Pharmaceutical combination, use thereof and treatment method

Abstract

The present invention relates to a pharmaceutical combination, the use thereof, and a treatment method. The present invention particularly relates to a combination of two or more of an anti-Trop -2 antibody drug conjugate, an anti-Her2 antibody drug conjugate and an anti-Her2 antibody or an antigen-binding fragment thereof, a method for preventing and / or treating cancer with same, and the use thereof in the preparation of a drug for preventing and / or treating cancer.

Description

Drug combinations, their uses, and treatment methods

[0001] This application is based on and claims priority to Chinese patent applications No. 202411808802.5, filed on December 10, 2024; No. 202511553752.5, filed on October 28, 2025; and No. 202511761386.2, filed on November 27, 2025, the disclosures of which are incorporated herein by reference in their entirety. Technical Field

[0002] This disclosure pertains to the fields of tumor therapy and molecular immunology, and relates to pharmaceutical combinations, their uses, and treatment methods. Specifically, it relates to combinations of two or more of anti-Trop-2 antibody-drug conjugates, anti-Her2 antibody-drug conjugates, and anti-Her2 antibodies or their antigen-binding fragments, as well as methods for their use in the prevention and / or treatment of tumors or cancer, and their use in the preparation of medicaments for the prevention and / or treatment of tumors or 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] ErbB family receptor tyrosine kinases are important mediators of cell growth, differentiation, and survival. This family includes four members: epidermal growth factor receptor (EGFR or ErbB1), Her2 (ErbB2), Her3 (ErbB3), and Her4 (ErbB4). Clinically, the anti-Her2 antibody trastuzumab (trade name Herceptin) is commonly used to treat breast cancer with high Her2 expression.

[0005] Trop-2 is a transmembrane glycoprotein involved in calcium signaling and expressed in various tumor types. Trop-2 expression in normal trophoblasts promotes trophoblast cell growth, migration, and proliferation. Trop-2 is involved in multiple cell signaling pathways, including intracellular calcium transduction, the MAPK signaling pathway, RAF, NF-κB, and cyclin D / E.

[0006] Selectively killing tumor cells while minimizing damage to normal cells is a trend in cancer therapy development. Recent studies have found that therapeutic antibodies can be linked to bioactive molecules to form antibody-drug conjugates (ADCs). ADCs are complexes formed by linking individual antibodies to small-molecule cytotoxic drugs via linkers. Once in the bloodstream, the antibody component of an ADC specifically binds to tumor cell surface antigens, enters the cells via endocytosis, and releases the cytotoxic drug to kill the tumor cells. ADCs directly target tumor cells, significantly reducing the toxic side effects of chemotherapy drugs on other normal cells, thereby reducing systemic adverse events. Multiple early clinical trials have demonstrated that Trop-2-targeting ADCs and Her2-targeting ADCs have good safety and clinical benefits in various tumor types. Summary of the Invention

[0007] Based on the promising results shown by anti-Her2 antibodies, anti-Trop-2 antibody-drug conjugates, and anti-Her2 antibody-drug conjugates as monotherapy for cancer, combinations of these therapeutic agents with different mechanisms of action and non-additive toxicities have the potential to provide more significant therapeutic effects in many cancer types.

[0008] This disclosure provides a pharmaceutical combination comprising two or more of an anti-Trop-2 antibody drug conjugate, an anti-Her2 antibody drug conjugate, and an anti-Her2 antibody or an antigen-binding fragment thereof.

[0009] In some embodiments, the drug combination is a combination of an anti-Trop-2 antibody drug conjugate and an anti-Her2 antibody drug conjugate.

[0010] In some embodiments, the drug combination is a combination of an anti-Trop-2 antibody drug conjugate and an anti-Her2 antibody or its antigen-binding fragment.

[0011] In some embodiments, the drug combination is a combination of an anti-Trop-2 antibody drug conjugate, an anti-Her2 antibody drug conjugate, and an anti-Her2 antibody or an antigen-binding fragment thereof.

[0012] In some embodiments, the drug combination is a combination of an anti-Her2 antibody drug conjugate and an anti-Her2 antibody or its antigen-binding fragment.

[0013] In some embodiments, the drug combination is a combination of two or more of the anti-Her2 antibody or its antigen-binding fragment.

[0014] In some embodiments, the anti-Her2 antibody drug conjugate has the following chemical structure:

[0015] in:

[0016] A represents an anti-Her2 antibody or its antigen-binding fragment;

[0017] X and Y are each independently N or CR 1 (In some implementations, Y is CR) 1 (where X is N), and each R 1 Independently H or Cl-C 10 Alkyl, in some embodiments being H or C1-C6 alkyl (in some embodiments being methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, pentyl or hexyl);

[0018] L is a divalent linker;

[0019] D represents a cytotoxic drug group; and

[0020] n is an integer selected from 1 to 10, and in some implementations it is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10.

[0021] In some embodiments, the anti-Her2 antibody drug conjugate meets one or more of the following conditions:

[0022] (1) L is selected from p is an integer from 1 to 10, and in some implementations it is 1, 2, 3, 4, 5 or 6;

[0023] (2) Cytotoxic drugs are selected from compounds of the following general formula or their stereoisomers:

[0024] Among them, R 2 Selected from -CH2N3, -CONHSO2 (cyclopropyl), thiazolyl-2-yl, -CH3 and -COOH;

[0025] R 3 Selected from H and -OH; and

[0026] R 4 Selected from H, -NH2, Cl, Br, I, -OS(O)2R 6 , where R 6 It is H, C1-C8 alkyl, C3-C8 cycloalkyl, or C6-C 14 The aryl group, wherein the alkyl, cycloalkyl and aryl groups are each optionally substituted by one or more (e.g., 1, 2, 3, 4 or 5) substituents selected from halogens, such as F;

[0027] In some embodiments, the cytotoxic drug is

[0028] (3) n is an integer from 1 to 8, which is 1, 2, 3, 4, 5, 6, 7 or 8 in some implementations, 2, 3 or 4 in some implementations, and 2 in some implementations;

[0029] (4) A is Trastuzumab or its antigen-binding fragment.

[0030] In some embodiments, the anti-Her2 antibody drug conjugate has the following chemical structure:

[0031] Wherein, A is a group obtained by removing n amino groups from the anti-Her2 antibody or its antigen-binding fragment, and n is an integer from 1 to 8, which in some embodiments is 1, 2, 3, 4, 5, 6, 7 or 8.

[0032] In some embodiments, the anti-Her2 antibody or its antigen-binding fragment comprises:

[0033] (1) The following heavy chain variable regions (VH) and / or light chain variable regions (VL), wherein the CDR is defined according to the Chothia numbering system:

[0034] (1a) A heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with the sequence of SEQ ID NO:5 or a variant thereof, CDR-H2 with the sequence of SEQ ID NO:6 or a variant thereof, and CDR-H3 with the sequence of SEQ ID NO:7 or a variant thereof; and / or, a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with the sequence of SEQ ID NO:8 or a variant thereof, CDR-L2 with the sequence of SEQ ID NO:9 or a variant thereof, and CDR-L3 with the sequence of SEQ ID NO:10 or a variant thereof; or,

[0035] (1b) A heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with the sequence of SEQ ID NO:20 or a variant thereof, CDR-H2 with the sequence of SEQ ID NO:21 or a variant thereof, and CDR-H3 with the sequence of SEQ ID NO:22 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with the sequence of SEQ ID NO:23 or a variant thereof, CDR-L2 with the sequence of SEQ ID NO:24 or a variant thereof, and CDR-L3 with the sequence of SEQ ID NO:25 or a variant thereof;

[0036] Wherein, the variant described in any one of (1a) and (1b) 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 is derived, 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 is derived; in some embodiments, the substitutions are conservative substitutions;

[0037] or,

[0038] (2) The following heavy chain variable regions (VH) and / or light chain variable regions (VL), wherein the CDR is defined according to the AbM numbering system:

[0039] (2a) A heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with the sequence SEQ ID NO:18 or a variant thereof, CDR-H2 with the sequence SEQ ID NO:19 or a variant thereof, and CDR-H3 with the sequence SEQ ID NO:7 or a variant thereof; and / or, a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with the sequence SEQ ID NO:8 or a variant thereof, CDR-L2 with the sequence SEQ ID NO:9 or a variant thereof, and CDR-L3 with the sequence SEQ ID NO:10 or a variant thereof; or,

[0040] (2b) A heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with sequence SEQ ID NO:33 or a variant thereof, CDR-H2 with sequence SEQ ID NO:34 or a variant thereof, and CDR-H3 with sequence SEQ ID NO:22 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with sequence SEQ ID NO:23 or a variant thereof, CDR-L2 with sequence SEQ ID NO:24 or a variant thereof, and CDR-L3 with sequence SEQ ID NO:25 or a variant thereof;

[0041] Wherein, the variant described in any of (2a) and (2b) 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 is derived, 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 is derived; in some embodiments, the substitutions are conservative substitutions;

[0042] or,

[0043] (3) The following heavy chain variable regions (VH) and / or light chain variable regions (VL), wherein the CDR is defined according to the Kabat numbering system:

[0044] (3a) A heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with the sequence of SEQ ID NO:11 or a variant thereof, CDR-H2 with the sequence of SEQ ID NO:12 or a variant thereof, and CDR-H3 with the sequence of SEQ ID NO:7 or a variant thereof; and / or, a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with the sequence of SEQ ID NO:8 or a variant thereof, CDR-L2 with the sequence of SEQ ID NO:9 or a variant thereof, and CDR-L3 with the sequence of SEQ ID NO:10 or a variant thereof; or,

[0045] (3b) A heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with sequence SEQ ID NO:26 or a variant thereof, CDR-H2 with sequence SEQ ID NO:27 or a variant thereof, and CDR-H3 with sequence SEQ ID NO:22 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with sequence SEQ ID NO:23 or a variant thereof, CDR-L2 with sequence SEQ ID NO:24 or a variant thereof, and CDR-L3 with sequence SEQ ID NO:25 or a variant thereof;

[0046] Wherein, the variant described in any of (3a) and (3b) 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 is derived, 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 is derived; in some embodiments, the substitutions are conservative substitutions;

[0047] or,

[0048] (4) The following heavy chain variable regions (VH) and / or light chain variable regions (VL), wherein the CDR is defined according to the IMGT numbering system:

[0049] (4a) A heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with sequence SEQ ID NO:13 or a variant thereof, CDR-H2 with sequence SEQ ID NO:14 or a variant thereof, and CDR-H3 with sequence SEQ ID NO:15 or a variant thereof; and / or, a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with sequence SEQ ID NO:16 or a variant thereof, CDR-L2 with sequence SEQ ID NO:17 or a variant thereof, and CDR-L3 with sequence SEQ ID NO:10 or a variant thereof; or,

[0050] (4b) A heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with sequence SEQ ID NO:28 or a variant thereof, CDR-H2 with sequence SEQ ID NO:29 or a variant thereof, and CDR-H3 with sequence SEQ ID NO:30 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with sequence SEQ ID NO:31 or a variant thereof, CDR-L2 with sequence SEQ ID NO:32 or a variant thereof, and CDR-L3 with sequence SEQ ID NO:25 or a variant thereof;

[0051] Wherein, the variant described in any one of (4a) and (4b) 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 is derived, 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 is derived; in some embodiments, the substitutions are conservative substitutions.

[0052] In some embodiments, the anti-Her2 antibody or its antigen-binding fragment comprises:

[0053] (1) The following heavy chain variable regions (VH) and light chain variable regions (VL), where CDR is defined according to the Chothia numbering system:

[0054] (1a) A heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 of SEQ ID NO:5, CDR-H2 of SEQ ID NO:6, and CDR-H3 of SEQ ID NO:7; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 of SEQ ID NO:8, CDR-L2 of SEQ ID NO:9, and CDR-L3 of SEQ ID NO:10; or,

[0055] (1b) A heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 of SEQ ID NO:20, CDR-H2 of SEQ ID NO:21, and CDR-H3 of SEQ ID NO:22; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 of SEQ ID NO:23, CDR-L2 of SEQ ID NO:24, and CDR-L3 of SEQ ID NO:25;

[0056] or,

[0057] (2) The following heavy chain variable regions (VH) and light chain variable regions (VL), wherein the CDR is defined according to the AbM numbering system:

[0058] (2a) A heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 of SEQ ID NO:18, CDR-H2 of SEQ ID NO:19, and CDR-H3 of SEQ ID NO:7; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 of SEQ ID NO:8, CDR-L2 of SEQ ID NO:9, and CDR-L3 of SEQ ID NO:10; or,

[0059] (2b) A heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 of SEQ ID NO:33, CDR-H2 of SEQ ID NO:34, and CDR-H3 of SEQ ID NO:22; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 of SEQ ID NO:23, CDR-L2 of SEQ ID NO:24, and CDR-L3 of SEQ ID NO:25;

[0060] or,

[0061] (3) The following heavy chain variable regions (VH) and light chain variable regions (VL), where CDR is defined according to the Kabat numbering system:

[0062] (3a) A heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 of SEQ ID NO:11, CDR-H2 of SEQ ID NO:12, and CDR-H3 of SEQ ID NO:7; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 of SEQ ID NO:8, CDR-L2 of SEQ ID NO:9, and CDR-L3 of SEQ ID NO:10; or,

[0063] (3b) A heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 of SEQ ID NO:26, CDR-H2 of SEQ ID NO:27, and CDR-H3 of SEQ ID NO:22; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 of SEQ ID NO:23, CDR-L2 of SEQ ID NO:24, and CDR-L3 of SEQ ID NO:25;

[0064] or,

[0065] (4) The following heavy chain variable regions (VH) and light chain variable regions (VL), wherein the CDR is defined according to the IMGT numbering system:

[0066] (4a) A heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 of SEQ ID NO:13, CDR-H2 of SEQ ID NO:14, and CDR-H3 of SEQ ID NO:15; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 of SEQ ID NO:16, CDR-L2 of SEQ ID NO:17, and CDR-L3 of SEQ ID NO:10; or,

[0067] (4b) A heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 of SEQ ID NO:28, CDR-H2 of SEQ ID NO:29, and CDR-H3 of SEQ ID NO:30; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 of SEQ ID NO:31, CDR-L2 of SEQ ID NO:32, and CDR-L3 of SEQ ID NO:25.

[0068] In some embodiments, the anti-Her2 antibody or its antigen-binding fragment comprises:

[0069] (a) VH or a variant thereof shown in SEQ ID NO: 1, and / or VL or a variant thereof shown in SEQ ID NO: 2; or

[0070] (b) VH or a variant thereof shown in SEQ ID NO: 3, and / or VL or a variant thereof shown in SEQ ID NO: 4;

[0071] 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, 3, 4, or 5 amino acids) compared to the sequence from which it originates; in some embodiments, the substitutions are conservative substitutions.

[0072] In some embodiments, the anti-Her2 antibody or its antigen-binding fragment comprises:

[0073] (a) VH shown in SEQ ID NO: 1, and VL shown in SEQ ID NO: 2; or

[0074] (b) VH shown in SEQ ID NO: 3 and VL shown in SEQ ID NO: 4.

[0075] In some embodiments, the anti-Her2 antibody or its antigen-binding fragment further comprises:

[0076] (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 its derived wild-type sequence (e.g., substitutions, deletions, or additions of up to 20, 15, 10, or 5 amino acids; e.g., substitutions, deletions, or additions of 1, 2, 3, 4, or 5 amino acids); and

[0077] (b) The light chain constant region (CL) of human immunoglobulin or a variant thereof, which has one or more amino acid substitutions, deletions or additions compared to the wild-type sequence from which it is derived (e.g., substitutions, deletions or additions of up to 20, up to 15, up to 10 or up to 5 amino acids; e.g., substitutions, deletions or additions of 1, 2, 3, 4 or 5 amino acids).

[0078] In some embodiments, the heavy chain constant region is an IgG heavy chain constant region, such as the IgG1, IgG2, IgG3, or IgG4 heavy chain constant region, such as the human IgG1 heavy chain constant region or the human IgG4 heavy chain constant region.

[0079] In some embodiments, the antibody or its antigen-binding fragment comprises a heavy chain constant region (CH) as shown in SEQ ID NO: 35 or a variant thereof, the variant having up to 20 conserved substitutions (e.g., up to 15, up to 10, or up to 5 amino acid substitutions; e.g., 1, 2, 3, 4, or 5 amino acid substitutions) compared to SEQ ID NO: 35.

[0080] In some embodiments, the antibody or its antigen-binding fragment comprises a light chain constant region (CL) as shown in SEQ ID NO: 36 or a variant thereof, the variant having up to 20 conserved substitutions (e.g., up to 15, up to 10, or up to 5 amino acid substitutions; e.g., 1, 2, 3, 4, or 5 amino acid substitutions) compared to SEQ ID NO: 36.

[0081] In some embodiments, the antibody or its antigen-binding fragment comprises a heavy chain constant region (CH) as shown in SEQ ID NO: 35 and a light chain constant region (CL) as shown in SEQ ID NO: 36.

[0082] In some embodiments, the anti-Her2 antibody or its antigen-binding fragment comprises:

[0083] (1) A heavy chain comprising the VH of the sequence shown in SEQ ID NO: 1 and the heavy chain constant region (CH) shown in SEQ ID NO: 35, and a light chain comprising the VL of the sequence shown in SEQ ID NO: 2 and the light chain constant region (CL) shown in SEQ ID NO: 36;

[0084] (2) A heavy chain comprising the VH of the sequence shown in SEQ ID NO: 3 and the heavy chain constant region (CH) shown in SEQ ID NO: 35, and a light chain comprising the VL of the sequence shown in SEQ ID NO: 4 and the light chain constant region (CL) shown in SEQ ID NO: 36;

[0085] (3) The heavy chain shown in SEQ ID NO:37 and the light chain shown in SEQ ID NO:38; or

[0086] (4) The heavy chain shown in SEQ ID NO:39 and the light chain shown in SEQ ID NO:40;

[0087] Optionally, the N-terminal glutamine of the VH of the sequence shown in SEQ ID NO:1 or 3 or a variant thereof, or the N-terminal glutamine of the heavy chain of the sequence shown in SEQ ID NO:37 or 39 or a variant thereof, undergoes cyclization to form pyroglutamic acid or pyroglutamic acid salt.

[0088] Optionally, the heavy chain constant region (CH) of the heavy chain as shown in SEQ ID NO: 35 or a variant thereof, or the heavy chain of the sequence shown in SEQ ID NO: 37 or 39 or a variant thereof, lacks a C-terminal lysine.

[0089] In some embodiments, the anti-Her2 antibody or its antigen-binding fragment is selected from trastuzumab or pertuzumab or their antigen-binding fragments or combinations thereof.

[0090] In some embodiments, the anti-Her2 antibody or its antigen-binding fragment in the anti-Her2 antibody drug conjugate is Trastuzumab.

[0091] In some embodiments, the anti-Her2 antibody drug conjugate is antibody drug conjugate A, which has the following structure:

[0092] Wherein, A is the group obtained by removing n amino groups from Trastuzumab, and n is an integer from 1 to 8, which in some embodiments is 1, 2, 3, 4, 5, 6, 7 or 8.

[0093] In some embodiments, the DAR value of the anti-Her2 antibody-drug conjugate is 1-10. In some embodiments, the DAR value of the anti-Her2 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. In some embodiments, the DAR value of the anti-Her2 antibody-drug conjugate is 1-4. In some embodiments, the DAR value of the anti-Her2 antibody-drug conjugate is 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.5, 1.7, 1.8, 1.9, 2.0, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3.0, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, or 4.0.

[0094] In some embodiments, the anti-Her2 antibody drug conjugate has the following chemical structure:

[0095] A1 is the group obtained by removing two amino groups from Trastuzumab.

[0096] In some embodiments, the anti-Trop-2 antibody-drug conjugate has the structure of formula (I): {D1-[L1-(L2)m1-(L3)m2-(L4)m3-E]} q -Ab Formula (I)

[0097] in,

[0098] 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.

[0099] 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.

[0100] L3 is a 5-12 member heterocyclic aromatic ring;

[0101] 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;

[0102] E is In this embodiment, each R4 is independently hydrogen (in some embodiments, protium or deuterium), β is 0, 1 or 2, and the 2 position of E is connected to Ab, and the 1 position of E is connected to L4.

[0103] m1, m2 and m3 are each independently 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;

[0104] D1 is the bioactive molecular moiety;

[0105] q refers to {D1-[L1-(L2)} which forms a thioether bond with the thiol group of Ab. m1 -(L3) m2 -(L4) m3 The number of the -E]} part is selected from 1 to 10 (in some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10);

[0106] Ab represents an anti-Trop-2 antibody or its antigen-binding fragment.

[0107] In some embodiments, the anti-Trop-2 antibody-drug conjugate satisfies one or more of the following:

[0108] (1) L1 is selected from Furthermore, position 1 of L1 is connected to D1, and position 2 of L1 is connected to L2;

[0109] (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.

[0110] (3) L3 is selected from 5-6 membered heteroaryl rings, and in some embodiments it is pyrazole or triazole;

[0111] (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;

[0112] (5) E is In this embodiment, each R4 is independently hydrogen (in some embodiments, protium or deuterium), β is 0, 1 or 2, and E is connected to Ab at the 2 position (e.g., to a thiol group on Ab) and to L4 at the 1 position.

[0113] (6) m1, m2 and m3 are all 1;

[0114] (7) The bioactive molecules are selected from In some implementations, D1 is selected from

[0115] (8) q is selected from an integer between 3 and 8 (in some implementations, it is 3, 4, 5, 6, 7 or 8);

[0116] (9)Ab is Sacituzumab or its antigen-binding fragment.

[0117] In some embodiments, the anti-Trop-2 antibody-drug conjugate has the following chemical structure:

[0118] Wherein, Ab is an anti-Trop-2 antibody or its antigen-binding fragment; q is selected from 1 to 10 (in some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10); in some embodiments, q is selected from 3 to 8 (in some embodiments, 3, 4, 5, 6, 7 or 8).

[0119] In some embodiments, the anti-Trop-2 antibody or its antigen-binding fragment comprises:

[0120] (1) The following heavy chain variable regions (VH) and / or light chain variable regions (VL), wherein the CDR is defined according to the Chothia numbering system:

[0121] Heavy chain variable region (VH) containing the following 3 CDRs: CDR-H1 with sequence SEQ ID NO:43 or a variant thereof, CDR-H2 with sequence SEQ ID NO:44 or a variant thereof, and CDR-H3 with sequence SEQ ID NO:45 or a variant thereof; and / or, light chain variable region (VL) containing the following 3 CDRs: CDR-L1 with sequence SEQ ID NO:46 or a variant thereof, CDR-L2 with sequence SEQ ID NO:47 or a variant thereof, and CDR-L3 with sequence SEQ ID NO:48 or a variant thereof;

[0122] 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; in some embodiments, the substitutions are conservative substitutions.

[0123] or,

[0124] (2) The following heavy chain variable regions (VH) and / or light chain variable regions (VL), wherein the CDR is defined according to the AbM numbering system:

[0125] Heavy chain variable region (VH) containing the following 3 CDRs: CDR-H1 with sequence SEQ ID NO:56 or a variant thereof, CDR-H2 with sequence SEQ ID NO:57 or a variant thereof, and CDR-H3 with sequence SEQ ID NO:45 or a variant thereof; and / or, light chain variable region (VL) containing the following 3 CDRs: CDR-L1 with sequence SEQ ID NO:46 or a variant thereof, CDR-L2 with sequence SEQ ID NO:47 or a variant thereof, and CDR-L3 with sequence SEQ ID NO:48 or a variant thereof;

[0126] 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; in some embodiments, the substitutions are conservative substitutions.

[0127] or,

[0128] (3) The following heavy chain variable regions (VH) and / or light chain variable regions (VL), wherein the CDR is defined according to the Kabat numbering system:

[0129] Heavy chain variable region (VH) containing the following 3 CDRs: CDR-H1 with sequence SEQ ID NO:49 or a variant thereof, CDR-H2 with sequence SEQ ID NO:50 or a variant thereof, and CDR-H3 with sequence SEQ ID NO:45 or a variant thereof; and / or, light chain variable region (VL) containing the following 3 CDRs: CDR-L1 with sequence SEQ ID NO:46 or a variant thereof, CDR-L2 with sequence SEQ ID NO:47 or a variant thereof, and CDR-L3 with sequence SEQ ID NO:48 or a variant thereof;

[0130] 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; in some embodiments, the substitutions are conservative substitutions.

[0131] or,

[0132] (4) The following heavy chain variable regions (VH) and / or light chain variable regions (VL), wherein the CDR is defined according to the IMGT numbering system:

[0133] Heavy chain variable region (VH) containing the following 3 CDRs: CDR-H1 with sequence SEQ ID NO:51 or a variant thereof, CDR-H2 with sequence SEQ ID NO:52 or a variant thereof, and CDR-H3 with sequence SEQ ID NO:53 or a variant thereof; and / or, light chain variable region (VL) containing the following 3 CDRs: CDR-L1 with sequence SEQ ID NO:54 or a variant thereof, CDR-L2 with sequence SEQ ID NO:55 or a variant thereof, and CDR-L3 with sequence SEQ ID NO:48 or a variant thereof;

[0134] 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 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; in some embodiments, the substitutions are conservative substitutions.

[0135] In some embodiments, the anti-Trop-2 antibody or its antigen-binding fragment comprises:

[0136] (1) The following heavy chain variable regions (VH) and light chain variable regions (VL), where CDR is defined according to the Chothia numbering system:

[0137] Heavy chain variable region (VH) containing the following three CDRs: CDR-H1 of SEQ ID NO:43, CDR-H2 of SEQ ID NO:44, and CDR-H3 of SEQ ID NO:45; and light chain variable region (VL) containing the following three CDRs: CDR-L1 of SEQ ID NO:46, CDR-L2 of SEQ ID NO:47, and CDR-L3 of SEQ ID NO:48; or,

[0138] (2) The following heavy chain variable regions (VH) and light chain variable regions (VL), wherein the CDR is defined according to the AbM numbering system:

[0139] Heavy chain variable region (VH) containing the following three CDRs: CDR-H1 of SEQ ID NO:56, CDR-H2 of SEQ ID NO:57, and CDR-H3 of SEQ ID NO:45; and light chain variable region (VL) containing the following three CDRs: CDR-L1 of SEQ ID NO:46, CDR-L2 of SEQ ID NO:47, and CDR-L3 of SEQ ID NO:48; or,

[0140] (3) The following heavy chain variable regions (VH) and light chain variable regions (VL), where CDR is defined according to the Kabat numbering system:

[0141] Heavy chain variable region (VH) containing the following three CDRs: CDR-H1 of SEQ ID NO:49, CDR-H2 of SEQ ID NO:50, and CDR-H3 of SEQ ID NO:45; and light chain variable region (VL) containing the following three CDRs: CDR-L1 of SEQ ID NO:46, CDR-L2 of SEQ ID NO:47, and CDR-L3 of SEQ ID NO:48; or,

[0142] (4) The following heavy chain variable regions (VH) and light chain variable regions (VL), wherein the CDR is defined according to the IMGT numbering system:

[0143] The heavy chain variable region (VH) contains the following three CDRs: CDR-H1 with sequence SEQ ID NO:51, CDR-H2 with sequence SEQ ID NO:52, and CDR-H3 with sequence SEQ ID NO:53; and the light chain variable region (VL) contains the following three CDRs: CDR-L1 with sequence SEQ ID NO:54, CDR-L2 with sequence SEQ ID NO:55, and CDR-L3 with sequence SEQ ID NO:48.

[0144] In some embodiments, the anti-Trop-2 antibody or its antigen-binding fragment comprises: VH or a variant thereof shown in SEQ ID NO: 41, and / or VL or a variant thereof shown in SEQ ID NO: 42;

[0145] 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, 3, 4, or 5 amino acids) compared to the sequence from which it originates; in some embodiments, the substitutions are conservative substitutions.

[0146] In some embodiments, the anti-Trop-2 antibody or its antigen-binding fragment comprises: VH as shown in SEQ ID NO: 41, and VL as shown in SEQ ID NO: 42.

[0147] In some embodiments, the anti-Trop-2 antibody or its antigen-binding fragment further comprises:

[0148] (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 its derived wild-type sequence (e.g., substitutions, deletions, or additions of up to 20, 15, 10, or 5 amino acids; e.g., substitutions, deletions, or additions of 1, 2, 3, 4, or 5 amino acids); and

[0149] (b) The light chain constant region (CL) of human immunoglobulin or a variant thereof, which has one or more amino acid substitutions, deletions or additions compared to the wild-type sequence from which it is derived (e.g., substitutions, deletions or additions of up to 20, up to 15, up to 10 or up to 5 amino acids; e.g., substitutions, deletions or additions of 1, 2, 3, 4 or 5 amino acids).

[0150] In some embodiments, the heavy chain constant region is an IgG heavy chain constant region, such as the IgG1, IgG2, IgG3, or IgG4 heavy chain constant region, such as the human IgG1 heavy chain constant region or the human IgG4 heavy chain constant region.

[0151] In some embodiments, the anti-Trop-2 antibody or its antigen-binding fragment comprises the heavy chain shown in SEQ ID NO. 58 and the light chain shown in SEQ ID NO. 59.

[0152] In some embodiments, the anti-Trop-2 antibody or its antigen-binding fragment is sacituzumab or its antigen-binding fragment.

[0153] In some embodiments, the anti-Trop-2 antibody-drug conjugate is antibody-drug conjugate B, which has the following chemical structure:

[0154] Where q is selected from 1 to 10.

[0155] In some implementations, q in antibody-drug conjugate B is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.

[0156] In some embodiments, the DAR value of the anti-Trop-2 antibody-drug conjugate is 1-10. 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. In some embodiments, the DAR value of the anti-Trop-2 antibody-drug conjugate is 3-8. In some embodiments, the DAR value of the anti-Trop-2 antibody-drug conjugate is 5-8. 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.

[0157] In some embodiments, the anti-Her2 antibody or its antigen-binding fragment in the drug combination is selected from the anti-Her2 antibody or its antigen-binding fragment as described in any of the preceding embodiments. In some embodiments, the anti-Her2 antibody or its antigen-binding fragment in the drug combination is selected from Trastuzumab and Pertuzumab. In some embodiments, the anti-Her2 antibody or its antigen-binding fragment in the drug combination is Trastuzumab. In some embodiments, the anti-Her2 antibody or its antigen-binding fragment in the drug combination is Pertuzumab. In some embodiments, the anti-Her2 antibody or its antigen-binding fragment in the drug combination is a combination of Trastuzumab and Pertuzumab.

[0158] In some embodiments, the amino acid sequence of the Trastuzumab has a lookup accession number (IMGT / mAb-DB ID) of 97 in the IMGT database, and the amino acid sequence of the Pertuzumab has a lookup accession number (IMGT / mAb-DB ID) of 80 in the IMGT database.

[0159] In some embodiments, the drug combination is a combination of antibody-drug conjugate A and antibody-drug conjugate B.

[0160] In some embodiments, the drug combination is a combination of an anti-Trop-2 antibody drug conjugate and an anti-Her2 antibody drug conjugate, wherein the anti-Trop-2 antibody drug conjugate has the following structure:

[0161] Wherein, q is selected from 1 to 10, for example 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, and the DAR value of the anti-Trop-2 antibody-drug conjugate is 3 to 8, for example 5 to 8, and further for example 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;

[0162] The anti-Her2 antibody-drug conjugate has the following structure:

[0163] Wherein, A is Trastuzumab, n is an integer from 1 to 8, such as 1, 2, 3, 4, 5, 6, 7 or 8, and the DAR value of the anti-Her2 antibody-drug conjugate is 1-4, such as 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.5, 1.7, 1.8, 1.9, 2.0, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3.0, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, or 4.0.

[0164] In some embodiments, the drug combination is a combination of antibody-drug conjugate B and trastuzumab.

[0165] In some implementations, the drug combination is a combination of antibody-drug conjugate B and Pertuzumab.

[0166] In some embodiments, the drug combination is a combination of antibody-drug conjugate B, trastuzumab, and pertuzumab.

[0167] In some embodiments, the drug combination is a combination of an anti-Trop-2 antibody drug conjugate and an anti-Her2 antibody or an antigen-binding fragment thereof, wherein the anti-Trop-2 antibody drug conjugate has the following structure:

[0168] Wherein, q is selected from 1 to 10, for example 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, and the DAR value of the anti-Trop-2 antibody-drug conjugate is 3 to 8, for example 5 to 8, and further for example 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;

[0169] The anti-Her2 antibody or its antigen-binding fragment is selected from one or both of Trastuzumab and Pertuzumab.

[0170] In some embodiments, the drug combination is a combination of antibody-drug conjugate A, antibody-drug conjugate B, and Pertuzumab.

[0171] In some embodiments, the drug combination is a combination of antibody-drug conjugate A, antibody-drug conjugate B, and Trastuzumab.

[0172] In some embodiments, the drug combination is a combination of antibody-drug conjugate A, antibody-drug conjugate B, trastuzumab, and pertuzumab.

[0173] In some embodiments, the drug combination is a combination of an anti-Trop-2 antibody drug conjugate, an anti-Her2 antibody drug conjugate, and an anti-Her2 antibody or an antigen-binding fragment thereof, wherein the anti-Trop-2 antibody drug conjugate has the following structure:

[0174] Wherein, q is selected from 1 to 10, for example 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, and the DAR value of the anti-Trop-2 antibody-drug conjugate is 3 to 8, for example 5 to 8, and further for example 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;

[0175] The anti-Her2 antibody-drug conjugate has the following structure:

[0176] Where A is Trastuzumab, n is an integer from 1 to 8, such as 1, 2, 3, 4, 5, 6, 7 or 8, and the DAR value of the anti-Her2 antibody-drug conjugate is 1-4, such as 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.5, 1.7, 1.8, 1.9, 2.0, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3.0, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, or 4.0;

[0177] The anti-Her2 antibody or its antigen-binding fragment is selected from one or both of Trastuzumab and Pertuzumab.

[0178] In some embodiments, the drug combination is a combination of antibody-drug conjugate A and Trastuzumab.

[0179] In some embodiments, the drug combination is a combination of antibody-drug conjugate A and Pertuzumab.

[0180] In some embodiments, the drug combination is a combination of antibody-drug conjugate A, Trastuzumab, and Pertuzumab.

[0181] In some embodiments, the drug combination is a combination of an anti-Her2 antibody drug conjugate and an anti-Her2 antibody or an antigen-binding fragment thereof, wherein the anti-Her2 antibody drug conjugate has the following structure:

[0182] Where A is Trastuzumab, n is an integer from 1 to 8, such as 1, 2, 3, 4, 5, 6, 7 or 8, and the DAR value of the anti-Her2 antibody-drug conjugate is 1-4, such as 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.5, 1.7, 1.8, 1.9, 2.0, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3.0, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, or 4.0;

[0183] The anti-Her2 antibody or its antigen-binding fragment is selected from one or both of Trastuzumab and Pertuzumab.

[0184] In some implementations, the drug combination is a combination of Trastuzumab and Pertuzumab.

[0185] In some embodiments, the drug combination, namely the anti-Trop-2 antibody drug conjugate, the anti-Her2 antibody drug conjugate, and / or the anti-Her2 antibody or its antigen-binding fragment, is present in a unit formulation.

[0186] In some embodiments, the drug combination, namely the anti-Trop-2 antibody drug conjugate, the anti-Her2 antibody drug conjugate, and / or the anti-Her2 antibody or its antigen-binding fragment, is present in the same formulation unit.

[0187] In some embodiments, the drug combination, namely the anti-Trop-2 antibody drug conjugate, the anti-Her2 antibody drug conjugate, and / or the anti-Her2 antibody or its antigen-binding fragment, is present in different formulation units.

[0188] This disclosure further provides the use of anti-Trop-2 antibody-drug conjugates and anti-Her2 antibody-drug conjugates in the preparation of medicaments for the prevention and / or treatment of tumors or cancers in a subject. In some embodiments, the anti-Trop-2 antibody-drug conjugate and the anti-Her2 antibody-drug conjugate are as defined in any of the preceding embodiments.

[0189] This disclosure further provides the use of anti-Trop-2 antibody-drug conjugates, anti-Her2 antibody-drug conjugates, and anti-Her2 antibodies or antigen-binding fragments thereof in the preparation of medicaments for the prevention and / or treatment of tumors or cancers in a subject. In some embodiments, the anti-Trop-2 antibody-drug conjugate, the anti-Her2 antibody-drug conjugate, and the anti-Her2 antibody or antigen-binding fragment thereof are as defined in any of the preceding embodiments.

[0190] This disclosure further provides the use of anti-Trop-2 antibody-drug conjugates and anti-Her2 antibodies or antigen-binding fragments thereof in the preparation of medicaments for the prevention and / or treatment of tumors or cancers in subjects. In some embodiments, the anti-Trop-2 antibody-drug conjugate and the anti-Her2 antibody or antigen-binding fragment thereof are as defined in any of the preceding embodiments.

[0191] This disclosure further provides the use of anti-Her2 antibody drug conjugates and anti-Her2 antibodies or antigen-binding fragments thereof in the preparation of medicaments for the prevention and / or treatment of tumors or cancers in subjects. In some embodiments, the anti-Her2 antibody drug conjugate and the anti-Her2 antibody or antigen-binding fragment thereof are as defined in any of the preceding embodiments.

[0192] This disclosure further provides the use of two or more of the anti-Her2 antibodies or antigen-binding fragments thereof in the preparation of a medicament for the prevention and / or treatment of a subject's tumor or cancer. In some embodiments, the anti-Her2 antibody or antigen-binding fragment thereof is as defined in any of the preceding embodiments.

[0193] This disclosure further provides the use of the aforementioned pharmaceutical combination in the preparation of a medicament for the prevention and / or treatment of a subject’s tumor or cancer.

[0194] The tumors or cancers described herein are selected from solid tumors or non-solid tumors. In some embodiments, the tumors or cancers are 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), 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.

[0195] In some implementations, the tumor or cancer is selected from lung cancer, breast cancer, and ovarian epithelial cancer.

[0196] In some implementations, the tumor or cancer is breast cancer.

[0197] In some implementations, the breast cancer is ER- / HER2+ breast cancer.

[0198] In some implementations, the breast cancer is HR- / HER2+ breast cancer.

[0199] In some embodiments, the drug combination, namely the anti-Trop-2 antibody drug conjugate, the anti-Her2 antibody drug conjugate, and / or the anti-Her2 antibody or its antigen-binding fragment, is administered simultaneously.

[0200] In some embodiments, the drug combination, namely the anti-Trop-2 antibody drug conjugate, the anti-Her2 antibody drug conjugate, and / or the anti-Her2 antibody or its antigen-binding fragment, is administered separately.

[0201] In some embodiments, the drug combination, namely the anti-Trop-2 antibody drug conjugate, the anti-Her2 antibody drug conjugate, and / or the anti-Her2 antibody or its antigen-binding fragment, is administered sequentially.

[0202] In some embodiments, the drug combination, namely the anti-Trop-2 antibody drug conjugate, the anti-Her2 antibody drug conjugate, and / or the anti-Her2 antibody or its antigen-binding fragment, is administered sequentially.

[0203] In some embodiments, the anti-Trop-2 antibody drug conjugate, the anti-Her2 antibody drug conjugate, and the anti-Her2 antibody or its antigen-binding fragment are administered simultaneously.

[0204] In some embodiments, the anti-Trop-2 antibody drug conjugate, the anti-Her2 antibody drug conjugate, and the anti-Her2 antibody or its antigen-binding fragment are administered separately.

[0205] In some embodiments, the anti-Trop-2 antibody drug conjugate, the anti-Her2 antibody drug conjugate, and the anti-Her2 antibody or its antigen-binding fragment are administered sequentially.

[0206] In some embodiments, the anti-Trop-2 antibody drug conjugate, the anti-Her2 antibody or its antigen-binding fragment, and the anti-Her2 antibody drug conjugate are administered sequentially.

[0207] In some embodiments, the anti-Her2 antibody drug conjugate, the anti-Trop-2 antibody drug conjugate, and the anti-Her2 antibody or its antigen-binding fragment are administered sequentially.

[0208] In some embodiments, the anti-Her2 antibody drug conjugate, the anti-Her2 antibody or its antigen-binding fragment, and the anti-Trop-2 antibody drug conjugate are administered sequentially.

[0209] In some embodiments, the anti-Her2 antibody or its antigen-binding fragment, the anti-Trop-2 antibody-drug conjugate, and the anti-Her2 antibody-drug conjugate are administered sequentially.

[0210] In some embodiments, the anti-Her2 antibody or its antigen-binding fragment, the anti-Her2 antibody drug conjugate, and the anti-Trop-2 antibody drug conjugate are administered sequentially.

[0211] In some embodiments, the anti-Trop-2 antibody drug conjugate, the anti-Her2 antibody drug conjugate, and the anti-Her2 antibody or its antigen-binding fragment are administered sequentially.

[0212] In some embodiments, the anti-Trop-2 antibody drug conjugate, the anti-Her2 antibody or its antigen-binding fragment, and the anti-Her2 antibody drug conjugate are administered sequentially.

[0213] In some embodiments, the anti-Her2 antibody drug conjugate, the anti-Trop-2 antibody drug conjugate, and the anti-Her2 antibody or its antigen-binding fragment are administered sequentially.

[0214] In some embodiments, the anti-Her2 antibody drug conjugate, the anti-Her2 antibody or its antigen-binding fragment, and the anti-Trop-2 antibody drug conjugate are administered sequentially.

[0215] In some embodiments, the anti-Her2 antibody or its antigen-binding fragment, the anti-Trop-2 antibody-drug conjugate, and the anti-Her2 antibody-drug conjugate are administered sequentially.

[0216] In some embodiments, the anti-Her2 antibody or its antigen-binding fragment, the anti-Her2 antibody drug conjugate, and the anti-Trop-2 antibody drug conjugate are administered sequentially.

[0217] In some implementations, the anti-Trop-2 antibody drug conjugate and the anti-Her2 antibody drug conjugate are administered simultaneously.

[0218] In some embodiments, the anti-Trop-2 antibody drug conjugate and the anti-Her2 antibody drug conjugate are administered separately.

[0219] In some embodiments, the anti-Trop-2 antibody drug conjugate and the anti-Her2 antibody drug conjugate are administered sequentially.

[0220] In some embodiments, the anti-Her2 antibody drug conjugate and the anti-Trop-2 antibody drug conjugate are administered sequentially.

[0221] In some embodiments, the anti-Trop-2 antibody drug conjugate and the anti-Her2 antibody drug conjugate are administered sequentially.

[0222] In some implementations, the anti-Her2 antibody drug conjugate and the anti-Trop-2 antibody drug conjugate are administered sequentially.

[0223] In some embodiments, the anti-Her2 antibody drug conjugate and the anti-Her2 antibody or its antigen-binding fragment are administered simultaneously.

[0224] In some embodiments, the anti-Her2 antibody drug conjugate and the anti-Her2 antibody or its antigen-binding fragment are administered separately.

[0225] In some embodiments, the anti-Her2 antibody drug conjugate and the anti-Her2 antibody or its antigen-binding fragment are administered sequentially.

[0226] In some embodiments, the anti-Her2 antibody or its antigen-binding fragment and the anti-Her2 antibody drug conjugate are administered sequentially.

[0227] In some embodiments, the anti-Her2 antibody drug conjugate and the anti-Her2 antibody or its antigen-binding fragment are administered sequentially.

[0228] In some embodiments, the anti-Her2 antibody or its antigen-binding fragment and the anti-Her2 antibody drug conjugate are administered sequentially.

[0229] In some embodiments, the anti-Trop-2 antibody-drug conjugate and the anti-Her2 antibody or its antigen-binding fragment are administered simultaneously.

[0230] In some embodiments, the anti-Trop-2 antibody-drug conjugate and the anti-Her2 antibody or its antigen-binding fragment are administered separately.

[0231] In some embodiments, the anti-Trop-2 antibody-drug conjugate and the anti-Her2 antibody or its antigen-binding fragment are administered sequentially.

[0232] In some embodiments, the anti-Her2 antibody or its antigen-binding fragment and the anti-Trop-2 antibody drug conjugate are administered sequentially.

[0233] In some embodiments, the anti-Trop-2 antibody-drug conjugate and the anti-Her2 antibody or its antigen-binding fragment are administered sequentially.

[0234] In some embodiments, the anti-Her2 antibody or its antigen-binding fragment and the anti-Trop-2 antibody drug conjugate are administered sequentially.

[0235] In some embodiments, the anti-Trop-2 antibody-drug conjugate, anti-Her2 antibody-drug conjugate, and / or anti-Her2 antibody or its antigen-binding fragment are 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.

[0236] In some embodiments, the anti-Trop-2 antibody drug conjugate and the anti-Her2 antibody drug conjugate are 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.

[0237] In some embodiments, the anti-Her2 antibody drug conjugate and the anti-Her2 antibody or its antigen-binding fragment are 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.

[0238] In some embodiments, the anti-Trop-2 antibody-drug conjugate and the anti-Her2 antibody or its antigen-binding fragment are 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.

[0239] 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 14 days, 21 days, 28 days, or 42 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.

[0240] In some embodiments, the anti-Trop-2 antibody-drug conjugate is administered 1 to 20 times over a period of 1 to 4 weeks. In some embodiments, the anti-Trop-2 antibody-drug conjugate is administered twice a week, once a week, once every 2 weeks, or once every 3 weeks.

[0241] In some embodiments, the dose of the anti-Trop-2 antibody-drug conjugate administered per dose is selected from 0.1-20 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 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 dose is 0.5 mg / kg, 1.0 mg / kg, 1.5 mg / kg, 2.0 mg / kg, 2.5 mg / kg, 3.0 mg / kg, 3.5 mg / kg, 4.0 mg / kg, 4.5 mg / kg, 5.0 mg / kg, 6.0 mg / kg, 7.0 mg / kg, 8.0 mg / kg, 9.0 mg / kg, or 10.0 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 2.5 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 3.0 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 4.0 mg / kg, based on the subject's weight.

[0242] 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. In some embodiments, the dose of the anti-Trop-2 antibody-drug conjugate is 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, or 0.1-10 mg. In some embodiments, the dosage of the anti-Trop-2 antibody-drug conjugate is 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, or 500 mg.

[0243] In some embodiments, the dose concentration of the anti-Trop-2 antibody-drug conjugate administered per dose is selected from 0.1-50 mg / ml. In some embodiments, the dose concentration of the anti-Trop-2 antibody-drug conjugate administered per dose is 0.1-40 mg / ml, 0.1-30 mg / ml, 0.1-20 mg / ml, or 0.1-10 mg / ml. In some embodiments, the dose concentration of the anti-Trop-2 antibody-drug conjugate administered at each dose is 0.1 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, or 50 mg / ml.

[0244] In some embodiments, the anti-Trop-2 antibody-drug conjugate is administered via an enteral route. In some embodiments, the anti-Trop-2 antibody-drug conjugate is administered intravenously. In some embodiments, the Trop-2 antibody-drug conjugate is administered subcutaneously or intramuscularly.

[0245] In some embodiments, the dosing period of the anti-Her2 antibody drug conjugate is 14-42 days. In some embodiments, the dosing period of the Her2 antibody drug conjugate is 14 days, 21 days, 28 days, or 42 days. In some embodiments, the dosing period of the anti-Her2 antibody drug conjugate is 21 days. In some embodiments, the dosing period of the anti-Her2 antibody drug conjugate is 28 days.

[0246] In some embodiments, the dose of the anti-Her2 antibody-drug conjugate administered per dose is selected from 0.1-20 mg / kg, based on the subject's weight. In some embodiments, the dose of the anti-Her2 antibody-drug conjugate administered per dose is 0.1-10 mg / kg, 0.2-8 mg / kg, or 0.3-6 mg / kg, based on the subject's weight. In some embodiments, the dose of the anti-Her2 antibody-drug conjugate administered per dose is 0.5 mg / kg, 1.0 mg / kg, 1.5 mg / kg, 2.0 mg / kg, 2.5 mg / kg, 3.0 mg / kg, 3.5 mg / kg, 4.0 mg / kg, 4.5 mg / kg, 5.0 mg / kg, 6.0 mg / kg, 7.0 mg / kg, 8.0 mg / kg, 9.0 mg / kg, or 10.0 mg / kg, based on the subject's weight.

[0247] In some embodiments, the dose of the anti-Her2 antibody drug conjugate (e.g., a single-dose dose or a unit dose) is selected from 0.1-1000 mg. In some embodiments, the dose of the anti-Her2 antibody drug conjugate is 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, or 0.1-10 mg. In some embodiments, the dosage of the anti-Her2 antibody drug conjugate is 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, or 500 mg.

[0248] In some embodiments, the dose concentration of the anti-Her2 antibody-drug conjugate administered per dose is selected from 0.1-50 mg / ml. In some embodiments, the dose concentration of the anti-Her2 antibody-drug conjugate administered per dose is 0.1-40 mg / ml, 0.1-30 mg / ml, 0.1-20 mg / ml, or 0.1-10 mg / ml. In some embodiments, the dose concentration of the anti-Her2 antibody-drug conjugate administered each time is 0.1 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, or 50 mg / ml.

[0249] In some embodiments, the anti-Her2 antibody-drug conjugate is administered 1 to 20 times over a period of 1 to 4 weeks. In some embodiments, the anti-Her2 antibody-drug conjugate is administered once a week, once every 2 weeks, once every 3 weeks, or once every 4 weeks.

[0250] In some embodiments, the anti-Her2 antibody drug conjugate is administered via an enteral route. In some embodiments, the anti-Trop-2 antibody drug conjugate is administered intravenously. In some embodiments, the Trop-2 antibody drug conjugate is administered subcutaneously or intramuscularly.

[0251] In some embodiments, the administration period of the anti-Her2 antibody or its antigen-binding fragment is 14-42 days. In some embodiments, the administration period of the anti-Her2 antibody is 14 days, 21 days, 28 days, or 42 days. In some embodiments, the administration period of the anti-Her2 antibody is 21 days. In some embodiments, the administration period of the anti-Her2 antibody is 28 days.

[0252] In some embodiments, the dose of the anti-Her2 antibody or its antigen-binding fragment administered per administration is selected from 0.1-20 mg / kg, based on the subject's weight. In some embodiments, the dose of the anti-Her2 antibody or its antigen-binding fragment administered per administration is 0.1-10 mg / kg, based on the subject's weight. In some embodiments, the dose of the anti-Her2 antibody or its antigen-binding fragment administered per administration is 0.1-8 mg / kg, 0.2-6 mg / kg, or 0.5-5 mg / kg, based on the subject's weight. In some implementations, the dose of the anti-Her2 antibody or its antigen-binding fragment administered per administration is 0.5 mg / kg, 1.0 mg / kg, 1.5 mg / kg, 2.0 mg / kg, 2.5 mg / kg, 3.0 mg / kg, 3.5 mg / kg, 4.0 mg / kg, 4.5 mg / kg, 5.0 mg / kg, 6.0 mg / kg, 7.0 mg / kg, 8.0 mg / kg, 9.0 mg / kg, or 10.0 mg / kg, based on the subject's weight.

[0253] In some embodiments, the anti-Her2 antibody or its antigen-binding fragment is administered 1 to 20 times over a period of 1 to 4 weeks. In some embodiments, the anti-Her2 antibody or its antigen-binding fragment is administered once a week, twice a week, once every 2 weeks, or once every 3 weeks.

[0254] In some embodiments, the dose of the anti-Her2 antibody or its antigen-binding fragment (e.g., a single-dose dose or a unit-dose formulation) is selected from 0.1-1000 mg. In some embodiments, the dose of the anti-Her2 antibody or its antigen-binding fragment is 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, or 0.1-10 mg. In some embodiments, the dose of the anti-Her2 antibody or its antigen-binding fragment is 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, or 500 mg.

[0255] In some embodiments, the dose concentration of the anti-Her2 antibody or its antigen-binding fragment administered per administration is selected from 0.1-50 mg / ml. In some embodiments, the dose concentration of the anti-Her2 antibody or its antigen-binding fragment administered per administration is 0.1-40 mg / ml, 0.1-30 mg / ml, 0.1-20 mg / ml, or 0.1-10 mg / ml. In some embodiments, the dose concentration of the anti-Her2 antibody or its antigen-binding fragment administered each time is 0.1 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, or 50 mg / ml.

[0256] In some embodiments, the anti-Her2 antibody or its antigen-binding fragment is administered via an enteral route. In some embodiments, the anti-Trop-2 antibody-drug conjugate is administered intravenously. In some embodiments, the Trop-2 antibody-drug conjugate is administered subcutaneously or intramuscularly.

[0257] This disclosure further provides a method for preventing and / or treating a tumor or cancer in a subject, comprising the steps of administering to the subject a therapeutically effective amount of two or more of the aforementioned anti-Trop-2 antibody drug conjugate, anti-Her2 antibody drug conjugate, and anti-Her2 antibody or antigen-binding fragment thereof.

[0258] This disclosure further provides a method for preventing and / or treating a tumor or cancer in a subject, comprising the step of administering to the subject a therapeutically effective amount of the aforementioned anti-Trop-2 antibody drug conjugate and anti-Her2 antibody drug conjugate.

[0259] This disclosure further provides a method for preventing and / or treating a tumor or cancer in a subject, comprising the step of administering to the subject a therapeutically effective amount of the aforementioned anti-Trop-2 antibody-drug conjugate and anti-Her2 antibody or an antigen-binding fragment thereof.

[0260] This disclosure further provides a method for preventing and / or treating a tumor or cancer in a subject, comprising the steps of administering to the subject a therapeutically effective amount of the aforementioned anti-Trop-2 antibody drug conjugate, anti-Her2 antibody drug conjugate, and anti-Her2 antibody or its antigen-binding fragment.

[0261] This disclosure further provides a method for preventing and / or treating a tumor or cancer in a subject, comprising the step of administering to the subject a therapeutically effective amount of the aforementioned anti-Her2 antibody drug conjugate and anti-Her2 antibody or an antigen-binding fragment thereof.

[0262] This disclosure further provides a method for preventing and / or treating a tumor or cancer in a subject, comprising the step of administering to the subject a therapeutically effective amount of two or more of the aforementioned anti-Her2 antibody or its antigen-binding fragment.

[0263] This disclosure further provides a method for preventing and / or treating a tumor or cancer in a subject, comprising the step of administering a therapeutically effective amount of the aforementioned combination of drugs to the subject.

[0264] In some embodiments, the anti-Trop-2 antibody-drug conjugate includes its dosing cycle, dosing frequency, dosing dose, route of administration, etc., as defined in any of the preceding descriptions.

[0265] In some implementations, the anti-Her2 antibody drug conjugate includes its dosing cycle, dosing frequency, dosing dose, route of administration, etc., as defined in any of the preceding descriptions.

[0266] In some embodiments, the anti-Her2 antibody or its antigen-binding fragment, including its dosing cycle, dosing frequency, dosing dose, route of administration, etc., are as defined in any of the preceding descriptions.

[0267] In some embodiments, the method includes administering each therapeutic agent to the subject according to the following protocol:

[0268] (1) Antibody-drug conjugate A, administered 1 to 20 times over a period of 1 to 4 weeks (e.g., once weekly, once every 2 weeks, once every 3 weeks, once every 4 weeks), with each dose selected from 0.1-20 mg / kg (e.g., 0.5 mg / kg, 1.0 mg / kg, 1.5 mg / kg, 2.0 mg / kg, 2.5 mg / kg, 3.0 mg / kg, 3.5 mg / kg, 4.0 mg / kg, 4.5 mg / kg, 5.0 mg / kg, 6.0 mg / kg, 7.0 mg / kg, 8.0 mg / kg, 9.0 mg / kg, or 10.0 mg / kg) based on the subject's weight; and

[0269] (2) Antibody-drug conjugate B, administered 1 to 20 times over a period of 1 to 4 weeks (e.g., twice a week, once a week, once every 2 weeks, or once every 3 weeks), with the dose per administration selected from 0.1 to 20 mg / kg (e.g., 0.5 mg / kg, 1.0 mg / kg, 1.5 mg / kg, 2.0 mg / kg, 2.5 mg / kg, 3.0 mg / kg, 3.5 mg / kg, 4.0 mg / kg, 4.5 mg / kg, 5.0 mg / kg, 6.0 mg / kg, 7.0 mg / kg, 8.0 mg / kg, 9.0 mg / kg, or 10.0 mg / kg).

[0270] In some embodiments, the antibody-drug conjugate A and antibody-drug conjugate B are administered 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.

[0271] In some embodiments, the method includes administering each therapeutic agent to the subject according to the following protocol:

[0272] (1) Antibody-drug conjugate A, administered 1 to 20 times over a period of 1 to 4 weeks (e.g., once weekly, once every 2 weeks, once every 3 weeks, once every 4 weeks), with each dose selected from 0.1-20 mg / kg (e.g., 0.5 mg / kg, 1.0 mg / kg, 1.5 mg / kg, 2.0 mg / kg, 2.5 mg / kg, 3.0 mg / kg, 3.5 mg / kg, 4.0 mg / kg, 4.5 mg / kg, 5.0 mg / kg, 6.0 mg / kg, 7.0 mg / kg, 8.0 mg / kg, 9.0 mg / kg, or 10.0 mg / kg) based on the subject's weight; and

[0273] (2) Trastuzumab, administered 1 to 20 times over a period of 1 to 4 weeks (e.g., once a week, twice a week, once every 2 weeks or once every 3 weeks), with the dose per administration selected from 0.1 to 20 mg / kg (e.g., 0.5 mg / kg, 1.0 mg / kg, 1.5 mg / kg, 2.0 mg / kg, 2.5 mg / kg, 3.0 mg / kg, 3.5 mg / kg, 4.0 mg / kg, 4.5 mg / kg, 5.0 mg / kg, 6.0 mg / kg, 7.0 mg / kg, 8.0 mg / kg, 9.0 mg / kg or 10.0 mg / kg).

[0274] In some embodiments, the antibody-drug conjugate A and Trastuzumab are administered 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.

[0275] In some embodiments, the method includes administering each therapeutic agent to the subject according to the following protocol:

[0276] (1) Antibody-drug conjugate A, administered 1 to 20 times over a period of 1 to 4 weeks (e.g., once weekly, once every 2 weeks, once every 3 weeks, once every 4 weeks), with each dose selected from 0.1-20 mg / kg (e.g., 0.5 mg / kg, 1.0 mg / kg, 1.5 mg / kg, 2.0 mg / kg, 2.5 mg / kg, 3.0 mg / kg, 3.5 mg / kg, 4.0 mg / kg, 4.5 mg / kg, 5.0 mg / kg, 6.0 mg / kg, 7.0 mg / kg, 8.0 mg / kg, 9.0 mg / kg, or 10.0 mg / kg) based on the subject's weight; and

[0277] (2) Pertuzumab, administered 1 to 20 times over a period of 1 to 4 weeks (e.g., once a week, twice a week, once every 2 weeks or once every 3 weeks), with the dose per administration selected from 0.1 to 20 mg / kg (e.g., 0.5 mg / kg, 1.0 mg / kg, 1.5 mg / kg, 2.0 mg / kg, 2.5 mg / kg, 3.0 mg / kg, 3.5 mg / kg, 4.0 mg / kg, 4.5 mg / kg, 5.0 mg / kg, 6.0 mg / kg, 7.0 mg / kg, 8.0 mg / kg, 9.0 mg / kg or 10.0 mg / kg).

[0278] In some embodiments, the antibody-drug conjugate A and Pertuzumab are administered 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.

[0279] In some embodiments, the method includes administering each therapeutic agent to the subject according to the following protocol:

[0280] (1) Antibody-drug conjugate A, administered 1 to 20 times over a period of 1 to 4 weeks (e.g., once a week, once every 2 weeks, once every 3 weeks, once every 4 weeks), with the dose per administration selected from 0.1 to 20 mg / kg (e.g., 0.5 mg / kg, 1.0 mg / kg, 1.5 mg / kg, 2.0 mg / kg, 2.5 mg / kg, 3.0 mg / kg, 3.5 mg / kg, 4.0 mg / kg, 4.5 mg / kg, 5.0 mg / kg, 6.0 mg / kg, 7.0 mg / kg, 8.0 mg / kg, 9.0 mg / kg or 10.0 mg / kg);

[0281] (2) Trastuzumab, administered 1 to 20 times over 1 to 4 weeks (e.g., once weekly, twice weekly, once every 2 weeks, or once every 3 weeks), with each dose selected from 0.1-20 mg / kg (e.g., 0.5 mg / kg, 1.0 mg / kg, 1.5 mg / kg, 2.0 mg / kg, 2.5 mg / kg, 3.0 mg / kg, 3.5 mg / kg, 4.0 mg / kg, 4.5 mg / kg, 5.0 mg / kg, 6.0 mg / kg, 7.0 mg / kg, 8.0 mg / kg, 9.0 mg / kg, or 10.0 mg / kg) based on the subject's weight; and

[0282] (3) Pertuzumab, administered 1 to 20 times over a period of 1 to 4 weeks (e.g., once a week, twice a week, once every 2 weeks or once every 3 weeks), with the dose selected from 0.1 to 20 mg / kg based on the subject's weight (e.g., 0.5 mg / kg, 1.0 mg / kg, 1.5 mg / kg, 2.0 mg / kg, 2.5 mg / kg, 3.0 mg / kg, 3.5 mg / kg, 4.0 mg / kg, 4.5 mg / kg, 5.0 mg / kg, 6.0 mg / kg, 7.0 mg / kg, 8.0 mg / kg, 9.0 mg / kg or 10.0 mg / kg).

[0283] In some embodiments, the antibody-drug conjugates A, Trastuzumab, and Pertuzumab are administered 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.

[0284] In some embodiments, the method includes administering each therapeutic agent to the subject according to the following protocol:

[0285] (1) Antibody-drug conjugate B, administered 1 to 20 times over a period of 1 to 4 weeks (e.g., twice weekly, once weekly, once every 2 weeks, or once every 3 weeks), with each dose selected from 0.1-20 mg / kg (e.g., 0.5 mg / kg, 1.0 mg / kg, 1.5 mg / kg, 2.0 mg / kg, 2.5 mg / kg, 3.0 mg / kg, 3.5 mg / kg, 4.0 mg / kg, 4.5 mg / kg, 5.0 mg / kg, 6.0 mg / kg, 7.0 mg / kg, 8.0 mg / kg, 9.0 mg / kg, or 10.0 mg / kg) based on the subject's weight; and

[0286] (2) Trastuzumab, administered 1 to 20 times over a period of 1 to 4 weeks (e.g., once a week, twice a week, once every 2 weeks or once every 3 weeks), with the dose per administration selected from 0.1 to 20 mg / kg (e.g., 0.5 mg / kg, 1.0 mg / kg, 1.5 mg / kg, 2.0 mg / kg, 2.5 mg / kg, 3.0 mg / kg, 3.5 mg / kg, 4.0 mg / kg, 4.5 mg / kg, 5.0 mg / kg, 6.0 mg / kg, 7.0 mg / kg, 8.0 mg / kg, 9.0 mg / kg or 10.0 mg / kg).

[0287] In some embodiments, the antibody-drug conjugate B and Trastuzumab are administered 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.

[0288] In some embodiments, the method includes administering each therapeutic agent to the subject according to the following protocol:

[0289] (1) Antibody-drug conjugate B, administered 1 to 20 times over a period of 1 to 4 weeks (e.g., twice weekly, once weekly, once every 2 weeks, or once every 3 weeks), with each dose selected from 0.1-20 mg / kg (e.g., 0.5 mg / kg, 1.0 mg / kg, 1.5 mg / kg, 2.0 mg / kg, 2.5 mg / kg, 3.0 mg / kg, 3.5 mg / kg, 4.0 mg / kg, 4.5 mg / kg, 5.0 mg / kg, 6.0 mg / kg, 7.0 mg / kg, 8.0 mg / kg, 9.0 mg / kg, or 10.0 mg / kg) based on the subject's weight; and

[0290] (2) Pertuzumab, administered 1 to 20 times over a period of 1 to 4 weeks (e.g., once a week, twice a week, once every 2 weeks or once every 3 weeks), with the dose per administration selected from 0.1 to 20 mg / kg (e.g., 0.5 mg / kg, 1.0 mg / kg, 1.5 mg / kg, 2.0 mg / kg, 2.5 mg / kg, 3.0 mg / kg, 3.5 mg / kg, 4.0 mg / kg, 4.5 mg / kg, 5.0 mg / kg, 6.0 mg / kg, 7.0 mg / kg, 8.0 mg / kg, 9.0 mg / kg or 10.0 mg / kg).

[0291] In some embodiments, the antibody-drug conjugate B and Pertuzumab are administered 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.

[0292] In some embodiments, the method includes administering each therapeutic agent to the subject according to the following protocol:

[0293] (1) Antibody-drug conjugate B, administered 1 to 20 times over a period of 1 to 4 weeks (e.g., twice a week, once a week, once every 2 weeks or once every 3 weeks), with the dose per administration selected from 0.1 to 20 mg / kg (e.g., 0.5 mg / kg, 1.0 mg / kg, 1.5 mg / kg, 2.0 mg / kg, 2.5 mg / kg, 3.0 mg / kg, 3.5 mg / kg, 4.0 mg / kg, 4.5 mg / kg, 5.0 mg / kg, 6.0 mg / kg, 7.0 mg / kg, 8.0 mg / kg, 9.0 mg / kg or 10.0 mg / kg);

[0294] (2) Trastuzumab, administered 1 to 20 times over 1 to 4 weeks (e.g., once weekly, twice weekly, once every 2 weeks, or once every 3 weeks), with each dose selected from 0.1-20 mg / kg (e.g., 0.5 mg / kg, 1.0 mg / kg, 1.5 mg / kg, 2.0 mg / kg, 2.5 mg / kg, 3.0 mg / kg, 3.5 mg / kg, 4.0 mg / kg, 4.5 mg / kg, 5.0 mg / kg, 6.0 mg / kg, 7.0 mg / kg, 8.0 mg / kg, 9.0 mg / kg, or 10.0 mg / kg) based on the subject's weight; and

[0295] (3) Pertuzumab, administered 1 to 20 times over a period of 1 to 4 weeks (e.g., once a week, twice a week, once every 2 weeks or once every 3 weeks), with the dose selected from 0.1 to 20 mg / kg based on the subject's weight (e.g., 0.5 mg / kg, 1.0 mg / kg, 1.5 mg / kg, 2.0 mg / kg, 2.5 mg / kg, 3.0 mg / kg, 3.5 mg / kg, 4.0 mg / kg, 4.5 mg / kg, 5.0 mg / kg, 6.0 mg / kg, 7.0 mg / kg, 8.0 mg / kg, 9.0 mg / kg or 10.0 mg / kg).

[0296] In some embodiments, the antibody-drug conjugates A, Trastuzumab, and Pertuzumab are administered 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.

[0297] In some embodiments, the method includes administering each therapeutic agent to the subject according to the following protocol:

[0298] (1) Antibody-drug conjugate A, administered 1 to 20 times over a period of 1 to 4 weeks (e.g., once a week, once every 2 weeks, once every 3 weeks, once every 4 weeks), with the dose per administration selected from 0.1 to 20 mg / kg (e.g., 0.5 mg / kg, 1.0 mg / kg, 1.5 mg / kg, 2.0 mg / kg, 2.5 mg / kg, 3.0 mg / kg, 3.5 mg / kg, 4.0 mg / kg, 4.5 mg / kg, 5.0 mg / kg, 6.0 mg / kg, 7.0 mg / kg, 8.0 mg / kg, 9.0 mg / kg or 10.0 mg / kg);

[0299] (2) Antibody-drug conjugate B, administered 1 to 20 times over a period of 1 to 4 weeks (e.g., twice weekly, once weekly, once every 2 weeks, or once every 3 weeks), with each dose selected from 0.1-20 mg / kg (e.g., 0.5 mg / kg, 1.0 mg / kg, 1.5 mg / kg, 2.0 mg / kg, 2.5 mg / kg, 3.0 mg / kg, 3.5 mg / kg, 4.0 mg / kg, 4.5 mg / kg, 5.0 mg / kg, 6.0 mg / kg, 7.0 mg / kg, 8.0 mg / kg, 9.0 mg / kg, or 10.0 mg / kg) based on the subject's weight; and

[0300] (3) Trastuzumab, administered 1 to 20 times over a period of 1 to 4 weeks (e.g., once a week, twice a week, once every 2 weeks or once every 3 weeks), with the dose selected from 0.1 to 20 mg / kg based on the subject's weight (e.g., 0.5 mg / kg, 1.0 mg / kg, 1.5 mg / kg, 2.0 mg / kg, 2.5 mg / kg, 3.0 mg / kg, 3.5 mg / kg, 4.0 mg / kg, 4.5 mg / kg, 5.0 mg / kg, 6.0 mg / kg, 7.0 mg / kg, 8.0 mg / kg, 9.0 mg / kg or 10.0 mg / kg).

[0301] In some embodiments, the antibody-drug conjugate A, antibody-drug conjugate B, and Trastuzumab are administered 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.

[0302] In some embodiments, the method includes administering each therapeutic agent to the subject according to the following protocol:

[0303] (1) Antibody-drug conjugate A, administered 1 to 20 times over a period of 1 to 4 weeks (e.g., once a week, once every 2 weeks, once every 3 weeks, once every 4 weeks), with the dose per administration selected from 0.1 to 20 mg / kg (e.g., 0.5 mg / kg, 1.0 mg / kg, 1.5 mg / kg, 2.0 mg / kg, 2.5 mg / kg, 3.0 mg / kg, 3.5 mg / kg, 4.0 mg / kg, 4.5 mg / kg, 5.0 mg / kg, 6.0 mg / kg, 7.0 mg / kg, 8.0 mg / kg, 9.0 mg / kg or 10.0 mg / kg);

[0304] (2) Antibody-drug conjugate B, administered 1 to 20 times over a period of 1 to 4 weeks (e.g., twice weekly, once weekly, once every 2 weeks, or once every 3 weeks), with each dose selected from 0.1-20 mg / kg (e.g., 0.5 mg / kg, 1.0 mg / kg, 1.5 mg / kg, 2.0 mg / kg, 2.5 mg / kg, 3.0 mg / kg, 3.5 mg / kg, 4.0 mg / kg, 4.5 mg / kg, 5.0 mg / kg, 6.0 mg / kg, 7.0 mg / kg, 8.0 mg / kg, 9.0 mg / kg, or 10.0 mg / kg) based on the subject's weight; and

[0305] (3) Pertuzumab, administered 1 to 20 times over a period of 1 to 4 weeks (e.g., once a week, twice a week, once every 2 weeks or once every 3 weeks), with the dose selected from 0.1 to 20 mg / kg based on the subject's weight (e.g., 0.5 mg / kg, 1.0 mg / kg, 1.5 mg / kg, 2.0 mg / kg, 2.5 mg / kg, 3.0 mg / kg, 3.5 mg / kg, 4.0 mg / kg, 4.5 mg / kg, 5.0 mg / kg, 6.0 mg / kg, 7.0 mg / kg, 8.0 mg / kg, 9.0 mg / kg or 10.0 mg / kg).

[0306] In some embodiments, the antibody-drug conjugate A, antibody-drug conjugate B, and Pertuzumab are administered 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.

[0307] In some embodiments, the method includes administering each therapeutic agent to the subject according to the following protocol:

[0308] (1) Antibody-drug conjugate A, administered 1 to 20 times over a period of 1 to 4 weeks (e.g., once a week, once every 2 weeks, once every 3 weeks, once every 4 weeks), with the dose per administration selected from 0.1 to 20 mg / kg (e.g., 0.5 mg / kg, 1.0 mg / kg, 1.5 mg / kg, 2.0 mg / kg, 2.5 mg / kg, 3.0 mg / kg, 3.5 mg / kg, 4.0 mg / kg, 4.5 mg / kg, 5.0 mg / kg, 6.0 mg / kg, 7.0 mg / kg, 8.0 mg / kg, 9.0 mg / kg or 10.0 mg / kg);

[0309] (2) Antibody-drug conjugate B, administered 1 to 20 times over a period of 1 to 4 weeks (e.g., twice a week, once a week, once every 2 weeks, or once every 3 weeks), with the dose per administration selected from 0.1 to 20 mg / kg based on the subject's weight (e.g., 0.5 mg / kg, 1.0 mg / kg, 1.5 mg / kg, 2.0 mg / kg, 2.5 mg / kg, 3.0 mg / kg, 3.5 mg / kg, 4.0 mg / kg, 4.5 mg / kg, 5.0 mg / kg, 6.0 mg / kg, 7.0 mg / kg, 8.0 mg / kg, 9.0 mg / kg, or 10.0 mg / kg);

[0310] (3) Trastuzumab, administered 1 to 20 times over 1 to 4 weeks (e.g., once weekly, twice weekly, once every 2 weeks, or once every 3 weeks), with each dose selected from 0.1-20 mg / kg (e.g., 0.5 mg / kg, 1.0 mg / kg, 1.5 mg / kg, 2.0 mg / kg, 2.5 mg / kg, 3.0 mg / kg, 3.5 mg / kg, 4.0 mg / kg, 4.5 mg / kg, 5.0 mg / kg, 6.0 mg / kg, 7.0 mg / kg, 8.0 mg / kg, 9.0 mg / kg, or 10.0 mg / kg) based on the subject's weight; and

[0311] (4) Pertuzumab, administered 1 to 20 times over a period of 1 to 4 weeks (e.g., once a week, twice a week, once every 2 weeks or once every 3 weeks), with the dose per administration selected from 0.1 to 20 mg / kg (e.g., 0.5 mg / kg, 1.0 mg / kg, 1.5 mg / kg, 2.0 mg / kg, 2.5 mg / kg, 3.0 mg / kg, 3.5 mg / kg, 4.0 mg / kg, 4.5 mg / kg, 5.0 mg / kg, 6.0 mg / kg, 7.0 mg / kg, 8.0 mg / kg, 9.0 mg / kg or 10.0 mg / kg).

[0312] In some embodiments, the antibody-drug conjugate A, antibody-drug conjugate B, trastuzumab, and pertuzumab are administered 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.

[0313] In some embodiments, the method includes administering each therapeutic agent to the subject according to the following protocol:

[0314] (1) Trastuzumab, administered 1 to 20 times over 1 to 4 weeks (e.g., once weekly, twice weekly, once every 2 weeks, or once every 3 weeks), with each dose selected from 0.1-20 mg / kg (e.g., 0.5 mg / kg, 1.0 mg / kg, 1.5 mg / kg, 2.0 mg / kg, 2.5 mg / kg, 3.0 mg / kg, 3.5 mg / kg, 4.0 mg / kg, 4.5 mg / kg, 5.0 mg / kg, 6.0 mg / kg, 7.0 mg / kg, 8.0 mg / kg, 9.0 mg / kg, or 10.0 mg / kg) based on the subject's weight; and

[0315] (2) Pertuzumab, administered 1 to 20 times over a period of 1 to 4 weeks (e.g., once a week, twice a week, once every 2 weeks or once every 3 weeks), with the dose per administration selected from 0.1 to 20 mg / kg (e.g., 0.5 mg / kg, 1.0 mg / kg, 1.5 mg / kg, 2.0 mg / kg, 2.5 mg / kg, 3.0 mg / kg, 3.5 mg / kg, 4.0 mg / kg, 4.5 mg / kg, 5.0 mg / kg, 6.0 mg / kg, 7.0 mg / kg, 8.0 mg / kg, 9.0 mg / kg or 10.0 mg / kg).

[0316] In some implementations, trastuzumab and pertuzumab are administered 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.

[0317] In some embodiments, the method reduces the tumor size by at least about 10%. In some embodiments, the method reduces the tumor size by about 10%, 20%, 30%, or more.

[0318] 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%.

[0319] In some embodiments, the tumor growth inhibition rate (TGI) of the method is 70% or higher. 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.

[0320] In some implementations, the method reduces the ability of tumors to grow and stabilizes the disease.

[0321] In some implementations, the method offers improved treatment safety.

[0322] In some embodiments, the drug combination has a synergistic effect in preventing and / or treating a subject's tumor or cancer, for example, the rate or amount of the effect in preventing and / or treating a subject's tumor or cancer is greater than the rate or amount expected by simply combining the ingredients together.

[0323] Another aspect of this disclosure provides the aforementioned pharmaceutical combinations for the prevention and / or treatment of tumors or cancer in a subject. In some embodiments, two or more of the aforementioned anti-Trop-2 antibody drug conjugate, anti-Her2 antibody drug conjugate, and anti-Her2 antibody or antigen-binding fragment thereof are provided for the prevention and / or treatment of tumors or cancer in a subject. In some embodiments, the aforementioned anti-Trop-2 antibody drug conjugate and anti-Her2 antibody drug conjugate are provided for the prevention and / or treatment of tumors or cancer in a subject. In some embodiments, the aforementioned anti-Trop-2 antibody drug conjugate and anti-Her2 antibody or antigen-binding fragment thereof are provided for the prevention and / or treatment of tumors or cancer in a subject. In some embodiments, the aforementioned anti-Trop-2 antibody drug conjugate, anti-Her2 antibody drug conjugate, and anti-Her2 antibody or antigen-binding fragment thereof are provided for the prevention and / or treatment of tumors or cancer in a subject. In some embodiments, the anti-Her2 antibody drug conjugate and the anti-Her2 antibody or its antigen-binding fragment, as described above, are provided for the prevention and / or treatment of tumors or cancers in a subject. In some embodiments, two or more of the anti-Her2 antibodies or their antigen-binding fragments, as described above, are provided for the prevention and / or treatment of tumors or cancers in a subject.

[0324] Another aspect of this disclosure provides a kit or reagent kit comprising the drug combination described above. In some embodiments, a kit or reagent kit is provided comprising two or more of the anti-Trop-2 antibody drug conjugate, anti-Her2 antibody drug conjugate, and anti-Her2 antibody or antigen-binding fragment thereof described above. In some embodiments, a kit or reagent kit is provided comprising the anti-Trop-2 antibody drug conjugate and anti-Her2 antibody drug conjugate described above. In some embodiments, a kit or reagent kit is provided comprising the anti-Trop-2 antibody drug conjugate and anti-Her2 antibody or antigen-binding fragment thereof described above. In some embodiments, a kit or reagent kit is provided comprising the anti-Trop-2 antibody drug conjugate, anti-Her2 antibody drug conjugate, and anti-Her2 antibody or antigen-binding fragment thereof described above. In some embodiments, a kit or reagent kit is provided comprising the anti-Her2 antibody drug conjugate and anti-Her2 antibody or antigen-binding fragment thereof described above. In some implementations, a kit or reagent kit is provided that includes two or more of the anti-Her2 antibodies or antigen-binding fragments thereof described above.

[0325] In some implementations, the kit or reagent is used to treat the tumors or cancers described above.

[0326] In some embodiments, the kit or reagent kit includes an anti-Trop-2 antibody drug conjugate as described above in one compartment and an anti-Her2 antibody drug conjugate as described above in another compartment.

[0327] In some embodiments, the kit or reagent kit includes an anti-Trop-2 antibody drug conjugate as described above in one compartment, and an anti-Her2 antibody or its antigen-binding fragment as described above in another compartment.

[0328] In some embodiments, the kit or reagent kit includes an anti-Trop-2 antibody drug conjugate as described above in one compartment, an anti-Her2 antibody drug conjugate as described above in another compartment, and an anti-Her2 antibody or its antigen-binding fragment as described above in yet another compartment.

[0329] In some embodiments, the kit or reagent kit includes an anti-Her2 antibody drug conjugate as described above in one compartment, and an anti-Her2 antibody or its antigen-binding fragment as described above in another compartment.

[0330] In some embodiments, the kit or reagent kit includes an anti-Her2 antibody or antigen-binding fragment thereof as described above in one compartment, and another anti-Her2 antibody or antigen-binding fragment thereof as described above in another compartment.

[0331] In some embodiments, the kit or reagent kit also includes instructions for administering the anti-Trop-2 antibody drug conjugate, the anti-Her2 antibody drug conjugate, and / or the anti-Her2 antibody or its antigen-binding fragment.

[0332] In some implementations, the kit or reagent is used for the prevention and / or treatment of tumors or cancers as described above.

[0333] Another aspect of this disclosure provides a pharmaceutical combination product comprising the pharmaceutical combination described in any of the preceding embodiments. In some embodiments, the pharmaceutical combination product comprises two or more of the aforementioned anti-Trop-2 antibody drug conjugate, anti-Her2 antibody drug conjugate, and anti-Her2 antibody or antigen-binding fragment thereof. In some embodiments, the pharmaceutical combination product comprises the aforementioned anti-Trop-2 antibody drug conjugate and the aforementioned anti-Her2 antibody drug conjugate. In some embodiments, the pharmaceutical combination product comprises the aforementioned anti-Trop-2 antibody drug conjugate and the aforementioned anti-Her2 antibody or antigen-binding fragment thereof. In some embodiments, the pharmaceutical combination product comprises the aforementioned anti-Trop-2 antibody drug conjugate, the aforementioned anti-Her2 antibody drug conjugate, and the aforementioned anti-Her2 antibody or antigen-binding fragment thereof. In some embodiments, the pharmaceutical combination product comprises the aforementioned anti-Her2 antibody drug conjugate and the aforementioned anti-Her2 antibody or antigen-binding fragment thereof. In some embodiments, the pharmaceutical combination product comprises two or more of the anti-Her2 antibodies or their antigen-binding fragments described above. In some embodiments, the pharmaceutical combination product comprises antibody-drug conjugate A and antibody-drug conjugate B described above. In some embodiments, the pharmaceutical combination product comprises antibody-drug conjugate A and Trastuzumab described above. In some embodiments, the pharmaceutical combination product comprises antibody-drug conjugate A and Pertuzumab described above. In some embodiments, the pharmaceutical combination product comprises antibody-drug conjugate A, Trastuzumab, and Pertuzumab described above. In some embodiments, the pharmaceutical combination product comprises antibody-drug conjugate B and Trastuzumab described above. In some embodiments, the pharmaceutical combination product comprises antibody-drug conjugate B and Pertuzumab described above. In some embodiments, the pharmaceutical combination product comprises antibody-drug conjugate B, Trastuzumab, and Pertuzumab described above. In some embodiments, the pharmaceutical combination product comprises antibody-drug conjugate A, antibody-drug conjugate B, and Pertuzumab described above. In some embodiments, the drug combination product includes antibody-drug conjugate A, antibody-drug conjugate B, and trastuzumab as described above. In some embodiments, the drug combination product includes antibody-drug conjugate A, antibody-drug conjugate B, trastuzumab, and pertuzumab as described above. In some embodiments, the drug combination product includes trastuzumab and pertuzumab as described above.

[0334] In some embodiments, the drug combination or drug combination product is a pharmaceutical composition. In some embodiments, the drug combination or drug combination product is a kit or reagent kit.

[0335] In some implementations, the drug combination or drug combination product may also include one or more pharmaceutically acceptable excipients, diluents or carriers.

[0336] In some embodiments, the drug combination or drug combination product comprises the anti-Trop-2 antibody-drug conjugate in the following amounts: 0.1-1000 mg. In some embodiments, the anti-Trop-2 antibody-drug conjugate comprised in the drug combination or drug combination product is 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, or 0.1-10 mg. In some embodiments, the amount of the anti-Trop-2 antibody-drug conjugate included in the drug combination or drug combination product is 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, or 500 mg.

[0337] In some embodiments, the pharmaceutical combination or pharmaceutical combination product contains the anti-Her2 antibody drug conjugate in the following amounts: 0.1-1000 mg. In some embodiments, the amount of the anti-Her2 antibody drug conjugate contained in the pharmaceutical combination or pharmaceutical combination product is 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, or 0.1-10 mg. In some embodiments, the amount of the anti-Her2 antibody drug conjugate included in the drug combination or drug combination product is 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, or 500 mg.

[0338] In some embodiments, the pharmaceutical combination or pharmaceutical combination product contains the anti-Her2 antibody or its antigen-binding fragment in the following amounts: 0.1-1000 mg. In some embodiments, the anti-Her2 antibody or its antigen-binding fragment contained in the pharmaceutical combination or pharmaceutical combination product is 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, or 0.1-10 mg. In some embodiments, the anti-Her2 antibody or its antigen-binding fragment contained in the drug combination or drug combination product is in the amount of 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, or 500 mg.

[0339] Another aspect of this disclosure provides the use of an anti-Trop-2 antibody drug conjugate in the preparation of a medicament for treating a subject’s tumor or cancer, wherein the medicament is administered in combination with an anti-Her2 antibody drug conjugate and / or an anti-Her2 antibody or an antigen-binding fragment thereof.

[0340] Another aspect of this disclosure provides the use of an anti-Her2 antibody drug conjugate 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 and / or an anti-Her2 antibody or an antigen-binding fragment thereof.

[0341] Another aspect of this disclosure provides the use of an anti-Her2 antibody or an antigen-binding fragment thereof 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 and / or an anti-Her2 antibody drug conjugate.

[0342] In some embodiments, the anti-Trop-2 antibody-drug conjugate includes its dosing cycle, dosing frequency, dosing dose, route of administration, etc., as defined in any of the preceding descriptions.

[0343] In some implementations, the anti-Her2 antibody drug conjugate includes its dosing cycle, dosing frequency, dosing dose, route of administration, etc., as defined in any of the preceding descriptions.

[0344] In some embodiments, the anti-Her2 antibody or its antigen-binding fragment, including its dosing cycle, dosing frequency, dosing dose, route of administration, etc., are as defined in any of the preceding descriptions.

[0345] The drugs, drug combinations, and drug compositions disclosed in this article are co-administered with hyaluronic acid-degrading enzymes.

[0346] The anti-Trop-2 antibody-drug conjugates, anti-Her2 antibody-drug conjugates, and / or anti-Her2 antibodies or their antigen-binding fragments disclosed herein can be administered via any suitable route and can be facilitated by promoters such as hyaluronidases (including hyaluronidase, soluble PH20 peptides, and variants thereof). For systemic administration, their pharmacological properties (e.g., serum half-life) can be enhanced by modifying promoters (e.g., with polymers 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. EP1858926B1, as well as numerous other patents and publications. In some embodiments, the route of administration is subcutaneous or intramuscular.

[0347] Therefore, the specific implementation plan involves:

[0348] (a) A combination of pharmaceuticals, pharmaceutical compositions, or fixed-dose pharmaceutical compositions comprising: (i) the anti-Trop-2 ADC and the anti-Her2 ADC disclosed herein; (ii) the anti-Trop-2 ADC and the anti-Her2 antibody disclosed herein, or an antigen-binding fragment thereof; (iii) the anti-Her2 ADC and the anti-Her2 antibody disclosed herein, or an antigen-binding fragment thereof; (iv) two or more of the anti-Her2 antibody disclosed herein or an antigen-binding fragment thereof; or (v) the anti-Trop-2 ADC, the anti-Her2 ADC and the anti-Her2 antibody disclosed herein, or an antigen-binding fragment thereof, and any one or more of hyaluronidase, hyaluronidase, soluble hyaluronidase, soluble PH20 polypeptide, or variants thereof;

[0349] (b) A kit comprising the following compositions, wherein the compositions comprise: (i) the anti-Trop-2 ADC and the anti-Her2 ADC disclosed herein; (ii) the anti-Trop-2 ADC and the anti-Her2 antibody or antigen-binding fragment thereof disclosed herein; (iii) the anti-Her2 ADC and the anti-Her2 antibody or antigen-binding fragment thereof disclosed herein; (iv) two or more of the anti-Her2 antibody or antigen-binding fragment thereof disclosed herein; or (v) the anti-Trop-2 ADC, the anti-Her2 ADC and the anti-Her2 antibody or antigen-binding fragment thereof disclosed herein, and any one of hyaluronidase, hyaluronidase, soluble hyaluronidase or soluble PH20 peptide; and

[0350] (c) A kit comprising: (i) the anti-Trop-2 ADC and the anti-Her2 ADC disclosed herein; (ii) the anti-Trop-2 ADC and the anti-Her2 antibody disclosed herein, or an antigen-binding fragment thereof; (iii) the anti-Her2 ADC and the anti-Her2 antibody disclosed herein, or an antigen-binding fragment thereof; (iv) two or more of the anti-Her2 antibody disclosed herein or an antigen-binding fragment thereof; or (v) the anti-Trop-2 ADC, the anti-Her2 ADC and the anti-Her2 antibody disclosed herein, or an antigen-binding fragment thereof, and any one of hyaluronidase, hyaluronidase, soluble hyaluronidase, and soluble PH20 peptide, wherein each component of the kit is in a separate container.

[0351] In certain embodiments of the aforementioned drug combinations, pharmaceutical compositions, and kits, the soluble hyaluronidase is soluble PH20 hyaluronidase, whose non-proprietary name is "hyaluronidase (human recombinant)", designated by the United States Adoption Names Committee (USAN), and whose chemical name is "36-482-hyaluronidase" 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 designated by the USAN Committee as the non-proprietary name "berahyaluronidase alfa" and is currently marketed by Alteogen under the trademark Berahyaluronidase. TM They sell products under the trademark name.

[0352] This disclosure also provides a composition comprising the aforementioned anti-Trop-2 antibody drug conjugate and hyaluronic acid degrading enzyme; the aforementioned anti-Her2 antibody drug conjugate and hyaluronic acid degrading enzyme; or the aforementioned anti-Her2 antibody or its antigen-binding fragment and hyaluronic acid degrading enzyme. In some embodiments, the hyaluronic acid degrading enzyme is a soluble hyaluronidase. In some embodiments, the soluble hyaluronidase is soluble PH20. In some embodiments, the soluble hyaluronidase is hyaluronidase (human recombinant) or berahyaluronidase alfa.

[0353] This disclosure also provides a kit comprising: (a) the anti-Trop-2 antibody drug conjugate and the anti-Her2 antibody drug conjugate of this disclosure; (b) the anti-Trop-2 antibody drug conjugate and the anti-Her2 antibody or antigen-binding fragment thereof of this disclosure; (c) the anti-Her2 antibody drug conjugate and the anti-Her2 antibody or antigen-binding fragment thereof of this disclosure; (d) one, two or more of the anti-Her2 antibody or antigen-binding fragment thereof of this disclosure; (e) the anti-Trop-2 antibody drug conjugate of this disclosure; (f) the anti-Her2 antibody drug conjugate of this disclosure; or (g) the anti-Trop-2 antibody drug conjugate, the anti-Her2 antibody drug conjugate and the anti-Her2 antibody or antigen-binding fragment thereof of this disclosure, and hyaluronic acid degrading enzyme. In some embodiments, the anti-Trop-2 antibody-drug conjugate, the anti-Her2 antibody-drug conjugate and / or the anti-Her2 antibody or its antigen-binding fragment, and the hyaluronic acid-degrading enzyme are each housed in a separate container. In some embodiments, the hyaluronic acid-degrading enzyme is a soluble hyaluronidase. In some embodiments, the soluble hyaluronidase is soluble pH20. In some embodiments, the soluble hyaluronidase is hyaluronidase (human recombinant) or berahyaluronidase alfa.

[0354] This disclosure also provides a composition selected from: (a) the anti-Trop-2 antibody drug conjugate and the anti-Her2 antibody drug conjugate of this disclosure; (b) the anti-Trop-2 antibody drug conjugate and the anti-Her2 antibody or antigen-binding fragment thereof of this disclosure; (c) the anti-Her2 antibody drug conjugate and the anti-Her2 antibody or antigen-binding fragment thereof of this disclosure; (d) one, two or more of the anti-Her2 antibody or antigen-binding fragment thereof of this disclosure; (e) the anti-Trop-2 antibody drug conjugate of this disclosure; (f) the anti-Her2 antibody drug conjugate of this disclosure; or (g) the anti-Trop-2 antibody drug conjugate, the anti-Her2 antibody drug conjugate and the anti-Her2 antibody or antigen-binding fragment thereof of this disclosure, and hyaluronic acid degrading enzyme, and their use in the preparation of a tumor or cancer medicament for treating a subject.

[0355] This disclosure also provides a composition selected from: (a) the anti-Trop-2 antibody drug conjugate and the anti-Her2 antibody drug conjugate of this disclosure; (b) the anti-Trop-2 antibody drug conjugate and the anti-Her2 antibody or antigen-binding fragment thereof of this disclosure; (c) the anti-Her2 antibody drug conjugate and the anti-Her2 antibody or antigen-binding fragment thereof of this disclosure; (d) one, two or more of the anti-Her2 antibody or antigen-binding fragment thereof of this disclosure; (e) the anti-Trop-2 antibody drug conjugate of this disclosure; (f) the anti-Her2 antibody drug conjugate of this disclosure; or (g) the anti-Trop-2 antibody drug conjugate, the anti-Her2 antibody drug conjugate and the anti-Her2 antibody or antigen-binding fragment thereof of this disclosure, and hyaluronic acid degrading enzyme, and the use thereof for treating a subject's tumor or cancer.

[0356] 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 for treating the tumor or cancer, the composition being selected from: (a) the anti-Trop-2 antibody-drug conjugate and the anti-Her2 antibody-drug conjugate of this disclosure; (b) the anti-Trop-2 antibody-drug conjugate and the anti-Her2 antibody of this disclosure or an antigen-binding fragment thereof; (c) the anti-Her2 antibody-drug conjugate and the anti-Her2 antibody of this disclosure or an antigen-binding fragment thereof; (d) one, two or more of the anti-Her2 antibody of this disclosure or an antigen-binding fragment thereof; (e) the anti-Trop-2 antibody-drug conjugate of this disclosure; (f) the anti-Her2 antibody-drug conjugate of this disclosure; or (g) the anti-Trop-2 antibody-drug conjugate, the anti-Her2 antibody-drug conjugate and the anti-Her2 antibody of this disclosure or an antigen-binding fragment thereof, and hyaluronic acid degrading enzyme.

[0357] In some embodiments, the tumor or cancer 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, 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, preferably breast cancer, such as ER- / HER2+ breast cancer or HR- / HER2+ breast cancer. In some embodiments, the hyaluronic acid degrading enzyme is a soluble hyaluronidase. In some embodiments, the soluble hyaluronidase is soluble PH20. In some embodiments, the soluble hyaluronidase is hyaluronidase (human recombinant) or berahyaluronidase alfa. In some embodiments, the anti-Trop-2 antibody-drug conjugate, the anti-Her2 antibody-drug conjugate and / or the anti-Her2 antibody or its antigen-binding fragment, and the hyaluronic acid degrading enzyme are administered simultaneously, separately, sequentially, or sequentially. In some embodiments, the anti-Trop-2 antibody-drug conjugate, the anti-Her2 antibody-drug conjugate and / or the anti-Her2 antibody or its antigen-binding fragment, and the hyaluronic acid-degrading enzyme are mixed to form a mixture, and the mixture is administered. In some embodiments, the anti-Trop-2 antibody-drug conjugate, the anti-Her2 antibody-drug conjugate and / or the anti-Her2 antibody or its antigen-binding fragment, and the hyaluronic acid-degrading enzyme are administered systemically. In some embodiments, the anti-Trop-2 antibody-drug conjugate, the anti-Her2 antibody-drug conjugate and / or the anti-Her2 antibody or its antigen-binding fragment, and the hyaluronic acid-degrading enzyme are administered subcutaneously or intramuscularly.

[0358] This disclosure further provides the use of an anti-Trop-2 antibody drug conjugate and optionally a hyaluronic acid-degrading enzyme in the preparation of a medicament for the prevention and / or treatment of a tumor or cancer in a subject, in combination with an anti-Her2 antibody drug conjugate and / or an anti-Her2 antibody or its antigen-binding fragment thereof. In some embodiments, the anti-Trop-2 antibody drug conjugate, the anti-Her2 antibody drug conjugate, the anti-Her2 antibody or its antigen-binding fragment thereof, the hyaluronic acid-degrading enzyme, and the tumor or cancer are as defined in any of the preceding embodiments.

[0359] This disclosure further provides the use of an anti-Her2 antibody drug conjugate and optionally a hyaluronic acid-degrading enzyme in the preparation of a medicament for the prevention and / or treatment of a subject’s tumor or cancer, in combination with a Trop-2 antibody drug conjugate and / or an anti-Her2 antibody or its antigen-binding fragment thereof. In some embodiments, the anti-Trop-2 antibody drug conjugate, the anti-Her2 antibody drug conjugate, the anti-Her2 antibody or its antigen-binding fragment thereof, the hyaluronic acid-degrading enzyme, and the tumor or cancer are as defined in any of the preceding embodiments.

[0360] This disclosure further provides the use of anti-Trop-2 antibody drug conjugates and optionally hyaluronic acid-degrading enzymes in the preparation of medicaments that enhance the efficacy of other therapeutic agents in treating tumors or cancers. In some embodiments, the other therapeutic agent is an anti-Her2 antibody drug conjugate and / or an anti-Her2 antibody or an antigen-binding fragment thereof. In some embodiments, the anti-Trop-2 antibody drug conjugate, the anti-Her2 antibody drug conjugate, the anti-Her2 antibody or an antigen-binding fragment thereof, the hyaluronic acid-degrading enzyme, and the tumor or cancer are as defined in any of the preceding embodiments.

[0361] This disclosure further provides the use of anti-Her2 antibody drug conjugates and optionally hyaluronic acid-degrading enzymes in the preparation of medicaments that enhance the efficacy of other therapeutic agents in treating tumors or cancers. In some embodiments, the other therapeutic agent is an anti-Trop-2 antibody drug conjugate and / or an anti-Her2 antibody or an antigen-binding fragment thereof. In some embodiments, the anti-Trop-2 antibody drug conjugate, the anti-Her2 antibody drug conjugate, the anti-Her2 antibody or an antigen-binding fragment thereof, the hyaluronic acid-degrading enzyme, and the tumor or cancer are as defined in any of the preceding embodiments.

[0362] All technical features disclosed in this specification, or all steps in the disclosed methods or processes, may be combined in any way, except for mutually exclusive technical features and / or steps. Detailed Implementation

[0363] Terminology Definition

[0364] Certain technical and scientific terms are specifically defined below. Unless otherwise defined 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.

[0365] As used herein, 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.

[0366] As used herein, the term "complementarity-determining region" or "CDR" refers to the amino acid residues in the antibody variable region 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).

[0367] In this disclosure, 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.

[0368] As used herein, the term “framework region” or “FR” residues refer to those amino acid residues in the antibody variable region other than the CDR residues as defined above.

[0369] As used herein, 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.

[0370] As used herein, the term “antigen-binding fragment” of an antibody refers to a fragment of a polypeptide, such as a fragment of a full-length antibody, that 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; this fragment 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.

[0371] As used herein, the term “Fd” refers to an antibody fragment consisting of VH and CH1 domains; the term “dAb fragment” refers to an antibody fragment consisting of VH domains (Ward et al., Nature 341:544 546 (1989)); the term “Fab fragment” refers to an antibody fragment consisting 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, consisting of a complete light chain and heavy chain Fd fragment (consisting of VH and CH1 domains).

[0372] As used herein, 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 (e.g., the Fd fragment, which contains only three antigen-specific CDRs) can recognize and bind to antigens, although its affinity may be lower than that of a complete binding site.

[0373] As used herein, the term "Fc" refers to an antibody fragment formed by the disulfide bonds between the second and third constant regions of the first heavy chain and 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.

[0374] As used herein, 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. Suitable prior art linkers consist of repeating GGGGS amino acid sequences or variants thereof. For example, a linker having the amino acid sequence (GGGGS)4 can be used, but variants thereof can also be used (Holliger et al. (1993), Proc. Natl. Acad. Sci. USA 90:6444-6448). Other linkers that can be used in this disclosure 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 domains of the scFv. In some embodiments, the VH and VL domains can be positioned relative to each other in any suitable arrangement. For example, containing NH2-VH-VH-COOH, NH 2- VL-VL-COOH of scFv.

[0375] As used herein, the term "single-domain antibody (sdAb)" has the meaning commonly understood by those skilled in the art as an antibody fragment consisting of a single monomeric variable antibody domain (e.g., a single heavy chain variable region) that maintains the ability to specifically bind 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.

[0376] 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.

[0377] 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.

[0378] Antigen-binding fragments (e.g., the antibody fragments described above) of a given antibody (e.g., the antibody fragments provided in this disclosure) can be obtained using conventional techniques known to those skilled in the art (e.g., recombinant DNA techniques 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.

[0379] As used herein, the term "identity" refers to the sequence matching between two polypeptides or two nucleic acids. Two compared sequences are identical at a position when the same base or amino acid monomeric subunit occupies the same location (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 share 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 readily available, for example, 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.

[0380] As used herein, the term "conservative substitution" means 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).

[0381] The twenty common amino acids discussed 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 disclosure, 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.

[0382] As used herein, the terms “anti-Trop-2 antibody” or “antibody targeting Trop-2” refer 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).

[0383] As used herein, the term "anti-Her2 antibody" or "Her2-targeting antibody" refers to an antibody that can specifically bind to Her2 with sufficient affinity, such that the antibody can be used as a diagnostic and / or therapeutic agent targeting Her2.

[0384] As used herein, the term "RS7 antibody" refers to Sacituzumab, a commercially available antibody targeting Trop-2, containing three heavy chain CDR-1, CDR-2, and CDR-3 sequences as SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3, respectively, and three light chain CDR-1, CDR-2, and CDR-3 sequences as SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, respectively (see U.S. Patent No. 7,517,964). The anti-Trop-2 antibody RS7 disclosed herein can also be obtained through screening using the vector design, construction, and antibody library construction methods disclosed in CN103476941A, or through Sorrento Therapeutics, Inc. The document was obtained through a screening process.

[0385] As used in this article, the terms “cancer” and “cancerous” refer to or describe a pathological condition in mammals characterized by unregulated cell growth in a population of cells.

[0386] As used herein, 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.

[0387] As used herein, the term "subject" refers to any animal (e.g., a mammal) receiving a particular 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. A mammal can be one or more animals 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 embodiment, the subject is a human.

[0388] As used in this document, “in combination with” includes giving simultaneously (in parallel) or consecutively in any order.

[0389] As used herein, 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 dose formulations 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 alternating therapies, 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.

[0390] 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.

[0391] The “effective amount” of antibodies, antibody-drug conjugates, or other 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.

[0392] As used herein, the term "therapeutic effective amount" 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 amount of a drug may 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 "therapeutic" herein. In the case of a drug that can prevent cancer cell growth and / or kill existing cancer cells, the drug may be a cell-inhibiting and / or cytotoxic drug.

[0393] As used herein, 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 disclosure 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.

[0394] 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.

[0395] 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.

[0396] 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.

[0397] Unless otherwise expressly stated, all ranges referenced in this disclosure 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 14 to 21 days is intended to include 14, 15, 16, 17, 18, 19, 20, and 21 days. Unless otherwise specified, the numerical values ​​provided in this disclosure 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 disclosure, the term “or” indicates alternatives that can be combined where appropriate; that is, the word “or” includes each alternative listed individually and combinations thereof.

[0398] 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.

[0399] This document describes exemplary methods and materials, although similar or equivalent methods and materials may also be used in practice or testing of this disclosure. The materials, methods, and examples are illustrative only and not limiting.

[0400] abbreviation

[0401] The abbreviations used in this article have the following meanings:

[0402] This application includes the following exemplary implementations:

[0403] Implementation Plan 1: Use of two or more of the following in the preparation of a medicament for the prevention and / or treatment of a subject’s tumor or cancer: anti-Trop-2 antibody-drug conjugate, anti-Her2 antibody-drug conjugate, and anti-Her2 antibody or its antigen-binding fragment.

[0404] Implementation Scheme 2, the use as described in Implementation Scheme 1, wherein the anti-Trop-2 antibody drug conjugate has the structure of the following formula (I): {D1-[L1-(L2)m1-(L3)m2-(L4)m3-E]} q -Ab Formula (I)

[0405] in,

[0406] 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.

[0407] 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.

[0408] L3 is a 5-12 member heterocyclic aromatic ring;

[0409] 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;

[0410] E is In this context, each R4 is independently hydrogen (e.g., protium or deuterium), β is 0, 1 or 2, and E at position 2 is connected to Ab, and E at position 1 is connected to L4.

[0411] m1, m2 and m3 are each independently 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;

[0412] D1 is the bioactive molecular moiety;

[0413] q refers to {D1-[L1-(L2)} which forms a thioether bond with the thiol group of Ab. m1 -(L3) m2 -(L4) m3 The number of the -E]}- part, which is selected from 1 to 10, or 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;

[0414] Ab represents anti-Trop-2 antibody or its antigen-binding fragment;

[0415] Preferably, the anti-Trop-2 antibody-drug conjugate satisfies one or more of the following:

[0416] (1) L1 is selected from Furthermore, position 1 of L1 is connected to D1, and position 2 of L1 is connected to L2;

[0417] (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.

[0418] (3) L3 is selected from 5-6 membered heteroaryl rings, such as pyrazole or triazole;

[0419] (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;

[0420] (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 Ab at position 2 (e.g., to a thiol group on Ab) and to L4 at position 1.

[0421] (6) m1, m2 and m3 are all 1;

[0422] (7) The bioactive molecules are selected from Preferably, D1 is selected from

[0423] (8) q is an integer between 3 and 8, or 3, 4, 5, 6, 7 or 8;

[0424] (9)Ab is Sacituzumab or its antigen-binding fragment.

[0425] Implementation Scheme 3, the use as described in Implementation Scheme 1 or 2, wherein the anti-Trop-2 antibody drug conjugate has the following chemical structure:

[0426] Wherein, Ab is an anti-Trop-2 antibody or its antigen-binding fragment; q is selected from 1 to 10 (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10), or q is selected from 3 to 8 (e.g., 3, 4, 5, 6, 7 or 8).

[0427] Implementation Scheme 4, the use as described in any one of Implementation Schemes 1-3, wherein the anti-Trop-2 antibody or its antigen-binding fragment comprises:

[0428] (1) The following heavy chain variable regions (VH) and / or light chain variable regions (VL), wherein the CDR is defined according to the Chothia numbering system:

[0429] Heavy chain variable region (VH) containing the following 3 CDRs: CDR-H1 with sequence SEQ ID NO:43, CDR-H2 with sequence SEQ ID NO:44, and CDR-H3 with sequence SEQ ID NO:45; and / or, light chain variable region (VL) containing the following 3 CDRs: CDR-L1 with sequence SEQ ID NO:46, CDR-L2 with sequence SEQ ID NO:47, and CDR-L3 with sequence SEQ ID NO:48;

[0430] or,

[0431] (2) The following heavy chain variable regions (VH) and / or light chain variable regions (VL), wherein the CDR is defined according to the AbM numbering system:

[0432] Heavy chain variable region (VH) containing the following 3 CDRs: CDR-H1 with sequence SEQ ID NO:56, CDR-H2 with sequence SEQ ID NO:57, and CDR-H3 with sequence SEQ ID NO:45; and / or, light chain variable region (VL) containing the following 3 CDRs: CDR-L1 with sequence SEQ ID NO:46, CDR-L2 with sequence SEQ ID NO:47, and CDR-L3 with sequence SEQ ID NO:48;

[0433] or,

[0434] (3) The following heavy chain variable regions (VH) and / or light chain variable regions (VL), wherein the CDR is defined according to the Kabat numbering system:

[0435] Heavy chain variable region (VH) containing the following 3 CDRs: CDR-H1 with sequence SEQ ID NO:49, CDR-H2 with sequence SEQ ID NO:50, and CDR-H3 with sequence SEQ ID NO:45; and / or, light chain variable region (VL) containing the following 3 CDRs: CDR-L1 with sequence SEQ ID NO:46, CDR-L2 with sequence SEQ ID NO:47, and CDR-L3 with sequence SEQ ID NO:48;

[0436] or,

[0437] (4) The following heavy chain variable regions (VH) and / or light chain variable regions (VL), wherein the CDR is defined according to the IMGT numbering system:

[0438] The heavy chain variable region (VH) contains the following three CDRs: CDR-H1 with sequence SEQ ID NO:51, CDR-H2 with sequence SEQ ID NO:52, and CDR-H3 with sequence SEQ ID NO:53; and / or the light chain variable region (VL) contains the following three CDRs: CDR-L1 with sequence SEQ ID NO:54, CDR-L2 with sequence SEQ ID NO:55, and CDR-L3 with sequence SEQ ID NO:48.

[0439] Implementation Scheme 5, the use as described in any one of Implementation Schemes 1-4, wherein the anti-Trop-2 antibody or its antigen-binding fragment comprises: VH as shown in SEQ ID NO: 41, and / or VL as shown in SEQ ID NO: 42.

[0440] Implementation Scheme 6, the use as described in any one of Implementation Schemes 1-5, wherein the anti-Trop-2 antibody or its antigen-binding fragment comprises: the heavy chain shown in SEQ ID NO:58 and the light chain shown in SEQ ID NO:59.

[0441] Implementation Scheme 7, the use as described in any one of Implementation Schemes 1-6, wherein the anti-Trop-2 antibody or its antigen-binding fragment is Sacituzumab or its antigen-binding fragment.

[0442] Implementation Scheme 8: The use as described in any one of Implementation Schemes 1-7, wherein the DAR value of the anti-Trop-2 antibody-drug conjugate is 1-10; or is 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. Integers or decimals of 5-6, 6-10, 6-9, 6-8, 6-7, 7-10, 7-9, 7-8, 8-10, 8-9, or 9-10; or DAR values ​​of 3-8 or 5-8; or 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.

[0443] Implementation Scheme 9: The use as described in any one of Implementation Schemes 1-8, wherein the anti-Her2 antibody drug conjugate has the following chemical structure:

[0444] in:

[0445] A represents an anti-Her2 antibody or its antigen-binding fragment;

[0446] X and Y are each independently N or CR 1 (Preferred Y is CR) 1 (where X is N), and each R 1 Independently H or Cl-C 10 Alkyl, preferably H or C1-C6 alkyl (e.g., methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, pentyl or hexyl);

[0447] L is a divalent linker;

[0448] D represents a cytotoxic drug group; and

[0449] n is an integer selected from 1 to 10, or 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;

[0450] Preferably, the anti-Her2 antibody drug conjugate meets one or more of the following conditions:

[0451] (1) L is selected from p is an integer from 1 to 10, or 1, 2, 3, 4, 5 or 6;

[0452] (2) Cytotoxic drugs are selected from compounds of the following general formula or their stereoisomers:

[0453] Among them, R 2 Selected from -CH2N3, -CONHSO2 (cyclopropyl), thiazolyl-2-yl, -CH3 and -COOH;

[0454] R 3 Selected from H and -OH; and

[0455] R 4 Selected from H, -NH2, Cl, Br, I, -OS(O)2R 6 , where R 6 It is H, C1-C8 alkyl, C3-C8 cycloalkyl, or C6-C 14 The aryl group, wherein the alkyl, cycloalkyl and aryl groups are each optionally substituted by one or more (e.g., 1, 2, 3, 4 or 5) substituents selected from halogens, such as F;

[0456] Alternatively, the cytotoxic drug is

[0457] (3) n is an integer from 1 to 8, or is 1, 2, 3, 4, 5, 6, 7 or 8, or n is 2, 3 or 4, or n is 2;

[0458] (4) A is Trastuzumab or its antigen-binding fragment.

[0459] Implementation Scheme 10: Use as described in any one of Implementation Schemes 1-9, wherein the anti-Her2 antibody drug conjugate has the following chemical structure:

[0460] Wherein, A is a group obtained by removing n amino groups from the anti-Her2 antibody or its antigen-binding fragment, and n is an integer from 1 to 8, or 1, 2, 3, 4, 5, 6, 7 or 8.

[0461] Implementation Scheme 11, the use as described in any one of Implementation Schemes 1-10, wherein the anti-Her2 antibody or its antigen-binding fragment comprises:

[0462] (1) The following heavy chain variable regions (VH) and / or light chain variable regions (VL), wherein the CDR is defined according to the Chothia numbering system:

[0463] (1a) A heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 of SEQ ID NO:5, CDR-H2 of SEQ ID NO:6, and CDR-H3 of SEQ ID NO:7; and / or, a light chain variable region (VL) comprising the following three CDRs: CDR-L1 of SEQ ID NO:8, CDR-L2 of SEQ ID NO:9, and CDR-L3 of SEQ ID NO:10; or,

[0464] (1b) A heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 of SEQ ID NO:20, CDR-H2 of SEQ ID NO:21, and CDR-H3 of SEQ ID NO:22; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 of SEQ ID NO:23, CDR-L2 of SEQ ID NO:24, and CDR-L3 of SEQ ID NO:25;

[0465] or,

[0466] (2) The following heavy chain variable regions (VH) and / or light chain variable regions (VL), wherein the CDR is defined according to the AbM numbering system:

[0467] (2a) A heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 of SEQ ID NO:18, CDR-H2 of SEQ ID NO:19, and CDR-H3 of SEQ ID NO:7; and / or, a light chain variable region (VL) comprising the following three CDRs: CDR-L1 of SEQ ID NO:8, CDR-L2 of SEQ ID NO:9, and CDR-L3 of SEQ ID NO:10; or,

[0468] (2b) A heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 of SEQ ID NO:33, CDR-H2 of SEQ ID NO:34, and CDR-H3 of SEQ ID NO:22; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 of SEQ ID NO:23, CDR-L2 of SEQ ID NO:24, and CDR-L3 of SEQ ID NO:25;

[0469] or,

[0470] (3) The following heavy chain variable regions (VH) and / or light chain variable regions (VL), wherein the CDR is defined according to the Kabat numbering system:

[0471] (3a) A heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 of SEQ ID NO:11, CDR-H2 of SEQ ID NO:12, and CDR-H3 of SEQ ID NO:7; and / or, a light chain variable region (VL) comprising the following three CDRs: CDR-L1 of SEQ ID NO:8, CDR-L2 of SEQ ID NO:9, and CDR-L3 of SEQ ID NO:10; or,

[0472] (3b) A heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 of SEQ ID NO:26, CDR-H2 of SEQ ID NO:27, and CDR-H3 of SEQ ID NO:22; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 of SEQ ID NO:23, CDR-L2 of SEQ ID NO:24, and CDR-L3 of SEQ ID NO:25;

[0473] or,

[0474] (4) The following heavy chain variable regions (VH) and / or light chain variable regions (VL), wherein the CDR is defined according to the IMGT numbering system:

[0475] (4a) A heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 of SEQ ID NO:13, CDR-H2 of SEQ ID NO:14, and CDR-H3 of SEQ ID NO:15; and / or, a light chain variable region (VL) comprising the following three CDRs: CDR-L1 of SEQ ID NO:16, CDR-L2 of SEQ ID NO:17, and CDR-L3 of SEQ ID NO:10; or,

[0476] (4b) A heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 of SEQ ID NO:28, CDR-H2 of SEQ ID NO:29, and CDR-H3 of SEQ ID NO:30; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 of SEQ ID NO:31, CDR-L2 of SEQ ID NO:32, and CDR-L3 of SEQ ID NO:25.

[0477] Implementation Scheme 12, the use as described in any one of Implementation Schemes 1-11, wherein the anti-Her2 antibody or its antigen-binding fragment comprises:

[0478] (a) VH as shown in SEQ ID NO: 1, and / or VL as shown in SEQ ID NO: 2; or

[0479] (b) VH as shown in SEQ ID NO: 3, and / or VL as shown in SEQ ID NO: 4.

[0480] Implementation Scheme 13, the use as described in any one of Implementation Schemes 1-12, wherein the anti-Her2 antibody or its antigen-binding fragment comprises:

[0481] (1) A heavy chain comprising the VH of the sequence shown in SEQ ID NO: 1 and the heavy chain constant region (CH) shown in SEQ ID NO: 35, and a light chain comprising the VL of the sequence shown in SEQ ID NO: 2 and the light chain constant region (CL) shown in SEQ ID NO: 36;

[0482] (2) A heavy chain comprising the VH of the sequence shown in SEQ ID NO: 3 and the heavy chain constant region (CH) shown in SEQ ID NO: 35, and a light chain comprising the VL of the sequence shown in SEQ ID NO: 4 and the light chain constant region (CL) shown in SEQ ID NO: 36;

[0483] (3) The heavy chain shown in SEQ ID NO:37 and the light chain shown in SEQ ID NO:38; or

[0484] (4) The heavy chain shown in SEQ ID NO:39 and the light chain shown in SEQ ID NO:40;

[0485] Optionally, the N-terminal glutamine of the VH of the sequence shown in SEQ ID NO:1 or 3, or the heavy chain of the sequence shown in SEQ ID NO:37 or 39, undergoes cyclization to form pyroglutamic acid or pyroglutamic acid salt.

[0486] Optionally, the heavy chain constant region (CH) of the sequence shown in SEQ ID NO: 35 or the heavy chain of the sequence shown in SEQ ID NO: 37 or 39 lacks a C-terminal lysine.

[0487] Implementation Scheme 14, the use as described in any one of Implementation Schemes 1-13, wherein the anti-Her2 antibody or its antigen-binding fragment is selected from Trastuzumab or Pertuzumab or its antigen-binding fragment or a combination thereof.

[0488] Implementation Scheme 15, the use as described in any one of Implementation Schemes 1-14, wherein the DAR value of the anti-Her2 antibody drug conjugate is 1-10; or 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. An integer or decimal of 5-6, 6-10, 6-9, 6-8, 6-7, 7-10, 7-9, 7-8, 8-10, 8-9, or 9-10; or a DAR value of 1-4; or 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3.0, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, or 4.0.

[0489] Implementation Scheme 16: The use as described in any one of Implementation Schemes 1-15, wherein the tumor or cancer 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, 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, preferably breast cancer, such as ER- / HER2+ breast cancer or HR- / HER2+ breast cancer.

[0490] Implementation Scheme 17, the use as described in any one of Implementation Schemes 1-16, wherein the dosing cycle of the anti-Trop-2 antibody drug conjugate, the anti-Her2 antibody drug conjugate, and the anti-Her2 antibody or its antigen-binding fragment is 14-42 days, or 14 days, 21 days, 28 days, or 42 days.

[0491] Implementation Scheme 18: The use as described in any one of Implementation Schemes 1-17, wherein the dosing cycle of the anti-Trop-2 antibody-drug conjugate is 14-42 days; and / or the dosing frequency is 1-20 times over a period of 1-4 weeks; or twice a week, once a week, once every 2 weeks, or once every 3 weeks; and / or, based on the subject's weight, the dose of the anti-Trop-2 antibody-drug conjugate per administration is selected from 0.1-20 mg / kg, or from 0.5-10 mg / kg, or from 0.5-5 mg / kg, or 0.5 mg / kg, 1.0 mg / kg, etc. / kg, 1.5mg / kg, 2.0mg / kg, 2.5mg / kg, 3.0mg / kg, 3.5mg / kg, 4.0mg / kg, 4.5mg / kg, 5.0mg / kg, 6.0mg / kg, 7.0mg / kg, 8.0mg / kg, 9.0mg / kg or 10.0mg / kg; and / or 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 to 1000 mg; and / or the dose concentration per administration is selected from 0.1 to 50 mg / ml.

[0492] Implementation Scheme 19: The use as described in any one of Implementation Schemes 1-18, wherein the dosing cycle of the anti-Her2 antibody drug conjugate is 14-42 days; and / or the dosing frequency is 1-20 times over a period of 1-4 weeks; or once a week, once every 2 weeks, once every 3 weeks, or once every 4 weeks; and / or, based on the subject's weight, the dose of the anti-Her2 antibody drug conjugate per administration is selected from 0.1-20 mg / kg, or a dose of 0.1-10 mg / kg, 0.2-8 mg / kg, 0.3-6 mg / kg, or 0.5 mg / kg, 1.0 mg / kg, etc. The dosage of the anti-Her2 antibody or its antigen-binding fragment (e.g., a single dose or a unit dose) is selected from 0.1 to 1000 mg; and / or the concentration of each administration is selected from 0.1 to 50 mg / ml.

[0493] Implementation Scheme 20: The use as described in any one of Implementation Schemes 1-19, wherein the administration cycle of the anti-Her2 antibody or its antigen-binding fragment is 14-42 days; and / or the administration frequency is 1-20 times over a period of 1-4 weeks; or once a week, twice a week, once every 2 weeks, or once every 3 weeks; and / or, based on the subject's weight, the dose of the anti-Her2 antibody or its antigen-binding fragment per administration is selected from 0.1-20 mg / kg, or selected from 0.1-10 mg / kg, or the dose is 0.1-8 mg / kg, 0.2-6 mg / kg, 0.5-5 mg / kg, or 0. The dosage of the anti-Her2 antibody or its antigen-binding fragment (e.g., a single dose or a unit dose) is selected from 0.1 to 1000 mg; and / or the concentration of the dose administered per application is selected from 0.1 to 50 mg / ml.

[0494] Implementation Scheme 21, the use as described in any one of Implementation Schemes 1-20, wherein the drug contains the anti-Trop-2 antibody drug conjugate and the anti-Her2 antibody drug conjugate.

[0495] Implementation Scheme 22, the use as described in any one of Implementation Schemes 1-20, wherein the drug contains the anti-Trop-2 antibody drug conjugate and the anti-Her2 antibody or its antigen-binding fragment.

[0496] Implementation Scheme 23, the use as described in any one of Implementation Schemes 1-20, wherein the drug contains the anti-Her2 antibody drug conjugate and the anti-Her2 antibody or its antigen-binding fragment.

[0497] Implementation Scheme 24, the use as described in any one of Implementation Schemes 1-20, wherein the drug contains the anti-Trop-2 antibody drug conjugate, the anti-Her2 antibody drug conjugate, and the anti-Her2 antibody or its antigen-binding fragment.

[0498] Implementation Scheme 25, the use as described in any one of Implementation Schemes 1-20, wherein the drug contains two or more of the anti-Her2 antibody or its antigen-binding fragment.

[0499] Implementation Scheme 26: A method for preventing and / or treating a tumor or cancer in a subject, comprising the steps of administering to the subject an effective amount of two or more of an anti-Trop-2 antibody drug conjugate, an anti-Her2 antibody drug conjugate, and an anti-Her2 antibody or an antigen-binding fragment thereof, for example, including the steps of administering to the subject an effective amount of an anti-Trop-2 antibody drug conjugate and administering an anti-Her2 antibody drug conjugate, or the steps of administering to the subject an effective amount of an anti-Trop-2 antibody drug conjugate and administering an anti-Her2 antibody or an antigen-binding fragment thereof, or the steps of administering to the subject an effective amount of an anti-Trop-2 antibody drug conjugate, administering an anti-Her2 antibody drug conjugate, and administering an anti-Her2 antibody or an antigen-binding fragment thereof, or the steps of administering to the subject an effective amount of an anti-Her2 antibody drug conjugate and administering an anti-Her2 antibody or an antigen-binding fragment thereof, or the steps of administering to the subject an effective amount of an anti-Her2 antibody or an antigen-binding fragment thereof, or two or more of the steps of administering to the subject an effective amount of an anti-Her2 antibody or an antigen-binding fragment thereof;

[0500] Preferably, the anti-Trop-2 antibody drug conjugate is as defined in any one of embodiments 2-8 and 17-18, the anti-Her2 antibody drug conjugate is as defined in any one of embodiments 9-15, 17 and 19, the anti-Her2 antibody or its antigen-binding fragment is as defined in any one of embodiments 11-14, 17 and 20, and the tumor or cancer is as defined in embodiment 16.

[0501] Preferably, the anti-Trop-2 antibody drug conjugate, the anti-Her2 antibody drug conjugate, and / or the anti-Her2 antibody or its antigen-binding fragment are administered simultaneously, separately, sequentially, or in sequence.

[0502] Implementation Scheme 27: A kit comprising two or more of the following: an anti-Trop-2 antibody drug conjugate, an anti-Her2 antibody drug conjugate, and an anti-Her2 antibody or an antigen-binding fragment thereof. For example, it may contain an anti-Trop-2 antibody drug conjugate and an anti-Her2 antibody drug conjugate, or an anti-Trop-2 antibody drug conjugate and an anti-Her2 antibody or an antigen-binding fragment thereof, or an anti-Trop-2 antibody drug conjugate, an anti-Her2 antibody drug conjugate, and an anti-Her2 antibody or an antigen-binding fragment thereof, or an anti-Her2 antibody drug conjugate and an anti-Her2 antibody or an antigen-binding fragment thereof, or two or more of the following: an anti-Her2 antibody or an antigen-binding fragment thereof.

[0503] Preferably, the anti-Trop-2 antibody drug conjugate is as defined in any one of embodiments 2-8 and 17-18, the anti-Her2 antibody drug conjugate is as defined in any one of embodiments 9-15, 17 and 19, and the anti-Her2 antibody or its antigen-binding fragment is as defined in any one of embodiments 11-14, 17 and 20.

[0504] Preferably, the kit is used for the prevention and / or treatment of tumors or cancers in a subject; preferably, the tumors or cancers are as defined in embodiment 16.

[0505] Implementation Scheme 28, a kit comprising: (a) an anti-Trop-2 antibody drug conjugate and an anti-Her2 antibody drug conjugate; (b) an anti-Trop-2 antibody drug conjugate and an anti-Her2 antibody or an antigen-binding fragment thereof; (c) an anti-Her2 antibody drug conjugate and an anti-Her2 antibody or an antigen-binding fragment thereof; (d) one, two or more of the anti-Her2 antibody or an antigen-binding fragment thereof; (e) an anti-Trop-2 antibody drug conjugate; (f) an anti-Her2 antibody drug conjugate; or (g) an anti-Trop-2 antibody drug conjugate, an anti-Her2 antibody drug conjugate and an anti-Her2 antibody or an antigen-binding fragment thereof; and hyaluronic acid degrading enzyme;

[0506] Preferably, the anti-Trop-2 antibody drug conjugate is as defined in any one of embodiments 2-8 and 17-18, the anti-Her2 antibody drug conjugate is as defined in any one of embodiments 9-15, 17 and 19, and the anti-Her2 antibody or its antigen-binding fragment is as defined in any one of embodiments 11-14, 17 and 20.

[0507] Preferably, the hyaluronic acid degrading enzyme is a soluble hyaluronidase, such as soluble PH20, or hyaluronidase (human recombinant) or berahyaluronidase alfa;

[0508] Preferably, the kit is used for the prevention and / or treatment of tumors or cancers in a subject; preferably, the tumors or cancers are as defined in embodiment 16.

[0509] Implementation Scheme 29: A drug combination or drug combination product comprising two or more of the following: an anti-Trop-2 antibody drug conjugate, an anti-Her2 antibody drug conjugate, and an anti-Her2 antibody or an antigen-binding fragment thereof. For example, it may comprise an anti-Trop-2 antibody drug conjugate and an anti-Her2 antibody drug conjugate, or an anti-Trop-2 antibody drug conjugate and an anti-Her2 antibody or an antigen-binding fragment thereof, or an anti-Trop-2 antibody drug conjugate, an anti-Her2 antibody drug conjugate, and an anti-Her2 antibody or an antigen-binding fragment thereof, or an anti-Her2 antibody drug conjugate and an anti-Her2 antibody or an antigen-binding fragment thereof, or two or more of the following: an anti-Her2 antibody or an antigen-binding fragment thereof.

[0510] Preferably, the anti-Trop-2 antibody drug conjugate is as defined in any one of embodiments 2-8 and 17-18, the anti-Her2 antibody drug conjugate is as defined in any one of embodiments 9-15, 17 and 19, and the anti-Her2 antibody or its antigen-binding fragment is as defined in any one of embodiments 11-14, 17 and 20.

[0511] Preferably, the drug combination or drug combination product is a pharmaceutical composition;

[0512] Preferably, the drug combination or drug combination product is used for the prevention and / or treatment of a tumor or cancer in a subject; preferably, the tumor or cancer is as defined in embodiment 16.

[0513] Implementation Scheme 30: A drug combination or drug combination product comprising: (a) an anti-Trop-2 antibody drug conjugate and an anti-Her2 antibody drug conjugate; (b) an anti-Trop-2 antibody drug conjugate and an anti-Her2 antibody or an antigen-binding fragment thereof; (c) an anti-Her2 antibody drug conjugate and an anti-Her2 antibody or an antigen-binding fragment thereof; (d) one, two or more of the anti-Her2 antibody or an antigen-binding fragment thereof; (e) an anti-Trop-2 antibody drug conjugate; (f) an anti-Her2 antibody drug conjugate; or (g) an anti-Trop-2 antibody drug conjugate, an anti-Her2 antibody drug conjugate and an anti-Her2 antibody or an antigen-binding fragment thereof; and hyaluronic acid degrading enzyme;

[0514] Preferably, the anti-Trop-2 antibody drug conjugate is as defined in any one of embodiments 2-8 and 17-18, the anti-Her2 antibody drug conjugate is as defined in any one of embodiments 9-15, 17 and 19, and the anti-Her2 antibody or its antigen-binding fragment is as defined in any one of embodiments 11-14, 17 and 20.

[0515] Preferably, the hyaluronic acid degrading enzyme is a soluble hyaluronidase, such as soluble PH20, or hyaluronidase (human recombinant) or berahyaluronidase alfa;

[0516] Preferably, the kit is used for the prevention and / or treatment of tumors or cancers in a subject; preferably, the tumors or cancers are as defined in embodiment 16.

[0517] Implementation Scheme 31: A method for preventing and / or treating a tumor or cancer in a subject, comprising administering to the subject an effective amount of the kit described in Implementation Scheme 27 or 28, or the drug combination or drug combination product described in Implementation Scheme 29 or 30, wherein the tumor or cancer is preferably as defined in Implementation Scheme 16.

[0518] Implementation Scheme 32, the method as described in Implementation Scheme 31, wherein the anti-Trop-2 antibody drug conjugate, the anti-Her2 antibody drug conjugate, and / or the anti-Her2 antibody or its antigen-binding fragment, and the hyaluronic acid degrading enzyme are administered simultaneously, separately, sequentially, or in sequence.

[0519] Implementation Scheme 33, the method as described in Implementation Scheme 31 or 32, wherein the anti-Trop-2 antibody drug conjugate, the anti-Her2 antibody drug conjugate, and / or the anti-Her2 antibody or its antigen-binding fragment, and the hyaluronic acid degrading enzyme are mixed to form a mixture, and the mixture is administered.

[0520] Implementation Scheme 34, the method of any one of Implementation Schemes 26, 31-33, wherein the anti-Trop-2 antibody-drug conjugate is applied according to one or more of the following:

[0521] (1) The dosing cycle is 14-42 days;

[0522] (2) The frequency of administration is 1 to 20 times within 1 to 4 weeks; or twice a week, once a week, once every 2 weeks or once every 3 weeks;

[0523] (3) 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 from 0.5-10 mg / kg, or from 0.5-5 mg / kg, or is 0.5 mg / kg, 1.0 mg / kg, 1.5 mg / kg, 2.0 mg / kg, 2.5 mg / kg, 3.0 mg / kg, 3.5 mg / kg, 4.0 mg / kg, 4.5 mg / kg, 5.0 mg / kg, 6.0 mg / kg, 7.0 mg / kg, 8.0 mg / kg, 9.0 mg / kg or 10.0 mg / kg;

[0524] (4) 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;

[0525] (5) The dosage concentration for each application is selected from 0.1-50 mg / ml.

[0526] Implementation Scheme 35, the method of any one of Implementation Schemes 26, 31-34, wherein the anti-Her2 antibody drug conjugate is applied according to one or more of the following:

[0527] (1) The dosing cycle is 14-42 days;

[0528] (2) The frequency of administration is 1 to 20 times within 1 to 4 weeks; or once a week, once every 2 weeks, once every 3 weeks, or once every 4 weeks;

[0529] (3) Based on the subject's weight, the dose of the anti-Her2 antibody-drug conjugate administered each time is selected from 0.1-20 mg / kg, or the dose is 0.1-10 mg / kg, 0.2-8 mg / kg, 0.3-6 mg / kg, or 0.5 mg / kg, 1.0 mg / kg, 1.5 mg / kg, 2.0 mg / kg, 2.5 mg / kg, 3.0 mg / kg, 3.5 mg / kg, 4.0 mg / kg, 4.5 mg / kg, 5.0 mg / kg, 6.0 mg / kg, 7.0 mg / kg, 8.0 mg / kg, 9.0 mg / kg or 10.0 mg / kg;

[0530] (4) The dosage of the anti-Her2 antibody drug conjugate (e.g., a single-dose dose or a unit dose) is selected from 0.1-1000 mg;

[0531] (5) The dosage concentration for each application is selected from 0.1-50 mg / ml.

[0532] Implementation Scheme 36, the method of any one of Implementation Schemes 26, 31-35, wherein the anti-Her2 antibody or its antigen-binding fragment is applied in accordance with one or more of the following:

[0533] (1) The dosing cycle is 14-42 days;

[0534] (2) The frequency of administration is 1 to 20 times within 1 to 4 weeks; or once a week, twice a week, once every 2 weeks or once every 3 weeks;

[0535] (3) Based on the subject's weight, the dose of the anti-Her2 antibody or its antigen-binding fragment administered each time is selected from 0.1-20 mg / kg, or selected from 0.1-10 mg / kg, or the dose is 0.1-8 mg / kg, 0.2-6 mg / kg, 0.5-5 mg / kg, or 0.5 mg / kg, 1.0 mg / kg, 1.5 mg / kg, 2.0 mg / kg, 2.5 mg / kg, 3.0 mg / kg, 3.5 mg / kg, 4.0 mg / kg, 4.5 mg / kg, 5.0 mg / kg, 6.0 mg / kg, 7.0 mg / kg, 8.0 mg / kg, 9.0 mg / kg or 10.0 mg / kg;

[0536] (4) The dose of the anti-Her2 antibody or its antigen-binding fragment (e.g., a single-dose dose or a unit dose) is selected from 0.1-1000 mg;

[0537] (5) The dosage concentration for each application is selected from 0.1-50 mg / ml.

[0538] Implementation scheme 37, the use of anti-Trop-2 antibody drug conjugate and optional hyaluronic acid degrading enzyme in the preparation of a medicament for the prevention and / or treatment of tumors or cancers in a subject, in combination with the anti-Her2 antibody drug conjugate and / or anti-Her2 antibody or its antigen-binding fragment, or in the preparation of a medicament for improving the efficacy of the anti-Her2 antibody drug conjugate and / or anti-Her2 antibody or its antigen-binding fragment in the treatment of tumors or cancers;

[0539] Preferably, the anti-Trop-2 antibody drug conjugate is as defined in any one of embodiments 2-8 and 17-18, the anti-Her2 antibody drug conjugate is as defined in any one of embodiments 9-15, 17 and 19, and the anti-Her2 antibody or its antigen-binding fragment is as defined in any one of embodiments 11-14, 17 and 20.

[0540] Preferably, the hyaluronic acid degrading enzyme is a soluble hyaluronidase, such as soluble PH20, or hyaluronidase (human recombinant) or berahyaluronidase alfa;

[0541] Preferably, the tumor or cancer is as defined in embodiment 16.

[0542] Implementation scheme 38, the use of anti-Her2 antibody drug conjugate and optional hyaluronic acid degrading enzyme in the preparation of a medicament for the prevention and / or treatment of tumors or cancers in combination with anti-Trop-2 antibody drug conjugate and / or anti-Her2 antibody or its antigen-binding fragment for the prevention and / or treatment of tumors or cancers in a subject, or in the preparation of a medicament for the improvement of the efficacy of anti-Trop-2 antibody drug conjugate and / or anti-Her2 antibody or its antigen-binding fragment in the treatment of tumors or cancers;

[0543] Preferably, the anti-Trop-2 antibody drug conjugate is as defined in any one of embodiments 2-8 and 17-18, the anti-Her2 antibody drug conjugate is as defined in any one of embodiments 9-15, 17 and 19, and the anti-Her2 antibody or its antigen-binding fragment is as defined in any one of embodiments 11-14, 17 and 20.

[0544] Preferably, the hyaluronic acid degrading enzyme is a soluble hyaluronidase, such as soluble PH20, or hyaluronidase (human recombinant) or berahyaluronidase alfa;

[0545] Preferably, the tumor or cancer is as defined in embodiment 16.

[0546] Sequence information

[0547] The sequence information disclosed herein is provided as follows:

[0548] Example

[0549] 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.

[0550] The test drugs used in the following examples are shown below:

[0551] (1) Anti-Trop-2 antibody-drug conjugate (hereinafter referred to as Trop-2 ADC): The anti-Trop-2 antibody-drug conjugate used in the examples is BT001021, which was prepared according to the method described in Example 32 of WO2019114666.

[0552] (2) Anti-Her2 antibody drug conjugate (hereinafter referred to as Her2 ADC): The Her2 antibody drug conjugate used in the examples was prepared according to the method described in Example 1 of WO2017088734A1.

[0553] (3) Anti-Her2 antibody: Pertuzumab, i.e., pertuzumab injection (trade name: Perjeta), was purchased from Roche at a concentration of 30 mg / ml and stored at 2-8℃; Trastuzumab, i.e. trastuzumab for injection (trade name: Hanquyou), was purchased from Shanghai Henlius Biotech. It was reconstituted with 10 ml of sterile water for injection according to the instructions for use, and the prepared trastuzumab for injection concentration was 21 mg / ml. After aliquoting, it was stored at -80±20℃.

[0554] (4) DS-8201: DS8201 is an ADC targeting human Her2 developed by Daiichi Sankyo. The sample used in the example was prepared by Kelun Biotech according to the sequence and conjugation strategy in its patent, with a concentration of 12.6 mg / ml, and stored at -80±20℃.

[0555] Before administration, dilute the anti-Trop-2 antibody-drug conjugate, anti-Her2 antibody-drug conjugate, Trastuzumab, Pertuzumab, and DS-8201 with 0.9% sodium chloride injection to the dosing concentrations in the table, and prepare immediately before use.

[0556] Example 1: Study on the efficacy of combined administration of Trop-2 ADC, Her2 ADC and anti-Her2 antibody, and the combined administration of the three drugs and individual administration of each drug on NOD SCID nude mice with breast cancer (ER-, HER2+).

[0557] 1. Grouping of test animals and dosing regimen

[0558] Table 1 below shows the grouping of the test animals and the dosing regimen.

[0559] Table 1. Grouping and Dosing Regimens of Experimental Animals

[0560] Note: The dosing frequency column refers to the day on which the drug is administered. For example, P0 / P7 / P14 means the drug is administered on day 0, day 7, and day 14, and so on; iv, tail vein administration.

[0561] 2. Experimental Procedures and Results

[0562] Female NOD SCID mice, 6 - 8 weeks old and weighing 16 - 18 g (supplied by Jiangsu Genscript Biotech Co., Ltd.), were acclimated to the environment for at least 3 days before the experiment. Healthy mice were selected as the test animals. JIMT-1 cells (purchased from Nanjing Kebai Co., Ltd.) were cultured in DMEM medium supplemented with 10% fetal bovine serum in an incubator at 37°C with 5% CO2 air. When the cells were in the exponential growth phase, the culture medium was taken for mycoplasma detection. After passing the detection, the cells were collected and counted. Each mouse was subcutaneously inoculated with 5×10 6 JIMT-1 cells (suspended in 0.1 ml of serum-free medium containing 50% Matrigel) in the right axilla. When the average tumor volume grew to 100 - 200 mm 3 , mice with too small or too large tumor volumes were excluded. The remaining mice were randomly grouped according to tumor volume and animal weight and administered drugs according to the experimental protocol. The day of drug administration was recorded as P0. The body weight of the mice was weighed twice a week and the tumor volume was measured, and the data were recorded. The formula for calculating the tumor volume (V) is: V = 1 / 2 × a × b 2 , where a and b represent the length and width respectively. The anti-tumor drug efficacy was evaluated by the tumor growth inhibition rate TGI (%), and the calculation formula is: TGI (%) (tumor volume) = [1 - (T Vt - T V0 ) / (C Vt - C V0 )] × 100%, where T V0 is the average tumor volume of the test compound group at the time of grouping and drug administration, T Vt is the average tumor volume of the test compound group t days after drug administration; C V0 is the average tumor volume of the vehicle group at the time of grouping and drug administration; C Vt is the average tumor volume of the vehicle group t days after drug administration. When the tumor regresses, TGI (%) (tumor volume) = 100% - (T Vt - T V0 ) / T V0 × 100%. If the tumor shrinks compared to the initial volume, that is, when Vt < V0, it is defined as partial regression (PR) of the tumor; if the tumor completely disappears, it is defined as complete regression (CR) of the tumor. After the experiment, the mice were euthanized by rapid asphyxiation with carbon dioxide, and then the tumors were dissected, weighed, and the tumor weight was recorded. The tumor inhibition rate was calculated based on the tumor weight (W), and the formula is: TGI (%) (瘤重) = 100% - T W / C W × 100%, where T W is the average tumor weight of the test compound group at the end of the experiment, and C W is the average tumor weight of the vehicle group at the end of the experiment.

[0563] The experimental results showed that no animals died or experienced significant weight loss during the experimental period, indicating good tolerance to the test substances. Tumor volume data showed that the efficacy of the dual-drug and multi-drug combination groups was significantly superior to the Trop-2 ADC 2 mg / kg group (p<0.0001), Her2 ADC 1.5 mg / kg group (p<0.0001), Trastuzumab 2.5 mg / kg group (p<0.0001), and Pertuzumab 2 mg / kg group (p<0.001). Detailed results are shown in Table 2. Furthermore, the tumor weight results were consistent with the tumor volume results.

[0564] Table 2. Tumor volume analysis of mice in each group (N=5)

[0565] Note: NA indicates not applicable; Two-tails T-test, compared with G1 0.9% sodium chloride injection group: * p<0.05; ** p<0.01; *** p<0.001; T-test, compared with the G2 DS-8201 group in the combination therapy group: & p<0.05; && p<0.01; &&& , p<0.001.

[0566] The above experimental results exemplify that, in the JIMT-1 human breast cancer subcutaneous xenograft model, the combined drug administration groups showed significantly enhanced antitumor effects compared to the single-drug groups, and were well tolerated by mice. Furthermore, based on these experimental results, and according to models such as Chou-Talalay, the combined drug administration groups exhibited synergistic antitumor effects.

[0567] Example 2: Pharmacological effects of a human breast cancer mouse subcutaneous xenograft (PDX) model.

[0568] 1. Grouping of test animals and dosing regimen

[0569] Table 3 below shows the grouping of the test animals and the dosing regimen.

[0570] Table 3. Grouping and Dosing Regimens of Experimental Animals

[0571] Note: "QW" means once a week.

[0572] 2. Experimental Procedures and Results

[0573] Female NU / NU mice aged 42 - 62 days (supplied by Zhejiang Vital River Laboratory Animal Technology Co., Ltd.) were adaptively fed for at least 3 days before the experiment. The human breast cancer tumor tissue LD1 - 2009 - 362721 (supplied by Shanghai Lide Biotechnology Co., Ltd.) was evenly cut into tumor blocks approximately 3 mm × 3 mm × 3 mm in size and weighing about 20 - 30 mg, and then inoculated subcutaneously on the right side of NU / NU mice. Select 35 tumor-bearing mice with an average tumor volume of 138.00 mm 3 (104.31 - 187.37 mm 3 ) and randomly stratified into 7 groups with 5 mice in each group. The day of grouping was defined as day 0, and drug administration started. The specific drug administration method, dosage, and administration route are shown in Table 3. Weigh the mice twice a week and measure the tumor volume using a vernier caliper. The tumor volume calculation formula is V = 0.5a × b 2 , where a and b represent the long diameter and short diameter of the tumor respectively. The antitumor drug efficacy was evaluated by the tumor growth inhibition rate TGI (%), and the calculation formula: TGI (%) (tumor volume) = [1 - (T Vt - T V0 ) / (C Vt - C V0 )] × 100%, T V0 is the average tumor volume of the test compound group at the time of grouping and drug administration, T Vt is the average tumor volume of the test compound group t days after drug administration; C V0 is the average tumor volume of the vehicle group at the time of grouping and drug administration; C Vt is the average tumor volume of the vehicle group t days after drug administration. When the tumor regresses, TGI (%) (tumor volume) = 100% - (T Vt - T V0 ) / T V0 × 100%. If the tumor shrinks compared to the initial volume, that is, when Vt < V0, it is defined as partial regression (PR) of the tumor; if the tumor completely disappears, it is defined as complete regression (CR) of the tumor. At the end of the experiment (day 36), all tumor-bearing mice were euthanized, and then the subcutaneous transplanted tumor blocks were dissected and weighed.

[0574] The experimental results showed that no animals died in any group during the experimental period (35 days), and the body weight of all tumor-bearing mice fluctuated within the normal range (e.g., the body weight change rate of each experimental group on day 35 relative to day 0 was in the range of 4-14%). The tumor-bearing mice had good tolerance to the tested single drugs and combination treatments at the tested doses. Tumor volume data showed that, compared with the Vehicle, both the 1 mg / kg TROP-2 ADC + 1 mg / kg HER2 ADC treatment group and the 1 mg / kg TROP-2 ADC + 1 mg / kg HER2 ADC + 3 mg / kg Pertuzumab treatment group significantly inhibited the growth of the LD1-2009-362721 mouse subcutaneous PDX model, demonstrating statistically significant inhibitory effects (p<0.05). Furthermore, the complete remission rate of the 1 mg / kg TROP-2 ADC + 1 mg / kg HER2 ADC treatment group against LD1-2009-362721 mouse subcutaneous PDX tumors was 20% (1 / 5). Detailed results are shown in Table 4. Additionally, the tumor weight and tumor volume results were largely consistent.

[0575] Furthermore, the combination of TROP-2 ADC and HER2 ADC can produce a significant synergistic effect. Specifically, according to the drug interaction coefficient (CDI) calculation formula: CDI = AB / (A×B), where A or B is the single-drug group T Vt With C Vt The ratio, AB is the T value of the two-drug combination group. Vt With C Vt The ratio of drug interaction coefficient (CDI) < 1 indicates synergistic effect; CDI < 0.7 indicates significant synergistic effect; CDI = 1 indicates additive effect; CDI > 1 indicates antagonistic effect. The CDI value of the 1 mg / kg TROP-2 ADC + 1 mg / kg HER2 ADC combination group was 0.394, indicating that the combination of the two drugs had a significant synergistic effect compared with the single drug group. In addition, according to the method provided in the reference "Binchen Mao, Sheng Guo. Statistical Assessment of Drug Synergy from In Vivo Combination Studies Using Mouse Tumor Models. Cancer Res Commun. 2023 Oct; 3(10):2146-2157.", the 1 mg / kg TROP-2 ADC + 1 mg / kg HER2 ADC combination group also had a significant synergistic effect.

[0576] Table 4 Tumor volume (Mean±SEM) of each experimental group

[0577] Note: Compared with the Vehicle group, * indicates p<0.05, ** indicates p<0.01, *** indicates p<0.001, and **** indicates p<0.0001.

[0578] The above experimental results exemplify that in the LD1-2009-362721 breast cancer PDX model, each combined administration group showed significant anti-tumor effects and good tolerance in mice.

[0579] The above description illustrates specific exemplary embodiments of the present invention, but is not intended to limit the invention to the exemplified embodiments. Any modifications, equivalent substitutions, improvements, etc., that can be made within the spirit and principles shown herein should be included within the scope of protection of the present invention. Furthermore, the technical solutions of the various embodiments can be combined with each other, but any such combination must be something that would be reasonably done by a person with typical expertise in the art, without involving any unusual or unforeseen modifications; when a combination is contradictory or cannot be implemented, it should be interpreted as such combination not existing or infeasible, and therefore not within the scope of protection of the present invention.

Claims

1. Use of two or more of the following in the preparation of a medicament for the prevention and / or treatment of a subject’s tumor or cancer: an anti-Trop-2 antibody-drug conjugate, an anti-Her2 antibody-drug conjugate, and an anti-Her2 antibody or an antigen-binding fragment thereof.

2. The use as claimed in claim 1, wherein the anti-Trop-2 antibody drug conjugate has the structure of the following formula (I): {D1-[L1-(L2)m1-(L3)m2-(L4)m3-E]} q -Ab 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 at position 2 is connected to Ab, and E at position 1 is connected to L4. m1, m2 and m3 are each independently 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; D1 is the bioactive molecular moiety; q refers to {D1-[L1-(L2)} which forms a thioether bond with the thiol group of Ab. m1 -(L3) m2 -(L4) m3 The number of the -E]}- part, which is selected from 1 to 10, or 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; Ab represents anti-Trop-2 antibody or its antigen-binding fragment; Preferably, 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 D1, and position 2 of L1 is connected to L2; (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. (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 Ab at position 2 (e.g., to a thiol group on Ab) and to L4 at position 1. (6) m1, m2 and m3 are all 1; (7) The bioactive molecules are selected from Preferably, D1 is selected from (8) q is an integer between 3 and 8, or 3, 4, 5, 6, 7 or 8; (9)Ab is Sacituzumab or its antigen-binding fragment.

3. The use as described in claim 1 or 2, wherein the anti-Trop-2 antibody-drug conjugate has the following chemical structure: in, Ab is an anti-Trop-2 antibody or its antigen-binding fragment; q is selected from 1 to 10 (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10), or q is selected from 3 to 8 (e.g., 3, 4, 5, 6, 7 or 8).

4. The use as described in any one of claims 1-3, 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), wherein the CDR is defined according to the Chothia numbering system: Heavy chain variable region (VH) containing the following 3 CDRs: CDR-H1 with sequence SEQ ID NO:43, CDR-H2 with sequence SEQ ID NO:44, and CDR-H3 with sequence SEQ ID NO:45; and / or, light chain variable region (VL) containing the following 3 CDRs: CDR-L1 with sequence SEQ ID NO:46, CDR-L2 with sequence SEQ ID NO:47, and CDR-L3 with sequence SEQ ID NO:48; or, (2) The following heavy chain variable regions (VH) and / or light chain variable regions (VL), wherein the CDR is defined according to the AbM numbering system: Heavy chain variable region (VH) containing the following 3 CDRs: CDR-H1 with sequence SEQ ID NO:56, CDR-H2 with sequence SEQ ID NO:57, and CDR-H3 with sequence SEQ ID NO:45; and / or, light chain variable region (VL) containing the following 3 CDRs: CDR-L1 with sequence SEQ ID NO:46, CDR-L2 with sequence SEQ ID NO:47, and CDR-L3 with sequence SEQ ID NO:48; or, (3) The following heavy chain variable regions (VH) and / or light chain variable regions (VL), wherein the CDR is defined according to the Kabat numbering system: Heavy chain variable region (VH) containing the following 3 CDRs: CDR-H1 with sequence SEQ ID NO:49, CDR-H2 with sequence SEQ ID NO:50, and CDR-H3 with sequence SEQ ID NO:45; and / or, light chain variable region (VL) containing the following 3 CDRs: CDR-L1 with sequence SEQ ID NO:46, CDR-L2 with sequence SEQ ID NO:47, and CDR-L3 with sequence SEQ ID NO:48; or, (4) The following heavy chain variable regions (VH) and / or light chain variable regions (VL), wherein the CDR is defined according to the IMGT numbering system: The heavy chain variable region (VH) contains the following three CDRs: CDR-H1 with sequence SEQ ID NO:51, CDR-H2 with sequence SEQ ID NO:52, and CDR-H3 with sequence SEQ ID NO:53; and / or the light chain variable region (VL) contains the following three CDRs: CDR-L1 with sequence SEQ ID NO:54, CDR-L2 with sequence SEQ ID NO:55, and CDR-L3 with sequence SEQ ID NO:

48.

5. The use according to any one of claims 1-4, wherein the anti-Trop-2 antibody or its antigen-binding fragment comprises: VH as shown in SEQ ID NO: 41, and / or VL as shown in SEQ ID NO:

42.

6. The use according to any one of claims 1-5, wherein the anti-Trop-2 antibody or its antigen-binding fragment comprises: the heavy chain shown in SEQ ID NO:58 and the light chain shown in SEQ ID NO:

59.

7. The use as described in any one of claims 1-6, wherein the anti-Trop-2 antibody or its antigen-binding fragment is Sacituzumab or its antigen-binding fragment.

8. The use according to any one of claims 1-7, wherein the DAR value of the anti-Trop-2 antibody-drug conjugate is 1-10; or is 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 integers or decimals; or DAR values ​​of 3-8 or 5-8; or 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.

9. The use according to any one of claims 1-8, wherein the anti-Her2 antibody drug conjugate has the following chemical structure: in: A represents an anti-Her2 antibody or its antigen-binding fragment; X and Y are each independently N or CR 1 (Preferred Y is CR) 1 (where X is N), and each R 1 Independently H or Cl-C 10 Alkyl, preferably H or C1-C6 alkyl (e.g., methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, pentyl or hexyl); L is a divalent linker; D represents a cytotoxic drug group; and n is an integer selected from 1 to 10, or 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; Preferably, the anti-Her2 antibody drug conjugate meets one or more of the following conditions: (1) L is selected from p is an integer from 1 to 10, or 1, 2, 3, 4, 5 or 6; (2) Cytotoxic drugs are selected from compounds of the following general formula or their stereoisomers: Among them, R 2 Selected from -CH2N3, -CONHSO2 (cyclopropyl), thiazolyl-2-yl, -CH3 and -COOH; R 3 Selected from H and -OH; and R 4 Selected from H, -NH2, Cl, Br, I, -OS(O)2R 6 , where R 6 It is H, C1-C8 alkyl, C3-C8 cycloalkyl, or C6-C 14 The aryl group, wherein the alkyl, cycloalkyl and aryl groups are each optionally substituted by one or more (e.g., 1, 2, 3, 4 or 5) substituents selected from halogens, such as F; Alternatively, the cytotoxic drug is (3) n is an integer from 1 to 8, or is 1, 2, 3, 4, 5, 6, 7 or 8, or n is 2, 3 or 4, or n is 2; (4) A is Trastuzumab or its antigen-binding fragment.

10. The use according to any one of claims 1-9, wherein the anti-Her2 antibody drug conjugate has the following chemical structure: in, A is a group obtained by removing n amino groups from the anti-Her2 antibody or its antigen-binding fragment, where n is an integer from 1 to 8, or 1, 2, 3, 4, 5, 6, 7 or 8.

11. The use as described in any one of claims 1-10, wherein the anti-Her2 antibody or its antigen-binding fragment comprises: (1) The following heavy chain variable regions (VH) and / or light chain variable regions (VL), wherein the CDR is defined according to the Chothia numbering system: (1a) A heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 of SEQ ID NO:5, CDR-H2 of SEQ ID NO:6, and CDR-H3 of SEQ ID NO:7; and / or, a light chain variable region (VL) comprising the following three CDRs: CDR-L1 of SEQ ID NO:8, CDR-L2 of SEQ ID NO:9, and CDR-L3 of SEQ ID NO:10; or, (1b) A heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 of SEQ ID NO:20, CDR-H2 of SEQ ID NO:21, and CDR-H3 of SEQ ID NO:22; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 of SEQ ID NO:23, CDR-L2 of SEQ ID NO:24, and CDR-L3 of SEQ ID NO:25; or, (2) The following heavy chain variable regions (VH) and / or light chain variable regions (VL), wherein the CDR is defined according to the AbM numbering system: (2a) A heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 of SEQ ID NO:18, CDR-H2 of SEQ ID NO:19, and CDR-H3 of SEQ ID NO:7; and / or, a light chain variable region (VL) comprising the following three CDRs: CDR-L1 of SEQ ID NO:8, CDR-L2 of SEQ ID NO:9, and CDR-L3 of SEQ ID NO:10; or, (2b) A heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 of SEQ ID NO:33, CDR-H2 of SEQ ID NO:34, and CDR-H3 of SEQ ID NO:22; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 of SEQ ID NO:23, CDR-L2 of SEQ ID NO:24, and CDR-L3 of SEQ ID NO:25; or, (3) The following heavy chain variable regions (VH) and / or light chain variable regions (VL), wherein the CDR is defined according to the Kabat numbering system: (3a) A heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 of SEQ ID NO:11, CDR-H2 of SEQ ID NO:12, and CDR-H3 of SEQ ID NO:7; and / or, a light chain variable region (VL) comprising the following three CDRs: CDR-L1 of SEQ ID NO:8, CDR-L2 of SEQ ID NO:9, and CDR-L3 of SEQ ID NO:10; or, (3b) A heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 of SEQ ID NO:26, CDR-H2 of SEQ ID NO:27, and CDR-H3 of SEQ ID NO:22; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 of SEQ ID NO:23, CDR-L2 of SEQ ID NO:24, and CDR-L3 of SEQ ID NO:25; or, (4) The following heavy chain variable regions (VH) and / or light chain variable regions (VL), wherein the CDR is defined according to the IMGT numbering system: (4a) A heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 of SEQ ID NO:13, CDR-H2 of SEQ ID NO:14, and CDR-H3 of SEQ ID NO:15; and / or, a light chain variable region (VL) comprising the following three CDRs: CDR-L1 of SEQ ID NO:16, CDR-L2 of SEQ ID NO:17, and CDR-L3 of SEQ ID NO:10; or, (4b) A heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 of SEQ ID NO:28, CDR-H2 of SEQ ID NO:29, and CDR-H3 of SEQ ID NO:30; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 of SEQ ID NO:31, CDR-L2 of SEQ ID NO:32, and CDR-L3 of SEQ ID NO:

25.

12. The use as described in any one of claims 1-11, wherein the anti-Her2 antibody or its antigen-binding fragment comprises: (a) VH as shown in SEQ ID NO: 1, and / or VL as shown in SEQ ID NO: 2; or (b) VH as shown in SEQ ID NO: 3, and / or VL as shown in SEQ ID NO:

4.

13. The use as described in any one of claims 1-12, wherein the anti-Her2 antibody or its antigen-binding fragment comprises: (1) A heavy chain comprising the VH of the sequence shown in SEQ ID NO: 1 and the heavy chain constant region (CH) shown in SEQ ID NO: 35, and a light chain comprising the VL of the sequence shown in SEQ ID NO: 2 and the light chain constant region (CL) shown in SEQ ID NO: 36; (2) A heavy chain comprising the VH of the sequence shown in SEQ ID NO: 3 and the heavy chain constant region (CH) shown in SEQ ID NO: 35, and a light chain comprising the VL of the sequence shown in SEQ ID NO: 4 and the light chain constant region (CL) shown in SEQ ID NO: 36; (3) The heavy chain shown in SEQ ID NO:37 and the light chain shown in SEQ ID NO:38; or (4) The heavy chain shown in SEQ ID NO:39 and the light chain shown in SEQ ID NO:40; Optionally, the N-terminal glutamine of the VH of the sequence shown in SEQ ID NO:1 or 3, or the heavy chain of the sequence shown in SEQ ID NO:37 or 39, undergoes cyclization to form pyroglutamic acid or pyroglutamic acid salt. Optionally, the heavy chain constant region (CH) of the sequence shown in SEQ ID NO: 35 or the heavy chain of the sequence shown in SEQ ID NO: 37 or 39 lacks a C-terminal lysine.

14. The use as described in any one of claims 1-13, wherein the anti-Her2 antibody or its antigen-binding fragment is selected from Trastuzumab or Pertuzumab or its antigen-binding fragment or a combination thereof.

15. The use as described in any one of claims 1-14, wherein the DAR value of the anti-Her2 antibody drug conjugate is 1-10; or is 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, Integers or decimals of 5-6, 6-10, 6-9, 6-8, 6-7, 7-10, 7-9, 7-8, 8-10, 8-9, or 9-10; or DAR values ​​of 1-4; or 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3.0, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, or 4.

0.

16. The use as described in any one of claims 1-15, wherein the tumor or cancer 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, 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, preferably breast cancer, such as ER- / HER2+ breast cancer or HR- / HER2+ breast cancer.

17. The use according to any one of claims 1-16, wherein the dosing cycle of the anti-Trop-2 antibody drug conjugate, the anti-Her2 antibody drug conjugate, and the anti-Her2 antibody or its antigen-binding fragment is 14-42 days, or 14 days, 21 days, 28 days, or 42 days.

18. The use as described in any one of claims 1-17, wherein the dosing period of the anti-Trop-2 antibody-drug conjugate is 14-42 days; and / or the dosing frequency is 1-20 times over a period of 1-4 weeks; or twice a week, once a week, once every 2 weeks, or once every 3 weeks; and / or, based on the subject's weight, the dose of the anti-Trop-2 antibody-drug conjugate per administration is selected from 0.1-20 mg / kg, or selected from 0.5-10 mg / kg, or selected from 0.5-5 mg / kg, or 0.5 mg / kg, 1.0 mg / kg, etc. The dosage of the anti-Trop-2 antibody drug conjugate is selected from 0.1 to 1000 mg (g, 1.5 mg / kg, 2.0 mg / kg, 2.5 mg / kg, 3.0 mg / kg, 3.5 mg / kg, 4.0 mg / kg, 4.5 mg / kg, 5.0 mg / kg, 6.0 mg / kg, 7.0 mg / kg, 8.0 mg / kg, 9.0 mg / kg, or 10.0 mg / kg); and / or 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 to 1000 mg; and / or the concentration of the dose administered per application is selected from 0.1 to 50 mg / ml.

19. The use according to any one of claims 1-18, wherein the dosing cycle of the anti-Her2 antibody drug conjugate is 14-42 days; and / or the dosing frequency is 1-20 times over a period of 1-4 weeks; or once a week, once every 2 weeks, once every 3 weeks, or once every 4 weeks; and / or, based on the subject's weight, the dose of the anti-Her2 antibody drug conjugate per administration is selected from 0.1-20 mg / kg, or a dose of 0.1-10 mg / kg, 0.2-8 mg / kg, 0.3-6 mg / kg, or 0.5 mg / kg, 1.0 mg / kg, etc. The dosage of the anti-Her2 antibody or its antigen-binding fragment (e.g., a single dose or a unit dose) is selected from 0.1 to 1000 mg; and / or the concentration of each administration is selected from 0.1 to 50 mg / ml.

20. The use as described in any one of claims 1-19, wherein the administration period of the anti-Her2 antibody or its antigen-binding fragment is 14-42 days; and / or the administration frequency is 1-20 times over a period of 1-4 weeks; or once a week, twice a week, once every 2 weeks, or once every 3 weeks; and / or, based on the subject's weight, the dose of the anti-Her2 antibody or its antigen-binding fragment administered per dose is selected from 0.1-20 mg / kg, or selected from 0.1-10 mg / kg, or a dose of 0.1-8 mg / kg, 0.2-6 mg / kg, 0.5-5 mg / kg, or 0.5 mg / kg. The dosage of anti-Her2 antibody or its antigen-binding fragment (e.g., single-dose dose or unit dose) is selected from 0.1 to 1000 mg; and / or the concentration of each administration is selected from 0.1 to 50 mg / ml.

21. The use according to any one of claims 1-20, wherein the medicament comprises the anti-Trop-2 antibody drug conjugate and the anti-Her2 antibody drug conjugate.

22. The use as described in any one of claims 1-20, wherein the medicament comprises the anti-Trop-2 antibody-drug conjugate and the anti-Her2 antibody or its antigen-binding fragment.

23. The use according to any one of claims 1-20, wherein the medicament comprises the anti-Her2 antibody drug conjugate and the anti-Her2 antibody or its antigen-binding fragment.

24. The use according to any one of claims 1-20, wherein the medicament comprises the anti-Trop-2 antibody drug conjugate, the anti-Her2 antibody drug conjugate, and the anti-Her2 antibody or its antigen-binding fragment.

25. The use as described in any one of claims 1-20, wherein the medicament contains two or more of the anti-Her2 antibody or its antigen-binding fragment.

26. A method for preventing and / or treating a tumor or cancer in a subject, comprising the steps of administering to the subject an effective amount of two or more of an anti-Trop-2 antibody-drug conjugate, an anti-Her2 antibody-drug conjugate, and an anti-Her2 antibody or an antigen-binding fragment thereof, for example comprising the steps of administering to the subject an effective amount of an anti-Trop-2 antibody-drug conjugate and administering an anti-Her2 antibody-drug conjugate, or the steps of administering to the subject an effective amount of an anti-Trop-2 antibody-drug conjugate and administering an anti-Her2 antibody or an antigen-binding fragment thereof, or the steps of administering to the subject an effective amount of an anti-Trop-2 antibody-drug conjugate, administering an anti-Her2 antibody-drug conjugate, and administering an anti-Her2 antibody or an antigen-binding fragment thereof, or the steps of administering to the subject an effective amount of an anti-Her2 antibody-drug conjugate and administering an anti-Her2 antibody or an antigen-binding fragment thereof, or the steps of administering to the subject an effective amount of an anti-Her2 antibody or an antigen-binding fragment thereof; Preferably, the anti-Trop-2 antibody drug conjugate is as defined in any one of claims 2-8 and 17-18, the anti-Her2 antibody drug conjugate is as defined in any one of claims 9-15, 17 and 19, the anti-Her2 antibody or its antigen-binding fragment is as defined in any one of claims 11-14, 17 and 20, and the tumor or cancer is as defined in claim 16; Preferably, the anti-Trop-2 antibody drug conjugate, the anti-Her2 antibody drug conjugate, and / or the anti-Her2 antibody or its antigen-binding fragment are administered simultaneously, separately, sequentially, or in sequence.

27. A kit comprising two or more of the following: an anti-Trop-2 antibody drug conjugate, an anti-Her2 antibody drug conjugate, and an anti-Her2 antibody or an antigen-binding fragment thereof, for example, comprising an anti-Trop-2 antibody drug conjugate and an anti-Her2 antibody drug conjugate, or comprising an anti-Trop-2 antibody drug conjugate and an anti-Her2 antibody or an antigen-binding fragment thereof, or comprising an anti-Trop-2 antibody drug conjugate, an anti-Her2 antibody drug conjugate, and an anti-Her2 antibody or an antigen-binding fragment thereof, or comprising an anti-Her2 antibody drug conjugate and an anti-Her2 antibody or an antigen-binding fragment thereof, or comprising two or more of the following: an anti-Her2 antibody or an antigen-binding fragment thereof; Preferably, the anti-Trop-2 antibody drug conjugate is as defined in any one of claims 2-8 and 17-18, the anti-Her2 antibody drug conjugate is as defined in any one of claims 9-15, 17 and 19, and the anti-Her2 antibody or its antigen-binding fragment is as defined in any one of claims 11-14, 17 and 20; Preferably, the kit is used for the prevention and / or treatment of tumors or cancers in a subject; preferably, the tumors or cancers are as defined in claim 16.

28. A kit comprising: (a) an anti-Trop-2 antibody drug conjugate and an anti-Her2 antibody drug conjugate; (b) an anti-Trop-2 antibody drug conjugate and an anti-Her2 antibody or an antigen-binding fragment thereof; (c) an anti-Her2 antibody drug conjugate and an anti-Her2 antibody or an antigen-binding fragment thereof; (d) one, two or more of an anti-Her2 antibody or an antigen-binding fragment thereof; (e) an anti-Trop-2 antibody drug conjugate; (f) an anti-Her2 antibody drug conjugate; or (g) an anti-Trop-2 antibody drug conjugate, an anti-Her2 antibody drug conjugate and an anti-Her2 antibody or an antigen-binding fragment thereof; and hyaluronic acid degrading enzyme; Preferably, the anti-Trop-2 antibody drug conjugate is as defined in any one of claims 2-8 and 17-18, the anti-Her2 antibody drug conjugate is as defined in any one of claims 9-15, 17 and 19, and the anti-Her2 antibody or its antigen-binding fragment is as defined in any one of claims 11-14, 17 and 20; Preferably, the hyaluronic acid degrading enzyme is a soluble hyaluronidase, such as soluble PH20, or hyaluronidase (human recombinant) or berahyaluronidase alfa; Preferably, the kit is used for the prevention and / or treatment of tumors or cancers in a subject; preferably, the tumors or cancers are as defined in claim 16.

29. A combination of drugs or a combination of drugs product comprising two or more of the following: an anti-Trop-2 antibody drug conjugate, an anti-Her2 antibody drug conjugate, and an anti-Her2 antibody or an antigen-binding fragment thereof. For example, it may comprise an anti-Trop-2 antibody drug conjugate and an anti-Her2 antibody drug conjugate, or an anti-Trop-2 antibody drug conjugate and an anti-Her2 antibody or an antigen-binding fragment thereof, or an anti-Trop-2 antibody drug conjugate, an anti-Her2 antibody drug conjugate, and an anti-Her2 antibody or an antigen-binding fragment thereof, or an anti-Her2 antibody drug conjugate and an anti-Her2 antibody or an antigen-binding fragment thereof, or two or more of the following: an anti-Her2 antibody or an antigen-binding fragment thereof. Preferably, the anti-Trop-2 antibody drug conjugate is as defined in any one of claims 2-8 and 17-18, the anti-Her2 antibody drug conjugate is as defined in any one of claims 9-15, 17 and 19, and the anti-Her2 antibody or its antigen-binding fragment is as defined in any one of claims 11-14, 17 and 20; Preferably, the drug combination or drug combination product is a pharmaceutical composition; Preferably, the drug combination or drug combination product is used for the prevention and / or treatment of a tumor or cancer in a subject; preferably, the tumor or cancer is as defined in claim 16.

30. A combination of drugs or a combination of drugs comprising: (a) an anti-Trop-2 antibody drug conjugate and an anti-Her2 antibody drug conjugate; (b) an anti-Trop-2 antibody drug conjugate and an anti-Her2 antibody or an antigen-binding fragment thereof; (c) an anti-Her2 antibody drug conjugate and an anti-Her2 antibody or an antigen-binding fragment thereof; (d) one, two or more of an anti-Her2 antibody or an antigen-binding fragment thereof; (e) an anti-Trop-2 antibody drug conjugate; (f) an anti-Her2 antibody drug conjugate; or (g) an anti-Trop-2 antibody drug conjugate, an anti-Her2 antibody drug conjugate and an anti-Her2 antibody or an antigen-binding fragment thereof; and hyaluronidase; Preferably, the anti-Trop-2 antibody drug conjugate is as defined in any one of claims 2-8 and 17-18, the anti-Her2 antibody drug conjugate is as defined in any one of claims 9-15, 17 and 19, and the anti-Her2 antibody or its antigen-binding fragment is as defined in any one of claims 11-14, 17 and 20; Preferably, the hyaluronic acid degrading enzyme is a soluble hyaluronidase, such as soluble PH20, or hyaluronidase (human recombinant) or berahyaluronidase alfa; Preferably, the kit is used for the prevention and / or treatment of tumors or cancers in a subject; preferably, the tumors or cancers are as defined in claim 16.

31. A method for preventing and / or treating a tumor or cancer in a subject, comprising administering to the subject an effective amount of the kit of claim 27 or 28, or the combination of drugs or drug combination products of claim 29 or 30, wherein the tumor or cancer is preferably as defined in claim 16.

32. The method of claim 31, wherein, The anti-Trop-2 antibody drug conjugate, the anti-Her2 antibody drug conjugate, and / or the anti-Her2 antibody or its antigen-binding fragment, as well as the hyaluronic acid degrading enzyme, are administered simultaneously, separately, sequentially, or in sequence.

33. The method of claim 31 or 32, wherein, The anti-Trop-2 antibody drug conjugate, the anti-Her2 antibody drug conjugate, and / or the anti-Her2 antibody or its antigen-binding fragment, and the hyaluronic acid degrading enzyme are mixed to form a mixture, and the mixture is administered.

34. The method of any one of claims 26, 31-33, wherein the anti-Trop-2 antibody-drug conjugate is administered in accordance with one or more of the following: (1) The dosing cycle is 14-42 days; (2) The frequency of administration is 1 to 20 times within 1 to 4 weeks; or twice a week, once a week, once every 2 weeks or once every 3 weeks; (3) 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 from 0.5-10 mg / kg, or from 0.5-5 mg / kg, or is 0.5 mg / kg, 1.0 mg / kg, 1.5 mg / kg, 2.0 mg / kg, 2.5 mg / kg, 3.0 mg / kg, 3.5 mg / kg, 4.0 mg / kg, 4.5 mg / kg, 5.0 mg / kg, 6.0 mg / kg, 7.0 mg / kg, 8.0 mg / kg, 9.0 mg / kg or 10.0 mg / kg; (4) 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; (5) The dosage concentration for each application is selected from 0.1-50 mg / ml.

35. The method of any one of claims 26, 31-34, wherein the anti-Her2 antibody-drug conjugate is administered according to one or more of the following: (1) The dosing cycle is 14-42 days; (2) The frequency of administration is 1 to 20 times within 1 to 4 weeks; or once a week, once every 2 weeks, once every 3 weeks, or once every 4 weeks; (3) Based on the subject's weight, the dose of the anti-Her2 antibody-drug conjugate administered each time is selected from 0.1-20 mg / kg, or the dose is 0.1-10 mg / kg, 0.2-8 mg / kg, 0.3-6 mg / kg, or 0.5 mg / kg, 1.0 mg / kg, 1.5 mg / kg, 2.0 mg / kg, 2.5 mg / kg, 3.0 mg / kg, 3.5 mg / kg, 4.0 mg / kg, 4.5 mg / kg, 5.0 mg / kg, 6.0 mg / kg, 7.0 mg / kg, 8.0 mg / kg, 9.0 mg / kg or 10.0 mg / kg; (4) The dosage of the anti-Her2 antibody drug conjugate (e.g., a single-dose dose or a unit dose) is selected from 0.1-1000 mg; (5) The dosage concentration for each application is selected from 0.1-50 mg / ml.

36. The method of any one of claims 26, 31-35, wherein the anti-Her2 antibody or its antigen-binding fragment is administered in accordance with one or more of the following: (1) The dosing cycle is 14-42 days; (2) The frequency of administration is 1 to 20 times within 1 to 4 weeks; or once a week, twice a week, once every 2 weeks or once every 3 weeks; (3) Based on the subject's weight, the dose of the anti-Her2 antibody or its antigen-binding fragment administered each time is selected from 0.1-20 mg / kg, or selected from 0.1-10 mg / kg, or the dose is 0.1-8 mg / kg, 0.2-6 mg / kg, 0.5-5 mg / kg, or 0.5 mg / kg, 1.0 mg / kg, 1.5 mg / kg, 2.0 mg / kg, 2.5 mg / kg, 3.0 mg / kg, 3.5 mg / kg, 4.0 mg / kg, 4.5 mg / kg, 5.0 mg / kg, 6.0 mg / kg, 7.0 mg / kg, 8.0 mg / kg, 9.0 mg / kg or 10.0 mg / kg; (4) The dose of the anti-Her2 antibody or its antigen-binding fragment (e.g., a single-dose dose or a unit dose) is selected from 0.1-1000 mg; (5) The dosage concentration for each application is selected from 0.1-50 mg / ml.

37. Use of anti-Trop-2 antibody drug conjugates and optionally hyaluronic acid degrading enzymes in the preparation of medicaments for the prevention and / or treatment of tumors or cancers in subjects, in combination with anti-Her2 antibody drug conjugates and / or anti-Her2 antibodies or their antigen-binding fragments, or in the preparation of medicaments for the treatment of tumors or cancers to enhance the efficacy of anti-Her2 antibody drug conjugates and / or anti-Her2 antibodies or their antigen-binding fragments. Preferably, the anti-Trop-2 antibody drug conjugate is as defined in any one of claims 2-8 and 17-18, the anti-Her2 antibody drug conjugate is as defined in any one of claims 9-15, 17 and 19, and the anti-Her2 antibody or its antigen-binding fragment is as defined in any one of claims 11-14, 17 and 20; Preferably, the hyaluronic acid degrading enzyme is a soluble hyaluronidase, such as soluble PH20, or hyaluronidase (human recombinant) or berahyaluronidase alfa; Preferably, the tumor or cancer is as defined in claim 16.

38. Use of anti-Her2 antibody drug conjugates and optionally hyaluronic acid degrading enzymes in the preparation of medicaments for the prevention and / or treatment of tumors or cancers in subjects, in combination with anti-Trop-2 antibody drug conjugates and / or anti-Her2 antibodies or their antigen-binding fragments, or in the preparation of medicaments for the treatment of tumors or cancers to enhance the efficacy of anti-Trop-2 antibody drug conjugates and / or anti-Her2 antibodies or their antigen-binding fragments. Preferably, the anti-Trop-2 antibody drug conjugate is as defined in any one of claims 2-8 and 17-18, the anti-Her2 antibody drug conjugate is as defined in any one of claims 9-15, 17 and 19, and the anti-Her2 antibody or its antigen-binding fragment is as defined in any one of claims 11-14, 17 and 20; Preferably, the hyaluronic acid degrading enzyme is a soluble hyaluronidase, such as soluble PH20, or hyaluronidase (human recombinant) or berahyaluronidase alfa; Preferably, the tumor or cancer is as defined in claim 16.

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