0.1-30 mg, 0.1-20 mg, and 0.1-10 mg.

[0095] In some embodiments, the dose of the VEGF inhibitor (e.g., a single-dose dose or a unit dose) is selected from 0.1 mg, 1.0 mg, 2.0 mg, 3.0 mg, 4.0 mg, 5.0 mg, 6.0 mg, 7.0 mg, 8.0 mg, 9.0 mg, 10.0 mg, 15.0 mg, 20.0 mg, 25 mg, 30 mg, 35 mg, 40 mg, 45 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, 400 mg, 450 mg, and 500 mg.

[0096] In some implementations, the dose of the VEGF inhibitor is a single dose or a total dose for each dosing cycle.

[0097] In some embodiments, the dosing cycle of the EGFR inhibitor is 1-42 days. In some embodiments, the dosing cycle of the EGFR inhibitor is 7-42 days. In some embodiments, the dosing cycle of the EGFR inhibitor is 1 day, 7 days, 14 days, 21 days, 28 days, or 42 days. In some embodiments, the dosing cycle of the EGFR inhibitor is 1 day. In some embodiments, the dosing cycle of the EGFR inhibitor is 3 days. In some embodiments, the dosing cycle of the EGFR inhibitor is 7 days. In some embodiments, the dosing cycle of the EGFR inhibitor is 14 days. In some embodiments, the dosing cycle of the EGFR inhibitor is 21 days. In some embodiments, the dosing cycle of the EGFR inhibitor is 28 days.

[0098] In some embodiments, the EGFR inhibitor is administered 1 to 8 times over a period of 1 to 4 weeks. The EGFR inhibitor may be administered once a week, twice a week, once every 2 weeks, or once every 3 weeks.

[0099] In some implementations, the dose of the EGFR inhibitor administered per dose is selected from 0.5-50 mg / kg, based on the subject's weight.

[0100] In some implementations, the dose of the EGFR inhibitor administered per dose, based on the subject's weight, is selected from 0.5-40 mg / kg, 0.5-30 mg / kg, 0.5-20 mg / kg, 0.5-10 mg / kg, and 0.5-5 mg / kg.

[0101] In some implementations, the dose of the EGFR inhibitor administered per administration, based on the subject's weight, is selected from 0.5 mg / kg, 1 mg / kg, 1.5 mg / kg, 2 mg / kg, 2.5 mg / kg, 3 mg / kg, 3.5 mg / kg, 4 mg / kg, 4.5 mg / kg, 5 mg / kg, 5.5 mg / kg, 6 mg / kg, 6.5 mg / kg, 7 mg / kg, 7.5 mg / kg, 8 mg / kg, 8.5 mg / kg, 9 mg / kg, 9.5 mg / kg, 10 mg / kg, 15 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 35 mg / kg, 40 mg / kg, 45 mg / kg, or 50 mg / kg.

[0102] In some embodiments, the EGFR inhibitor is administered at a dose of 0.5 mg / kg, 1 mg / kg, 1.5 mg / kg, 2 mg / kg, 2.5 mg / kg, 3 mg / kg, 3.5 mg / kg, 4 mg / kg, 4.5 mg / kg, or 5 mg / kg, based on the subject's weight. In some embodiments, the EGFR inhibitor is administered at a dose of 1.0 mg / kg, based on the subject's weight. In some embodiments, the EGFR inhibitor is administered at a dose of 1.5 mg / kg, based on the subject's weight. In some embodiments, the EGFR inhibitor is administered at a dose of 2 mg / kg, based on the subject's weight. In some embodiments, the EGFR inhibitor is administered at a dose of 2.5 mg / kg, based on the subject's weight. In some embodiments, the EGFR inhibitor is administered at a dose of 3 mg / kg, based on the subject's weight. In some embodiments, the EGFR inhibitor is administered at a dose of 4 mg / kg, based on the subject's weight. In some embodiments, the EGFR inhibitor is administered at a dose of 5 mg / kg, based on the subject's weight. In some embodiments, the EGFR inhibitor is administered at a dose of 10 mg / kg per administration, based on the subject's weight. In some embodiments, the EGFR inhibitor is administered at a dose of 20 mg / kg per administration, based on the subject's weight.

[0103] In some embodiments, the dose of the EGFR inhibitor administered each time is selected from 0.5-50 mg / kg.

[0104] In some embodiments, the dose of the EGFR inhibitor administered per administration is selected from 0.5-40 mg / kg, 0.5-30 mg / kg, 0.5-20 mg / kg, 0.5-10 mg / kg, and 0.5-5 mg / kg.

[0105] In some embodiments, the dose of the EGFR inhibitor administered per administration is selected from 0.5 mg / kg, 1 mg / kg, 1.5 mg / kg, 2 mg / kg, 2.5 mg / kg, 3 mg / kg, 3.5 mg / kg, 4 mg / kg, 4.5 mg / kg, 5 mg / kg, 5.5 mg / kg, 6 mg / kg, 6.5 mg / kg, 7 mg / kg, 7.5 mg / kg, 8 mg / kg, 8.5 mg / kg, 9 mg / kg, 9.5 mg / kg, 10 mg / kg, 15 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 35 mg / kg, 40 mg / kg, 45 mg / kg, or 50 mg / kg.

[0106] In some embodiments, the EGFR inhibitor is administered at a dose of 0.5 mg / kg, 1 mg / kg, 1.5 mg / kg, 2 mg / kg, 2.5 mg / kg, 3 mg / kg, 3.5 mg / kg, 4 mg / kg, 4.5 mg / kg, or 5 mg / kg. In some embodiments, the EGFR inhibitor is administered at a dose of 1.0 mg / kg. In some embodiments, the EGFR inhibitor is administered at a dose of 1.5 mg / kg. In some embodiments, the EGFR inhibitor is administered at a dose of 2 mg / kg. In some embodiments, the EGFR inhibitor is administered at a dose of 2.5 mg / kg. In some embodiments, the EGFR inhibitor is administered at a dose of 3 mg / kg. In some embodiments, the EGFR inhibitor is administered at a dose of 4 mg / kg. In some embodiments, the EGFR inhibitor is administered at a dose of 5 mg / kg. In some embodiments, the EGFR inhibitor is administered at a dose of 10 mg / kg. In some embodiments, the EGFR inhibitor is administered at a dose of 20 mg / kg.

[0107] In some embodiments, the dose concentration of the EGFR inhibitor administered each time is selected from 0.05-50 mg / ml.

[0108] In some embodiments, the dose concentration of the EGFR inhibitor administered per dose is selected from 0.05-40 mg / ml, 0.05-30 mg / ml, 0.1-20 mg / ml, or 0.1-10 mg / ml.

[0109] In some embodiments, the dose concentration of the EGFR inhibitor administered per dose is selected from 0.05 mg / ml, 0.1 mg / ml, 0.15 mg / ml, 0.2 mg / ml, 0.3 mg / ml, 0.4 mg / ml, 0.5 mg / ml, 0.6 mg / ml, 0.7 mg / ml, 0.8 mg / ml, 0.9 mg / ml, 1.0 mg / ml, 2.0 mg / ml, 3.0 mg / ml, 4.0 mg / ml, 5.0 mg / ml, 6.0 mg / ml, 7.0 mg / ml, 8.0 mg / ml, 9.0 mg / ml, 10.0 mg / ml, 15.0 mg / ml, 20.0 mg / ml, 25 mg / ml, 30 mg / ml, 35 mg / ml, 40 mg / ml, 45 mg / ml, and 50 mg / ml.

[0110] In some embodiments, the dose of the EGFR inhibitor (e.g., a single-dose dose or a unit dose) is selected from 0.1-1000 mg.

[0111] In some embodiments, the dose of the EGFR inhibitor (e.g., a single-dose dose or a unit dose) is selected from 0.1-900 mg, 0.1-800 mg, 0.1-700 mg, 0.1-600 mg, 0.1-500 mg, 0.1-400 mg, 0.1-300 mg, 0.1-200 mg, 0.1-100 mg, 0.1-50 mg, 0.1-30 mg, 0.1-20 mg, and 0.1-10 mg.

[0112] In some embodiments, the dose of the EGFR inhibitor (e.g., a single-dose dose or a unit dose) is selected from 0.1 mg, 1.0 mg, 2.0 mg, 3.0 mg, 4.0 mg, 5.0 mg, 6.0 mg, 7.0 mg, 8.0 mg, 9.0 mg, 10.0 mg, 15.0 mg, 20.0 mg, 25 mg, 30 mg, 35 mg, 40 mg, 45 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, 400 mg, 450 mg, and 500 mg.

[0113] In some implementations, the dose of the EGFR inhibitor is a single dose or a total dose for each dosing cycle.

[0114] In some implementations, the treatment combination includes an anti-Trop-2 antibody-drug conjugate, and one or both of bevacizumab or a biosimilar thereof and an anti-EGFR antibody or a biosimilar thereof.

[0115] In some implementations, the bevacizumab biosimilar is selected from: MVASI, Zirabev, Bevax, Lumiere, Apotex, Equidacent, Avegra, BP 01, BCD500, Krabeva, BAT1706, BXT-2316, Bevalo, BI 695502, CT-P16, CHS-5217, DRZ BZ, Cizumab, Byvasda, MIL60, MYL 14020, ONS1045, HD204, Ankeda, Bevacizel, Aybintio, Onbevzi, HLX04, TX16, MB02, BI 695502, and Oyavas.

[0116] In some implementations, the anti-EGFR antibody and its biosimilar are selected from one or more of cetuximab, panitumumab, nexituzumab, nimotuzumab, Rybrevant, and Amivantamab.

[0117] In some implementations, the anti-EGFR antibody and its biosimilar are selected from cetuximab.

[0118] The dosing regimens for bevacizumab or its biosimilars, and cetuximab or its biosimilars, including dosing cycles, dosages, dosing frequencies, routes of administration, concentrations, dosing intervals, and dosages, are as described above for VEGF inhibitors and EGFR inhibitors. Adjustments to the specific dosing regimen are all within the scope of this application and may be made at levels lower or higher than those described in this application, depending on the patient's needs and response to treatment.

[0119] In some embodiments, the treatment combination may include the anti-Trop-2 antibody-drug conjugate and one or both of the EGFR inhibitor and VEGF inhibitor, and optionally other active therapeutic agents that can be administered simultaneously, separately, sequentially or in sequence.

[0120] The dosing cycle for the anti-Trop-2 antibody-drug conjugate is 1-42 days;

[0121] The anti-Trop-2 antibody-drug conjugate is administered 1-8 times over a period of 1-4 weeks;

[0122] Based on the subject's weight, the dose of the anti-Trop-2 antibody-drug conjugate administered per dose is selected from 0.1-20 mg / kg or more;

[0123] The dosage concentration of the anti-Trop-2 antibody-drug conjugate administered each time is selected from 0.01-50 mg / ml;

[0124] The dosage of the anti-Trop-2 antibody drug conjugate (e.g., a single-dose dose or a unit dose) is selected from 0.1-1000 mg;

[0125] The dosing cycle for the VEGF inhibitor is 1-42 days;

[0126] The VEGF inhibitor is administered 1-8 times over a period of 1-4 weeks;

[0127] Based on the subject's weight, the dose of the VEGF inhibitor administered each time is selected from 0.5-50 mg / kg;

[0128] The dosage concentration of the VEGF inhibitor administered each time is selected from 0.05-50 mg / ml;

[0129] The dosage of the VEGF inhibitor (e.g., a single-dose dose or a unit dose) is selected from 0.1-1000 mg;

[0130] The dosing cycle for the EGFR inhibitor is 1-42 days;

[0131] The EGFR inhibitor is administered 1-8 times over a period of 1-4 weeks;

[0132] Based on the subject's weight, the dose of the EGFR inhibitor administered each time is selected from 0.5-50 mg / kg;

[0133] The dosage concentration of the EGFR inhibitor administered each time is selected from 0.05-50 mg / ml;

[0134] The dosage of the EGFR inhibitor (e.g., a single-dose dose or a unit dose) is selected from 0.1-1000 mg;

[0135] The anti-Trop-2 antibody-drug conjugate, VEGF inhibitor, and / or EGFR inhibitor may be administered simultaneously, within one day, or at intervals of at least 1, 2, 3, 5, 6, 7, 10, 15, 21, 30, 45, 2 months, 75, 3 months, or 6 months.

[0136] In some embodiments, the treatment combination may include the anti-Trop-2 antibody-drug conjugate and one or both of the EGFR inhibitor and VEGF inhibitor, and optionally other active therapeutic agents that can be administered simultaneously, separately, sequentially or in sequence.

[0137] The dosing cycle of the anti-Trop-2 antibody-drug conjugate is 1-21 days, for example, 1-14 days;

[0138] The anti-Trop-2 antibody-drug conjugate is administered 1-4 times over a period of 1-2 weeks, for example, once a week or once every 2 weeks.

[0139] Based on the subject's weight, the dose of the anti-Trop-2 antibody-drug conjugate administered per dose is selected from 0.5-10 mg / kg, for example 0.5-5 mg / kg, for example 3-5 mg / kg, for example 3 mg / kg, 4 mg / kg or 5 mg / kg;

[0140] The dosage concentration of the anti-Trop-2 antibody-drug conjugate administered each time is selected from 0.05-50 mg / ml;

[0141] The single-dose dose of the anti-Trop-2 antibody-drug conjugate is selected from 100-500 mg;

[0142] The dosing cycle of the VEGF inhibitor is 1-28 days, for example 1-14 days or 1-21 days;

[0143] The VEGF inhibitor is administered 1-4 times over a period of 1-2 weeks, for example, once a week or twice a week.

[0144] Based on the subject's weight, the dose of the VEGF inhibitor administered each time is selected from 0.5-30 mg / kg, for example 0.5-20 mg / kg, 0.5-10 mg / kg or 0.5-5 mg / kg;

[0145] The dosage concentration of the VEGF inhibitor administered each time is selected from 1-20 mg / ml;

[0146] The single-dose dose of the VEGF inhibitor is selected from 0.1-1000 mg;

[0147] The dosing cycle of the EGFR inhibitor is 1-42 days, for example 1-14 days, 1-21 days or 1-28 days;

[0148] The EGFR inhibitor is administered 1-4 times over a period of 1-2 weeks, for example, once a week, once every 2 weeks, twice a week, or once every 3 weeks.

[0149] Based on the subject's weight, the dose of the EGFR inhibitor administered each time is selected from 0.5-30 mg / kg, for example 0.5-20 mg / kg, 0.5-10 mg / kg or 0.5-5 mg / kg;

[0150] The dosage concentration of the EGFR inhibitor administered each time is selected from 0.05-50 mg / ml;

[0151] The single-dose dose of the EGFR inhibitor is selected from 0.1-1000 mg, for example 1-900 mg, 1-800 mg, 1-700 mg, 1-600 mg, 1-500 mg, 1-400 mg, 1-300 mg, 1-200 mg, 1-100 mg, 1-50 mg, 1-30 mg, 1-20 mg or 1-10 mg;

[0152] The anti-Trop-2 antibody-drug conjugate, VEGF inhibitor, and / or EGFR inhibitor may be administered simultaneously, within one day, or at intervals of at least 1, 2, 3, 5, 6, 7, 10, 15, 21, 30, 45, 2 months, 75, 3 months, or 6 months.

[0153] In some embodiments, the anti-Trop-2 antibody drug conjugate, VEGF inhibitor, and / or EGFR inhibitor can be administered simultaneously or within one day, for example, the anti-Trop-2 antibody drug conjugate, VEGF inhibitor, and / or EGFR inhibitor can be administered separately, sequentially, or sequentially at intervals of 0.5-2 hours.

[0154] In some implementations, the anti-Trop-2 antibody-drug conjugate and the EGFR inhibitor in the treatment combination can be administered simultaneously, separately, sequentially, or in sequence.

[0155] The dosing cycle for the anti-Trop-2 antibody-drug conjugate is 1-42 days;

[0156] The anti-Trop-2 antibody-drug conjugate is administered 1-8 times over a period of 1-4 weeks;

[0157] Based on the subject's weight, the dose of the anti-Trop-2 antibody-drug conjugate administered per dose is selected from 0.1-20 mg / kg or more;

[0158] The dosage concentration of the anti-Trop-2 antibody-drug conjugate administered each time is selected from 0.01-50 mg / ml;

[0159] The dosage of the anti-Trop-2 antibody drug conjugate (e.g., a single-dose dose or a unit dose) is selected from 0.1-1000 mg;

[0160] The dosing cycle for the EGFR inhibitor is 1-42 days;

[0161] The EGFR inhibitor is administered 1-8 times over a period of 1-4 weeks;

[0162] Based on the subject's weight, the dose of the EGFR inhibitor administered each time is selected from 0.5-50 mg / kg;

[0163] The dosage concentration of the EGFR inhibitor administered each time is selected from 0.05-50 mg / ml;

[0164] The dosage of the EGFR inhibitor (e.g., a single-dose dose or a unit dose) is selected from 0.1-1000 mg;

[0165] The anti-Trop-2 antibody-drug conjugate and the EGFR inhibitor can be administered simultaneously, within 1 day, or at intervals of at least 1 day, 2 days, 3 days, 5 days, 6 days, 7 days, 10 days, 15 days, 21 days, 30 days, 45 days, 2 months, 75 days, 3 months, or 6 months.

[0166] In some implementations, the anti-Trop-2 antibody-drug conjugate and the VEGF inhibitor can be administered simultaneously, separately, sequentially, or in combination.

[0167] The dosing cycle for the anti-Trop-2 antibody-drug conjugate is 1-42 days;

[0168] The anti-Trop-2 antibody-drug conjugate is administered 1-8 times over a period of 1-4 weeks;

[0169] Based on the subject's weight, the dose of the anti-Trop-2 antibody-drug conjugate administered per dose is selected from 0.1-20 mg / kg or more;

[0170] The dosage concentration of the anti-Trop-2 antibody-drug conjugate administered each time is selected from 0.01-50 mg / ml;

[0171] The dosage of the anti-Trop-2 antibody drug conjugate (e.g., a single-dose dose or a unit dose) is selected from 0.1-1000 mg;

[0172] The dosing cycle for the VEGF inhibitor is 1-42 days;

[0173] The VEGF inhibitor is administered 1-8 times over a period of 1-4 weeks;

[0174] Based on the subject's weight, the dose of the VEGF inhibitor administered each time is selected from 0.5-50 mg / kg;

[0175] The dosage concentration of the VEGF inhibitor administered each time is selected from 0.05-50 mg / ml;

[0176] The dosage of the VEGF inhibitor (e.g., a single-dose dose or a unit dose) is selected from 0.1-1000 mg;

[0177] The anti-Trop-2 antibody-drug conjugate and the VEGF inhibitor can be administered simultaneously, within one day, or at intervals of at least 1 day, 2 days, 3 days, 5 days, 6 days, 7 days, 10 days, 15 days, 21 days, 30 days, 45 days, 2 months, 75 days, 3 months, or 6 months.

[0178] In some embodiments, the treatment combination may include the anti-Trop-2 antibody-drug conjugate and one or both of the EGFR inhibitor and VEGF inhibitor, and optionally other active therapeutic agents that can be administered simultaneously, separately, sequentially or in sequence.

[0179] The dosing cycle of the anti-Trop-2 antibody-drug conjugate is 1 day, 3 days, 7 days, 14 days, 21 days, 28 days or 42 days;

[0180] The anti-Trop-2 antibody-drug conjugate is administered once a week, twice a week, once every two weeks, or once every three weeks.

[0181] Based on the subject's weight, the dose of the anti-Trop-2 antibody-drug conjugate administered per dose is selected from 0.5 mg / kg, 1 mg / kg, 2 mg / kg, 2.5 mg / kg, 3 mg / kg, 3.5 mg / kg, 4 mg / kg, 4.5 mg / kg, 5 mg / kg, 5.5 mg / kg, 6 mg / kg, 6.5 mg / kg, 7 mg / kg, 7.5 mg / kg, 8 mg / kg, 8.5 mg / kg, 9 mg / kg, 9.5 mg / kg, or 10 mg / kg;

[0182] The dosage concentration of the anti-Trop-2 antibody-drug conjugate administered at each dose is selected from 0.01 mg / ml, 0.03 mg / ml, 0.05 mg / ml, 0.06 mg / ml, 0.1 mg / ml, 0.3 mg / ml, 0.5 mg / ml, 0.6 mg / ml, 0.7 mg / ml, 0.8 mg / ml, 0.9 mg / ml, 1.0 mg / ml, 2.0 mg / ml, 3.0 mg / ml, 4.0 mg / ml, 5.0 mg / ml, 6.0 mg / ml, 7.0 mg / ml, 8.0 mg / ml, 9.0 mg / ml, 10.0 mg / ml, 15.0 mg / ml, 20.0 mg / ml, 25 mg / ml, 30 mg / ml, 35 mg / ml, 40 mg / ml, 45 mg / ml, and 50 mg / ml.

[0183] The dosage (e.g., single-dose dose or unit dose) of the anti-Trop-2 antibody-drug conjugate is selected from 0.1 mg, 1.0 mg, 2.0 mg, 3.0 mg, 4.0 mg, 5.0 mg, 6.0 mg, 7.0 mg, 8.0 mg, 9.0 mg, 10.0 mg, 15.0 mg, 20.0 mg, 25 mg, 30 mg, 35 mg, 40 mg, 45 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, 400 mg, 450 mg, and 500 mg.

[0184] The dosing cycle of the VEGF inhibitor is 1 day, 7 days, 14 days, 21 days, 28 days or 42 days;

[0185] The VEGF inhibitor is administered once a week, twice a week, once every two weeks, or once every three weeks.

[0186] Based on the subject's weight, the dose of the VEGF inhibitor administered each time is selected from 0.5 mg / kg, 1 mg / kg, 1.5 mg / kg, 2 mg / kg, 2.5 mg / kg, 3 mg / kg, 3.5 mg / kg, 4 mg / kg, 4.5 mg / kg, 5 mg / kg, 5.5 mg / kg, 6 mg / kg, 6.5 mg / kg, 7 mg / kg, 7.5 mg / kg, 8 mg / kg, 8.5 mg / kg, 9 mg / kg, 9.5 mg / kg, 10 mg / kg, 15 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 35 mg / kg, 40 mg / kg, 45 mg / kg, or 50 mg / kg;

[0187] The VEGF inhibitor is administered at a concentration selected from 0.05 mg / ml, 0.1 mg / ml, 0.15 mg / ml, 0.2 mg / ml, 0.3 mg / ml, 0.4 mg / ml, 0.5 mg / ml, 0.6 mg / ml, 0.7 mg / ml, 0.8 mg / ml, 0.9 mg / ml, 1.0 mg / ml, 2.0 mg / ml, 3.0 mg / ml, 4.0 mg / ml, 5.0 mg / ml, 6.0 mg / ml, 7.0 mg / ml, 8.0 mg / ml, 9.0 mg / ml, 10.0 mg / ml, 15.0 mg / ml, 20.0 mg / ml, 25 mg / ml, 30 mg / ml, 35 mg / ml, 40 mg / ml, 45 mg / ml, and 50 mg / ml.

[0188] The dosage of the VEGF inhibitor per dosing cycle (e.g., a single-dose dose or a unit dose) is selected from 0.1 mg, 1.0 mg, 2.0 mg, 3.0 mg, 4.0 mg, 5.0 mg, 6.0 mg, 7.0 mg, 8.0 mg, 9.0 mg, 10.0 mg, 15.0 mg, 20.0 mg, 25 mg, 30 mg, 35 mg, 40 mg, 45 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, 400 mg, 450 mg, and 500 mg.

[0189] The dosing cycle of the EGFR inhibitor is 1 day, 7 days, 14 days, 21 days, 28 days or 42 days;

[0190] The EGFR inhibitor is administered once a week, twice a week, once every two weeks, or once every three weeks.

[0191] Based on the subject's weight, the dose of the EGFR inhibitor administered each time is selected from 0.5 mg / kg, 1 mg / kg, 1.5 mg / kg, 2 mg / kg, 2.5 mg / kg, 3 mg / kg, 3.5 mg / kg, 4 mg / kg, 4.5 mg / kg, 5 mg / kg, 5.5 mg / kg, 6 mg / kg, 6.5 mg / kg, 7 mg / kg, 7.5 mg / kg, 8 mg / kg, 8.5 mg / kg, 9 mg / kg, 9.5 mg / kg, 10 mg / kg, 15 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 35 mg / kg, 40 mg / kg, 45 mg / kg, or 50 mg / kg;

[0192] The EGFR inhibitor is administered at a concentration selected from 0.05 mg / ml, 0.1 mg / ml, 0.15 mg / ml, 0.2 mg / ml, 0.3 mg / ml, 0.4 mg / ml, 0.5 mg / ml, 0.6 mg / ml, 0.7 mg / ml, 0.8 mg / ml, 0.9 mg / ml, 1.0 mg / ml, 2.0 mg / ml, 3.0 mg / ml, 4.0 mg / ml, 5.0 mg / ml, 6.0 mg / ml, 7.0 mg / ml, 8.0 mg / ml, 9.0 mg / ml, 10.0 mg / ml, 15.0 mg / ml, 20.0 mg / ml, 25 mg / ml, 30 mg / ml, 35 mg / ml, 40 mg / ml, 45 mg / ml, and 50 mg / ml.

[0193] The dosage of the EGFR inhibitor (e.g., a single-dose dose or a unit dose) is selected from 0.1 mg, 1.0 mg, 2.0 mg, 3.0 mg, 4.0 mg, 5.0 mg, 6.0 mg, 7.0 mg, 8.0 mg, 9.0 mg, 10.0 mg, 15.0 mg, 20.0 mg, 25 mg, 30 mg, 35 mg, 40 mg, 45 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, 400 mg, 450 mg, and 500 mg;

[0194] The anti-Trop-2 antibody-drug conjugate, VEGF inhibitor, and / or EGFR inhibitor may be administered simultaneously, within one day, or at intervals of at least 1, 2, 3, 5, 6, 7, 10, 15, 21, 30, 45, 2 months, 75, 3 months, or 6 months.

[0195] In some implementations, the anti-Trop-2 antibody-drug conjugate and the EGFR inhibitor in the treatment combination can be administered simultaneously, separately, sequentially, or in combination.

[0196] The dosing cycle of the anti-Trop-2 antibody-drug conjugate is 1 day, 3 days, 7 days, 14 days, 21 days, 28 days or 42 days;

[0197] The anti-Trop-2 antibody-drug conjugate is administered once a week, twice a week, once every two weeks, or once every three weeks.

[0198] Based on the subject's weight, the dose of the anti-Trop-2 antibody-drug conjugate administered per dose is selected from 0.5 mg / kg, 1 mg / kg, 2 mg / kg, 2.5 mg / kg, 3 mg / kg, 3.5 mg / kg, 4 mg / kg, 4.5 mg / kg, 5 mg / kg, 5.5 mg / kg, 6 mg / kg, 6.5 mg / kg, 7 mg / kg, 7.5 mg / kg, 8 mg / kg, 8.5 mg / kg, 9 mg / kg, 9.5 mg / kg, or 10 mg / kg;

[0199] The dosage concentration of the anti-Trop-2 antibody-drug conjugate administered at each dose is selected from 0.01 mg / ml, 0.03 mg / ml, 0.05 mg / ml, 0.06 mg / ml, 0.1 mg / ml, 0.3 mg / ml, 0.5 mg / ml, 0.6 mg / ml, 0.7 mg / ml, 0.8 mg / ml, 0.9 mg / ml, 1.0 mg / ml, 2.0 mg / ml, 3.0 mg / ml, 4.0 mg / ml, 5.0 mg / ml, 6.0 mg / ml, 7.0 mg / ml, 8.0 mg / ml, 9.0 mg / ml, 10.0 mg / ml, 15.0 mg / ml, 20.0 mg / ml, 25 mg / ml, 30 mg / ml, 35 mg / ml, 40 mg / ml, 45 mg / ml, and 50 mg / ml.

[0200] The dosage (e.g., single-dose dose or unit dose) of the anti-Trop-2 antibody-drug conjugate is selected from 0.1 mg, 1.0 mg, 2.0 mg, 3.0 mg, 4.0 mg, 5.0 mg, 6.0 mg, 7.0 mg, 8.0 mg, 9.0 mg, 10.0 mg, 15.0 mg, 20.0 mg, 25 mg, 30 mg, 35 mg, 40 mg, 45 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, 400 mg, 450 mg, and 500 mg.

[0201] The dosing cycle of the EGFR inhibitor is 1 day, 7 days, 14 days, 21 days, 28 days or 42 days;

[0202] The EGFR inhibitor is administered once a week, twice a week, once every two weeks, or once every three weeks.

[0203] Based on the subject's weight, the dose of the EGFR inhibitor administered each time is selected from 0.5 mg / kg, 1 mg / kg, 1.5 mg / kg, 2 mg / kg, 2.5 mg / kg, 3 mg / kg, 3.5 mg / kg, 4 mg / kg, 4.5 mg / kg, 5 mg / kg, 5.5 mg / kg, 6 mg / kg, 6.5 mg / kg, 7 mg / kg, 7.5 mg / kg, 8 mg / kg, 8.5 mg / kg, 9 mg / kg, 9.5 mg / kg, 10 mg / kg, 15 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 35 mg / kg, 40 mg / kg, 45 mg / kg, or 50 mg / kg;

[0204] The EGFR inhibitor is administered at a concentration selected from 0.05 mg / ml, 0.1 mg / ml, 0.15 mg / ml, 0.2 mg / ml, 0.3 mg / ml, 0.4 mg / ml, 0.5 mg / ml, 0.6 mg / ml, 0.7 mg / ml, 0.8 mg / ml, 0.9 mg / ml, 1.0 mg / ml, 2.0 mg / ml, 3.0 mg / ml, 4.0 mg / ml, 5.0 mg / ml, 6.0 mg / ml, 7.0 mg / ml, 8.0 mg / ml, 9.0 mg / ml, 10.0 mg / ml, 15.0 mg / ml, 20.0 mg / ml, 25 mg / ml, 30 mg / ml, 35 mg / ml, 40 mg / ml, 45 mg / ml, and 50 mg / ml.

[0205] The dosage of the EGFR inhibitor (e.g., a single-dose dose or a unit dose) is selected from 0.1 mg, 1.0 mg, 2.0 mg, 3.0 mg, 4.0 mg, 5.0 mg, 6.0 mg, 7.0 mg, 8.0 mg, 9.0 mg, 10.0 mg, 15.0 mg, 20.0 mg, 25 mg, 30 mg, 35 mg, 40 mg, 45 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, 400 mg, 450 mg, and 500 mg;

[0206] The anti-Trop-2 antibody-drug conjugate and the EGFR inhibitor can be administered simultaneously, within 1 day, or at intervals of at least 1 day, 2 days, 3 days, 5 days, 6 days, 7 days, 10 days, 15 days, 21 days, 30 days, 45 days, 2 months, 75 days, 3 months, or 6 months.

[0207] In some implementations, the anti-Trop-2 antibody-drug conjugate and the VEGF inhibitor can be administered simultaneously, separately, sequentially, or in combination.

[0208] The dosing cycle of the anti-Trop-2 antibody-drug conjugate is 1 day, 3 days, 7 days, 14 days, 21 days, 28 days or 42 days;

[0209] The anti-Trop-2 antibody-drug conjugate is administered once a week, twice a week, once every two weeks, or once every three weeks.

[0210] Based on the subject's weight, the dose of the anti-Trop-2 antibody-drug conjugate administered per dose is selected from 0.5 mg / kg, 1 mg / kg, 2 mg / kg, 2.5 mg / kg, 3 mg / kg, 3.5 mg / kg, 4 mg / kg, 4.5 mg / kg, 5 mg / kg, 5.5 mg / kg, 6 mg / kg, 6.5 mg / kg, 7 mg / kg, 7.5 mg / kg, 8 mg / kg, 8.5 mg / kg, 9 mg / kg, 9.5 mg / kg, or 10 mg / kg;

[0211] The dosage concentration of the anti-Trop-2 antibody-drug conjugate administered at each dose is selected from 0.01 mg / ml, 0.03 mg / ml, 0.05 mg / ml, 0.06 mg / ml, 0.1 mg / ml, 0.3 mg / ml, 0.5 mg / ml, 0.6 mg / ml, 0.7 mg / ml, 0.8 mg / ml, 0.9 mg / ml, 1.0 mg / ml, 2.0 mg / ml, 3.0 mg / ml, 4.0 mg / ml, 5.0 mg / ml, 6.0 mg / ml, 7.0 mg / ml, 8.0 mg / ml, 9.0 mg / ml, 10.0 mg / ml, 15.0 mg / ml, 20.0 mg / ml, 25 mg / ml, 30 mg / ml, 35 mg / ml, 40 mg / ml, 45 mg / ml, and 50 mg / ml.

[0212] The dosage (e.g., single-dose dose or unit dose) of the anti-Trop-2 antibody-drug conjugate is selected from 0.1 mg, 1.0 mg, 2.0 mg, 3.0 mg, 4.0 mg, 5.0 mg, 6.0 mg, 7.0 mg, 8.0 mg, 9.0 mg, 10.0 mg, 15.0 mg, 20.0 mg, 25 mg, 30 mg, 35 mg, 40 mg, 45 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, 400 mg, 450 mg, and 500 mg.

[0213] The dosing cycle of the VEGF inhibitor is 1 day, 7 days, 14 days, 21 days, 28 days or 42 days;

[0214] The VEGF inhibitor is administered once a week, twice a week, once every two weeks, or once every three weeks.

[0215] Based on the subject's weight, the dose of the VEGF inhibitor administered each time is selected from 0.5 mg / kg, 1 mg / kg, 1.5 mg / kg, 2 mg / kg, 2.5 mg / kg, 3 mg / kg, 3.5 mg / kg, 4 mg / kg, 4.5 mg / kg, 5 mg / kg, 5.5 mg / kg, 6 mg / kg, 6.5 mg / kg, 7 mg / kg, 7.5 mg / kg, 8 mg / kg, 8.5 mg / kg, 9 mg / kg, 9.5 mg / kg, 10 mg / kg, 15 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 35 mg / kg, 40 mg / kg, 45 mg / kg, or 50 mg / kg;

[0216] The VEGF inhibitor is administered at a concentration selected from 0.05 mg / ml, 0.1 mg / ml, 0.15 mg / ml, 0.2 mg / ml, 0.3 mg / ml, 0.4 mg / ml, 0.5 mg / ml, 0.6 mg / ml, 0.7 mg / ml, 0.8 mg / ml, 0.9 mg / ml, 1.0 mg / ml, 2.0 mg / ml, 3.0 mg / ml, 4.0 mg / ml, 5.0 mg / ml, 6.0 mg / ml, 7.0 mg / ml, 8.0 mg / ml, 9.0 mg / ml, 10.0 mg / ml, 15.0 mg / ml, 20.0 mg / ml, 25 mg / ml, 30 mg / ml, 35 mg / ml, 40 mg / ml, 45 mg / ml, and 50 mg / ml.

[0217] The dosage of the VEGF inhibitor (e.g., a single-dose dose or a unit dose) is selected from 0.1 mg, 1.0 mg, 2.0 mg, 3.0 mg, 4.0 mg, 5.0 mg, 6.0 mg, 7.0 mg, 8.0 mg, 9.0 mg, 10.0 mg, 15.0 mg, 20.0 mg, 25 mg, 30 mg, 35 mg, 40 mg, 45 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, 400 mg, 450 mg, and 500 mg;

[0218] The anti-Trop-2 antibody-drug conjugate and the VEGF inhibitor can be administered simultaneously, within one day, or at intervals of at least 1 day, 2 days, 3 days, 5 days, 6 days, 7 days, 10 days, 15 days, 21 days, 30 days, 45 days, 2 months, 75 days, 3 months, or 6 months.

[0219] In some embodiments, the anti-Trop-2 antibody drug conjugate has the structure of the following formula (I): {D-[L1-(L2)m1-(L3)m2-(L4)m3-E]} q -A formula (I)

[0220] in,

[0221] L1 is Each of R1 and R2 is independently hydrogen, halogen, carboxylic acid group, sulfonic acid group, cyano group, C 1-6 Alkyl, Halogenated C 1-6 alkyl and cyano substituted C 1-6 Alkyl, C 1-6 Alkoxy, C 2-10 alkenyl or C 2-10 Alkyne group; Z1 is an amino acid or a peptide composed of 2-10 amino acids; x1 and x2 are each independently 0, 1, 2, 3, 4, 5 or 6; and L1 is connected to D at position 1 and L2 at position 2.

[0222] L2 is Where y1 is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; and L2 is connected to L1 at position 1 and L2 is connected to L3 at position 2.

[0223] L3 is a 5-12 member heterocyclic aromatic ring;

[0224] L4 is Z2 is selected from C. 1-6 Alkylene, C 2-10 imidene group, C 2-10 etyne group, and C 3-8Cycloalkylene; R3 is selected from H and C 1-6 Alkyl group; Z3 is absent or is C 1-6 Alkylene; or, R3 and Z3 together with the nitrogen atom to which they are attached form a 4-8 membered heterocyclic group; α is 0, 1, 2, 3, 4, 5 or 6, and L4 is attached to E at the 2 position and to L3 at the 1 position;

[0225] E is In this case, each R4 is independently hydrogen, β is 0, 1 or 2, and the 2 position of E is connected to A, and the 1 position of E is connected to L4.

[0226] m1, m2 and m3 are each independently 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;

[0227] D represents a bioactive molecular fragment;

[0228] q refers to {D-[L1-(L2]} which forms a thioether bond with the thiol group of A. m1 -(L3) m2 -(L4) m3 The number of the -E]} part is selected from 1 to 10;

[0229] A represents an anti-Trop-2 antibody or its antigen-binding fragment.

[0230] In some implementations, in the structure of formula (I),

[0231] L1 is Each of R1 and R2 is independently protium or deuterium, halogen, carboxylic acid group, sulfonic acid group, cyano group, or C. 1-6 Alkyl, Halogenated C 1-6 Alkyl group, -CH2CN, C 1-6 Alkoxy, C 2-10 alkenyl or C 2-10 Alkyne group; Z1 is an amino acid or a peptide composed of 2-10 amino acids; x1 and x2 are each independently 0, 1, 2, 3, 4, 5 or 6; and L1 is connected to D at position 1 and L2 at position 2.

[0232] L2 is Where y1 is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; and L2 is connected to L1 at position 1 and L2 is connected to L3 at position 2.

[0233] L3 is a 5-12 member heterocyclic aromatic ring;

[0234] L4 is Z2 is selected from C. 1-6 Alkylene, C 2-10 imidene group, C 2-10etyne group, and C 3-8 Cycloalkylene; R3 is selected from H and C 1-6 Alkyl group; Z3 is absent or is C 1-6 Alkylene; or, R3 and Z3 together with the nitrogen atom to which they are attached form a 4-8 membered heterocyclic group; α is 0, 1, 2, 3, 4, 5 or 6, and L4 is attached to E at the 2 position and to L3 at the 1 position;

[0235] E is In this context, each R4 is independently protium or deuterium, β is 0, 1 or 2, and position 2 of E is connected to A, and position 1 of E is connected to L4.

[0236] m1, m2 and m3 are each independently 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;

[0237] D represents a bioactive molecular fragment;

[0238] q refers to {D-[L1-(L2]} which forms a thioether bond with the thiol group of A. m1 -(L3) m2 -(L4) m3 The number of the -E]} part is selected from 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;

[0239] A represents an anti-Trop-2 antibody or its antigen-binding fragment.

[0240] In some embodiments, the anti-Trop-2 antibody-drug conjugate meets one or more of the following characteristics:

[0241] (1) L1 is selected from Furthermore, position 1 of L1 is connected to D, and position 2 of L1 is connected to L2;

[0242] (2) L2 is Where y1 is 3, 4, 5, 6, 7, 8, 9 or 10; and L2 is connected to L1 at position 1 and L2 is connected to L3 at position 2.

[0243] (3) L3 is selected from 5-6 member heterocyclic aromatic rings;

[0244] (4) L4 is Z2 is selected from C. 1-3 Alkylene; R3 is H; Z3 is selected from C 1-3 Alkylene; α is 0 or 1, and L4 is connected to E at position 2 and to L3 at position 1;

[0245] (5) E is In this case, each R4 is independently hydrogen, β is 0, 1 or 2, and the 2 position of E is connected to A, and the 1 position of E is connected to L4.

[0246] (6) m1, m2 and m3 are all 1;

[0247] (7) The bioactive molecules are selected from

[0248] (8) q is selected from 3-8, 4-8, 5-8, 6-8, or 7-8; and / or,

[0249] (9) A is Sacituzumab or its antigen-binding fragment.

[0250] In some embodiments, the anti-Trop-2 antibody-drug conjugate meets one or more of the following characteristics:

[0251] (1) L1 is selected from Furthermore, position 1 of L1 is connected to D, and position 2 of L1 is connected to L2;

[0252] (2) L2 is Where y1 is 3, 4, 5, 6, 7, 8, 9 or 10; and L2 is connected to L1 at position 1 and L2 is connected to L3 at position 2.

[0253] (3) L3 is selected from pyrazole or triazole;

[0254] (4) L4 is Z2 is selected from C. 1-3 Alkylene; R3 is H; Z3 is selected from C 1-3 Alkylene; α is 0 or 1, and L4 is connected to E at position 2 and to L3 at position 1;

[0255] (5) E is In this case, each R4 is independently protium or deuterium, β is 0, 1 or 2, and the 2 position of E is connected to the thiol group on A, and the 1 position of E is connected to L4.

[0256] (6) m1, m2 and m3 are all 1;

[0257] (7) D is selected from

[0258] (8) q is selected from 3-8, 4-8, 5-8, 6-8, or 7-8; and / or,

[0259] (9) A is Sacituzumab or its antigen-binding fragment.

[0260] In some embodiments, the anti-Trop-2 antibody-drug conjugate has the following chemical structure:

[0261] Where A is an anti-Trop-2 antibody or its antigen-binding fragment; q is selected from 1-10.

[0262] In some implementations, q is selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.

[0263] In some implementations, q is selected from 3-8, 4-8, 5-8, 6-8, or 7-8.

[0264] In some implementations, q is selected from 3, 4, 5, 6, 7, or 8.

[0265] In some implementations, the DAR value of the anti-Trop-2 antibody-drug conjugate is approximately 1-10.

[0266] In some embodiments, the DAR value of the anti-Trop-2 antibody-drug conjugate is an integer or decimal of 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3, 1-2, 2-10, 2-9, 2-8, 2-7, 2-6, 2-5, 2-4, 2-3, 3-10, 3-9, 3-8, 3-7, 3-6, 3-5, 3-4, 4-10, 4-9, 4-8, 4-7, 4-6, 4-5, 5-10, 5-9, 5-8, 5-7, 5-6, 6-10, 6-9, 6-8, 6-7, 7-10, 7-9, 7-8, 8-10, 8-9, or 9-10.

[0267] In some implementations, the DAR value of the anti-Trop-2 antibody-drug conjugate is 3-8.

[0268] In some implementations, the DAR value of the anti-Trop-2 antibody-drug conjugate is 4-8.

[0269] In some implementations, the DAR value of the anti-Trop-2 antibody-drug conjugate is 5-8.

[0270] In some implementations, the DAR value of the anti-Trop-2 antibody-drug conjugate is 6-8.

[0271] In some implementations, the DAR value of the anti-Trop-2 antibody-drug conjugate is 7-8.

[0272] In some embodiments, the DAR value of the anti-Trop-2 antibody-drug conjugate is approximately 5.0, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6.0, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, 7.0, 7.1, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, or 8.0.

[0273] In some embodiments, the DAR value of the anti-Trop-2 antibody-drug conjugate is 5.0, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6.0, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, 7.0, 7.1, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, or 8.0.

[0274] In some embodiments, the anti-Trop-2 antibody or its antigen-binding fragment comprises:

[0275] The following are the variable regions (VH) of heavy chains and / or variable regions (VL) of light chains, as defined in the Chothia numbering system:

[0276] Heavy chain variable region (VH) containing the following 3 CDRs: CDR-H1 with sequence of SEQ ID NO:1 or a variant thereof, CDR-H2 with sequence of SEQ ID NO:2 or a variant thereof, and CDR-H3 with sequence of SEQ ID NO:3 or a variant thereof; and / or, light chain variable region (VL) containing the following 3 CDRs: CDR-L1 with sequence of SEQ ID NO:4 or a variant thereof, CDR-L2 with sequence of SEQ ID NO:5 or a variant thereof, and CDR-L3 with sequence of SEQ ID NO:6 or a variant thereof;

[0277] The variant has at least 70%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with the sequence from which it is derived, or the variant has one or more amino acid substitutions, deletions, or additions compared to the sequence from which it is derived;

[0278] or,

[0279] The following are the variable regions (VH) of heavy chains and / or variable regions (VL) of light chains, defined according to the AbM numbering system:

[0280] Heavy chain variable region (VH) containing the following 3 CDRs: CDR-H1 with sequence of SEQ ID NO:14 or a variant thereof, CDR-H2 with sequence of SEQ ID NO:15 or a variant thereof, and CDR-H3 with sequence of SEQ ID NO:3 or a variant thereof; and / or, light chain variable region (VL) containing the following 3 CDRs: CDR-L1 with sequence of SEQ ID NO:4 or a variant thereof, CDR-L2 with sequence of SEQ ID NO:5 or a variant thereof, and CDR-L3 with sequence of SEQ ID NO:6 or a variant thereof;

[0281] The variant has at least 70%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with the sequence from which it is derived, or the variant has one or more amino acid substitutions, deletions, or additions compared to the sequence from which it is derived;

[0282] or,

[0283] The following are the variable regions (VH) of heavy chains and / or variable regions (VL) of light chains, as defined in the Kabat numbering system:

[0284] Heavy chain variable region (VH) containing the following 3 CDRs: CDR-H1 with sequence of SEQ ID NO:7 or a variant thereof, CDR-H2 with sequence of SEQ ID NO:8 or a variant thereof, and CDR-H3 with sequence of SEQ ID NO:3 or a variant thereof; and / or, light chain variable region (VL) containing the following 3 CDRs: CDR-L1 with sequence of SEQ ID NO:4 or a variant thereof, CDR-L2 with sequence of SEQ ID NO:5 or a variant thereof, and CDR-L3 with sequence of SEQ ID NO:6 or a variant thereof;

[0285] The variant has at least 70%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with the sequence from which it is derived, or the variant has one or more amino acid substitutions, deletions, or additions compared to the sequence from which it is derived;

[0286] or,

[0287] The following are the variable regions (VH) of heavy chains and / or variable regions (VL) of light chains, as defined in the IMGT numbering system:

[0288] Heavy chain variable region (VH) containing the following 3 CDRs: CDR-H1 with sequence of SEQ ID NO:9 or a variant thereof, CDR-H2 with sequence of SEQ ID NO:10 or a variant thereof, and CDR-H3 with sequence of SEQ ID NO:11 or a variant thereof; and / or, light chain variable region (VL) containing the following 3 CDRs: CDR-L1 with sequence of SEQ ID NO:12 or a variant thereof, CDR-L2 with sequence of SEQ ID NO:13 or a variant thereof, and CDR-L3 with sequence of SEQ ID NO:6 or a variant thereof;

[0289] The variant has at least 70%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with respect to the sequence from which it originates, or the variant has one or more amino acid substitutions, deletions, or additions compared to the sequence from which it originates.

[0290] In some embodiments, the anti-Trop-2 antibody or its antigen-binding fragment comprises:

[0291] The following are the variable regions (VH) of heavy chains and / or variable regions (VL) of light chains, as defined in the Chothia numbering system:

[0292] Heavy chain variable region (VH) containing the following 3 CDRs: CDR-H1 with sequence of SEQ ID NO:1 or a variant thereof, CDR-H2 with sequence of SEQ ID NO:2 or a variant thereof, and CDR-H3 with sequence of SEQ ID NO:3 or a variant thereof; and / or, light chain variable region (VL) containing the following 3 CDRs: CDR-L1 with sequence of SEQ ID NO:4 or a variant thereof, CDR-L2 with sequence of SEQ ID NO:5 or a variant thereof, and CDR-L3 with sequence of SEQ ID NO:6 or a variant thereof;

[0293] The variant has at least 70%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with the sequence from which it originates, or the variant has one, two, or three amino acid substitutions, deletions, or additions compared to the sequence from which it originates;

[0294] or,

[0295] The following are the variable regions (VH) of heavy chains and / or variable regions (VL) of light chains, defined according to the AbM numbering system:

[0296] Heavy chain variable region (VH) containing the following 3 CDRs: CDR-H1 with sequence of SEQ ID NO:14 or a variant thereof, CDR-H2 with sequence of SEQ ID NO:15 or a variant thereof, and CDR-H3 with sequence of SEQ ID NO:3 or a variant thereof; and / or, light chain variable region (VL) containing the following 3 CDRs: CDR-L1 with sequence of SEQ ID NO:4 or a variant thereof, CDR-L2 with sequence of SEQ ID NO:5 or a variant thereof, and CDR-L3 with sequence of SEQ ID NO:6 or a variant thereof;

[0297] The variant has at least 70%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with the sequence from which it originates, or the variant has one, two, or three amino acid substitutions, deletions, or additions compared to the sequence from which it originates;

[0298] or,

[0299] The following are the variable regions (VH) of heavy chains and / or variable regions (VL) of light chains, as defined in the Kabat numbering system:

[0300] Heavy chain variable region (VH) containing the following 3 CDRs: CDR-H1 with sequence of SEQ ID NO:7 or a variant thereof, CDR-H2 with sequence of SEQ ID NO:8 or a variant thereof, and CDR-H3 with sequence of SEQ ID NO:3 or a variant thereof; and / or, light chain variable region (VL) containing the following 3 CDRs: CDR-L1 with sequence of SEQ ID NO:4 or a variant thereof, CDR-L2 with sequence of SEQ ID NO:5 or a variant thereof, and CDR-L3 with sequence of SEQ ID NO:6 or a variant thereof;

[0301] The variant has at least 70%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with the sequence from which it originates, or the variant has one, two, or three amino acid substitutions, deletions, or additions compared to the sequence from which it originates;

[0302] or,

[0303] The following are the variable regions (VH) of heavy chains and / or variable regions (VL) of light chains, as defined in the IMGT numbering system:

[0304] Heavy chain variable region (VH) containing the following 3 CDRs: CDR-H1 with sequence of SEQ ID NO:9 or a variant thereof, CDR-H2 with sequence of SEQ ID NO:10 or a variant thereof, and CDR-H3 with sequence of SEQ ID NO:11 or a variant thereof; and / or, light chain variable region (VL) containing the following 3 CDRs: CDR-L1 with sequence of SEQ ID NO:12 or a variant thereof, CDR-L2 with sequence of SEQ ID NO:13 or a variant thereof, and CDR-L3 with sequence of SEQ ID NO:6 or a variant thereof;

[0305] The variant has at least 70%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with respect to the sequence from which it originates, or the variant has one, two, or three amino acid substitutions, deletions, or additions compared to the sequence from which it originates.

[0306] In some embodiments, the anti-Trop-2 antibody or its antigen-binding fragment comprises:

[0307] (1) The following heavy chain variable regions (VH) and light chain variable regions (VL), as defined by the Chothia numbering system:

[0308] Heavy chain variable region (VH) containing the following 3 CDRs: CDR-H1 with sequence of SEQ ID NO:1 or a variant thereof, CDR-H2 with sequence of SEQ ID NO:2 or a variant thereof, and CDR-H3 with sequence of SEQ ID NO:3 or a variant thereof; and light chain variable region (VL) containing the following 3 CDRs: CDR-L1 with sequence of SEQ ID NO:4 or a variant thereof, CDR-L2 with sequence of SEQ ID NO:5 or a variant thereof, and CDR-L3 with sequence of SEQ ID NO:6 or a variant thereof;

[0309] or,

[0310] (2) The following heavy chain variable regions (VH) and light chain variable regions (VL), defined according to the AbM numbering system:

[0311] Heavy chain variable region (VH) containing the following three CDRs: CDR-H1 with sequence SEQ ID NO:14 or a variant thereof, CDR-H2 with sequence SEQ ID NO:15 or a variant thereof, and CDR-H3 with sequence SEQ ID NO:3 or a variant thereof; and light chain variable region (VL) containing the following three CDRs: CDR-L1 with sequence SEQ ID NO:4 or a variant thereof, CDR-L2 with sequence SEQ ID NO:5 or a variant thereof, and CDR-L3 with sequence SEQ ID NO:6 or a variant thereof;

[0312] or,

[0313] (3) The following heavy chain variable regions (VH) and light chain variable regions (VL), as defined by the Kabat numbering system:

[0314] Heavy chain variable region (VH) containing the following three CDRs: CDR-H1 with sequence of SEQ ID NO:7 or a variant thereof, CDR-H2 with sequence of SEQ ID NO:8 or a variant thereof, and CDR-H3 with sequence of SEQ ID NO:3 or a variant thereof; and light chain variable region (VL) containing the following three CDRs: CDR-L1 with sequence of SEQ ID NO:4 or a variant thereof, CDR-L2 with sequence of SEQ ID NO:5 or a variant thereof, and CDR-L3 with sequence of SEQ ID NO:6 or a variant thereof;

[0315] or,

[0316] (4) The following heavy chain variable regions (VH) and light chain variable regions (VL), as defined by the IMGT numbering system:

[0317] The heavy chain variable region (VH) contains the following three CDRs: CDR-H1 with sequence SEQ ID NO:9 or a variant thereof, CDR-H2 with sequence SEQ ID NO:10 or a variant thereof, and CDR-H3 with sequence SEQ ID NO:11 or a variant thereof; and the light chain variable region (VL) contains the following three CDRs: CDR-L1 with sequence SEQ ID NO:12 or a variant thereof, CDR-L2 with sequence SEQ ID NO:13 or a variant thereof, and CDR-L3 with sequence SEQ ID NO:6 or a variant thereof.

[0318] In some embodiments, the anti-Trop-2 antibody or its antigen-binding fragment comprises: VH or a variant thereof shown in SEQ ID NO: 16, and VL or a variant thereof shown in SEQ ID NO: 17;

[0319] The variant has at least 70%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with respect to the sequence from which it originates, or the variant has one or more amino acid substitutions, deletions, or additions compared to the sequence from which it originates.

[0320] In some embodiments, the anti-Trop-2 antibody or its antigen-binding fragment comprises: VH or a variant thereof shown in SEQ ID NO: 16, and VL or a variant thereof shown in SEQ ID NO: 17;

[0321] The variant has at least 70%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with respect to the sequence from which it originates, or the variant has one, two, three, four, or five amino acid substitutions, deletions, or additions compared to the sequence from which it originates.

[0322] In some implementations, the substitution is a conservative substitution.

[0323] In some embodiments, the anti-Trop-2 antibody or its antigen-binding fragment comprises: VH or a variant thereof shown in SEQ ID NO: 16, and VL or a variant thereof shown in SEQ ID NO: 17.

[0324] In some embodiments, the anti-Trop-2 antibody or its antigen-binding fragment further comprises:

[0325] (a) The heavy chain constant region (CH) of human immunoglobulin or a variant thereof, said variant having one or more amino acid substitutions, deletions, or additions compared to the wild-type sequence from which it is derived; and

[0326] (b) The light chain constant region (CL) of human immunoglobulin or a variant thereof, wherein the variant has one or more amino acid substitutions, deletions or additions compared to the wild-type sequence from which it is derived.

[0327] In some embodiments, the anti-Trop-2 antibody or its antigen-binding fragment further comprises:

[0328] (a) The heavy chain constant region (CH) of human immunoglobulin or a variant thereof, said variant having at most 20, 15, 10, or 5 amino acid substitutions, deletions, or additions compared to the wild-type sequence from which it is derived; and

[0329] (b) The light chain constant region (CL) of human immunoglobulin or a variant thereof, wherein the variant has at most 20, at most 15, at most 10, or at most 5 amino acid substitutions, deletions, or additions compared to the wild-type sequence from which it is derived.

[0330] In some embodiments, the anti-Trop-2 antibody or its antigen-binding fragment further comprises:

[0331] (a) The heavy chain constant region (CH) of human immunoglobulin or a variant thereof, said variant having one, two, three, four, or five amino acid substitutions, deletions, or additions compared to the wild-type sequence from which it is derived; and

[0332] (b) The light chain constant region (CL) of human immunoglobulin or a variant thereof, wherein the variant has one, two, three, four or five amino acid substitutions, deletions or additions compared to the wild-type sequence from which it is derived.

[0333] In some implementations, the heavy chain constant region is the IgG heavy chain constant region.

[0334] In some implementations, the heavy chain constant region is an IgG1, IgG2, IgG3, or IgG4 heavy chain constant region.

[0335] In some implementations, the heavy chain constant region is the human IgG1 heavy chain constant region or the human IgG4 heavy chain constant region.

[0336] In some embodiments, the anti-Trop-2 antibody or its antigen-binding fragment comprises the heavy chain shown in SEQ ID NO:18 and the light chain shown in SEQ ID NO:19.

[0337] In some embodiments, the anti-Trop-2 antibody or its antigen-binding fragment is sacituzumab or its antigen-binding fragment as described in WO2019114666A1.

[0338] In some embodiments, the anti-Trop-2 antibody-drug conjugate is the antibody-drug conjugate described in WO2019114666A1, the contents of which are incorporated herein by reference.

[0339] In some embodiments, the anti-Trop-2 antibody-drug conjugate is selected from antibody-drug conjugate B, which has the following chemical structure:

[0340] Where q is selected from 1 to 10.

[0341] In some implementations, q is selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.

[0342] In some implementations, the DAR value of the antibody-drug conjugate B is 1-10.

[0343] In some embodiments, the DAR value of the antibody-drug conjugate B is an integer or decimal of 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3, 1-2, 2-10, 2-9, 2-8, 2-7, 2-6, 2-5, 2-4, 2-3, 3-10, 3-9, 3-8, 3-7, 3-6, 3-5, 3-4, 4-10, 4-9, 4-8, 4-7, 4-6, 4-5, 5-10, 5-9, 5-8, 5-7, 5-6, 6-10, 6-9, 6-8, 6-7, 7-10, 7-9, 7-8, 8-10, 8-9, or 9-10.

[0344] In some implementations, the DAR value of the antibody-drug conjugate B is 3-8.

[0345] In some implementations, the DAR value of the antibody-drug conjugate B is 4-8.

[0346] In some implementations, the DAR value of the antibody-drug conjugate B is 5-8.

[0347] In some implementations, the DAR value of the antibody-drug conjugate B is 6-8.

[0348] In some implementations, the DAR value of the antibody-drug conjugate B is 7-8.

[0349] In some embodiments, the DAR value of the antibody-drug conjugate B is approximately 5.0, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6.0, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, 7.0, 7.1, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, or 8.0.

[0350] In some embodiments, the DAR value of the antibody-drug conjugate B is 5.0, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6.0, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, 7.0, 7.1, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, or 8.0.

[0351] In a second aspect, this application provides a pharmaceutical composition comprising:

[0352] (1) Antibody-drug conjugates;

[0353] (2) Selected from one or both of EGFR inhibitors and VEGF inhibitors;

[0354] (3) It may also optionally contain other active therapeutic agents.

[0355] In some embodiments, the antibody-drug conjugate is selected from anti-Trop-2 antibody-drug conjugates.

[0356] In some embodiments, the pharmaceutical composition further includes one or more pharmaceutically acceptable excipients, diluents, or carriers.

[0357] In some embodiments, the pharmaceutical composition comprises an anti-Trop-2 antibody-drug conjugate, and one or both of a VEGF inhibitor and an EGFR inhibitor.

[0358] In some embodiments, the pharmaceutical composition comprises an anti-Trop-2 antibody-drug conjugate and a VEGF inhibitor.

[0359] In some embodiments, the pharmaceutical composition comprises an anti-Trop-2 antibody-drug conjugate and an EGFR inhibitor.

[0360] In some embodiments, the pharmaceutical composition comprises an anti-Trop-2 antibody-drug conjugate, a VEGF inhibitor, and an EGFR inhibitor.

[0361] In some embodiments, the components of the pharmaceutical composition are present in the same formulation unit or different formulation units.

[0362] In some embodiments, the anti-Trop-2 antibody drug conjugate, as well as one or both of the VEGF inhibitor and EGFR inhibitor, and optionally other active therapeutic agents, are present in the same or different formulation units.

[0363] In some embodiments, the pharmaceutical composition comprises an anti-Trop-2 antibody-drug conjugate, one or both of a VEGF inhibitor and an EGFR inhibitor, and a pharmaceutically acceptable carrier.

[0364] In some embodiments, the anti-Trop-2 antibody-drug conjugate, as well as one or more of VEGF inhibitors and EGFR inhibitors, are present in the same formulation unit.

[0365] In some implementations, the anti-Trop-2 antibody-drug conjugate and the VEGF inhibitor are contained in the same formulation unit.

[0366] In some implementations, the anti-Trop-2 antibody drug conjugate and the EGFR inhibitor are contained in the same formulation unit.

[0367] In some implementations, one or more of the anti-Trop-2 antibody-drug conjugate, VEGF inhibitor, and EGFR inhibitor are present in different formulation units.

[0368] In some implementations, the anti-Trop-2 antibody-drug conjugate and the VEGF inhibitor are present in different formulation units.

[0369] In some implementations, the anti-Trop-2 antibody-drug conjugate and the EGFR inhibitor are contained in different formulation units.

[0370] In some embodiments, the treatment combination or pharmaceutical composition contains 0.1-1000 mg of the anti-Trop-2 antibody-drug conjugate.

[0371] In some embodiments, the treatment combination or pharmaceutical composition contains 0.1-1000 mg of the antibody-drug conjugate B.

[0372] In some embodiments, the treatment combination or pharmaceutical composition comprises the anti-Trop-2 antibody-drug conjugate in the following amounts: 0.1-900 mg, 0.1-800 mg, 0.1-700 mg, 0.1-600 mg, 0.1-500 mg, 0.1-400 mg, 0.1-300 mg, 0.1-200 mg, 0.1-100 mg, 0.1-50 mg, 0.1-30 mg, 0.1-20 mg, 0.1-10 mg.

[0373] In some embodiments, the treatment combination or pharmaceutical composition comprises the antibody-drug conjugate B in the following amounts: 0.1-900 mg, 0.1-800 mg, 0.1-700 mg, 0.1-600 mg, 0.1-500 mg, 0.1-400 mg, 0.1-300 mg, 0.1-200 mg, 0.1-100 mg, 0.1-50 mg, 0.1-30 mg, 0.1-20 mg, 0.1-10 mg.

[0374] In some embodiments, the treatment combination or pharmaceutical composition comprises the anti-Trop-2 antibody-drug conjugate in the following amounts: 0.1 mg, 1.0 mg, 2.0 mg, 3.0 mg, 4.0 mg, 5.0 mg, 6.0 mg, 7.0 mg, 8.0 mg, 9.0 mg, 10.0 mg, 15.0 mg, 20.0 mg, 25 mg, 30 mg, 35 mg, 40 mg, 45 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, 400 mg, 450 mg, and 500 mg.

[0375] In some embodiments, the treatment combination or pharmaceutical composition comprises the antibody-drug conjugate B in the following amounts: 0.1 mg, 1.0 mg, 2.0 mg, 3.0 mg, 4.0 mg, 5.0 mg, 6.0 mg, 7.0 mg, 8.0 mg, 9.0 mg, 10.0 mg, 15.0 mg, 20.0 mg, 25 mg, 30 mg, 35 mg, 40 mg, 45 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, 400 mg, 450 mg, and 500 mg.

[0376] In some embodiments, the drug combination or pharmaceutical composition contains 0.1-1000 mg of the VEGF inhibitor.

[0377] In some embodiments, the drug combination or pharmaceutical composition contains 0.1-1000 mg of bevacizumab or its biosimilar.

[0378] In some embodiments, the drug combination or pharmaceutical composition contains the VEGF inhibitor in the following amounts: 0.1-900 mg, 0.1-800 mg, 0.1-700 mg, 0.1-600 mg, 0.1-500 mg, 0.1-400 mg, 0.1-300 mg, 0.1-200 mg, 0.1-100 mg, 0.1-50 mg, 0.1-30 mg, 0.1-20 mg, 0.1-10 mg.

[0379] In some embodiments, the drug combination or pharmaceutical composition comprises bevacizumab or its biosimilar in the following amounts: 0.1-900 mg, 0.1-800 mg, 0.1-700 mg, 0.1-600 mg, 0.1-500 mg, 0.1-400 mg, 0.1-300 mg, 0.1-200 mg, 0.1-100 mg, 0.1-50 mg, 0.1-30 mg, 0.1-20 mg, 0.1-10 mg.

[0380] In some embodiments, the drug combination or pharmaceutical composition contains the VEGF inhibitor in the following amounts: 0.1 mg, 1.0 mg, 2.0 mg, 3.0 mg, 4.0 mg, 5.0 mg, 6.0 mg, 7.0 mg, 8.0 mg, 9.0 mg, 10.0 mg, 15.0 mg, 20.0 mg, 25 mg, 30 mg, 35 mg, 40 mg, 45 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, 400 mg, 450 mg, and 500 mg.

[0381] In some embodiments, the drug combination or pharmaceutical composition comprises the following amounts of bevacizumab or its biosimilar: 0.1 mg, 1.0 mg, 2.0 mg, 3.0 mg, 4.0 mg, 5.0 mg, 6.0 mg, 7.0 mg, 8.0 mg, 9.0 mg, 10.0 mg, 15.0 mg, 20.0 mg, 25 mg, 30 mg, 35 mg, 40 mg, 45 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, 400 mg, 450 mg, and 500 mg.

[0382] In some embodiments, the drug combination or pharmaceutical composition contains 0.1-1000 mg of the EGFR inhibitor.

[0383] In some embodiments, the drug combination or pharmaceutical composition contains 0.1-1000 mg of cetuximab or its biosimilar.

[0384] In some embodiments, the drug combination or pharmaceutical composition contains the EGFR inhibitor in the following amounts: 0.1-900 mg, 0.1-800 mg, 0.1-700 mg, 0.1-600 mg, 0.1-500 mg, 0.1-400 mg, 0.1-300 mg, 0.1-200 mg, 0.1-100 mg, 0.1-50 mg, 0.1-30 mg, 0.1-20 mg, 0.1-10 mg.

[0385] In some embodiments, the drug combination or drug composition contains the EGFR inhibitor in the following amounts: 0.1 mg, 1.0 mg, 2.0 mg, 3.0 mg, 4.0 mg, 5.0 mg, 6.0 mg, 7.0 mg, 8.0 mg, 9.0 mg, 10.0 mg, 15.0 mg, 20.0 mg, 25 mg, 30 mg, 35 mg, 40 mg, 45 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, 400 mg, 450 mg, and 500 mg.

[0386] In some embodiments, the drug combination or pharmaceutical composition contains cetuximab or its biosimilar in the following amounts: 0.1-900 mg, 0.1-800 mg, 0.1-700 mg, 0.1-600 mg, 0.1-500 mg, 0.1-400 mg, 0.1-300 mg, 0.1-200 mg, 0.1-100 mg, 0.1-50 mg, 0.1-30 mg, 0.1-20 mg, 0.1-10 mg.

[0387] In some embodiments, the drug combination or pharmaceutical composition comprises cetuximab or its biosimilar in the following amounts: 0.1 mg, 1.0 mg, 2.0 mg, 3.0 mg, 4.0 mg, 5.0 mg, 6.0 mg, 7.0 mg, 8.0 mg, 9.0 mg, 10.0 mg, 15.0 mg, 20.0 mg, 25 mg, 30 mg, 35 mg, 40 mg, 45 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, 400 mg, 450 mg, and 500 mg.

[0388] In some embodiments, the anti-Trop-2 antibody-drug conjugate, EGFR inhibitor, and VEGF inhibitor are as described in any of the first aspects above.

[0389] In a third aspect, this application provides a kit containing one or two of an anti-Trop-2 antibody-drug conjugate, a VEGF inhibitor, and an EGFR inhibitor, and optionally other active therapeutic agents.

[0390] In some embodiments, the kit contains an anti-Trop-2 antibody-drug conjugate, and one or both of a VEGF inhibitor and an EGFR inhibitor.

[0391] In some embodiments, the kit contains an anti-Trop-2 antibody-drug conjugate, a VEGF inhibitor, and an EGFR inhibitor.

[0392] In some embodiments, the kit contains an anti-Trop-2 antibody-drug conjugate and an EGFR inhibitor.

[0393] In some embodiments, the kit contains an anti-Trop-2 antibody-drug conjugate and a VEGF inhibitor.

[0394] In some implementations, the cassette is in the form of a drug dosage unit, which can provide a drug formulation unit according to the dosing regimen.

[0395] In some implementations, the kit is used before and / or during treatment.

[0396] In some embodiments, the kit includes an anti-Trop-2 antibody-drug conjugate as described above in one compartment, an EGFR inhibitor as described above in another compartment, and a VEGF inhibitor as described above in yet another compartment.

[0397] In some embodiments, the kit includes an anti-Trop-2 antibody-drug conjugate as described above in one compartment and an EGFR inhibitor as described above in another compartment.

[0398] In some embodiments, the kit includes an anti-Trop-2 antibody drug conjugate as described above in one compartment and an anti-EGFR antibody and / or antigen-binding fragment as described above in another compartment.

[0399] In some embodiments, the kit includes an anti-Trop-2 antibody-drug conjugate as described above in one compartment and a VEGF inhibitor as described above in another compartment.

[0400] In some embodiments, the kit includes an anti-Trop-2 antibody drug conjugate as described above in one compartment and an anti-VEGF antibody or its antigen-binding fragment as described above in another compartment.

[0401] In some embodiments, the kit may also include an anti-Trop-2 antibody drug conjugate, an anti-VEGF antibody or its antigen-binding fragment, an anti-EGFR antibody or its antigen-binding fragment, and instructions for use.

[0402] In some embodiments, the kit also includes an anti-Trop-2 antibody drug conjugate, an anti-VEGF antibody or its antigen-binding fragment, and instructions for use.

[0403] In some embodiments, the kit may also include an anti-Trop-2 antibody drug conjugate, the aforementioned anti-EGFR antibody or its antigen-binding fragment, and instructions for use.

[0404] In one embodiment, the kit includes means for individually storing the composition, such as a container, a separate bottle, or a separate foil package. The kit disclosed herein can be used for administration in different dosage forms, such as oral and parenteral, such as intravenous (iv), intramuscular (im), or subcutaneous (sc), for administering individual therapeutic agents at different dose intervals, or for infusing individual therapeutic agents relative to each other.

[0405] In one embodiment, the pillbox includes means for individually storing the composition, such as a container, a separate bottle, or a separate foil package. The pillboxes disclosed herein can be used for administration of different dosage forms, such as oral and parenteral, for administering the individual compositions at different dose intervals, or for dripping the individual compositions relative to each other.

[0406] In a fourth aspect, this application also provides the use of the aforementioned treatment combination, pharmaceutical composition, kit, or antibody-drug conjugate with a second therapeutic agent in the preparation of a medicament for the prevention and / or treatment of a subject’s tumor or cancer, wherein the second therapeutic agent is selected from one or both of EGFR inhibitors and VEGF inhibitors, as well as optional other active therapeutic agents.

[0407] In some implementations, the second therapeutic agent is an EGFR inhibitor, such as cetuximab or a biosimilar thereof.

[0408] In some implementations, the second therapeutic agent is a VEGF inhibitor, such as bevacizumab or a biosimilar thereof.

[0409] In some implementations, the second therapeutic agent is an EGFR inhibitor and a VEGF inhibitor, such as cetuximab and bevacizumab.

[0410] In some embodiments, this application also provides the use of the aforementioned treatment combinations, pharmaceutical compositions, kits, and anti-Trop-2 antibody drug conjugates in the preparation of medicaments for the prevention and / or treatment of tumors or cancers in a subject.

[0411] In some embodiments, this application provides the use of a treatment combination comprising an anti-Trop-2 antibody drug conjugate, and one or both of a VEGF inhibitor and an EGFR inhibitor, or a pharmaceutical composition thereof, or a kit thereof, in the preparation of a medicament for the prevention and / or treatment of a subject’s tumor or cancer.

[0412] In some embodiments, this application provides the use of a therapeutic combination comprising an anti-Trop-2 antibody-drug conjugate, and one or both of an anti-VEGF antibody or its antigen-binding fragment and an anti-EGFR antibody or its antigen-binding fragment, or a pharmaceutical composition thereof, or a kit thereof, in the preparation of a medicament for the prevention and / or treatment of a subject’s tumor or cancer.

[0413] In some embodiments, this application provides the use of a treatment combination comprising an anti-Trop-2 antibody-drug conjugate, and one or both of cetuximab or its antigen-binding fragment and bevacizumab or its antigen-binding fragment, or a pharmaceutical composition thereof, or a kit thereof, in the preparation of a medicament for the prevention and / or treatment of a subject’s tumor or cancer.

[0414] In some embodiments, this application provides the use of a treatment combination comprising an anti-Trop-2 antibody-drug conjugate, and one or both of cetuximab and bevacizumab, or a pharmaceutical composition thereof, or a kit thereof, in the preparation of a medicament for the prevention and / or treatment of a subject’s tumor or cancer.

[0415] In some embodiments, this application provides the use of a therapeutic combination comprising an anti-Trop-2 antibody-drug conjugate and cetuximab, or a pharmaceutical composition thereof, or a kit thereof, in the preparation of a medicament for the prevention and / or treatment of a subject’s tumor or cancer.

[0416] In some embodiments, this application provides the use of a therapeutic combination comprising an anti-Trop-2 antibody-drug conjugate and bevacizumab, or a pharmaceutical composition thereof, or a kit thereof, in the preparation of a medicament for the prevention and / or treatment of a subject’s tumor or cancer.

[0417] In some embodiments, this application also provides the treatment combinations, pharmaceutical compositions, kits, and antibody-drug conjugates (e.g., anti-Trop-2 antibody-drug conjugates) described above for the prevention and / or treatment of tumors or cancers in subjects.

[0418] In some embodiments, this application provides a treatment combination comprising an anti-Trop-2 antibody drug conjugate, and one or both of a VEGF inhibitor and an EGFR inhibitor, or a pharmaceutical composition thereof, or a kit thereof, for the prevention and / or treatment of a subject’s tumor or cancer.

[0419] In some embodiments, this application provides a therapeutic combination, or a combination of two of the following: an anti-Trop-2 antibody-drug conjugate, an anti-VEGF antibody or its antigen-binding fragment thereof, and an anti-EGFR antibody or its antigen-binding fragment thereof, or a pharmaceutical composition thereof, or a kit thereof, for the prevention and / or treatment of a subject’s tumor or cancer.

[0420] In some embodiments, this application provides a treatment combination, or a combination of two of the following: an anti-Trop-2 antibody-drug conjugate, and cetuximab or its antigen-binding fragment and bevacizumab or its antigen-binding fragment, or a pharmaceutical composition thereof, or a kit thereof, for the prevention and / or treatment of a subject’s tumor or cancer.

[0421] In some embodiments, this application provides a treatment combination comprising an anti-Trop-2 antibody-drug conjugate, and cetuximab and bevacizumab, or a pharmaceutical composition thereof, or a kit thereof for the prevention and / or treatment of a subject’s tumor or cancer.

[0422] In some embodiments, this application provides a treatment combination comprising an anti-Trop-2 antibody-drug conjugate and cetuximab, or a pharmaceutical composition thereof, or a kit thereof, for the prevention and / or treatment of a subject’s tumor or cancer.

[0423] In some embodiments, this application provides a treatment combination comprising an anti-Trop-2 antibody-drug conjugate and bevacizumab, or a pharmaceutical composition thereof, or a kit thereof, for the prevention and / or treatment of a subject’s tumor or cancer.

[0424] In some embodiments, the use of an anti-Trop-2 antibody-drug conjugate or a combination thereof in the preparation of a medicament for treating a subject’s tumor or cancer is provided, wherein the medicament is administered in combination with a second therapeutic agent selected from one or both of EGFR inhibitors and VEGF inhibitors, as well as optional other active therapeutic agents.

[0425] In some implementations, the second therapeutic agent is an EGFR inhibitor, such as cetuximab or a biosimilar thereof.

[0426] In some implementations, the second therapeutic agent is a VEGF inhibitor, such as bevacizumab or a biosimilar thereof.

[0427] In some implementations, the second therapeutic agent is an EGFR inhibitor and a VEGF inhibitor, such as cetuximab and bevacizumab.

[0428] In some embodiments, the use of VEGF inhibitors and / or EGFR inhibitors in the preparation of medicaments for treating tumors or cancer is provided, wherein the medicaments are administered in combination therapy with an anti-Trop-2 antibody drug conjugate or a combination thereof.

[0429] In some implementations, the EGFR inhibitor is selected from cetuximab or its biosimilar.

[0430] In some implementations, the VEGF inhibitor is selected from bevacizumab or its biosimilar.

[0431] In a fifth aspect, this application provides the use of antibody-drug conjugates (e.g., anti-Trop-2 antibody-drug conjugates) and therapeutic combinations of one or both of EGFR inhibitors and VEGF inhibitors.

[0432] In some embodiments, this application provides the use of a therapeutic combination of an anti-Trop-2 antibody-drug conjugate, an EGFR inhibitor, and a VEGF inhibitor.

[0433] In some embodiments, this application provides the use of a therapeutic combination of an anti-Trop-2 antibody-drug conjugate and a VEGF inhibitor.

[0434] In some embodiments, this application provides the use of a therapeutic combination of an anti-Trop-2 antibody-drug conjugate and an EGFR inhibitor.

[0435] The above uses are for the prevention and / or treatment of tumors or cancer.

[0436] In some embodiments, this application provides an anti-Trop-2 antibody-drug conjugate for the treatment of tumors or cancer, wherein the antibody-drug conjugate is administered in combination with other therapeutic agents.

[0437] In some embodiments, the other therapeutic agents comprise VEGF inhibitors and / or EGFR inhibitors, as well as optionally other active therapeutic agents.

[0438] In some implementations, the other therapeutic agents comprise VEGF inhibitors and / or EGFR inhibitors.

[0439] In some implementations, the other therapeutic agents comprise cetuximab and / or bevacizumab.

[0440] In a sixth aspect, this application provides the use of an anti-Trop-2 antibody-drug conjugate for use in combination with a VEGF inhibitor and / or an EGFR inhibitor to prepare a pharmaceutical composition for the prevention and / or treatment of a subject’s tumor or cancer.

[0441] In some embodiments, the anti-Trop-2 antibody-drug conjugate, the EGFR inhibitor, and the VEGF inhibitor are as described in any of the first aspects of this application.

[0442] In a seventh aspect, this application provides a method for preventing and / or treating a tumor or cancer in a subject, the method comprising administering an effective amount of the treatment combination, pharmaceutical composition, or kit of this application to a subject in need.

[0443] In some implementations, the prevention and / or treatment methods provided in this application include administration to subjects in need:

[0444] (a) An effective amount of the anti-Trop-2 antibody-drug conjugate described in any of the first aspects of this application for prevention and / or treatment;

[0445] (b) A preventive and / or therapeutically effective amount of the VEGF inhibitor described in any of the first aspects of this application; and / or an EGFR inhibitor; and

[0446] (c) Optional other active therapeutic agents.

[0447] In some implementations, the prevention and / or treatment methods provided in this application include administration to subjects in need:

[0448] (a) An effective amount of the anti-Trop-2 antibody-drug conjugate described in any of the first aspects of this application for prevention and / or treatment;

[0449] (b) A preventive and / or therapeutically effective amount of bevacizumab or a biosimilar thereof as described in any of the first aspects of this application above; and / or cetuximab or a biosimilar thereof; and

[0450] (c) Other optional active therapeutic agents.

[0451] In some implementations, the prevention and / or treatment methods provided in this application include administration to subjects in need:

[0452] (a) An effective amount of the anti-Trop-2 antibody-drug conjugate described in any of the first aspects of this application for prevention and / or treatment;

[0453] (b) A preventive and / or therapeutic effective amount of the VEGF inhibitor described in any of the first aspects of this application; and / or an EGFR inhibitor.

[0454] In some implementations, the prevention and / or treatment methods provided in this application include administration to subjects in need:

[0455] (a) An effective amount of the anti-Trop-2 antibody-drug conjugate described in any of the first aspects of this application for prevention and / or treatment;

[0456] (b) Prophylaxis and / or treatment with an effective amount of bevacizumab or a biosimilar thereof as described in any of the first aspects of this application above; and / or cetuximab or a biosimilar thereof.

[0457] In some implementations, the prevention and / or treatment methods provided in this application include administration to subjects in need:

[0458] (a) A therapeutically effective amount of the anti-Trop-2 antibody-drug conjugate described above in this application;

[0459] (b) A therapeutically effective amount of the VEGF inhibitor described above in this application; and / or an EGFR inhibitor;

[0460] (c) Optional inclusion of other active therapeutic agents.

[0461] In some implementations, the prevention and / or treatment methods provided in this application include administration to subjects in need:

[0462] (a) A therapeutically effective amount of the anti-Trop-2 antibody-drug conjugate described above in this application;

[0463] (b) A therapeutically effective amount of the bevacizumab or its analogues described above in this application; and / or cetuximab or its biosimilars;

[0464] (c) Optional inclusion of other active therapeutic agents.

[0465] In some implementations, the prevention and / or treatment methods provided in this application include administration to subjects in need:

[0466] (a) A therapeutically effective amount of the anti-Trop-2 antibody-drug conjugate described above in this application;

[0467] (b) A therapeutically effective amount of the VEGF inhibitor described above in this application; and / or an EGFR inhibitor.

[0468] In some implementations, the prevention and / or treatment methods provided in this application include administration to subjects in need:

[0469] (a) A therapeutically effective amount of the anti-Trop-2 antibody-drug conjugate described above in this application;

[0470] (b) A therapeutically effective amount of bevacizumab or its analogues as described above in this application; and / or cetuximab or its biosimilars.

[0471] In some implementations, the method reduces the tumor size by at least about 10%.

[0472] In some implementations, the method reduces the tumor size by at least about 10%, 20%, 30% or more.

[0473] In some embodiments, the method reduces the tumor size by approximately 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100%.

[0474] In some embodiments, the method can reduce tumor size by about 15%. In some embodiments, the method can reduce tumor size by about 20%. In some embodiments, the method can reduce tumor size by about 25%. In some embodiments, the method can reduce tumor size by about 30%. In some embodiments, the method can reduce tumor size by about 35%. In some embodiments, the method can reduce tumor size by about 40%. In some embodiments, the method can reduce tumor size by about 45%. In some embodiments, the method can reduce tumor size by about 50%. In some embodiments, the method can reduce tumor size by about 55%. In some embodiments, the method can reduce tumor size by about 60%. In some embodiments, the method can reduce tumor size by about 65%. In some embodiments, the method can reduce tumor size by about 70%. In some embodiments, the method can reduce tumor size by about 75%. In some embodiments, the method can reduce tumor size by about 80%. In some embodiments, the method can reduce tumor size by about 85%. In some embodiments, the method can reduce tumor size by about 90%. In some embodiments, the method can reduce tumor volume by about 95%. In some embodiments, the method can reduce tumor volume by about 100%.

[0475] In some implementations, the tumor growth inhibition rate (TGI) of the method is above 70%.

[0476] In some embodiments, the tumor growth inhibition rate (TGI) of the method is 80% or higher, 90% or higher, 100% or higher, 110% or higher, 120% or higher, 130% or higher, 140% or higher, 150% or higher, 160% or higher, 170% or higher, or 180% or higher.

[0477] In some embodiments, the tumor growth inhibition rate (TGI) of the method is 80% or higher. In some embodiments, the tumor growth inhibition rate (TGI) of the method is 90% or higher. In some embodiments, the tumor growth inhibition rate (TGI) of the method is 100% or higher. In some embodiments, the tumor growth inhibition rate (TGI) of the method is 110% or higher. In some embodiments, the tumor growth inhibition rate (TGI) of the method is 120% or higher. In some embodiments, the tumor growth inhibition rate (TGI) of the method is 130% or higher. In some embodiments, the tumor growth inhibition rate (TGI) of the method is 140% or higher. In some embodiments, the tumor growth inhibition rate (TGI) of the method is 150% or higher. In some embodiments, the tumor growth inhibition rate (TGI) of the method is 160% or higher. In some embodiments, the tumor growth inhibition rate (TGI) of the method is 170% or higher. In some implementations, the tumor growth inhibition rate (TGI) of the method is greater than 180%.

[0478] In some implementations, the method reduces the ability of tumors to grow and stabilizes the disease.

[0479] In some implementations, the method offers improved treatment safety.

[0480] In some implementations, the administered therapeutic agents have a synergistic effect in preventing and / or treating cancer in the subject, for example, by having an increased response rate through synergistic action.

[0481] In some implementations, the drug combination has a synergistic effect in preventing and / or treating cancer in the subject, such as by having an increased response rate through synergistic action.

[0482] In the eighth aspect, this application provides the aforementioned treatment combinations, anti-Trop-2 antibody drug conjugates, pharmaceutical compositions, and kits for the prevention and / or treatment of tumors or cancer.

[0483] In some embodiments, this application also provides combination regimens for treating tumors or cancer, which include administering a therapeutically effective amount of the aforementioned treatment combination or pharmaceutical composition to a patient with tumors and / or cancer.

[0484] In some embodiments, this application also provides a method for improving the efficacy of treatment for tumors or cancer, which includes, in addition to administering the aforementioned anti-Trop-2 antibody drug conjugate to the tumor and / or cancer patient, further combining the administration of a therapeutically effective amount of the aforementioned VEGF inhibitor and / or EGFR inhibitor.

[0485] In some embodiments, this application also provides a method for improving the efficacy of treating tumors or cancer, which includes, in addition to administering the aforementioned anti-Trop-2 antibody-drug conjugate to a tumor and / or cancer patient, further combining the administration of a therapeutically effective amount of bevacizumab or its biosimilar and / or cetuximab or its biosimilar.

[0486] In some embodiments, the administration is preferably by injection.

[0487] The anti-Trop-2 antibody-drug conjugates, EGFR inhibitors, and VEGF inhibitors, as well as their order of administration, administration cycle, dosage, frequency of administration, concentration, route of administration, dosing interval, and dosage, in aspects four, five, six, seven, and eight of this application are as described in any of the preceding aspects one.

[0488] In some embodiments, the dosing cycle, dosage, dosing frequency, dose concentration, route of administration, dosing interval, and dosage of the treatment combination, pharmaceutical composition, anti-Trop-2 antibody-drug conjugate, EGFR inhibitor, and VEGF inhibitor described in this application are as described in any of the first aspects above.

[0489] Specifically, in some embodiments, the anti-Trop-2 antibody drug conjugate, as well as the EGFR inhibitor and / or VEGF inhibitor, are administered simultaneously, separately, sequentially, or in sequence.

[0490] In some implementations, the anti-Trop-2 antibody-drug conjugate, along with an EGFR inhibitor and / or a VEGF inhibitor, are administered simultaneously.

[0491] In some embodiments, the anti-Trop-2 antibody-drug conjugate, as well as the EGFR inhibitor and / or VEGF inhibitor, are administered separately.

[0492] In some embodiments, the anti-Trop-2 antibody-drug conjugate, along with an EGFR inhibitor and / or a VEGF inhibitor, are administered sequentially.

[0493] In some embodiments, the anti-Trop-2 antibody-drug conjugate, along with a VEGF inhibitor and / or an EGFR inhibitor, are administered sequentially.

[0494] In some implementations, the EGFR inhibitor, as well as the anti-Trop-2 antibody-drug conjugate and / or VEGF inhibitor, are administered sequentially.

[0495] In some implementations, the EGFR inhibitor, as well as the VEGF inhibitor and / or anti-Trop-2 antibody drug conjugate, are administered sequentially.

[0496] In some implementations, the VEGF inhibitor, as well as the anti-Trop-2 antibody-drug conjugate and / or EGFR inhibitor, are administered sequentially.

[0497] In some embodiments, the VEGF inhibitor, and the EGFR inhibitor and / or anti-Trop-2 antibody drug conjugate are administered sequentially. In some embodiments, the anti-Trop-2 antibody drug conjugate, and the EGFR inhibitor and / or VEGF inhibitor are administered sequentially.

[0498] In some implementations, the anti-Trop-2 antibody drug conjugate, along with a VEGF inhibitor and / or an EGFR inhibitor, are administered sequentially.

[0499] In some implementations, the EGFR inhibitor, as well as the anti-Trop-2 antibody drug conjugate and / or VEGF inhibitor, are administered sequentially.

[0500] In some implementations, the EGFR inhibitor, as well as the VEGF inhibitor and / or anti-Trop-2 antibody drug conjugate, are administered sequentially.

[0501] In some implementations, the VEGF inhibitor, as well as the anti-Trop-2 antibody drug conjugate and / or EGFR inhibitor, are administered sequentially.

[0502] In some embodiments, the VEGF inhibitor, as well as the EGFR inhibitor and / or anti-Trop-2 antibody drug conjugate, are administered sequentially. In some embodiments, the anti-Trop-2 antibody drug conjugate and the EGFR inhibitor are administered simultaneously.

[0503] In some implementations, the anti-Trop-2 antibody-drug conjugate and the EGFR inhibitor are administered separately.

[0504] In some implementations, the anti-Trop-2 antibody-drug conjugate and the EGFR inhibitor are administered sequentially.

[0505] In some implementations, the EGFR inhibitor and the anti-Trop-2 antibody drug conjugate are administered sequentially.

[0506] In some implementations, the anti-Trop-2 antibody-drug conjugate and the EGFR inhibitor are administered sequentially.

[0507] In some implementations, the EGFR inhibitor and the anti-Trop-2 antibody drug conjugate are administered sequentially.

[0508] In some implementations, the anti-Trop-2 antibody-drug conjugate and the VEGF inhibitor are administered simultaneously.

[0509] In some implementations, the anti-Trop-2 antibody-drug conjugate and the VEGF inhibitor are administered separately.

[0510] In some implementations, the anti-Trop-2 antibody-drug conjugate and the VEGF inhibitor are administered sequentially.

[0511] In some implementations, the VEGF inhibitor and the anti-Trop-2 antibody-drug conjugate are administered sequentially.

[0512] In some implementations, the anti-Trop-2 antibody-drug conjugate and the VEGF inhibitor are administered sequentially.

[0513] In some implementations, the VEGF inhibitor and the anti-Trop-2 antibody drug conjugate are administered sequentially.

[0514] In some embodiments, the dosing period of the anti-Trop-2 antibody-drug conjugate is 1-42 days. In some embodiments, the dosing period of the anti-Trop-2 antibody-drug conjugate is 7-42 days. In some embodiments, the dosing period of the anti-Trop-2 antibody-drug conjugate is 14-42 days. In some embodiments, the dosing period of the anti-Trop-2 antibody-drug conjugate is 1 day. In some embodiments, the dosing period of the anti-Trop-2 antibody-drug conjugate is 3 days. In some embodiments, the dosing period of the anti-Trop-2 antibody-drug conjugate is 7 days. In some embodiments, the dosing period of the anti-Trop-2 antibody-drug conjugate is 14 days. In some embodiments, the dosing period of the anti-Trop-2 antibody-drug conjugate is 21 days. In some embodiments, the dosing period of the anti-Trop-2 antibody-drug conjugate is 28 days.

[0515] In some embodiments, the anti-Trop-2 antibody drug conjugate, VEGF inhibitor, and / or EGFR inhibitor may be administered simultaneously, within one day, or at intervals of at least 1 day, 2 days, 3 days, 5 days, 6 days, 7 days, 10 days, 15 days, 21 days, 30 days, 45 days, 2 months, 75 days, 3 months, or 6 months.

[0516] In some implementations, the treatment combination or any component of the treatment combination may be repeatedly applied, with the applications spaced at least 1 day, 2 days, 3 days, 5 days, 6 days, 7 days, 10 days, 15 days, 21 days, 30 days, 45 days, 2 months, 75 days, 3 months, or 6 months apart.

[0517] In some embodiments, the anti-Trop-2 antibody-drug conjugate is administered 1 to 8 times over a period of 1 to 4 weeks.

[0518] In some implementations, the anti-Trop-2 antibody-drug conjugate is administered once a week, twice a week, twice every two weeks, once every two weeks, twice every three weeks, or once every three weeks.

[0519] In some implementations, the anti-Trop-2 antibody-drug conjugate is administered once a week, twice a week, once every two weeks, or once every three weeks.

[0520] In some implementations, the dose of the anti-Trop-2 antibody-drug conjugate administered per dose is selected from 0.1-20 mg / kg or more, based on the subject's weight.

[0521] In some implementations, the dose of the anti-Trop-2 antibody-drug conjugate administered per dose is selected from 0.5-10 mg / kg, based on the subject's weight.

[0522] In some implementations, the dose of the anti-Trop-2 antibody-drug conjugate administered per dose is selected from 0.5-5 mg / kg, based on the subject's weight.

[0523] In some embodiments, the dose of the anti-Trop-2 antibody-drug conjugate administered per administration, based on the subject's weight, is selected from 0.5 mg / kg, 1 mg / kg, 2 mg / kg, 2.5 mg / kg, 3 mg / kg, 3.5 mg / kg, 4 mg / kg, 4.5 mg / kg, 5 mg / kg, 5.5 mg / kg, 6 mg / kg, 6.5 mg / kg, 7 mg / kg, 7.5 mg / kg, 8 mg / kg, 8.5 mg / kg, 9 mg / kg, 9.5 mg / kg, or 10 mg / kg. In some embodiments, the dose of the anti-Trop-2 antibody-drug conjugate administered per administration is 0.5 mg / kg, 1 mg / kg, 2 mg / kg, 3 mg / kg, 4 mg / kg, or 5 mg / kg, based on the subject's weight. In some embodiments, the dose of the anti-Trop-2 antibody-drug conjugate administered per administration is 0.5 mg / kg, based on the subject's weight. In some embodiments, the dose of the anti-Trop-2 antibody-drug conjugate administered per dose is 1 mg / kg, based on the subject's weight. In some embodiments, the dose of the anti-Trop-2 antibody-drug conjugate administered per dose is 2 mg / kg, based on the subject's weight. In some embodiments, the dose of the anti-Trop-2 antibody-drug conjugate administered per dose is 3 mg / kg, based on the subject's weight. In some embodiments, the dose of the anti-Trop-2 antibody-drug conjugate administered per dose is 4 mg / kg, based on the subject's weight. In some embodiments, the dose of the anti-Trop-2 antibody-drug conjugate administered per dose is 5 mg / kg, based on the subject's weight.

[0524] In some embodiments, the dose of the anti-Trop-2 antibody-drug conjugate administered at a time is selected from 0.1-20 mg / kg or more.

[0525] In some embodiments, the dose of the anti-Trop-2 antibody-drug conjugate administered at a time is selected from 0.5-10 mg / kg.

[0526] In some embodiments, the dose of the anti-Trop-2 antibody-drug conjugate administered at a time is selected from 0.5-5 mg / kg.

[0527] In some embodiments, the dose of the anti-Trop-2 antibody-drug conjugate administered per administration is selected from 0.5 mg / kg, 1 mg / kg, 2 mg / kg, 2.5 mg / kg, 3 mg / kg, 3.5 mg / kg, 4 mg / kg, 4.5 mg / kg, 5 mg / kg, 5.5 mg / kg, 6 mg / kg, 6.5 mg / kg, 7 mg / kg, 7.5 mg / kg, 8 mg / kg, 8.5 mg / kg, 9 mg / kg, 9.5 mg / kg, or 10 mg / kg. In some embodiments, the dose of the anti-Trop-2 antibody-drug conjugate administered per administration is 0.5 mg / kg, 1 mg / kg, 2 mg / kg, 3 mg / kg, 4 mg / kg, or 5 mg / kg. In some embodiments, the dose of the anti-Trop-2 antibody-drug conjugate administered per administration is 0.5 mg / kg. In some embodiments, the dose of the anti-Trop-2 antibody-drug conjugate administered per administration is 1 mg / kg. In some embodiments, the anti-Trop-2 antibody-drug conjugate is administered at a dose of 2 mg / kg. In some embodiments, the anti-Trop-2 antibody-drug conjugate is administered at a dose of 3 mg / kg. In some embodiments, the anti-Trop-2 antibody-drug conjugate is administered at a dose of 4 mg / kg. In some embodiments, the anti-Trop-2 antibody-drug conjugate is administered at a dose of 5 mg / kg.

[0528] In some embodiments, the dose concentration of the anti-Trop-2 antibody-drug conjugate administered per dose is selected from 0.01-50 mg / ml.

[0529] In some embodiments, the dose concentration of the anti-Trop-2 antibody-drug conjugate administered per dose is selected from 0.01-40 mg / ml, 0.01-30 mg / ml, 0.01-20 mg / ml, or 0.01-10 mg / ml.

[0530] In some embodiments, the dose concentration of the anti-Trop-2 antibody-drug conjugate administered per dose is selected from 0.01 mg / ml, 0.03 mg / ml, 0.05 mg / ml, 0.06 mg / ml, 0.1 mg / ml, 0.3 mg / ml, 0.5 mg / ml, 0.6 mg / ml, 0.7 mg / ml, 0.8 mg / ml, 0.9 mg / ml, 1.0 mg / ml, 2.0 mg / ml, 3.0 mg / ml, 4.0 mg / ml, 5.0 mg / ml, 6.0 mg / ml, 7.0 mg / ml, 8.0 mg / ml, 9.0 mg / ml, 10.0 mg / ml, 15.0 mg / ml, 20.0 mg / ml, 25 mg / ml, 30 mg / ml, 35 mg / ml, 40 mg / ml, 45 mg / ml, and 50 mg / ml.

[0531] In some embodiments, the dose of the anti-Trop-2 antibody-drug conjugate per dosing cycle (e.g., a single-dose dose or a unit dose) is selected from 0.1-1000 mg.

[0532] In some embodiments, the dose of the anti-Trop-2 antibody-drug conjugate (e.g., a single-dose dose or a unit dose) is selected from 0.1-900 mg, 0.1-800 mg, 0.1-700 mg, 0.1-600 mg, 0.1-500 mg, 0.1-400 mg, 0.1-300 mg, 0.1-200 mg, 0.1-100 mg, 0.1-50 mg, 0.1-30 mg, 0.1-20 mg, and 0.1-10 mg.

[0533] In some embodiments, the dose (e.g., a single-dose dose or a unit dose) or total dose of the anti-Trop-2 antibody-drug conjugate is selected from 0.1 mg, 1.0 mg, 2.0 mg, 3.0 mg, 4.0 mg, 5.0 mg, 6.0 mg, 7.0 mg, 8.0 mg, 9.0 mg, 10.0 mg, 15.0 mg, 20.0 mg, 25 mg, 30 mg, 35 mg, 40 mg, 45 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, 400 mg, 450 mg, and 500 mg.

[0534] In some embodiments, the dosing period of the VEGF inhibitor is 1-42 days. In some embodiments, the dosing period of the VEGF inhibitor is 7-42 days. In some embodiments, the dosing period of the VEGF inhibitor is 1 day, 7 days, 14 days, 21 days, 28 days, or 42 days. In some embodiments, the dosing period of the VEGF inhibitor is 1 day. In some embodiments, the dosing period of the VEGF inhibitor is 3 days. In some embodiments, the dosing period of the VEGF inhibitor is 7 days. In some embodiments, the dosing period of the VEGF inhibitor is 14 days. In some embodiments, the dosing period of the VEGF inhibitor is 21 days. In some embodiments, the dosing period of the VEGF inhibitor is 28 days.

[0535] In some embodiments, the VEGF inhibitor is administered 1 to 8 times over a period of 1 to 4 weeks.

[0536] In some implementations, the VEGF inhibitor is administered once a week, twice a week, twice every two weeks, once every two weeks, twice every three weeks, or once every three weeks.

[0537] In some implementations, the VEGF inhibitor is administered once a week, twice a week, once every two weeks, or once every three weeks.

[0538] In some implementations, the dose of the VEGF inhibitor administered per dose is selected from 0.5-50 mg / kg, based on the subject's weight.

[0539] In some implementations, the dose of the VEGF inhibitor administered per dose, based on the subject's weight, is selected from 0.5-40 mg / kg, 0.5-30 mg / kg, 0.5-20 mg / kg, 0.5-10 mg / kg, 0.5-5 mg / kg, or for example 0.5 mg / kg, 1 mg / kg, 1.5 mg / kg, 2 mg / kg, 2.5 mg / kg, 3 mg / kg, 3.5 mg / kg, 4 mg / kg, 4.5 mg / kg, 5 mg / kg, 5.5 mg / kg, 6 mg / kg, 6.5 mg / kg, 7 mg / kg, 7.5 mg / kg, 8 mg / kg, 8.5 mg / kg, 9 mg / kg, 9.5 mg / kg, 10 mg / kg, 15 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 35 mg / kg, 40 mg / kg, 45 mg / kg, or 50 mg / kg.

[0540] In some embodiments, the VEGF inhibitor is administered at a dose of 0.5 mg / kg, 1 mg / kg, 1.5 mg / kg, 2 mg / kg, 2.5 mg / kg, 3 mg / kg, 3.5 mg / kg, 4 mg / kg, 4.5 mg / kg, or 5 mg / kg, based on the subject's weight. In some embodiments, the VEGF inhibitor is administered at a dose of 1.0 mg / kg, based on the subject's weight. In some embodiments, the VEGF inhibitor is administered at a dose of 1.5 mg / kg, based on the subject's weight. In some embodiments, the VEGF inhibitor is administered at a dose of 2 mg / kg, based on the subject's weight. In some embodiments, the VEGF inhibitor is administered at a dose of 2.5 mg / kg, based on the subject's weight. In some embodiments, the VEGF inhibitor is administered at a dose of 3 mg / kg, based on the subject's weight. In some embodiments, the VEGF inhibitor is administered at a dose of 4 mg / kg, based on the subject's weight. In some embodiments, the VEGF inhibitor is administered at a dose of 5 mg / kg, based on the subject's weight. In some embodiments, the VEGF inhibitor is administered at a dose of 10 mg / kg per administration, based on the subject's weight. In some embodiments, the VEGF inhibitor is administered at a dose of 20 mg / kg per administration, based on the subject's weight.

[0541] In some embodiments, the dose of the VEGF inhibitor administered each time is selected from 0.5-50 mg / kg.

[0542] In some embodiments, the dose of the VEGF inhibitor administered per administration is selected from 0.5-40 mg / kg, 0.5-30 mg / kg, 0.5-20 mg / kg, 0.5-10 mg / kg, 0.5-5 mg / kg, or for example 0.5 mg / kg, 1 mg / kg, 1.5 mg / kg, 2 mg / kg, 2.5 mg / kg, 3 mg / kg, 3.5 mg / kg, 4 mg / kg, 4.5 mg / kg, 5 mg / kg, 5.5 mg / kg, 6 mg / kg, 6.5 mg / kg, 7 mg / kg, 7.5 mg / kg, 8 mg / kg, 8.5 mg / kg, 9 mg / kg, 9.5 mg / kg, 10 mg / kg, 15 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 35 mg / kg, 40 mg / kg, 45 mg / kg, or 50 mg / kg.

[0543] In some embodiments, the VEGF inhibitor is administered at a dose of 0.5 mg / kg, 1 mg / kg, 1.5 mg / kg, 2 mg / kg, 2.5 mg / kg, 3 mg / kg, 3.5 mg / kg, 4 mg / kg, 4.5 mg / kg, or 5 mg / kg. In some embodiments, the VEGF inhibitor is administered at a dose of 1.0 mg / kg. In some embodiments, the VEGF inhibitor is administered at a dose of 1.5 mg / kg. In some embodiments, the VEGF inhibitor is administered at a dose of 2 mg / kg. In some embodiments, the VEGF inhibitor is administered at a dose of 2.5 mg / kg. In some embodiments, the VEGF inhibitor is administered at a dose of 3 mg / kg. In some embodiments, the VEGF inhibitor is administered at a dose of 4 mg / kg. In some embodiments, the VEGF inhibitor is administered at a dose of 5 mg / kg. In some embodiments, the VEGF inhibitor is administered at a dose of 10 mg / kg. In some embodiments, the VEGF inhibitor is administered at a dose of 20 mg / kg.

[0544] In some embodiments, the VEGF inhibitor is administered at a concentration selected from 0.05-50 mg / ml per dose.

[0545] In some embodiments, the VEGF inhibitor is administered at a concentration selected from 0.05-40 mg / ml, 0.05-30 mg / ml, 0.1-20 mg / ml, or 0.1-10 mg / ml, for example, 0.05 mg / ml, 0.1 mg / ml, 0.15 mg / ml, 0.2 mg / ml, 0.3 mg / ml, 0.4 mg / ml, 0.5 mg / ml, 0.6 mg / ml, 0.7 mg / ml, 0.8 mg / ml. / ml, 0.9mg / ml, 1.0mg / ml, 2.0mg / ml, 3.0mg / ml, 4.0mg / ml, 5.0mg / ml, 6.0mg / ml, 7.0mg / ml, 8.0mg / ml, 9.0mg / ml, 10.0mg / ml, 15.0mg / ml, 20.0mg / ml, 25mg / ml, 30mg / ml, 35mg / ml, 40mg / ml, 45mg / ml and 50mg / ml.

[0546] In some embodiments, the dose of the VEGF inhibitor (e.g., a single-dose dose or a unit dose) is selected from 0.1-1000 mg.

[0547] In some embodiments, the dose of the VEGF inhibitor (e.g., a single-dose dose or a unit dose) is selected from 0.1-900 mg, 0.1-800 mg, 0.1-700 mg, 0.1-600 mg, 0.1-500 mg, 0.1-400 mg, 0.1-300 mg, 0.1-200 mg, 0.1-100 mg, 0.1-50 mg, 0.1-30 mg, 0.1-20 mg, and 0.1-10 mg.

[0548] In some embodiments, the dose of the VEGF inhibitor (e.g., a single-dose dose or a unit dose) is selected from 0.1 mg, 1.0 mg, 2.0 mg, 3.0 mg, 4.0 mg, 5.0 mg, 6.0 mg, 7.0 mg, 8.0 mg, 9.0 mg, 10.0 mg, 15.0 mg, 20.0 mg, 25 mg, 30 mg, 35 mg, 40 mg, 45 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, 400 mg, 450 mg, and 500 mg.

[0549] In some embodiments, the dosing cycle of the EGFR inhibitor is 1-42 days. In some embodiments, the dosing cycle of the EGFR inhibitor is 7-42 days. In some embodiments, the dosing cycle of the EGFR inhibitor is 1 day, 7 days, 14 days, 21 days, 28 days, or 42 days. In some embodiments, the dosing cycle of the EGFR inhibitor is 1 day. In some embodiments, the dosing cycle of the EGFR inhibitor is 3 days. In some embodiments, the dosing cycle of the EGFR inhibitor is 7 days. In some embodiments, the dosing cycle of the EGFR inhibitor is 14 days. In some embodiments, the dosing cycle of the EGFR inhibitor is 21 days. In some embodiments, the dosing cycle of the EGFR inhibitor is 28 days.

[0550] In some implementations, the EGFR inhibitor is administered 1 to 8 times over a period of 1 to 4 weeks.

[0551] In some implementations, the EGFR inhibitor is administered once a week, twice a week, twice every two weeks, once every two weeks, twice every three weeks, or once every three weeks.

[0552] In some implementations, the EGFR inhibitor is administered once a week, twice a week, once every two weeks, or once every three weeks.

[0553] In some implementations, the dose of the EGFR inhibitor administered per dose is selected from 0.5-50 mg / kg, based on the subject's weight.

[0554] In some implementations, the dose of the EGFR inhibitor administered per administration, based on the subject's weight, is selected from 0.5-40 mg / kg, 0.5-30 mg / kg, 0.5-20 mg / kg, 0.5-10 mg / kg, 0.5-5 mg / kg, or for example 0.5 mg / kg, 1 mg / kg, 1.5 mg / kg, 2 mg / kg, 2.5 mg / kg, 3 mg / kg, 3.5 mg / kg, 4 mg / kg, 4.5 mg / kg, 5 mg / kg, 5.5 mg / kg, 6 mg / kg, 6.5 mg / kg, 7 mg / kg, 7.5 mg / kg, 8 mg / kg, 8.5 mg / kg, 9 mg / kg, 9.5 mg / kg, 10 mg / kg, 15 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 35 mg / kg, 40 mg / kg, 45 mg / kg, or 50 mg / kg.

[0555] In some embodiments, the EGFR inhibitor is administered at a dose of 0.5 mg / kg, 1 mg / kg, 1.5 mg / kg, 2 mg / kg, 2.5 mg / kg, 3 mg / kg, 3.5 mg / kg, 4 mg / kg, 4.5 mg / kg, or 5 mg / kg, based on the subject's weight. In some embodiments, the EGFR inhibitor is administered at a dose of 1.0 mg / kg, based on the subject's weight. In some embodiments, the EGFR inhibitor is administered at a dose of 1.5 mg / kg, based on the subject's weight. In some embodiments, the EGFR inhibitor is administered at a dose of 2 mg / kg, based on the subject's weight. In some embodiments, the EGFR inhibitor is administered at a dose of 2.5 mg / kg, based on the subject's weight. In some embodiments, the EGFR inhibitor is administered at a dose of 3 mg / kg, based on the subject's weight. In some embodiments, the EGFR inhibitor is administered at a dose of 4 mg / kg, based on the subject's weight. In some embodiments, the EGFR inhibitor is administered at a dose of 5 mg / kg, based on the subject's weight. In some embodiments, the EGFR inhibitor is administered at a dose of 10 mg / kg per administration, based on the subject's weight. In some embodiments, the EGFR inhibitor is administered at a dose of 20 mg / kg per administration, based on the subject's weight.

[0556] In some embodiments, the dose of the EGFR inhibitor administered each time is selected from 0.5-50 mg / kg.

[0557] In some embodiments, the dose of the EGFR inhibitor administered per administration is selected from 0.5-40 mg / kg, 0.5-30 mg / kg, 0.5-20 mg / kg, 0.5-10 mg / kg, 0.5-5 mg / kg, or for example 0.5 mg / kg, 1 mg / kg, 1.5 mg / kg, 2 mg / kg, 2.5 mg / kg, 3 mg / kg, 3.5 mg / kg, 4 mg / kg, 4.5 mg / kg, 5 mg / kg, 5.5 mg / kg, 6 mg / kg, 6.5 mg / kg, 7 mg / kg, 7.5 mg / kg, 8 mg / kg, 8.5 mg / kg, 9 mg / kg, 9.5 mg / kg, 10 mg / kg, 15 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 35 mg / kg, 40 mg / kg, 45 mg / kg, or 50 mg / kg.

[0558] In some embodiments, the EGFR inhibitor is administered at a dose of 0.5 mg / kg, 1 mg / kg, 1.5 mg / kg, 2 mg / kg, 2.5 mg / kg, 3 mg / kg, 3.5 mg / kg, 4 mg / kg, 4.5 mg / kg, or 5 mg / kg. In some embodiments, the EGFR inhibitor is administered at a dose of 1.0 mg / kg. In some embodiments, the EGFR inhibitor is administered at a dose of 1.5 mg / kg. In some embodiments, the EGFR inhibitor is administered at a dose of 2 mg / kg. In some embodiments, the EGFR inhibitor is administered at a dose of 2.5 mg / kg. In some embodiments, the EGFR inhibitor is administered at a dose of 3 mg / kg. In some embodiments, the EGFR inhibitor is administered at a dose of 4 mg / kg. In some embodiments, the EGFR inhibitor is administered at a dose of 5 mg / kg. In some embodiments, the EGFR inhibitor is administered at a dose of 10 mg / kg. In some embodiments, the EGFR inhibitor is administered at a dose of 20 mg / kg.

[0559] In some embodiments, the dose concentration of the EGFR inhibitor administered each time is selected from 0.05-50 mg / ml.

[0560] In some embodiments, the dosage concentration of the EGFR inhibitor administered per dose is selected from 0.05-40 mg / ml, 0.05-30 mg / ml, 0.1-20 mg / ml, or 0.1-10 mg / ml, for example 0.05 mg / ml, 0.1 mg / ml, 0.15 mg / ml, 0.2 mg / ml, 0.3 mg / ml, 0.4 mg / ml, 0.5 mg / ml, 0.6 mg / ml, 0.7 mg / ml, 0.8 mg / ml. / ml, 0.9mg / ml, 1.0mg / ml, 2.0mg / ml, 3.0mg / ml, 4.0mg / ml, 5.0mg / ml, 6.0mg / ml, 7.0mg / ml, 8.0mg / ml, 9.0mg / ml, 10.0mg / ml, 15.0mg / ml, 20.0mg / ml, 25mg / ml, 30mg / ml, 35mg / ml, 40mg / ml, 45mg / ml and 50mg / ml.

[0561] In some embodiments, the dose of the EGFR inhibitor (e.g., a single-dose dose or a unit dose) is selected from 0.1-1000 mg.

[0562] In some embodiments, the dose of the EGFR inhibitor (e.g., a single-dose dose or a unit dose) is selected from 0.1-900 mg, 0.1-800 mg, 0.1-700 mg, 0.1-600 mg, 0.1-500 mg, 0.1-400 mg, 0.1-300 mg, 0.1-200 mg, 0.1-100 mg, 0.1-50 mg, 0.1-30 mg, 0.1-20 mg, and 0.1-10 mg.

[0563] In some embodiments, the dose of the EGFR inhibitor (e.g., a single-dose dose or a unit dose) is selected from 0.1 mg, 1.0 mg, 2.0 mg, 3.0 mg, 4.0 mg, 5.0 mg, 6.0 mg, 7.0 mg, 8.0 mg, 9.0 mg, 10.0 mg, 15.0 mg, 20.0 mg, 25 mg, 30 mg, 35 mg, 40 mg, 45 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, 400 mg, 450 mg, and 500 mg.

[0564] In some embodiments, the anti-Trop-2 antibody-drug conjugate used in the treatment regimens disclosed herein is described in WO2019114666A1.

[0565] The tumors or cancers described in aspects four, five, six, seven and eight of this application are selected from solid tumors or non-solid tumors.

[0566] The tumors or cancers described in aspects four, five, six, seven and eight of this application are selected from esophageal cancer, lung cancer, squamous cell carcinoma, bladder cancer, gastric cancer, ovarian cancer, peritoneal cancer, pancreatic cancer, breast cancer, cervical cancer, endometrial cancer, colorectal cancer, liver cancer, kidney cancer, prostate cancer and colon cancer.

[0567] The tumors or cancers described in aspects four, five, six, seven and eight of this application are selected from esophageal adenocarcinoma, esophageal squamous cell carcinoma, small cell lung cancer, non-small cell lung cancer, squamous cell carcinoma, bladder cancer, gastric cancer, ovarian epithelial cancer, fallopian tube cancer, peritoneal cancer, pancreatic cancer, breast cancer, cervical cancer, endometrial cancer, colorectal cancer, liver cancer, kidney cancer, prostate cancer and colon cancer.

[0568] The tumors or cancers described in aspects four, five, six, seven and eight of this application are selected from esophageal cancer, lung cancer, squamous cell carcinoma, bladder cancer, gastric cancer, ovarian cancer, peritoneal cancer, pancreatic cancer, breast cancer, cervical cancer, endometrial cancer, colorectal cancer, liver cancer, kidney cancer and prostate cancer.

[0569] The tumors or cancers described in aspects four, five, six, seven and eight of this application are selected from esophageal adenocarcinoma, esophageal squamous cell carcinoma, small cell lung cancer, non-small cell lung cancer, squamous cell carcinoma, bladder cancer, gastric cancer, ovarian epithelial cancer, fallopian tube cancer, peritoneal cancer, pancreatic cancer, breast cancer, cervical cancer, endometrial cancer, colorectal cancer, liver cancer, kidney cancer and prostate cancer.

[0570] In some implementations, the tumor or cancer is selected from gastric cancer, breast cancer, colorectal cancer, and ovarian epithelial cancer.

[0571] In some implementations, the tumor or cancer is selected from gastric cancer and lung cancer.

[0572] In some implementations, the tumor or cancer is selected from non-small cell lung cancer.

[0573] The treatment combination, pharmaceutical composition, kit, and co-administration of hyaluronic acid-degrading enzyme disclosed in this article

[0574] Anti-Trop-2 antibody-drug conjugates (ADCs), anti-EGFR and VEGF inhibitors (including any combination disclosed herein) can be administered via any suitable route and may be administered using accelerators such as hyaluronidases, soluble PH20 peptides, and their variants. For systemic administration, their pharmacological properties (e.g., serum half-life) can be enhanced by modifying the accelerator (e.g., with a polymer such as polyethylene glycol (PEG)). See, for example, U.S. Patent Nos. 7,767,429; 8,431,380; 7,871,607, International Patent Application Publication No. WO2020022791, U.S. Patent Application Publication No. US20060104968, and European Patent No. 1858926B1, as well as numerous other patents and publications. In some embodiments, the route of administration is subcutaneous or intramuscular injection.

[0575] Therefore, specific embodiments involve:

[0576] (a) A pharmaceutical composition or fixed-dose pharmaceutical composition comprising: (i) the anti-Trop-2 ADC and EGFR inhibitor disclosed herein; (ii) the anti-Trop-2 ADC and VEGF inhibitor disclosed herein; (iii) the EGFR inhibitor and VEGF inhibitor disclosed herein; or (iv) the anti-Trop-2 ADC, EGFR inhibitor and VEGF inhibitor disclosed herein, and hyaluronidase, hyaluronidase, soluble hyaluronidase, soluble PH20 peptide or a variant thereof;

[0577] (b) A kit comprising: (i) the anti-Trop-2 ADC and EGFR inhibitor disclosed herein; (ii) the anti-Trop-2 antibody-drug conjugate (ADC) and VEGF inhibitor disclosed herein; (iii) the EGFR inhibitor and VEGF inhibitor disclosed herein; or (iv) the anti-Trop-2 ADC, EGFR inhibitor, and VEGF inhibitor disclosed herein, and any one of hyaluronidase, hyaluronidase, soluble hyaluronidase, or soluble PH20 peptide; and

[0578] (c) A kit comprising: (i) the anti-Trop-2 ADC and EGFR inhibitor disclosed herein; (ii) the anti-Trop-2 ADC and VEGF inhibitor disclosed herein; (iii) the EGFR inhibitor and VEGF inhibitor disclosed herein. Or (iv) the anti-Trop-2 ADC, EGFR inhibitor, and VEGF inhibitor disclosed herein, and any one of hyaluronidase, hyaluronidase, soluble hyaluronidase, or soluble PH20 peptide, wherein each component of the kit is in a separate container.

[0579] In some embodiments of the above-described treatment combinations, pharmaceutical compositions, and kits, the soluble hyaluronidase is soluble PH20 hyaluronidase, whose non-proprietary name is "Hyaluronidase (Recombinant Human)," designated by the United States Adoption of Names (USAN) Committee, and whose chemical name is "36-482-Hyaluroglucosaminease" or "Hyaluronidase 1 (Human Sperm Surface Protein PH20)-(1-447) Peptide," currently marketed by Halozyme under the name Hylenex. TM The protein is marketed under the trademark name [Berahyaluronidase Alfa]. In some embodiments, the hyaluronidase is a fusion protein of 3-305-hyaluronidase PH-20 (human), 302-322-hyaluronidase HYAL-1 (human), and 327-433-hyaluronidase PH-20 (human) (ACI), which has been granted the non-proprietary name "berahyaluronidase alfa" by the American College of Nutrition and is currently marketed by Alteogen under the trademark name Berahyaluronidase. TM They sell products under the trademark name.

[0580] This disclosure also provides a composition comprising the anti-Trop-2 antibody drug conjugate and hyaluronic acid degrading enzyme described above; the EGFR inhibitor and hyaluronic acid degrading enzyme described above; or the VEGF inhibitor and hyaluronic acid degrading enzyme described above; or the anti-Trop-2 antibody drug conjugate and EGFR inhibitor and / or VEGF inhibitor and hyaluronic acid degrading enzyme described above.

[0581] In some embodiments, the hyaluronic acid-degrading enzyme is a soluble hyaluronidase. In some embodiments, the soluble hyaluronidase is soluble hyaluronidase PH20. In some embodiments, the soluble hyaluronidase is recombinant human hyaluronidase or Bella hyaluronidase α.

[0582] This disclosure also provides a kit comprising: (a) the anti-Trop-2 antibody-drug conjugate and the EGFR inhibitor; (b) the anti-Trop-2 antibody-drug conjugate and the VEGF inhibitor; (c) the EGFR inhibitor and the VEGF inhibitor; (d) the VEGF inhibitor; (e) the anti-Trop-2 antibody-drug conjugate; (f) the anti-EGFR inhibitor; or (g) the anti-Trop-2 antibody-drug conjugate, the VEGF inhibitor, and the EGFR inhibitor, and a hyaluronic acid-degrading enzyme. In some embodiments, the anti-Trop-2 antibody-drug conjugate (ADC), the EGFR inhibitor and / or the VEGF inhibitor, and the hyaluronic acid-degrading enzyme are each placed in a separate container. In some embodiments, the hyaluronic acid-degrading enzyme is a soluble hyaluronidase. In some embodiments, the soluble hyaluronidase is soluble hyaluronidase PH20. In some embodiments, the soluble hyaluronidase is recombinant human hyaluronidase or recombinant human hyaluronidase α.

[0583] This disclosure also provides a composition selected from: (a) the anti-Trop-2 antibody-drug conjugate and the EGFR inhibitor; (b) the anti-Trop-2 antibody-drug conjugate and the VEGF inhibitor; (c) the EGFR inhibitor and the VEGF inhibitor; (d) the VEGF inhibitor; (e) the anti-Trop-2 antibody-drug conjugate; (f) the anti-EGFR inhibitor; or (g) the anti-Trop-2 antibody-drug conjugate, the VEGF inhibitor and the EGFR inhibitor, and hyaluronidase, and their use in the preparation of a tumor or cancer medicament for treating a subject.

[0584] This disclosure also provides a composition selected from: (a) the anti-Trop-2 antibody-drug conjugate and the EGFR inhibitor; (b) the anti-Trop-2 antibody-drug conjugate and the VEGF inhibitor; (c) the EGFR inhibitor and the VEGF inhibitor; (d) the VEGF inhibitor; (e) the anti-Trop-2 antibody-drug conjugate; (f) the anti-EGFR inhibitor; or (g) the anti-Trop-2 antibody-drug conjugate, the VEGF inhibitor and the EGFR inhibitor, and hyaluronidase, and the above for use in treating a subject's tumor or cancer.

[0585] This disclosure also provides a method of treating a tumor or cancer in a subject requiring treatment, the method comprising administering to the subject a therapeutically effective amount of a composition selected from: (a) the anti-Trop-2 antibody-drug conjugate and the EGFR inhibitor; (b) the anti-Trop-2 antibody-drug conjugate and the VEGF inhibitor; (c) the EGFR inhibitor and the VEGF inhibitor; (d) the VEGF inhibitor; (e) the anti-Trop-2 antibody-drug conjugate; (f) the anti-EGFR inhibitor; or (g) the anti-Trop-2 antibody-drug conjugate, the VEGF inhibitor, and the EGFR inhibitor, and a hyaluronic acid-degrading enzyme for treating tumors or cancer.

[0586] In some embodiments, the tumor or cancer is selected from solid tumors or non-solid tumors; for example, it is selected from esophageal cancer (e.g., esophageal adenocarcinoma and esophageal squamous cell carcinoma), lung cancer (e.g., small cell lung cancer and non-small cell lung cancer), squamous cell carcinoma, bladder cancer, gastric cancer, ovarian cancer (e.g., ovarian epithelial carcinoma, fallopian tube cancer), peritoneal cancer, pancreatic cancer, breast cancer, head and neck cancer, cervical cancer, endometrial cancer, colorectal cancer, liver cancer, kidney cancer, prostate cancer, and colon cancer. In some embodiments, the hyaluronic acid degrading enzyme is a soluble hyaluronidase. In some embodiments, the soluble hyaluronidase is PH20. In some embodiments, the soluble hyaluronidase is recombinant human hyaluronidase or Bera hyaluronidase α. In some embodiments, the anti-Trop-2 antibody-drug conjugate (ADC), EGFR inhibitor and / or VEGF inhibitor, and hyaluronic acid degrading enzyme are administered sequentially or simultaneously. In some embodiments, an anti-Trop-2 ADC, an EGFR inhibitor and / or a VEGF inhibitor, and a hyaluronic acid-degrading enzyme are mixed to form a mixture, and this mixture is administered. In some embodiments, the anti-Trop-2 ADC, EGFR inhibitor and / or VEGF inhibitor, and hyaluronic acid-degrading enzyme are administered systemically. In some embodiments, the anti-Trop-2 ADC, EGFR inhibitor and / or VEGF inhibitor, and hyaluronic acid-degrading enzyme are administered subcutaneously or intramuscularly, respectively.

[0587] All technical features disclosed in this specification, or all steps in all disclosed methods or processes, may be combined in any way, except for mutually exclusive technical features and / or steps. Detailed Implementation

[0588] Terminology Definition

[0589] Certain technical and scientific terms are specifically defined below. Unless otherwise defined elsewhere herein, all other technical and scientific terms used herein have the meanings commonly understood by one of ordinary skill in the art as to which this disclosure pertains.

[0590] The term "antibody" refers to an immunoglobulin molecule typically composed of two pairs of polypeptide chains (each pair consisting of one light chain (LC) and one heavy chain (HC)). Antibody light chains can be classified as κ (kappa) and λ (lambda) light chains. Heavy chains can be classified as μ, δ, γ, α, or ε, and antibody isotypes are defined as IgM, IgD, IgG, IgA, and IgE, respectively. Within both light and heavy chains, variable and constant regions are linked by a "J" region of approximately 12 or more amino acids, and the heavy chain also contains a "D" region of approximately 3 or more amino acids. 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 (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. Constant domains do not directly participate in antibody-antigen binding but exhibit various effector functions, such as mediating the binding of immunoglobulins 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. The VH and VL regions can be further subdivided into highly degenerated regions (called complementarity-determining regions (CDRs)) interspersed with more conserved regions called framework regions (FRs). Each VH and VL consists of three CDRs and four FRs arranged in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4, from the amino terminus to the carboxyl terminus. The variable regions (VH and VL) of each heavy / light chain pair form the antigen-binding sites. The amino acid assignment in each region or domain can follow various numbering systems known in the art. The term "antibody" also includes embodiments where the heavy chain constant region contains a C-terminal lysine, or lacks a C-terminal lysine, or is a C-terminal glycine-lysine dipeptide. The term also includes embodiments in which the N-terminal amino acid of the antibody variable region has been cyclized into pyroglutamate. Therefore, in compositions comprising the antibodies disclosed herein, various antibodies may independently comprise a C-terminal lysine, lack a C-terminal lysine, lack a C-terminal glycine-lysine, and / or comprise N-terminal glutamine or glutamic acid, or N-terminal amino acid cyclized into pyroglutamate.

[0591] The term "complementarity-determining region" or "CDR" refers to the amino acid residues in the variable region of an antibody that are responsible for antigen binding. Each of the heavy and light chain variable regions contains three CDRs, named CDR1, CDR2, and CDR3. The precise boundaries of these CDRs can be defined according to various numbering systems known in the art, such as the Kabat numbering system (Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, Md., 1991), the Chothia numbering system (Chothia & Lesk (1987) J. Mol. Biol. 196: 901-917; Chothia et al. (1989) Nature 342: 878-883), the IMGT numbering system (Lefranc et al., Dev. Comparat. Immunol. 27: 55-77, 2003), or the AbM numbering system (Martin ACR, Cheetham JC, Rees AR (1989) Modelling antibody hypervariable loops: A combined algorithm. Proc Natl Acad Sci USA 86: 9268-9272). For a given antibody, those skilled in the art will readily identify the CDR as defined by each numbering system. Furthermore, the correspondence between different numbering systems is well known to those skilled in the art (see, for example, Lefranc et al., Dev. Comparat. Immunol. 27:55-77, 2003).

[0592] In this application, the CDR contained in the antibody or its antigen-binding fragment can be determined according to various numbering systems known in the art, such as the Kabat, Chothia, IMGT or AbM numbering systems.

[0593] The term "framework region" or "FR" residues refers to the amino acid residues in the antibody variable region other than the CDR residues as defined above.

[0594] The term "antibody" is not limited to any particular method of producing antibodies. For example, it includes recombinant antibodies, monoclonal antibodies, and polyclonal antibodies. Antibodies can be different isotypes of antibodies, such as IgG (e.g., IgG1, IgG2, IgG3, or IgG4 subtypes), IgA1, IgA2, IgD, IgE, or IgM antibodies.

[0595] The term "antigen-binding fragment" in antibody refers to a fragment of the antibody polypeptide, such as a fragment of the full-length antibody polypeptide, which retains the ability to specifically bind to the same antigen bound by the full-length antibody, and / or competes with the full-length antibody for specific binding to the antigen; it is also referred to as the "antigen-binding moiety". See also Fundamental Immunology, Ch. 7 (Paul, W., ed., 2nd ed., Raven Press, NY (1989), which is incorporated herein by reference in its entirety for all purposes. Antigen-binding fragments of antibodies can be generated by recombinant DNA technology or by enzymatic or chemical cleavage of intact antibodies. Non-limiting examples of antigen-binding fragments include Fab fragments, Fab' fragments, F(ab)'2 fragments, F(ab)'3 fragments, Fd, Fv, scFv, di-scFv, (scFv)2, disulfide-stabilized Fv proteins (“dsFv”), single-domain antibodies (sdAb, nanobodies), and peptides containing at least a portion of an antibody sufficient to confer specific antigen-binding ability to the peptide. Engineered antibody variants are reviewed in Holliger et al., 2005; Nat Biotechnol, 23:1126-1136.

[0596] The term "Fd" refers to an antibody fragment composed of VH and CH1 domains; the term "dAb fragment" refers to an antibody fragment composed of VH domain (Ward et al., Nature 341:544 546 (1989)); the term "Fab fragment" refers to an antibody fragment composed of VL, VH, CL and CH1 domains; the term "F(ab')2 fragment" refers to an antibody fragment containing two Fab fragments connected by disulfide bridges on the hinge region; the term "Fab' fragment" refers to the fragment obtained by reducing the disulfide bonds connecting the two heavy chain fragments in the F(ab')2 fragment, which consists of a complete light chain and heavy chain Fd fragment (composed of VH and CH1 domains).

[0597] The term "Fv" refers to an antibody fragment consisting of the VL and VH domains of a single arm of the antibody. Fv fragments are generally considered to be the smallest antibody fragment capable of forming a complete antigen-binding site. It is generally believed that six CDRs confer antigen-binding specificity to the antibody. However, even a variable region (such as the Fd fragment, which contains only three antigen-specific CDRs) can recognize and bind to the antigen, although its affinity may be lower than that of a complete binding site.

[0598] The term "Fc" refers to an antibody fragment formed by disulfide bonds connecting the second and third constant regions of the first heavy chain to the second and third constant regions of the second heavy chain. The Fc fragment of an antibody has various functions but does not participate in antigen binding.

[0599] The term "scFv" refers to a single polypeptide chain containing VL and VH domains linked by a linker (see, for example, Bird et al., Science 242:423-426 (1988); Huston et al., Proc. Natl. Acad. Sci. USA 85:5879-5883 (1988); and Pluckthun, The Pharmacology of Monoclonal Antibodies, Vol. 113, edited by Roseburg and Moore, Springer-Verlag, New York, pp. 269-315 (1994)). Such scFv molecules may have a general structure: NH2-VL-linker-VH-COOH or NH2-VH-linker-VL-COOH. The linker may be selected from those suitable for use in the art or a variant thereof. Other connectors that can be used in this application are described by Alfthan et al. (1995), Protein Eng. 8:725-731, Choi et al. (2001), Eur. J. Immunol. 31:94-106, Hu et al. (1996), Cancer Res. 56:3055-3061, Kipriyanov et al. (1999), J. Mol. Biol. 293:41-56, and Roovers et al. (2001), Cancer Immunol. In some cases, a disulfide bond may also exist between the VH and VL of the scFv. In some embodiments, the VH and VL domains can be positioned relative to each other in any suitable arrangement. For example, NH2-VH-VH-COOH, NH 2- VL-VL-COOH of scFv.

[0600] The term "single-domain antibody (sdAb)" has the meaning commonly understood by those skilled in the art as an antibody fragment composed of a single monomeric variable antibody domain (e.g., a single heavy chain variable region) that maintains the ability to specifically bind to the same antigen bound by a full-length antibody (Holt, L. et al., Trends in Biotechnology, 21(11):484-490, 2003). Single-domain antibodies are also known as nanobodies.

[0601] Each of the above antibody fragments retains the ability to specifically bind to the same antigen bound by the full-length antibody, and / or competes with the full-length antibody for specific binding to the antigen.

[0602] In this article, unless the context clearly indicates otherwise, when referring to the term "antibody," it includes not only the complete antibody but also the antigen-binding fragment of the antibody.

[0603] Antigen-binding fragments (e.g., the antibody fragments described above) of a given antibody (e.g., the antibody provided in this application) can be obtained using conventional techniques known to those skilled in the art (e.g., recombinant DNA technology or enzymatic or chemical fragmentation methods), and the antigen-binding fragments of the antibody can be specifically screened in the same manner as those used for intact antibodies.

[0604] The term "identity" is used to refer to the sequence matching between two polypeptides or two nucleic acids. Two compared sequences are considered identical at that position when a position is occupied by the same base or amino acid monomer subunit (e.g., a position in each of two DNA molecules is occupied by adenine, or a position in each of two polypeptides is occupied by lysine). The "percentage identity" between two sequences is a function of the number of matching positions shared by the two sequences divided by the number of positions compared × 100. For example, if six out of ten positions in two sequences match, then the two sequences have 60% identity. For example, the DNA sequences CTGACT and CAGGTT have 50% identity (three out of six positions match). Typically, two sequences are compared to produce the maximum identity. Such comparisons can be made using methods conveniently performed, for example, by computer programs such as the Align program (DNAstar, Inc.) Needleman et al. (1970) J. Mol. Biol. 48: 443-453. The percentage identity between two amino acid sequences can also be determined using the algorithm of E. Meyers and W. Miller (Comput. Appl Biosci., 4:11-17 (1988)) integrated into the ALIGN program (version 2.0), which uses a PAM120 weight residue table, a gap length penalty of 12, and a gap penalty of 4. Alternatively, the percentage identity between two amino acid sequences can be determined using the Needleman and Wunsch algorithm (J MoI Biol. 48:444-453 (1970)) in the GAP program integrated into the GCG software package (available at www.gcg.com), which uses a Blossum 62 matrix or a PAM250 matrix, along with gap weights of 16, 14, 12, 10, 8, 6, or 4, and length weights of 1, 2, 3, 4, 5, or 6.

[0605] The term "conservative substitution" refers to an amino acid substitution that does not adversely affect or alter the intended properties of a protein / peptide containing an amino acid sequence. For example, conservative substitutions can be introduced using standard techniques known in the art, such as site-directed mutagenesis and PCR-mediated mutagenesis. Conservative amino acid substitutions include substitutions of amino acid residues with amino acid residues having similar side chains, such as substitutions with residues that are physically or functionally similar to the corresponding amino acid residues (e.g., having similar size, shape, charge, chemical properties, including the ability to form covalent or hydrogen bonds). Families of amino acid residues with similar side chains have been defined in the art. These families include amino acids with basic side chains (e.g., lysine, arginine, and histidine), acidic side chains (e.g., aspartic acid and glutamic acid), uncharged polar side chains (e.g., glycine, asparagine, glutamine, serine, threonine, tyrosine, cysteine, and tryptophan), nonpolar side chains (e.g., alanine, valine, leucine, isoleucine, proline, phenylalanine, and methionine), β-branched side chains (e.g., threonine, valine, and isoleucine), and aromatic side chains (e.g., tyrosine, phenylalanine, tryptophan, and histidine). Therefore, it is preferable to replace the corresponding amino acid residue with another amino acid residue from the same side chain family. Methods for identifying conserved amino acid substitutions are well known in the art (see, for example, Brummell et al., Biochem. 32:1180-1187 (1993); Kobayashi et al., Protein Eng. 12(10):879-884 (1999); and Burks et al., Proc. Natl Acad. Set USA 94:412-417 (1997), which are incorporated herein by reference).

[0606] The twenty common amino acids referred to herein are written in accordance with conventional usage. See, for example, Immunology-A Synthesis (2nd Edition, E.S. Golub and D.G. Ren, Eds., Sinauer Associates, Sunderland, Mass. (1991)), which is incorporated herein by reference. In this application, amino acids are generally represented by single-letter and three-letter abbreviations known in the art. For example, alanine may be represented as A or Ala.

[0607] The term "biosimilar" refers to a product that has a similar structure and properties to an existing biological product. Therefore, the term "biosimilar" is often used to describe a successor or product (often from a different source) to an previously approved and formally authorized "innovative biopharmaceutical product." A "biosimilar" may not be exactly the same as the innovative pharmaceutical product. However, biosimilars have demonstrated that they do not differ clinically in terms of safety and efficacy from their reference product. Therefore, because biosimilars are successors to known products and must demonstrate that they do not differ clinically in terms of efficacy from their reference product, the term "biosimilar" as used in this application includes currently known and approved "biosimilars" as well as any "biosimilars" developed in the future.

[0608] The term "anti-Trop-2 antibody" or "antibody targeting Trop-2" refers to an antibody that can bind to Trop-2 with sufficient affinity, such that the antibody can be used as a diagnostic and / or therapeutic agent targeting Trop-2 (e.g., RS7 antibody). The heavy chain terminal K (or Lys) is easily deleted, but such deletion does not affect biological activity, and the deleted antibody sequence is also included within the scope of this application.

[0609] Bevacizumab (trade name Avastin) is a humanized monoclonal antibody that inhibits angiogenesis by suppressing the activity of vascular endothelial growth factor A (VEGF-A). Bevacizumab binds to VEGF, thereby preventing VEGF from binding to its receptor (VEGFR). Bevacizumab is known in the art (see, for example, Overview of bevacizumab: A new cancer therapeutic strategy targeting vascular endothelial growth factor, Robert J. Ignoffo, American Journal of Health-System Pharmacy, Vol. 61, Issue Suppl_5, 1 November 2004, pages S21-S26).

[0610] The terms “cancer” and “cancerous” refer to or describe a pathological condition in mammals characterized by uncontrolled cell growth in a population of cells.

[0611] The terms “cancer cell,” “tumor cell,” and their grammatical equivalents refer to the total cell population derived from a tumor or precancerous lesion, including non-tumorigenic cells containing a large number of tumor cells and tumor-derived stem cells (cancer stem cells). As used herein, the term “tumor cell” when referring only to tumor cells lacking the capacity for renewal and differentiation will be modified with the term “non-tumorigenic” to distinguish tumor cells from cancer stem cells.

[0612] The term "subject" refers to any animal (e.g., a mammal) receiving a specific treatment, including (but not limited to) non-human primates, rodents, etc. Typically, when referring to a human individual, the terms "subject" and "patient" are used interchangeably herein. Mammals can be one or more selected from humans, bovids (e.g., cattle), swine (e.g., pigs), sheep (e.g., sheep), goats (e.g., goats), equines (e.g., horses), canines (e.g., domestic dogs), felines (e.g., domestic cats), lagomorphs (e.g., rabbits), rodents (e.g., rats or mice), etc. In a particular implementation, the subject is a human.

[0613] "Combined with" means to give simultaneously (in parallel) or in any order.

[0614] Combination therapies can provide "synergistic effects" and demonstrate "synergy," meaning that the effect achieved when the active ingredients are used together exceeds the sum of the effects of using the individual compounds alone. Synergistic effects can be achieved when: (1) the active ingredients are co-formulated and administered or delivered simultaneously in unit doses of the combination; (2) the active ingredients are delivered sequentially, alternately, or in parallel in independent formulations; or (3) the active ingredients are administered via some other regimen. When delivered in an alternating manner, synergistic effects can be achieved if the compounds are administered or delivered sequentially by, for example, different injections using independent syringes. The effect of a synergistic combination exceeds the sum of the effects of the individual components of the combination.

[0615] The therapeutic agents and drug combinations provided in this disclosure can be administered via any suitable enteral or non-enteric route. The term "enteric route" administration refers to administration through any part of the gastrointestinal tract. Examples of enteral routes include oral, mucosal, oral, and rectal routes, or gastric routes. "Non-enteric route" administration refers to administration via a route other than the gastrointestinal route. Examples of non-enteric routes include intravenous, intramuscular, intradermal, intraperitoneal, intratumoral, intrabladder, intraarterial, intrasheath, intracapsular, intra-sacral, intracardiac, tracheal, intra-articular, subcapsular, subarachnoid, intraspinal, epidural, and intrasternal, subcutaneous, or local administration. The therapeutic agents and drug combinations of this disclosure can be administered using any suitable method, such as by injection, infusion, implantable infusion pump, and osmotic pump. Suitable routes and methods of administration can vary depending on many factors, such as the specific therapeutic agent used, the desired absorption rate, the specific formulation or dosage form used, the type or severity of the disease being treated, the specific site of action, and the patient's condition, and can be readily selected by those skilled in the art.

[0616] The pharmaceutical compositions described herein can be formulated into pharmaceutical compositions using methods available in the art and the methods disclosed in this application, including the VEGF inhibitor, EGFR inhibitor, and antibody-drug conjugates provided in this application. The antibody-drug conjugates, EGFR inhibitors, and VEGF inhibitors provided in this application can all be provided in suitable pharmaceutical compositions and administered via suitable routes of administration. VEGF inhibitors and EGFR inhibitors can be formulated, administered, and applied according to commercially available instructions or other publicly available instructions.

[0617] The “effective amount” of the VEGF inhibitors, EGFR inhibitors, antibody-drug conjugates, or other active therapeutic agents disclosed herein is an amount sufficient to achieve the purpose specifically stated. The “effective amount” can be determined empirically and in a conventional manner for the stated purpose.

[0618] The term "therapeutic effective dose" refers to the amount of antibody, immune conjugate, or other drug that effectively "treats" a disease or condition in an individual or mammal. In the case of cancer, a therapeutically effective dose of a drug can reduce the number of cancer cells; reduce tumor size or burden; inhibit (i.e., slow down to some extent and stop in one implementation) the infiltration of cancer cells into surrounding organs; inhibit (i.e., slow down to some extent and stop in one implementation) tumor metastasis; inhibit tumor growth to some extent; alleviate one or more cancer-related symptoms to some extent; and / or induce a beneficial response. See the definition of "treatment" herein. In the case of a drug that can prevent cancer cell growth and / or kill existing cancer cells, the drug can be a cell-inhibiting and / or cytotoxic drug.

[0619] The terms "treatment" or "relief" refer to therapeutic measures that cure a diagnosed pathological condition or symptom, slow its progression, alleviate its symptoms, and / or stop its progression. Therefore, those requiring treatment include those diagnosed with or suspected of having the aforementioned condition. In some implementations, a patient’s cancer is considered successfully “treated” according to the method of this application if the patient exhibits one or more of the following: a reduction or complete absence of cancer cells; a reduction in tumor burden; suppression or absence of cancer cell infiltration in surrounding organs, such as soft tissue and bone; suppression or absence of tumor metastasis; suppression or absence of tumor growth; relief of one or more symptoms associated with the specific cancer; a reduction in morbidity and mortality; an improvement in quality of life; a reduction in tumorigenesis, tumorigenesis frequency, or tumorigenesis capacity; a reduction in the number or frequency of cancer stem cells in the tumor; differentiation of tumorigenesis cells into a non-tumorigenesis state; an increase in progression-free survival (PFS), disease-free survival (DFS), or overall survival (OS); duration of response (DOR); disease control rate (DCR); objective response rate (ORR); complete response (CR); partial response (PR); stable disease (SD); delayed disease progression (PD); prolonged time to progression (TTP); or any combination thereof.

[0620] Preventive or preventive measures refer to measures that prevent and / or slow the progression of a target pathological condition or symptom. Therefore, those who require preventive or preventive measures include those prone to having the condition and those who wish to prevent it.

[0621] As used herein, the term “DAR” or “drug-antibody ratio” refers to: (a) the number of linker / drug moieties linked to the antibody in a single antibody-drug conjugate molecule, which is an integer from 0 to 10, such as an integer from 1 to 10; or (b) the average number of linker / drug moieties linked to the antibody in a composition comprising more than one antibody-drug conjugate molecule, which is an integer or decimal from 0 to 10, such as an integer or decimal from 1 to 10. Methods for determining DAR are well known to those skilled in the art, including methods using reversed-phase chromatography or HPLC-MS.

[0622] It should be understood that while the embodiments are described herein with the language “comprising”, similar embodiments described with the terms “consisting of” and / or “substantially consisting of” are also provided.

[0623] Unless otherwise expressly stated, all ranges referenced in this application are inclusive; that is, a range includes the upper and lower limits of the range and all values ​​in between. For example, a range of 3 to 21 days is intended to include 3, 7, 14, 15, 16, 17, 18, 19, 20, and 21 days. Unless otherwise specified, the numerical values ​​provided in this application are all modified by the term “about” and may include variations of ±1%, ±2%, ±3%, ±4%, ±5%, ±10%, ±15%, and ±20%. All ranges are also intended to include all included subranges, although not necessarily explicitly stated. Furthermore, as used in this application, the term “or” indicates alternatives that can be combined where appropriate; that is, the word “or” includes each alternative listed individually and combinations thereof.

[0624] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure pertains. In case of conflict, this specification (including the definitions) shall prevail. Throughout the specification and claims, the word “comprise” (or variations such as “comprises” or “comprising”) shall be understood to imply inclusion of the stated integers or groups of integers, but not to exclude any other integers or groups of integers. Unless the context otherwise requires, singular terms shall include plural terms, and plural terms shall include singular terms. Any example following “for example” or “e.g.” is not intended to be exhaustive or limiting.

[0625] This application includes the following implementation scheme.

[0626] Implementation Scheme 1: Use of antibody-drug conjugates and a second therapeutic agent in the preparation of a drug for treating tumors or cancer, wherein the second therapeutic agent is selected from one or both of EGFR inhibitors and VEGF inhibitors, as well as optional other active therapeutic agents.

[0627] Implementation Scheme 2: The use described in Implementation Scheme 1, wherein the antibody-drug conjugate is selected from anti-Trop-2 antibody-drug conjugates.

[0628] Implementation Scheme 3: The use described in Implementation Scheme 2, wherein the anti-Trop-2 antibody drug conjugate has the structure of the following formula (I): {D-[L1-(L2)m1-(L3)m2-(L4)m3-E]} q -A formula (I)

[0629] in,

[0630] L1 is Each of R1 and R2 is independently hydrogen (e.g., protium or deuterium), halogen, carboxylic acid group, sulfonic acid group, cyano group, or C. 1-6 Alkyl, Halogenated C 1-6 alkyl and cyano substituted C1-6 Alkyl groups (e.g., -CH2CN), C 1-6 Alkoxy, C 2-10 alkenyl or C 2-10 Alkyne group; Z1 is an amino acid or a peptide composed of 2-10 amino acids; x1 and x2 are each independently 0, 1, 2, 3, 4, 5 or 6; and L1 is connected to D at position 1 and L2 at position 2.

[0631] L2 is Where y1 is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; and L2 is connected to L1 at position 1 and L2 is connected to L3 at position 2.

[0632] L3 is a 5-12 member heterocyclic aromatic ring;

[0633] L4 is Z2 is selected from C. 1-6 Alkylene, C 2-10 imidene group, C 2-10 etyne group, and C 3-8 Cycloalkylene; R3 is selected from H and C 1-6 Alkyl group; Z3 is absent or is C 1-6 Alkylene; or, R3 and Z3 together with the nitrogen atom to which they are attached form a 4-8 membered heterocyclic group; α is 0, 1, 2, 3, 4, 5 or 6, and L4 is attached to E at the 2 position and to L3 at the 1 position;

[0634] E is In this context, each R4 is independently hydrogen (e.g., protium or deuterium), β is 0, 1 or 2, and E is connected to A at position 2 and to L4 at position 1.

[0635] m1, m2 and m3 are each independently 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;

[0636] D represents a bioactive molecular fragment;

[0637] q refers to {D-[L1-(L2]} which forms a thioether bond with the thiol group of A. m1 -(L3) m2 -(L4) m3 The number of the -E]} part is selected from 1 to 10;

[0638] A represents an anti-Trop-2 antibody or its antigen-binding fragment.

[0639] Implementation Scheme 4: The use described in Implementation Scheme 3, wherein the anti-Trop-2 antibody drug conjugate satisfies one or more of the following:

[0640] (1) L1 is selected from Furthermore, position 1 of L1 is connected to D, and position 2 of L1 is connected to L2;

[0641] (2) L2 is Where y1 is 3, 4, 5, 6, 7, 8, 9 or 10; and L2 is connected to L1 at position 1 and L2 is connected to L3 at position 2.

[0642] (3) L3 is selected from 5-6 membered heteroaryl rings, such as pyrazole or triazole;

[0643] (4) L4 is Z2 is selected from C. 1-3 Alkylene; R3 is H; Z3 is selected from C 1-3 Alkylene; α is 0 or 1, and L4 is connected to E at position 2 and to L3 at position 1;

[0644] (5) E is In this configuration, each R4 is independently hydrogen (e.g., protium or deuterium), β is 0, 1 or 2, and E is connected to A at position 2 (e.g., to a thiol group on A) and to L4 at position 1.

[0645] (6) m1, m2 and m3 are all 1;

[0646] (7) The bioactive molecules are selected from Preferably, D is selected from

[0647] (8) q is selected from 3 to 8 (e.g., 3, 4, 5, 6, 7 or 8) and / or,

[0648] (9) A is Sacituzumab or its antigen-binding fragment.

[0649] Implementation Scheme 5: The use described in any one of Implementation Schemes 2-4, wherein the anti-Trop-2 antibody drug conjugate has the following chemical structure:

[0650] Where A is an anti-Trop-2 antibody or its antigen-binding fragment; q is selected from 1-10.

[0651] Implementation Scheme 6: The use described in any one of Implementation Schemes 3-5, wherein the anti-Trop-2 antibody or its antigen-binding fragment comprises:

[0652] (1) The following heavy chain variable regions (VH) and / or light chain variable regions (VL), as defined in the Chothia numbering system:

[0653] Heavy chain variable region (VH) containing the following 3 CDRs: CDR-H1 with sequence of SEQ ID NO:1 or a variant thereof, CDR-H2 with sequence of SEQ ID NO:2 or a variant thereof, and CDR-H3 with sequence of SEQ ID NO:3 or a variant thereof; and / or, light chain variable region (VL) containing the following 3 CDRs: CDR-L1 with sequence of SEQ ID NO:4 or a variant thereof, CDR-L2 with sequence of SEQ ID NO:5 or a variant thereof, and CDR-L3 with sequence of SEQ ID NO:6 or a variant thereof;

[0654] The variant has at least 70%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with its source sequence, or the variant has one or more amino acid substitutions, deletions, or additions (e.g., substitutions, deletions, or additions of 1, 2, or 3 amino acids) compared to its source sequence; preferably, the substitutions are conservative substitutions;

[0655] or,

[0656] (2) The following heavy chain variable regions (VH) and / or light chain variable regions (VL), defined according to the AbM numbering system:

[0657] Heavy chain variable region (VH) containing the following 3 CDRs: CDR-H1 with sequence of SEQ ID NO:14 or a variant thereof, CDR-H2 with sequence of SEQ ID NO:15 or a variant thereof, and CDR-H3 with sequence of SEQ ID NO:3 or a variant thereof; and / or, light chain variable region (VL) containing the following 3 CDRs: CDR-L1 with sequence of SEQ ID NO:4 or a variant thereof, CDR-L2 with sequence of SEQ ID NO:5 or a variant thereof, and CDR-L3 with sequence of SEQ ID NO:6 or a variant thereof;

[0658] The variant has at least 70%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with its source sequence, or the variant has one or more amino acid substitutions, deletions, or additions (e.g., substitutions, deletions, or additions of 1, 2, or 3 amino acids) compared to its source sequence; preferably, the substitutions are conservative substitutions;

[0659] or,

[0660] (3) The following heavy chain variable regions (VH) and / or light chain variable regions (VL), as defined in the Kabat numbering system:

[0661] Heavy chain variable region (VH) containing the following 3 CDRs: CDR-H1 with sequence of SEQ ID NO:7 or a variant thereof, CDR-H2 with sequence of SEQ ID NO:8 or a variant thereof, and CDR-H3 with sequence of SEQ ID NO:3 or a variant thereof; and / or, light chain variable region (VL) containing the following 3 CDRs: CDR-L1 with sequence of SEQ ID NO:4 or a variant thereof, CDR-L2 with sequence of SEQ ID NO:5 or a variant thereof, and CDR-L3 with sequence of SEQ ID NO:6 or a variant thereof;

[0662] The variant has at least 70%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with its source sequence, or the variant has one or more amino acid substitutions, deletions, or additions (e.g., substitutions, deletions, or additions of 1, 2, or 3 amino acids) compared to its source sequence; preferably, the substitutions are conservative substitutions;

[0663] or,

[0664] (4) The following heavy chain variable regions (VH) and / or light chain variable regions (VL), as defined by the IMGT numbering system:

[0665] Heavy chain variable region (VH) containing the following 3 CDRs: CDR-H1 with sequence of SEQ ID NO:9 or a variant thereof, CDR-H2 with sequence of SEQ ID NO:10 or a variant thereof, and CDR-H3 with sequence of SEQ ID NO:11 or a variant thereof; and / or, light chain variable region (VL) containing the following 3 CDRs: CDR-L1 with sequence of SEQ ID NO:12 or a variant thereof, CDR-L2 with sequence of SEQ ID NO:13 or a variant thereof, and CDR-L3 with sequence of SEQ ID NO:6 or a variant thereof;

[0666] The variant has at least 70%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with the sequence from which it originates, or the variant has one or more amino acid substitutions, deletions, or additions (e.g., substitutions, deletions, or additions of 1, 2, or 3 amino acids) compared to the sequence from which it originates; preferably, the substitutions are conservative substitutions.

[0667] Implementation Scheme 7: The use described in Implementation Scheme 6, wherein the anti-Trop-2 antibody or its antigen-binding fragment comprises: VH or a variant thereof shown in SEQ ID NO: 16, and VL or a variant thereof shown in SEQ ID NO: 17.

[0668] Implementation Scheme 8: The use described in any one of Implementation Schemes 5-7, wherein the anti-Trop-2 antibody or its antigen-binding fragment further comprises:

[0669] (a) The heavy chain constant region (CH) of human immunoglobulin or a variant thereof, said variant having one or more amino acid substitutions, deletions, or additions compared to the wild-type sequence from which it is derived; and

[0670] (b) The light chain constant region (CL) of human immunoglobulin or a variant thereof, wherein the variant has one or more amino acid substitutions, deletions or additions compared to the wild-type sequence from which it is derived.

[0671] Implementation Scheme 9: The use described in any one of Implementation Schemes 5-8, wherein the anti-Trop-2 antibody or its antigen-binding fragment comprises the heavy chain shown in SEQ ID NO:18 and the light chain shown in SEQ ID NO:19.

[0672] Implementation Scheme 10: The use described in any one of Implementation Schemes 2-9, wherein the anti-Trop-2 antibody drug conjugate has the following chemical structure:

[0673] Where q is selected from 1 to 10.

[0674] Implementation Scheme 11: For any of the uses described in Implementation Schemes 2-10, the DAR value of the anti-Trop-2 antibody drug conjugate is approximately an integer or decimal of 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3, 1-2, 2-10, 2-9, 2-8, 2-7, 2-6, 2-5, 2-4, 2-3, 3-10, 3-9, 3-8, 3-7, 3-6, 3-5, 3-4, 4-10, 4-9, 4-8, 4-7, 4-6, 4-5, 5-10, 5-9, 5-8, 5-7, 5-6, 6-10, 6-9, 6-8, 6-7, 7-10, 7-9, 7-8, 8-10, 8-9, or 9-10.

[0675] Implementation Scheme 12: The use described in Implementation Scheme 11, wherein the DAR value of the anti-Trop-2 antibody drug conjugate is approximately 5.0, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6.0, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, 7.0, 7.1, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, or 8.0.

[0676] Implementation Scheme 13: The use described in any one of Implementation Schemes 2-12, wherein the anti-Trop-2 antibody drug conjugate, EGFR inhibitor, VEGF inhibitor and other active therapeutic agents are administered simultaneously, separately, sequentially or in sequence.

[0677] Implementation Scheme 14: The use described in any one of Implementation Schemes 2-13, wherein the anti-Trop-2 antibody drug conjugate possesses one or more of the following characteristics:

[0678] (1) Administer the medication according to the dosing cycle of 1-42 days;

[0679] (2) The frequency of administration is 1 to 8 times within 1 to 4 weeks; for example, once a week, twice a week, once every 2 weeks or once every 3 weeks;

[0680] (3) The dose administered each time is selected from 0.1-20 mg / kg or more, such as 0.5-10 mg / kg, such as 0.5-5 mg / kg, such as 3 mg / kg, 4 mg / kg or 5 mg / kg, based on the subject’s weight;

[0681] (4) The dosage concentration for each application is selected from 0.01-50 mg / ml; and / or,

[0682] (5) Dosage (e.g., single dose or unit dose) is selected from 0.1-1000 mg.

[0683] Implementation Scheme 15: The use described in any one of Implementation Schemes 2-14, wherein the VEGF inhibitor possesses one or more of the following characteristics:

[0684] (1) Administer the medication according to a dosing cycle of 1-42 days, for example, 1-28 days, for example, 1-14 days or 1-21 days;

[0685] (2) The frequency of administration is 1 to 8 times within 1 to 4 weeks; for example, once a week, twice a week, once every 2 weeks or once every 3 weeks;

[0686] (3) The dose administered each time is selected from 0.5 mg / kg to 50 mg / kg, for example 0.5-30 mg / kg, for example 0.5-20 mg / kg, 0.5-10 mg / kg or 0.5-5 mg / kg, based on the subject’s weight;

[0687] (4) The dosage concentration for each application is selected from 0.1-50 mg / ml, for example 1-20 mg / ml;

[0688] (5) Dosage (e.g., single-dose dose or unit dose) is selected from 0.1-1000 mg; and / or

[0689] (6) The conjugate with the anti-Trop-2 antibody drug can be administered simultaneously, within 1 day (e.g., at intervals of 0.5 to 2 hours) or at intervals of at least 1 day, 2 days, 3 days, 5 days, 6 days, 7 days, 10 days, 15 days, 21 days, 30 days, 45 days, 2 months, 75 days, 3 months or 6 months.

[0690] Implementation Scheme 16: The use described in any one of Implementation Schemes 2-15, wherein the EGFR inhibitor possesses one or more of the following characteristics:

[0691] (1) Administer the medication according to the dosing cycle of 1-42 days;

[0692] (2) The frequency of administration is 1 to 8 times within 1 to 4 weeks; for example, once a week, twice a week, once every 2 weeks or once every 3 weeks;

[0693] (3) The dose administered each time is selected from 0.5 mg / kg to 50 mg / kg based on the subject’s weight, for example, from 0.5 to 30 mg / kg, such as 0.5 to 20 mg / kg, 0.5 to 10 mg / kg or 0.5 to 5 mg / kg;

[0694] (4) The dosage concentration for each application is selected from 0.1-50 mg / ml;

[0695] (5) The dosage (e.g., a single-dose dose or a unit dose) is selected from 0.1-1000 mg, such as 1-900 mg, 1-800 mg, 1-700 mg, 1-600 mg, 1-500 mg, 1-400 mg, 1-300 mg, 1-200 mg, 1-100 mg, 1-50 mg, 1-30 mg, 1-20 mg, or 1-10 mg; and / or

[0696] (6) It can be administered simultaneously with anti-Trop-2 antibody drug conjugates and / or VEGF inhibitors, within 1 day (e.g., at intervals of 0.5 to 2 hours) or at intervals of at least 1 day, 2 days, 3 days, 5 days, 6 days, 7 days, 10 days, 15 days, 21 days, 30 days, 45 days, 2 months, 75 days, 3 months or 6 months.

[0697] Implementation Scheme 17: The use described in any one of Implementation Schemes 1-16, wherein the VEGF inhibitor is selected from anti-VEGF antibodies and / or their antigen-binding fragments;

[0698] Preferably, the VEGF inhibitor is selected from one or more of bevacizumab, ramucirumab, ranibizumab, and faricimab or their biosimilars;

[0699] The bevacizumab biosimilars mentioned are selected from: MVASI, Zirabev, Bevax, Lumiere, Equidacent, Avegra, BP 01, BCD500, Krabeva, BAT1706, BXT-2316, Bevalo, BI 695502, CT-P16, CHS-5217, DRZBZ, Cizumab, Byvasda, MIL60, MYL 14020, ONS1045, HD204, Ankeda, Bevacizel, Aybintio, Onbevzi, HLX04, TX16, MB02, and Oyavas;

[0700] Preferably, the VEGF inhibitor is bevacizumab or its biosimilar.

[0701] Implementation Scheme 18: The use described in any one of Implementation Schemes 1-17, wherein the EGFR inhibitor is selected from anti-EGFR antibodies and / or their antigen-binding fragments;

[0702] Preferably, the EGFR inhibitor is selected from one or more of cetuximab, panitumumab, nexituzumab, nimotuzumab, Rybrevant, and Amivantamab.

[0703] Preferably, the EGFR inhibitor is cetuximab or its biosimilar.

[0704] Implementation Scheme 19: The use described in any one of Implementation Schemes 1-18, wherein the second therapeutic agent is an EGFR inhibitor.

[0705] Implementation Scheme 20: The use described in any one of Implementation Schemes 1-18, wherein the second therapeutic agent is a VEGF inhibitor.

[0706] Implementation Scheme 21: The use described in any one of Implementation Schemes 1-18, wherein the second therapeutic agent is an EGFR inhibitor and a VEGF inhibitor.

[0707] Implementation Scheme 22: Use of the composition of the anti-Trop-2 antibody drug conjugate in the preparation of a medicament for treating tumors or cancer, wherein the other therapeutic agents are VEGF inhibitors and / or EGFR inhibitors as described in any one of Implementation Schemes 1-21, and the composition of the anti-Trop-2 antibody drug conjugate comprises one or more anti-Trop-2 antibody drug conjugates as described in any one of Implementation Schemes 2-21.

[0708] Implementation Scheme 23: Use of the anti-Trop-2 antibody-drug conjugate according to any one of Implementation Schemes 2-21 in the preparation of a medicament for improving the efficacy of other therapeutic agents in the treatment of tumors or cancer, said other therapeutic agents being VEGF inhibitors and / or EGFR inhibitors as described in any one of Implementation Schemes 1-21.

[0709] Implementation Scheme 24: The use described in any one of Implementation Schemes 1-23, wherein the tumor or cancer is selected from: solid tumors or non-solid tumors; for example, selected from esophageal cancer (e.g., esophageal adenocarcinoma and esophageal squamous cell carcinoma), lung cancer (e.g., small cell lung cancer and non-small cell lung cancer), squamous cell carcinoma, bladder cancer, gastric cancer, ovarian cancer (e.g., ovarian epithelial carcinoma, fallopian tube cancer), peritoneal cancer, pancreatic cancer, breast cancer, cervical cancer, endometrial cancer, colorectal cancer, liver cancer, kidney cancer, prostate cancer, and colon cancer.

[0710] Implementation Scheme 25: A treatment combination or composition comprising the anti-Trop-2 antibody-drug conjugate as described in any one of Implementation Schemes 2-21, the VEGF inhibitor and / or EGFR inhibitor as described in any one of Implementation Schemes 1-21, and optionally other active therapeutic agents.

[0711] Implementation Scheme 26: A treatment combination or composition comprising the anti-Trop-2 antibody-drug conjugate as described in any one of Implementation Schemes 2-21, the VEGF inhibitor and / or EGFR inhibitor as described in any one of Implementation Schemes 1-21, and hyaluronic acid degrading enzyme.

[0712] Implementation Scheme 27: The treatment combination or composition described in Implementation Scheme 26, wherein the hyaluronic acid degrading enzyme is a soluble hyaluronidase.

[0713] Implementation Scheme 28: The treatment combination or composition described in Implementation Scheme 27, wherein the soluble hyaluronidase is hyaluronidase PH20.

[0714] Implementation Scheme 29: The treatment combination or composition described in Implementation Scheme 28, wherein the soluble hyaluronidase is recombinant human hyaluronidase or recombinant hyaluronidase α.

[0715] Implementation Scheme 30: A pharmaceutical composition comprising the anti-Trop-2 antibody-drug conjugate of any one of Implementation Schemes 2-21, the VEGF inhibitor and / or EGFR inhibitor of any one of Implementation Schemes 1-21, and one or more pharmaceutically acceptable excipients, diluents or carriers.

[0716] Implementation Scheme 31: A kit comprising the anti-Trop-2 antibody-drug conjugate as described in any one of Implementation Schemes 2-21, the VEGF inhibitor and / or EGFR inhibitor as described in any one of Implementation Schemes 1-21, and optionally further comprising other active therapeutic agents and / or instructions for use.

[0717] Implementation Scheme 32: A kit comprising: (a) the anti-Trop-2 antibody drug conjugate and the EGFR inhibitor of any one of Implementation Schemes 2-21; (b) the anti-Trop-2 antibody drug conjugate and the VEGF inhibitor of any one of Implementation Schemes 1-21; (c) the EGFR inhibitor and the VEGF inhibitor of any one of Implementation Schemes 1-21; (d) the VEGF inhibitor of any one of Implementation Schemes 1-21; (e) the anti-Trop-2 antibody drug conjugate of any one of Implementation Schemes 2-21; (f) the anti-EGFR inhibitor of any one of Implementation Schemes 1-21; or (g) the anti-Trop-2 antibody drug conjugate, the VEGF inhibitor and the EGFR inhibitor of any one of Implementation Schemes 1-21, and hyaluronic acid degrading enzyme.

[0718] Implementation Scheme 33: The medicine box described in Implementation Scheme 31 or 32, wherein each component is in a different container.

[0719] Implementation Scheme 34: The medicine box described in Implementation Scheme 32, wherein the hyaluronic acid degrading enzyme is a soluble hyaluronidase.

[0720] Implementation Scheme 35: The medicine box described in Implementation Scheme 34, wherein the soluble hyaluronidase is soluble hyaluronidase PH20.

[0721] Implementation Scheme 36: The medicine box described in Implementation Scheme 35, wherein the soluble hyaluronidase is recombinant human hyaluronidase or recombinant human hyaluronidase α.

[0722] Implementation Scheme 37: The anti-Trop-2 antibody-drug conjugate described in any one of Implementation Schemes 2-21, used for the treatment of tumors or cancer, wherein the anti-Trop-2 antibody-drug conjugate is administered in combination with other therapeutic agents.

[0723] Implementation Scheme 38: The anti-Trop-2 antibody-drug conjugate described in Implementation Scheme 37, wherein the other therapeutic agents are such as the VEGF inhibitor or EGFR inhibitor described in any one of Implementation Schemes 1-21, and optionally the hyaluronic acid degrading enzyme described in any one of Implementation Schemes 26-29, preferably, the VEGF inhibitor is selected from bevacizumab, and the EGFR inhibitor is selected from cetuximab; the hyaluronic acid degrading enzyme is a soluble hyaluronidase, preferably, the hyaluronic acid degrading enzyme is hyaluronidase PH20, recombinant human hyaluronidase, or recombinant hyaluronidase α;

[0724] Preferably, the anti-Trop-2 antibody-drug conjugate and other therapeutic agents are administered according to any one of embodiments 13-16.

[0725] Implementation Scheme 39: A method for preventing and / or treating a tumor or cancer in a subject, the method comprising administering to a subject in need an effective amount of the treatment combination or composition of any one of Implementation Schemes 25-29, the pharmaceutical composition of Implementation Scheme 30, or the kit of any one of Implementation Schemes 31-36.

[0726] Implementation Scheme 40: The method described in Implementation Scheme 39, wherein the tumor or cancer is selected from: solid tumors or non-solid tumors; for example, selected from esophageal cancer (e.g., esophageal adenocarcinoma and esophageal squamous cell carcinoma), lung cancer (e.g., small cell lung cancer and non-small cell lung cancer), squamous cell carcinoma, bladder cancer, gastric cancer, ovarian cancer (e.g., ovarian epithelial carcinoma, fallopian tube cancer), peritoneal cancer, pancreatic cancer, breast cancer, cervical cancer, endometrial cancer, colorectal cancer, liver cancer, kidney cancer, prostate cancer, and colon cancer.

[0727] Implementation Scheme 41: The method described in Implementation Scheme 39 or 40, wherein the anti-Trop-2 antibody drug conjugate, EGFR inhibitor, VEGF inhibitor and other active therapeutic agents are administered simultaneously, separately, sequentially or in sequence.

[0728] Implementation Scheme 42: The method described in any one of Implementation Schemes 39-41, wherein the anti-Trop-2 antibody drug conjugate is applied according to one or more of the following:

[0729] (1) Administer the medication according to the dosing cycle of 1-42 days;

[0730] (2) The frequency of administration is 1 to 8 times within 1 to 4 weeks; for example, once a week, twice a week, once every 2 weeks or once every 3 weeks;

[0731] (3) The dose administered each time is selected from 0.1-20 mg / kg or more, such as 0.5-10 mg / kg, such as 0.5-5 mg / kg, such as 3 mg / kg, 4 mg / kg or 5 mg / kg, based on the subject’s weight;

[0732] (4) The dosage concentration for each application is selected from 0.01-50 mg / ml; and / or,

[0733] (5) Dosage (e.g., single dose or unit dose) is selected from 0.1-1000 mg.

[0734] Implementation Scheme 43: The method described in any one of Implementation Schemes 39-41, wherein the VEGF inhibitor is applied according to one or more of the following:

[0735] (1) Administer the medication according to the dosing cycle of 1-42 days;

[0736] (2) The frequency of administration is 1 to 8 times within 1 to 4 weeks; for example, once a week, twice a week, once every 2 weeks or once every 3 weeks;

[0737] (3) The dose administered each time is selected from 0.5 mg / kg to 50 mg / kg, for example 0.5-30 mg / kg, for example 0.5-20 mg / kg, 0.5-10 mg / kg or 0.5-5 mg / kg, based on the subject’s weight;

[0738] (4) The dosage concentration for each application is selected from 0.1-50 mg / ml, for example 1-20 mg / ml;

[0739] (5) Dosage (e.g., single-dose dose or unit dose) is selected from 0.1-1000 mg; and / or

[0740] (6) The conjugate with the anti-Trop-2 antibody drug can be administered simultaneously, within 1 day (e.g., at intervals of 0.5 to 2 hours) or at intervals of at least 1 day, 2 days, 3 days, 5 days, 6 days, 7 days, 10 days, 15 days, 21 days, 30 days, 45 days, 2 months, 75 days, 3 months or 6 months.

[0741] Implementation Scheme 44: The method described in any one of Implementation Schemes 39-41, wherein the EGFR inhibitor is applied according to one or more of the following:

[0742] (1) Administer the medication according to the dosing cycle of 1-42 days;

[0743] (2) The frequency of administration is 1 to 8 times within 1 to 4 weeks; for example, once a week, twice a week, once every 2 weeks or once every 3 weeks;

[0744] (3) The dose administered each time is selected from 0.5 mg / kg to 50 mg / kg based on the subject’s weight, for example, from 0.5 to 30 mg / kg, such as 0.5 to 20 mg / kg, 0.5 to 10 mg / kg or 0.5 to 5 mg / kg;

[0745] (4) The dosage concentration for each application is selected from 0.1-50 mg / ml;

[0746] (5) The dosage (e.g., a single-dose dose or a unit dose) is selected from 0.1-1000 mg, such as 1-900 mg, 1-800 mg, 1-700 mg, 1-600 mg, 1-500 mg, 1-400 mg, 1-300 mg, 1-200 mg, 1-100 mg, 1-50 mg, 1-30 mg, 1-20 mg, or 1-10 mg; and / or

[0747] (6) It can be administered simultaneously with anti-Trop-2 antibody drug conjugates and / or VEGF inhibitors, within 1 day (e.g., at intervals of 0.5 to 2 hours) or at intervals of at least 1 day, 2 days, 3 days, 5 days, 6 days, 7 days, 10 days, 15 days, 21 days, 30 days, 45 days, 2 months, 75 days, 3 months or 6 months.

[0748] Implementation Scheme 45: Use of an anti-Trop-2 antibody drug conjugate or a composition thereof in the preparation of a medicament for treating a subject’s tumor or cancer, wherein the medicament is administered in combination with a second therapeutic agent, the anti-Trop-2 antibody drug conjugate being as described in any one of Implementation Schemes 3-21, the composition of the anti-Trop-2 antibody drug conjugate comprising one or more of the anti-Trop-2 antibody drug conjugates, the second therapeutic agent being as described in any one of Implementation Schemes 1, 17-21, and optionally, any one of Implementation Schemes 26-29, a hyaluronic acid-degrading enzyme;

[0749] Preferably, the drug and the second therapeutic agent are administered according to any one of embodiments 13-16;

[0750] Preferably, the tumor or cancer is as described in embodiment 24.

[0751] Implementation Scheme 46: Use of a VEGF inhibitor and / or an EGFR inhibitor in the preparation of a medicament for treating a subject’s tumor or cancer, wherein the medicament is administered in combination with an anti-Trop-2 antibody-drug conjugate or a composition thereof, the anti-Trop-2 antibody-drug conjugate being as described in any one of Implementation Schemes 3-21, the composition of the anti-Trop-2 antibody-drug conjugate comprising one or more of the anti-Trop-2 antibody-drug conjugates, the VEGF inhibitor being as described in Implementation Scheme 17, the EGFR inhibitor being as described in Implementation Scheme 18, and optionally, a hyaluronidase as described in any one of Implementation Schemes 26-29;

[0752] Preferably, the drug, VEGF inhibitor, and EGFR inhibitor are administered according to any one of embodiments 13-16;

[0753] Preferably, the tumor or cancer is as described in embodiment 24.

[0754] Implementation Scheme 47: Use of antibody-drug conjugates, and one or both of EGFR inhibitors and VEGF inhibitors, and optionally including other active therapeutic agents, in the preparation of a drug for treating tumors or cancer.

[0755] Implementation Scheme 48: The use described in Implementation Scheme 47, wherein the antibody drug conjugate is selected from anti-Trop-2 antibody drug conjugates.

[0756] Implementation Scheme 49: The use described in Implementation Scheme 48, wherein the anti-Trop-2 antibody drug conjugate has the structure of the following formula (I): {D-[L1-(L2)m1-(L3)m2-(L4)m3-E]} q -A formula (I)

[0757] in,

[0758] L1 is Each of R1 and R2 is independently hydrogen (e.g., protium or deuterium), halogen, carboxylic acid group, sulfonic acid group, cyano group, or C. 1-6 Alkyl, Halogenated C 1-6 alkyl and cyano substituted C 1-6 Alkyl groups (e.g., -CH2CN), C 1-6 Alkoxy, C 2-10 alkenyl or C 2-10Alkyne group; Z1 is an amino acid or a peptide composed of 2-10 amino acids; x1 and x2 are each independently 0, 1, 2, 3, 4, 5 or 6; and L1 is connected to D at position 1 and L2 at position 2.

[0759] L2 is Where y1 is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; and L2 is connected to L1 at position 1 and L2 is connected to L3 at position 2.

[0760] L3 is a 5-12 member heterocyclic aromatic ring;

[0761] L4 is Z2 is selected from C. 1-6 Alkylene, C 2-10 imidene group, C 2-10 etyne group, and C 3-8 Cycloalkylene; R3 is selected from H and C 1-6 Alkyl group; Z3 is absent or is C 1-6 Alkylene; or, R3 and Z3 together with the nitrogen atom to which they are attached form a 4-8 membered heterocyclic group; α is 0, 1, 2, 3, 4, 5 or 6, and L4 is attached to E at the 2 position and to L3 at the 1 position;

[0762] E is In this context, each R4 is independently hydrogen (e.g., protium or deuterium), β is 0, 1 or 2, and E is connected to A at position 2 and to L4 at position 1.

[0763] m1, m2 and m3 are each independently 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;

[0764] D represents a bioactive molecular fragment;

[0765] q refers to {D-[L1-(L2]} which forms a thioether bond with the thiol group of A. m1 -(L3) m2 -(L4) m3 The number of the -E]} part is selected from 1 to 10;

[0766] A represents an anti-Trop-2 antibody or its antigen-binding fragment.

[0767] Implementation Scheme 50: The use described in Implementation Scheme 49, wherein the anti-Trop-2 antibody drug conjugate satisfies one or more of the following:

[0768] (1) L1 is selected from Furthermore, position 1 of L1 is connected to D, and position 2 of L1 is connected to L2;

[0769] (2) L2 is Where y1 is 3, 4, 5, 6, 7, 8, 9 or 10; and L2 is connected to L1 at position 1 and L2 is connected to L3 at position 2.

[0770] (3) L3 is selected from 5-6 membered heteroaryl rings, such as pyrazole or triazole;

[0771] (4) L4 is Z2 is selected from C. 1-3 Alkylene; R3 is H; Z3 is selected from C 1-3 Alkylene; α is 0 or 1, and L4 is connected to E at position 2 and to L3 at position 1;

[0772] (5) E is In this configuration, each R4 is independently hydrogen (e.g., protium or deuterium), β is 0, 1 or 2, and E is connected to A at position 2 (e.g., to a thiol group on A) and to L4 at position 1.

[0773] (6) m1, m2 and m3 are all 1;

[0774] (7) The bioactive molecules are selected from Preferably, D is selected from

[0775] (8) q is selected from 3 to 8 (e.g., 3, 4, 5, 6, 7 or 8) and / or,

[0776] (9)Ab is Sacituzumab or its antigen-binding fragment.

[0777] Implementation Scheme 51: The use described in any one of Implementation Schemes 48-50, wherein the anti-Trop-2 antibody drug conjugate has the following chemical structure:

[0778] Where A is an anti-Trop-2 antibody or its antigen-binding fragment; q is selected from 1-10.

[0779] Implementation Scheme 52: The use described in any one of Implementation Schemes 49-51, wherein the anti-Trop-2 antibody or its antigen-binding fragment comprises:

[0780] (1) The following heavy chain variable regions (VH) and / or light chain variable regions (VL), as defined in the Chothia numbering system:

[0781] Heavy chain variable region (VH) containing the following 3 CDRs: CDR-H1 with sequence of SEQ ID NO:1 or a variant thereof, CDR-H2 with sequence of SEQ ID NO:2 or a variant thereof, and CDR-H3 with sequence of SEQ ID NO:3 or a variant thereof; and / or, light chain variable region (VL) containing the following 3 CDRs: CDR-L1 with sequence of SEQ ID NO:4 or a variant thereof, CDR-L2 with sequence of SEQ ID NO:5 or a variant thereof, and CDR-L3 with sequence of SEQ ID NO:6 or a variant thereof;

[0782] The variant has at least 70%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with its source sequence, or the variant has one or more amino acid substitutions, deletions, or additions (e.g., substitutions, deletions, or additions of 1, 2, or 3 amino acids) compared to its source sequence; preferably, the substitutions are conservative substitutions;

[0783] or,

[0784] (2) The following heavy chain variable regions (VH) and / or light chain variable regions (VL), defined according to the AbM numbering system:

[0785] Heavy chain variable region (VH) containing the following 3 CDRs: CDR-H1 with sequence of SEQ ID NO:14 or a variant thereof, CDR-H2 with sequence of SEQ ID NO:15 or a variant thereof, and CDR-H3 with sequence of SEQ ID NO:3 or a variant thereof; and / or, light chain variable region (VL) containing the following 3 CDRs: CDR-L1 with sequence of SEQ ID NO:4 or a variant thereof, CDR-L2 with sequence of SEQ ID NO:5 or a variant thereof, and CDR-L3 with sequence of SEQ ID NO:6 or a variant thereof;

[0786] The variant has at least 70%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with its source sequence, or the variant has one or more amino acid substitutions, deletions, or additions (e.g., substitutions, deletions, or additions of 1, 2, or 3 amino acids) compared to its source sequence; preferably, the substitutions are conservative substitutions;

[0787] or,

[0788] (3) The following heavy chain variable regions (VH) and / or light chain variable regions (VL), as defined in the Kabat numbering system:

[0789] Heavy chain variable region (VH) containing the following 3 CDRs: CDR-H1 with sequence of SEQ ID NO:7 or a variant thereof, CDR-H2 with sequence of SEQ ID NO:8 or a variant thereof, and CDR-H3 with sequence of SEQ ID NO:3 or a variant thereof; and / or, light chain variable region (VL) containing the following 3 CDRs: CDR-L1 with sequence of SEQ ID NO:4 or a variant thereof, CDR-L2 with sequence of SEQ ID NO:5 or a variant thereof, and CDR-L3 with sequence of SEQ ID NO:6 or a variant thereof;

[0790] The variant has at least 70%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with its source sequence, or the variant has one or more amino acid substitutions, deletions, or additions (e.g., substitutions, deletions, or additions of 1, 2, or 3 amino acids) compared to its source sequence; preferably, the substitutions are conservative substitutions;

[0791] or,

[0792] (4) The following heavy chain variable regions (VH) and / or light chain variable regions (VL), as defined by the IMGT numbering system:

[0793] Heavy chain variable region (VH) containing the following 3 CDRs: CDR-H1 with sequence of SEQ ID NO:9 or a variant thereof, CDR-H2 with sequence of SEQ ID NO:10 or a variant thereof, and CDR-H3 with sequence of SEQ ID NO:11 or a variant thereof; and / or, light chain variable region (VL) containing the following 3 CDRs: CDR-L1 with sequence of SEQ ID NO:12 or a variant thereof, CDR-L2 with sequence of SEQ ID NO:13 or a variant thereof, and CDR-L3 with sequence of SEQ ID NO:6 or a variant thereof;

[0794] The variant has at least 70%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with the sequence from which it originates, or the variant has one or more amino acid substitutions, deletions, or additions (e.g., substitutions, deletions, or additions of 1, 2, or 3 amino acids) compared to the sequence from which it originates; preferably, the substitutions are conservative substitutions.

[0795] Implementation Scheme 53: The use described in Implementation Scheme 52, wherein the anti-Trop-2 antibody or its antigen-binding fragment comprises: VH or a variant thereof shown in SEQ ID NO: 16, and VL or a variant thereof shown in SEQ ID NO: 17.

[0796] Implementation Scheme 54: The use described in any one of Implementation Schemes 51-53, wherein the anti-Trop-2 antibody or its antigen-binding fragment further comprises:

[0797] (a) The heavy chain constant region (CH) of human immunoglobulin or a variant thereof, said variant having one or more amino acid substitutions, deletions, or additions compared to the wild-type sequence from which it is derived; and

[0798] (b) The light chain constant region (CL) of human immunoglobulin or a variant thereof, wherein the variant has one or more amino acid substitutions, deletions or additions compared to the wild-type sequence from which it is derived.

[0799] Implementation Scheme 55: The use described in any one of Implementation Schemes 51-54, wherein the anti-Trop-2 antibody or its antigen-binding fragment comprises the heavy chain shown in SEQ ID NO:18 and the light chain shown in SEQ ID NO:19.

[0800] Implementation Scheme 56: The use described in any one of Implementation Schemes 48-55, wherein the anti-Trop-2 antibody drug conjugate has the following chemical structure:

[0801] Where q is selected from 1 to 10.

[0802] Implementation Scheme 57: The use described in any one of Implementation Schemes 48-56, wherein the DAR value of the anti-Trop-2 antibody drug conjugate is approximately an integer or decimal of 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3, 1-2, 2-10, 2-9, 2-8, 2-7, 2-6, 2-5, 2-4, 2-3, 3-10, 3-9, 3-8, 3-7, 3-6, 3-5, 3-4, 4-10, 4-9, 4-8, 4-7, 4-6, 4-5, 5-10, 5-9, 5-8, 5-7, 5-6, 6-10, 6-9, 6-8, 6-7, 7-10, 7-9, 7-8, 8-10, 8-9, or 9-10.

[0803] Implementation Scheme 58: The use described in Implementation Scheme 57, wherein the DAR value of the anti-Trop-2 antibody drug conjugate is approximately 5.0, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6.0, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, 7.0, 7.1, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, or 8.0.

[0804] Implementation Scheme 59: The use described in any one of Implementation Schemes 48-58, wherein the anti-Trop-2 antibody-drug conjugate, EGFR inhibitor, VEGF inhibitor, and optionally other active therapeutic agents can be administered simultaneously, separately, sequentially, and in combination.

[0805] Implementation Scheme 60: The use described in any one of Implementation Schemes 48-59, wherein the anti-Trop-2 antibody drug conjugate possesses one or more of the following characteristics:

[0806] (1) Administer the medication according to the dosing cycle of 1-42 days;

[0807] (2) The frequency of administration is 1 to 8 times within 1 to 4 weeks; for example, once a week, twice a week, once every 2 weeks or once every 3 weeks;

[0808] (3) The dosage for each application is selected from 0.1-20 mg / kg or more;

[0809] (4) The dosage concentration for each application is selected from 0.01-50 mg / ml; and / or,

[0810] (5) The content is selected from 0.1-1000mg.

[0811] Implementation Scheme 61: The use described in any one of Implementation Schemes 48-60, wherein the VEGF inhibitor possesses one or more of the following characteristics:

[0812] (1) Administer the medication according to the dosing cycle of 1-42 days;

[0813] (2) The frequency of administration is 1 to 8 times within 1 to 4 weeks; for example, once a week, twice a week, once every 2 weeks or once every 3 weeks;

[0814] (3) The dosage for each application is selected from 0.5 mg / kg to 50 mg / kg;

[0815] (4) The dosage concentration for each application is selected from 0.1-50 mg / ml;

[0816] (5) The content is selected from 0.1-1000 mg; and / or

[0817] (6) The anti-Trop-2 antibody conjugate can be administered simultaneously, within 1 day, or at least 1, 2, 3, 5, 6, 7, 10, 15, 21, 30, 45, 2 months, 75, 3 months, or 6 months apart.

[0818] Implementation Scheme 62: The use described in any one of Implementation Schemes 48-61, wherein the EGFR inhibitor possesses one or more of the following characteristics:

[0819] (1) Administer the medication according to the dosing cycle of 1-42 days;

[0820] (2) The frequency of administration is 1 to 8 times within 1 to 4 weeks; for example, once a week, twice a week, once every 2 weeks or once every 3 weeks;

[0821] (3) The dosage for each application is selected from 0.5 mg / kg to 50 mg / kg;

[0822] (4) The dosage concentration for each application is selected from 0.1-50 mg / ml;

[0823] (5) The content is selected from 0.1-1000 mg; and / or

[0824] (6) It can be administered simultaneously with anti-Trop-2 antibody drug conjugates and / or VEGF inhibitors, or administered within 1 day or at intervals of at least 1 day, 2 days, 3 days, 5 days, 6 days, 7 days, 10 days, 15 days, 21 days, 30 days, 45 days, 2 months, 75 days, 3 months or 6 months.

[0825] Implementation Scheme 63: The use described in any one of Implementation Schemes 47-62, wherein the VEGF inhibitor is selected from anti-VEGF antibodies and / or their antigen-binding fragments, and the EGFR inhibitor is selected from anti-EGFR antibodies and / or their antigen-binding fragments.

[0826] Implementation Scheme 64: The use described in any one of Implementation Schemes 47-63, wherein the VEGF inhibitor is selected from one or more of bevacizumab, ramucirumab, ranibizumab, and faricimab or their biosimilars; preferably, the anti-VEGF antibody is bevacizumab or its biosimilar; the EGFR inhibitor is selected from one or more of cetuximab, panitumumab, nexituzumab, nimotuzumab, rybrevant, and amivantamab.

[0827] Implementation Scheme 65: Use of a composition of an anti-Trop-2 antibody drug conjugate in the preparation of a medicament for treating tumors or cancer, wherein the other therapeutic agents are VEGF inhibitors and / or EGFR inhibitors as described in any one of Implementation Schemes 47-64, and the composition of the anti-Trop-2 antibody drug conjugate comprises one or more anti-Trop-2 antibody drug conjugates as described in any one of Implementation Schemes 48-64.

[0828] Implementation Scheme 66: Use of the anti-Trop-2 antibody-drug conjugate according to any one of Implementation Schemes 48-64 in the preparation of a medicament to enhance the efficacy of other therapeutic agents for the treatment of tumors or cancer, said other therapeutic agents being VEGF inhibitors and / or EGFR inhibitors as described in any one of Implementation Schemes 47-64.

[0829] Implementation Scheme 67: The use described in any one of Implementation Schemes 47-66, wherein the cancer is selected from: solid tumors or non-solid tumors; for example, selected from esophageal cancer (e.g., esophageal adenocarcinoma and esophageal squamous cell carcinoma), lung cancer (e.g., small cell lung cancer and non-small cell lung cancer), squamous cell carcinoma, bladder cancer, gastric cancer, ovarian cancer (e.g., ovarian epithelial carcinoma and fallopian tube cancer), peritoneal cancer, pancreatic cancer, breast cancer, cervical cancer, endometrial cancer, colorectal cancer, liver cancer, kidney cancer, and prostate cancer.

[0830] Implementation Scheme 68: A treatment combination comprising the anti-Trop-2 antibody-drug conjugate as described in any one of Implementation Schemes 48-64, the VEGF inhibitor and / or EGFR inhibitor as described in any one of Implementation Schemes 47-64, and optionally other active therapeutic agents.

[0831] Implementation Scheme 69: A pharmaceutical composition comprising the anti-Trop-2 antibody-drug conjugate of any one of Implementation Schemes 48-64, the VEGF inhibitor and / or EGFR inhibitor of any one of Implementation Schemes 47-64, and one or more pharmaceutically acceptable excipients, diluents or carriers.

[0832] Implementation Scheme 70: A kit containing the anti-Trop-2 antibody-drug conjugate as described in any one of Implementation Schemes 48-64, the VEGF inhibitor and / or EGFR inhibitor as described in any one of Implementation Schemes 47-64, and optionally further containing other active therapeutic agents and / or instructions for use.

[0833] Implementation Scheme 71: The anti-Trop-2 antibody drug conjugate described in any one of Implementation Schemes 48-64, for the treatment of tumors or cancer, wherein the anti-Trop-2 antibody drug conjugate is administered in combination with other therapeutic agents.

[0834] Implementation Scheme 72: The anti-Trop-2 antibody-drug conjugate described in Implementation Scheme 71, wherein the other therapeutic agents are VEGF inhibitors and / or EGFR inhibitors as described in any one of Implementation Schemes 47-64, preferably, the VEGF inhibitor is selected from bevacizumab and the EGFR inhibitor is selected from cetuximab.

[0835] Implementation Scheme 73: A method for preventing and / or treating a tumor or cancer in a subject, the method comprising administering to a subject in need an effective amount of the treatment combination of Implementation Scheme 68, the pharmaceutical composition of Implementation Scheme 69, or the kit of Implementation Scheme 70.

[0836] Implementation Scheme 74: The method described in Implementation Scheme 73, wherein the cancer is selected from: solid tumors or non-solid tumors; for example, selected from esophageal cancer (e.g., esophageal adenocarcinoma and esophageal squamous cell carcinoma), lung cancer (e.g., small cell lung cancer and non-small cell lung cancer), squamous cell carcinoma, bladder cancer, gastric cancer, ovarian cancer (e.g., ovarian epithelial carcinoma and fallopian tube cancer), peritoneal cancer, pancreatic cancer, breast cancer, cervical cancer, endometrial cancer, colorectal cancer, liver cancer, kidney cancer, and prostate cancer.

[0837] Detailed Implementation

[0838] The following description of specific embodiments further illustrates this application, but it is not intended to limit the scope of the application. Those skilled in the art can make various modifications or improvements based on the teachings of this application without departing from its fundamental ideas and scope. Exemplary methods and materials are described herein, although similar or equivalent methods and materials can also be used in the practice or testing of this disclosure. The materials, methods, and examples are illustrative only and not restrictive.

[0839] The sequence information involved in this application is described in the table below:

[0840] Example

[0841] It should be understood that the embodiments and implementations described herein are for illustrative purposes only, and those skilled in the art will make various modifications or changes based on these embodiments and implementations, all of which are included within the spirit and scope of this application.

[0842] Example 1: Pharmacodynamic study in a human subcutaneous gastric cancer xenograft model (NCI-N87)

[0843] BALB / c Nude nude mice (from Chengdu Yaokang Biotechnology Co., Ltd.) were subcutaneously inoculated with human gastric cancer NCI-N87 cells to construct a xenograft tumor model. Antibody-drug conjugate B (from Sichuan Kelun Biotech Co., Ltd., prepared according to the method described in Example 32 of WO2019114666A1, DAR=7.3) and bevacizumab (purchased from Roche) were injected via tail vein (iv). hIgG1 served as a negative control group. The combined efficacy and tolerability of the test drugs in this tumor-bearing mouse model were observed.

[0844] NCI-N87 cells (purchased from Nanjing Kebai) were cultured in vitro as a monolayer in RPMI 1640 medium supplemented with 10% fetal bovine serum at 37°C in an incubator containing 5% CO2. Cells were passaged by trypsin-EDTA digestion 2-3 times per week. When the cells reached the exponential growth phase, the culture medium was collected for mycoplasma testing. After passing the test, the cells were collected and counted.

[0845] Approximately 5 × 10⁵ female BALB / c Nude mice were subcutaneously injected into the right axilla. 6 One NCI-N87 cell (suspended in 0.1 ml of serum-free culture medium). Incubate until the average tumor volume reaches 100–200 mm. 3 Mice with tumors that were too small or too large were removed, and the remaining mice were randomly divided into 6 groups of 8 mice each according to tumor volume and animal weight. The drugs were administered via tail vein injection according to the dosage and frequency specified in Table 1.

[0846] Table 1. NCI-N87 Model Study (N=8)

[0847] The tumor was measured regularly using vernier calipers, and the tumor volume (V) was calculated using the following formula: V = 0.5 × a × b 2 , where a and b represent the long and short diameters of the tumor, respectively. The experimental results are shown in Table 2.

[0848] Table 2. Tumor volume analysis in mice (N=8)

[0849] The results showed that, in the NCI-N87 human gastric cancer subcutaneous xenograft model, the combination of antibody-drug conjugate B and bevacizumab in groups G5 and G6 significantly reduced tumor volume and significantly enhanced antitumor effect compared to the single-drug groups, and the mice tolerated it well. Groups G5 and G6 showed significant differences compared to the single-drug groups G2, G3, and G4; for example, p<0.05 for G5 compared to G2, p<0.01 for G5 compared to G3, and p<0.05 for G6 compared to G3.

[0850] Example 2: Pharmacodynamic study in a human non-small cell lung cancer subcutaneous xenograft model (HCC827)

[0851] BALB / c Nude mice (from Chengdu Yaokang Biotechnology Co., Ltd.) were subcutaneously inoculated with human non-small cell lung cancer HCC827 cells to construct a xenograft tumor model. Antibody-drug conjugate B (from Sichuan Kelun Biotech Co., Ltd., prepared according to the method described in Example 32 of WO2019114666A1, DAR=7.3), cetuximab (from Sichuan Kelun Biotech Co., Ltd., prepared according to WO2004085474A2), and bevacizumab (purchased from Roche) were injected via tail vein (iv). 0.9% NaCl served as a negative control. The combined efficacy and tolerability of the test drugs in this tumor-bearing mouse model were observed.

[0852] HCC827 cells (purchased from Nanjing Kebai) were cultured in vitro as a monolayer in RPMI 1640 medium supplemented with 10% fetal bovine serum at 37°C in an incubator containing 5% CO2. Cells were passaged by trypsin-EDTA digestion 2-3 times per week. When the cells reached the exponential growth phase, the culture medium was collected for mycoplasma testing. After passing the test, the cells were collected and counted.

[0853] Approximately 5 × 10⁵ female BALB / c Nude mice were subcutaneously injected into the right axilla. 6 HCC827 cells (suspended in 0.1 ml PBS or serum-free medium containing 50% matrix gel). Incubate until the average tumor volume reaches 100–250 mm. 3 Mice with tumors that were too small or too large were removed, and the remaining mice were randomly divided into 7 groups of 7 mice each according to tumor volume and animal weight. The drugs were administered via tail vein injection according to the dosage and frequency specified in Table 3.

[0854] Table 3. Study Design of HCC827 Model (N=7)

[0855] The tumors of the tumor-bearing mice were measured periodically using vernier calipers, and the tumor volume (V) was calculated using the following formula: V = 0.5 × a × b 2Where a and b represent the long and short diameters of the tumor, respectively. The tumor growth inhibition rate (TGI) is calculated using the following formula to evaluate the antitumor efficacy of the drug: TGI (%). (瘤体积) =[1-(T) Vt -T V0 ) / (C Vt -C V0 )]×100%, T V0 T represents the average tumor volume of the test compound group when administered in groups. Vt The mean tumor volume of the test compound group on day t after administration; C V0 C represents the average tumor volume in the solvent group during the grouped drug administration. Vt The mean tumor volume of the solvent group is t days after drug administration.

[0856] The experimental data were processed using GraphPad Prism 9.5.1 software, and a two-tailed t-test was used for analysis. p < 0.05 was considered statistically significant. The experimental results are shown in Table 4.

[0857] Table 4. Tumor volume analysis of mice in each group.

[0858] Note: / indicates not applicable. There is one mouse in each of the G1 and G6 groups that meets the exclusion criteria. After exclusion, there are 6 mice in each of the two groups.

[0859] The results showed that in the HCC827 human non-small cell lung cancer subcutaneous xenograft model, compared with the single-drug groups, the tumor volume was significantly reduced in the combination groups G4 (antibody-drug conjugate B with bevacizumab), G6 (antibody-drug conjugate B with cetuximab), and G7 (antibody-drug conjugate B with both cetuximab and bevacizumab), and the antitumor effect was significantly enhanced. Furthermore, the mice tolerated the treatment well, demonstrating a significant synergistic effect. Group G4 showed significant differences compared with the single-drug groups G1, G2, and G3 (p < 0.001 compared to G1, p < 0.05 compared to G2), and groups G6 and G7 showed p < 0.001 compared to group G1.

[0860] The above description is merely a preferred embodiment of this application and is not intended to limit this application. Any modifications, equivalent substitutions, or improvements made within the spirit and principles of this application should be included within the protection scope of this application. Furthermore, the technical solutions of the various embodiments can be combined with each other, but this must be based on the ability of those skilled in the art to implement them. When the combination of technical solutions is contradictory or cannot be implemented, it should be considered that such a combination of technical solutions does not exist and is not within the protection scope claimed by this application.

Claims

1. Use of an antibody-drug conjugate and a second therapeutic agent in the preparation of a drug for treating tumors or cancer, wherein the second therapeutic agent is selected from one or both of EGFR inhibitors and VEGF inhibitors, and optionally other active therapeutic agents.

2. The use according to claim 1, wherein the antibody-drug conjugate is selected from anti-Trop-2 antibody-drug conjugates.

3. The use according to claim 2, wherein the anti-Trop-2 antibody-drug conjugate has the structure of the following formula (I): {D-[L1-(L2)m1-(L3)m2-(L4)m3-E]} q -A Formula (I) in, L1 is Each of R1 and R2 is independently hydrogen (e.g., protium or deuterium), halogen, carboxylic acid group, sulfonic acid group, cyano group, or C. 1-6 Alkyl, Halogenated C 1-6 alkyl and cyano substituted C 1-6 Alkyl groups (e.g., -CH2CN), C 1-6 Alkoxy, C 2-10 alkenyl or C 2-10 Alkyne group; Z1 is an amino acid or a peptide composed of 2-10 amino acids; x1 and x2 are each independently 0, 1, 2, 3, 4, 5 or 6; and L1 is connected to D at position 1 and L2 at position 2. L2 is Where y1 is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; and L2 is connected to L1 at position 1 and L2 is connected to L3 at position 2. L3 is a 5-12 member heterocyclic aromatic ring; L4 is Z2 is selected from C. 1-6 Alkylene, C 2-10 imidene group, C 2-10 etyne group, and C 3-8 Cycloalkylene; R3 is selected from H and C 1-6 Alkyl group; Z3 is absent or is C 1-6 Alkylene; or, R3 and Z3 together with the nitrogen atom to which they are attached form a 4-8 membered heterocyclic group; α is 0, 1, 2, 3, 4, 5 or 6, and L4 is attached to E at the 2 position and to L3 at the 1 position; E is In this context, each R4 is independently hydrogen (e.g., protium or deuterium), β is 0, 1 or 2, and E is connected to A at position 2 and to L4 at position 1. m1, m2 and m3 are each independently 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; D represents a bioactive molecular fragment; q refers to {D-[L1-(L2]} which forms a thioether bond with the thiol group of A. m1 -(L3) m2 -(L4) m3 The number of the -E]} part is selected from 1 to 10; A represents an anti-Trop-2 antibody or its antigen-binding fragment.

4. The use according to claim 3, wherein the anti-Trop-2 antibody-drug conjugate satisfies one or more of the following: (1) L1 is selected from Furthermore, position 1 of L1 is connected to D, and position 2 of L1 is connected to L2; (2) L2 is in, y1 is 3, 4, 5, 6, 7, 8, 9 or 10; and L2 is connected to L1 at position 1 and L2 is connected to L3 at position 2. (3) L3 is selected from 5-6 membered heteroaryl rings, such as pyrazole or triazole; (4) L4 is Z2 is selected from C. 1-3 Alkylene; R3 is H; Z3 is selected from C 1-3 Alkylene; α is 0 or 1, and L4 is connected to E at position 2 and to L3 at position 1; (5) E is In this configuration, each R4 is independently hydrogen (e.g., protium or deuterium), β is 0, 1 or 2, and E is connected to A at position 2 (e.g., to a thiol group on A) and to L4 at position 1. (6) m1, m2 and m3 are all 1; (7) The bioactive molecules are selected from Preferably, D is selected from (8) q is selected from 3 to 8 (e.g., 3, 4, 5, 6, 7 or 8) and / or, (9) A is Sacituzumab or its antigen-binding fragment.

5. The use according to any one of claims 2-4, wherein, The anti-Trop-2 antibody-drug conjugate has the following chemical structure: Wherein, A is an anti-Trop-2 antibody or its antigen-binding fragment; q is selected from 1-10.

6. The use according to any one of claims 3-5, wherein the anti-Trop-2 antibody or its antigen-binding fragment comprises: (1) The following heavy chain variable regions (VH) and / or light chain variable regions (VL), as defined in the Chothia numbering system: Heavy chain variable region (VH) containing the following 3 CDRs: CDR-H1 with sequence of SEQ ID NO:1 or a variant thereof, CDR-H2 with sequence of SEQ ID NO:2 or a variant thereof, and CDR-H3 with sequence of SEQ ID NO:3 or a variant thereof; and / or, light chain variable region (VL) containing the following 3 CDRs: CDR-L1 with sequence of SEQ ID NO:4 or a variant thereof, CDR-L2 with sequence of SEQ ID NO:5 or a variant thereof, and CDR-L3 with sequence of SEQ ID NO:6 or a variant thereof; in, The variant has at least 70%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with its source sequence, or the variant has one or more amino acid substitutions, deletions, or additions (e.g., substitutions, deletions, or additions of 1, 2, or 3 amino acids) compared to its source sequence; preferably, the substitutions are conservative substitutions; or, (2) The following heavy chain variable regions (VH) and / or light chain variable regions (VL), defined according to the AbM numbering system: Heavy chain variable region (VH) containing the following 3 CDRs: CDR-H1 with sequence of SEQ ID NO:14 or a variant thereof, CDR-H2 with sequence of SEQ ID NO:15 or a variant thereof, and CDR-H3 with sequence of SEQ ID NO:3 or a variant thereof; and / or, light chain variable region (VL) containing the following 3 CDRs: CDR-L1 with sequence of SEQ ID NO:4 or a variant thereof, CDR-L2 with sequence of SEQ ID NO:5 or a variant thereof, and CDR-L3 with sequence of SEQ ID NO:6 or a variant thereof; The variant has at least 70%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with its source sequence, or the variant has one or more amino acid substitutions, deletions, or additions (e.g., substitutions, deletions, or additions of 1, 2, or 3 amino acids) compared to its source sequence; preferably, the substitutions are conservative substitutions; or, (3) The following heavy chain variable regions (VH) and / or light chain variable regions (VL), as defined in the Kabat numbering system: Heavy chain variable region (VH) containing the following 3 CDRs: CDR-H1 with sequence of SEQ ID NO:7 or a variant thereof, CDR-H2 with sequence of SEQ ID NO:8 or a variant thereof, and CDR-H3 with sequence of SEQ ID NO:3 or a variant thereof; and / or, light chain variable region (VL) containing the following 3 CDRs: CDR-L1 with sequence of SEQ ID NO:4 or a variant thereof, CDR-L2 with sequence of SEQ ID NO:5 or a variant thereof, and CDR-L3 with sequence of SEQ ID NO:6 or a variant thereof; The variant has at least 70%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with its source sequence, or the variant has one or more amino acid substitutions, deletions, or additions (e.g., substitutions, deletions, or additions of 1, 2, or 3 amino acids) compared to its source sequence; preferably, the substitutions are conservative substitutions; or, (4) The following heavy chain variable regions (VH) and / or light chain variable regions (VL), as defined by the IMGT numbering system: Heavy chain variable region (VH) containing the following 3 CDRs: CDR-H1 with sequence of SEQ ID NO:9 or a variant thereof, CDR-H2 with sequence of SEQ ID NO:10 or a variant thereof, and CDR-H3 with sequence of SEQ ID NO:11 or a variant thereof; and / or, light chain variable region (VL) containing the following 3 CDRs: CDR-L1 with sequence of SEQ ID NO:12 or a variant thereof, CDR-L2 with sequence of SEQ ID NO:13 or a variant thereof, and CDR-L3 with sequence of SEQ ID NO:6 or a variant thereof; The variant has at least 70%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with the sequence from which it originates, or the variant has one or more amino acid substitutions, deletions, or additions (e.g., substitutions, deletions, or additions of 1, 2, or 3 amino acids) compared to the sequence from which it originates; preferably, the substitutions are conservative substitutions.

7. The use according to claim 6, wherein the anti-Trop-2 antibody or its antigen-binding fragment comprises: VH or a variant thereof shown in SEQ ID NO: 16, and VL or a variant thereof shown in SEQ ID NO:

17.

8. The use according to any one of claims 5-7, wherein the anti-Trop-2 antibody or its antigen-binding fragment further comprises: (a) The heavy chain constant region (CH) of human immunoglobulin or a variant thereof, said variant having one or more amino acid substitutions, deletions, or additions compared to the wild-type sequence from which it is derived; and (b) The light chain constant region (CL) of human immunoglobulin or a variant thereof, wherein the variant has one or more amino acid substitutions, deletions or additions compared to the wild-type sequence from which it is derived.

9. The use according to any one of claims 5-8, wherein the anti-Trop-2 antibody or its antigen-binding fragment comprises the heavy chain shown in SEQ ID NO:18 and the light chain shown in SEQ ID NO:

19.

10. The use according to any one of claims 2-9, wherein the anti-Trop-2 antibody-drug conjugate has the following chemical structure: in, q is selected from 1-10.

11. The use according to any one of claims 2-10, wherein the DAR value of the anti-Trop-2 antibody-drug conjugate is an integer or decimal of approximately 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3, 1-2, 2-10, 2-9, 2-8, 2-7, 2-6, 2-5, 2-4, 2-3, 3-10, 3-9, 3-8, 3-7, 3-6, 3-5, 3-4, 4-10, 4-9, 4-8, 4-7, 4-6, 4-5, 5-10, 5-9, 5-8, 5-7, 5-6, 6-10, 6-9, 6-8, 6-7, 7-10, 7-9, 7-8, 8-10, 8-9, or 9-10.

12. The use as described in claim 11, wherein the DAR value of the anti-Trop-2 antibody-drug conjugate is approximately 5.0, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6.0, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, 7.0, 7.1, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, or 8.

0.

13. The use according to any one of claims 2-12, wherein the anti-Trop-2 antibody-drug conjugate, EGFR inhibitor, VEGF inhibitor, and other active therapeutic agents are administered simultaneously, separately, sequentially, or in sequence.

14. The use according to any one of claims 2-13, wherein the anti-Trop-2 antibody-drug conjugate possesses one or more of the following characteristics: (1) Administer the medication according to the dosing cycle of 1-42 days; (2) The frequency of administration is 1 to 8 times within 1 to 4 weeks; for example, once a week, twice a week, once every 2 weeks or once every 3 weeks; (3) The dose administered each time is selected from 0.1-20 mg / kg or more, such as 0.5-10 mg / kg, such as 0.5-5 mg / kg, such as 3 mg / kg, 4 mg / kg or 5 mg / kg, based on the subject’s weight; (4) The dosage concentration for each administration is selected from 0.01-50 mg / ml; and / or, (5) Dosage (e.g., single dose or unit dose) is selected from 0.1-1000 mg.

15. The use according to any one of claims 2-14, wherein the VEGF inhibitor possesses one or more of the following characteristics: (1) Administer the medication according to a dosing cycle of 1-42 days, for example, 1-28 days, for example, 1-14 days or 1-21 days; (2) The frequency of administration is 1 to 8 times within 1 to 4 weeks; for example, once a week, twice a week, once every 2 weeks or once every 3 weeks; (3) The dose administered each time is selected from 0.5 mg / kg to 50 mg / kg, for example 0.5-30 mg / kg, for example 0.5-20 mg / kg, 0.5-10 mg / kg or 0.5-5 mg / kg, based on the subject’s weight; (4) The dosage concentration for each application is selected from 0.1-50 mg / ml, for example 1-20 mg / ml; (5) Dosage (e.g., single-dose dose or unit dose) is selected from 0.1-1000 mg; and / or (6) The conjugate with the anti-Trop-2 antibody drug can be administered simultaneously, within 1 day (e.g., at intervals of 0.5 to 2 hours) or at intervals of at least 1 day, 2 days, 3 days, 5 days, 6 days, 7 days, 10 days, 15 days, 21 days, 30 days, 45 days, 2 months, 75 days, 3 months or 6 months.

16. The use according to any one of claims 2-15, wherein the EGFR inhibitor possesses one or more of the following characteristics: (1) Administer the medication according to the dosing cycle of 1-42 days; (2) The frequency of administration is 1 to 8 times within 1 to 4 weeks; for example, once a week, twice a week, once every 2 weeks or once every 3 weeks; (3) The dose administered each time is selected from 0.5 mg / kg to 50 mg / kg based on the subject’s weight, for example, from 0.5 to 30 mg / kg, such as 0.5 to 20 mg / kg, 0.5 to 10 mg / kg or 0.5 to 5 mg / kg; (4) The dosage concentration for each application is selected from 0.1-50 mg / ml; (5) The dosage (e.g., a single-dose dose or a unit dose) is selected from 0.1-1000 mg, such as 1-900 mg, 1-800 mg, 1-700 mg, 1-600 mg, 1-500 mg, 1-400 mg, 1-300 mg, 1-200 mg, 1-100 mg, 1-50 mg, 1-30 mg, 1-20 mg, or 1-10 mg; and / or (6) It can be administered simultaneously with anti-Trop-2 antibody drug conjugates and / or VEGF inhibitors, within 1 day (e.g., at intervals of 0.5 to 2 hours) or at intervals of at least 1 day, 2 days, 3 days, 5 days, 6 days, 7 days, 10 days, 15 days, 21 days, 30 days, 45 days, 2 months, 75 days, 3 months or 6 months.

17. The use according to any one of claims 1-16, wherein the VEGF inhibitor is selected from anti-VEGF antibodies and / or their antigen-binding fragments; Preferably, the VEGF inhibitor is selected from one or more of bevacizumab, ramucirumab, ranibizumab, and faricimab or their biosimilars; The bevacizumab biosimilars mentioned are selected from: MVASI, Zirabev, Bevax, Lumiere, Equidacent, Avegra, BP 01, BCD500, Krabeva, BAT1706, BXT-2316, Bevalo, BI 695502, CT-P16, CHS-5217, DRZBZ, Cizumab, Byvasda, MIL60, MYL 14020, ONS1045, HD204, Ankeda, Bevacizel, Aybintio, Onbevzi, HLX04, TX16, MB02, and Oyavas; Preferably, the VEGF inhibitor is bevacizumab or its biosimilar.

18. The use according to any one of claims 1-17, wherein the EGFR inhibitor is selected from anti-EGFR antibodies and / or their antigen-binding fragments; Preferably, the EGFR inhibitor is selected from one or more of cetuximab, panitumumab, nexituzumab, nimotuzumab, Rybrevant, and Amivantamab. Preferably, the EGFR inhibitor is cetuximab or its biosimilar.

19. The use according to any one of claims 1-18, wherein the second therapeutic agent is an EGFR inhibitor.

20. The use according to any one of claims 1-18, wherein the second therapeutic agent is a VEGF inhibitor.

21. The use according to any one of claims 1-18, wherein the second therapeutic agent is an EGFR inhibitor and a VEGF inhibitor.

22. Use of the composition of the anti-Trop-2 antibody drug conjugate in the preparation of a medicament for treating tumors or cancer, wherein the other therapeutic agents are VEGF inhibitors and / or EGFR inhibitors as described in any one of claims 1-21, and the composition of the anti-Trop-2 antibody drug conjugate comprises one or more anti-Trop-2 antibody drug conjugates as described in any one of claims 2-21.

23. Use of the anti-Trop-2 antibody-drug conjugate of any one of claims 2-21 in the preparation of a medicament for improving the efficacy of other therapeutic agents in the treatment of tumors or cancer, wherein the other therapeutic agents are the VEGF inhibitors and / or EGFR inhibitors of any one of claims 1-21.

24. The use according to any one of claims 1-23, wherein the tumor or cancer is selected from: solid tumors or non-solid tumors; for example, selected from esophageal cancer (e.g., esophageal adenocarcinoma and esophageal squamous cell carcinoma), lung cancer (e.g., small cell lung cancer and non-small cell lung cancer), squamous cell carcinoma, bladder cancer, gastric cancer, ovarian cancer (e.g., ovarian epithelial carcinoma, fallopian tube cancer), peritoneal cancer, pancreatic cancer, breast cancer, cervical cancer, endometrial cancer, colorectal cancer, liver cancer, kidney cancer, prostate cancer, and colon cancer.

25. A treatment combination or composition comprising the anti-Trop-2 antibody-drug conjugate of any one of claims 2-21, the VEGF inhibitor and / or EGFR inhibitor of any one of claims 1-21, and optionally comprising other active therapeutic agents.

26. A treatment combination or composition comprising the anti-Trop-2 antibody-drug conjugate of any one of claims 2-21, the VEGF inhibitor and / or EGFR inhibitor of any one of claims 1-21, and hyaluronic acid degrading enzyme.

27. The treatment combination or composition of claim 26, wherein the hyaluronic acid degrading enzyme is a soluble hyaluronidase.

28. The therapeutic combination or composition of claim 27, wherein the soluble hyaluronidase is hyaluronidase PH20.

29. The therapeutic combination or composition of claim 28, wherein the soluble hyaluronidase is recombinant human hyaluronidase or recombinant hyaluronidase α.

30. A pharmaceutical composition comprising the anti-Trop-2 antibody-drug conjugate of any one of claims 2-21, the VEGF inhibitor and / or EGFR inhibitor of any one of claims 1-21, and one or more pharmaceutically acceptable excipients, diluents or carriers.

31. A kit comprising the anti-Trop-2 antibody-drug conjugate according to any one of claims 2-21, the VEGF inhibitor and / or EGFR inhibitor according to any one of claims 1-21, optionally further comprising other active therapeutic agents and / or instructions for use.

32. A kit comprising: (a) the anti-Trop-2 antibody-drug conjugate of any one of claims 2-21 and the EGFR inhibitor; (b) the anti-Trop-2 antibody-drug conjugate of any one of claims 2-21 and the VEGF inhibitor of any one of claims 1-21; (c) the EGFR inhibitor of any one of claims 1-21 and the VEGF inhibitor; (d) the VEGF inhibitor of any one of claims 1-21; (e) the anti-Trop-2 antibody-drug conjugate of any one of claims 2-21; (f) the anti-EGFR inhibitor of any one of claims 1-21; or (g) the anti-Trop-2 antibody-drug conjugate of any one of claims 2-21, the VEGF inhibitor of any one of claims 1-21 and the EGFR inhibitor, and hyaluronidase.

33. The medicine box according to claim 31 or 32, wherein the components are in different containers.

34. The medicine box according to claim 32, wherein the hyaluronic acid degrading enzyme is a soluble hyaluronidase.

35. The medicine box according to claim 34, wherein the soluble hyaluronidase is soluble hyaluronidase PH20.

36. The medicine box according to claim 35, wherein the soluble hyaluronidase is recombinant human hyaluronidase or recombinant human hyaluronidase α.

37. The anti-Trop-2 antibody-drug conjugate according to any one of claims 2-21, for the treatment of tumors or cancer, wherein the anti-Trop-2 antibody-drug conjugate is administered in combination with other therapeutic agents.

38. The anti-Trop-2 antibody-drug conjugate of claim 37, wherein the other therapeutic agent is a VEGF inhibitor or EGFR inhibitor as described in any one of claims 1-21, and optionally a hyaluronic acid degrading enzyme as described in any one of claims 26-29, preferably, the VEGF inhibitor is selected from bevacizumab, and the EGFR inhibitor is selected from cetuximab; the hyaluronic acid degrading enzyme is a soluble hyaluronidase, preferably, the hyaluronic acid degrading enzyme is hyaluronidase PH20, recombinant human hyaluronidase, or recombinant hyaluronidase α; Preferably, the anti-Trop-2 antibody-drug conjugate and other therapeutic agents are administered according to any one of claims 13-16.

39. A method for preventing and / or treating a tumor or cancer in a subject, the method comprising administering to a subject in need an effective amount of the treatment combination or composition of any one of claims 25-29, the pharmaceutical composition of claim 30, or the kit of any one of claims 31-36.

40. The method of claim 39, wherein the tumor or cancer is selected from: solid tumors or non-solid tumors; for example, selected from esophageal cancer (e.g., esophageal adenocarcinoma and esophageal squamous cell carcinoma), lung cancer (e.g., small cell lung cancer and non-small cell lung cancer), squamous cell carcinoma, bladder cancer, gastric cancer, ovarian cancer (e.g., ovarian epithelial carcinoma, fallopian tube cancer), peritoneal cancer, pancreatic cancer, breast cancer, cervical cancer, endometrial cancer, colorectal cancer, liver cancer, kidney cancer, prostate cancer, and colon cancer.

41. The method of claim 39 or 40, wherein the anti-Trop-2 antibody-drug conjugate, EGFR inhibitor, VEGF inhibitor, and other active therapeutic agents are administered simultaneously, separately, sequentially, or in sequence.

42. The method according to any one of claims 39-41, wherein the anti-Trop-2 antibody-drug conjugate is applied in accordance with one or more of the following: (1) Administer the medication according to the dosing cycle of 1-42 days; (2) The frequency of administration is 1 to 8 times within 1 to 4 weeks; for example, once a week, twice a week, once every 2 weeks or once every 3 weeks; (3) The dose administered each time is selected from 0.1-20 mg / kg or more, such as 0.5-10 mg / kg, such as 0.5-5 mg / kg, such as 3 mg / kg, 4 mg / kg or 5 mg / kg, based on the subject’s weight; (4) The dosage concentration for each administration is selected from 0.01-50 mg / ml; and / or, (5) Dosage (e.g., single dose or unit dose) is selected from 0.1-1000 mg.

43. The method of any one of claims 39-41, wherein the VEGF inhibitor is applied according to one or more of the following: (1) Administer the medication according to the dosing cycle of 1-42 days; (2) The frequency of administration is 1 to 8 times within 1 to 4 weeks; for example, once a week, twice a week, once every 2 weeks or once every 3 weeks; (3) The dose administered each time is selected from 0.5 mg / kg to 50 mg / kg, for example 0.5-30 mg / kg, for example 0.5-20 mg / kg, 0.5-10 mg / kg or 0.5-5 mg / kg, based on the subject’s weight; (4) The dosage concentration for each application is selected from 0.1-50 mg / ml, for example 1-20 mg / ml; (5) Dosage (e.g., single-dose dose or unit dose) is selected from 0.1-1000 mg; and / or (6) The conjugate with the anti-Trop-2 antibody drug can be administered simultaneously, within 1 day (e.g., at intervals of 0.5 to 2 hours) or at intervals of at least 1 day, 2 days, 3 days, 5 days, 6 days, 7 days, 10 days, 15 days, 21 days, 30 days, 45 days, 2 months, 75 days, 3 months or 6 months.

44. The method of any one of claims 39-41, wherein the EGFR inhibitor is administered according to one or more of the following: (1) Administer the medication according to the dosing cycle of 1-42 days; (2) The frequency of administration is 1 to 8 times within 1 to 4 weeks; for example, once a week, twice a week, once every 2 weeks or once every 3 weeks; (3) The dose administered each time is selected from 0.5 mg / kg to 50 mg / kg based on the subject’s weight, for example, from 0.5 to 30 mg / kg, such as 0.5 to 20 mg / kg, 0.5 to 10 mg / kg or 0.5 to 5 mg / kg; (4) The dosage concentration for each application is selected from 0.1-50 mg / ml; (5) The dosage (e.g., a single-dose dose or a unit dose) is selected from 0.1-1000 mg, such as 1-900 mg, 1-800 mg, 1-700 mg, 1-600 mg, 1-500 mg, 1-400 mg, 1-300 mg, 1-200 mg, 1-100 mg, 1-50 mg, 1-30 mg, 1-20 mg, or 1-10 mg; and / or (6) It can be administered simultaneously with anti-Trop-2 antibody drug conjugates and / or VEGF inhibitors, within 1 day (e.g., at intervals of 0.5 to 2 hours) or at intervals of at least 1 day, 2 days, 3 days, 5 days, 6 days, 7 days, 10 days, 15 days, 21 days, 30 days, 45 days, 2 months, 75 days, 3 months or 6 months.

45. Use of an anti-Trop-2 antibody-drug conjugate or a combination thereof in the preparation of a medicament for treating a subject's tumor or cancer, wherein, The drug is administered in combination with a second therapeutic agent, the anti-Trop-2 antibody drug conjugate as described in any one of claims 3-21, the composition of the anti-Trop-2 antibody drug conjugate comprising one or more of the anti-Trop-2 antibody drug conjugates, the second therapeutic agent as described in any one of claims 1, 17-21, and optionally the hyaluronic acid degrading enzyme as described in any one of claims 26-29; Preferably, the drug and the second therapeutic agent are administered according to any one of claims 13-16; Preferably, the tumor or cancer is as described in claim 24.

46. ​​Use of VEGF inhibitors and / or EGFR inhibitors in the preparation of medicaments for treating tumors or cancers in a subject, wherein, The drug is administered in combination with an anti-Trop-2 antibody-drug conjugate or a composition thereof, wherein the anti-Trop-2 antibody-drug conjugate is as described in any one of claims 3-21, the composition of the anti-Trop-2 antibody-drug conjugate comprises one or more of the anti-Trop-2 antibody-drug conjugates, the VEGF inhibitor is as described in claim 17, the EGFR inhibitor is as described in claim 18, and optionally the hyaluronidase as described in any one of claims 26-29; Preferably, the drug, VEGF inhibitor, and EGFR inhibitor are administered according to any one of claims 13-16; Preferably, the tumor or cancer is as described in claim 24.

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