Combination of antibody-drug conjugate and Anti-PD-1 / tim-3 bispecific binding protein

Abstract

A pharmaceutical product for administration of an antibody-drug conjugate in combination with an anti-PD- l / TIM-3 bispecific binding protein is provided. The antibody-drug conjugate is an antibody-drug conjugate in which a drug-linker represented by the following formula (wherein A represents the connecting position to an antibody) is conjugated to an antibody, in particular an anti-TROP2 antibody or an anti-HER2 antibody, via a thioether bond. Also provided is a therapeutic use and method wherein the antibody-drug conjugate and the anti- PD-l / TIM-3 bispecific binding protein are administered in combination to a subject.

Description

[0001] COMBINATION OF ANTIBODY-DRUG CONJUGATE AND ANTI-PD-1 / TIM-3 BISPECIFIC BINDING PROTEIN The present application claims the benefit of priority to U.S. Provisional Application No. 63 / 545,492, filed on 24 October 2023, the content of which is hereby incorporated by reference in its entirety for all purposes. [Technical Field] The present disclosure relates to a pharmaceutical product for administration of a specific antibody-drug conjugate, having an antitumor drug conjugated to an antibody, in particular an anti-TROP2 or anti-HER2 antibody, via a linker structure, in combination with a bispecific binding protein, in particular an anti-PD- 1 / TIM-3 bispecific binding protein, and to a therapeutic use and method wherein the antibody-drug conjugate and the bispecific binding protein are administered in combination to a subject. [Background] Cancer continues to be a major global health burden. Despite progress in immuno-oncology, there continues to be an unmet medical need for effective therapies, especially for those patients with immuno-oncology (IO) acquired resistance. A number of molecular targets have been identified for their potential utility as IO therapeutics against cancer. Some molecular targets that are being investigated for their therapeutic potential in the area of immuno-oncology therapy include cytotoxic T lymphocyte antigen-4 (CTLA-4 or CD152), Programmed Death Ligand 1 (PD-L1 or B7-H1 or CD274), Programmed Death 1 (PD-1), OX40 (CD134 or TNFRSF4) and T-cell inhibitory receptor T- cell immunoglobulin and mucin-domain containing-3 (TIM- 3). However, not all patients respond to immune-therapy and some patients stop responding over time. Reasons for such IO-acquired resistance have eluded researchers. As such, there remains a need to continue to identify candidate targets for immunotherapies, in particular immunotherapies that overcome IO-acquired resistance and enhance patient response above current clinically evaluated immunotherapeutic strategies. In this regard, bispecific binding proteins that bind specifically to two immune checkpoint targets are under development. Examples include the anti-PD-1 / CTLA-4 bispecific antibodies AK104 (cadonilimab) and MEDI5752 (US Patent No. 10,457,732), which comprise a first domain that binds specifically to PD-1 and a second domain that binds specifically to CTLA-4, and the anti-PD-1 / TIM-3 bispecific antibody AZD7789, which comprises a first domain that binds specifically to PD-1 and a second domain that binds specifically to TIM-3. AZD7789 is under clinical development for solid tumors including squamouns and non-squamous non-small cell lung carcinoma. For example, anti-PD-1 / CTLA-4 and anti-PD-1 / TIM-3 bispecific antibodies are disclosed in WO2017 / 193032. AZD7789 is further disclosed in WO2022 / 221245. Antibody-drug conjugates (ADCs), which are composed of a cytotoxic drug conjugated to an antibody, can deliver the drug selectively to and within cancer cells, leading to cancer cell death (Ducry, L., et al., Bioconjugate Chem. (2010) 21, 5-13; Alley, S. C., et al., Current Opinion in Chemical Biology (2010) 14, 529-537; Damle N. K. Expert Opin. Biol. Ther. (2004) 4, 1445-1452; Senter P. D., et al., Nature Biotechnology (2012) 30, 631-637; Burris HA., et al., J. Clin. Oncol. (2011) 29(4): 398-405). One such antibody-drug conjugate is datopotamab deruxtecan (Dato-DXd, DS-1062), which is composed of a TROP2-targeting antibody and a derivative of exatecan. In particular, WO2015 / 098099 and WO2020 / 240467 provide detailed descriptions of exemplary TROP2-targeting antibody-drug conjugates, including datopotamab deruxtecan. Datopotamab deruxtecan has shown clinical efficacy in multiple tumor types, including lung cancer and breast cancer. Another such antibody-drug conjugate is trastuzumab deruxtecan, which is composed of a HER2-targeting antibody and a derivative of exatecan (Ogitani Y. et al., Clinical Cancer Research (2016) 22(20), 5097-5108; Ogitani Y. et al., Cancer Science (2016) 107, 1039-1046). Trastuzumab deruxtecan (Enhertu®, DS-8201) has shown significant clinical efficacy in HER2-expressing solid tumors, including breast cancer, gastric cancer, colorectal cancer and non-small cell lung cancer. Significantly, DS-8201 has demonstrated promising activity in HER2 low tumors in the above indications. References disclosing combined administration of an antibody-drug conjugate and an immune checkpoint inhibitor include Müller P. et al., Science Translational Medicine (2015) 7(315), 315ra188 (trastuzumab emtansine (T-DM1) combined with both anti-CTLA-4 and anti-PD-1 antibodies); and WO2018 / 110515 (trastuzumab deruxtecan (DS-8201) combined with anti-PD-1, anti-PD-L1, anti-CD4 and anti-CD8 antibodies). However, there is a need to identify further combination partners for antibody-drug conjugates, including for anti-TROP2 antibody-drug conjugates such as DS-1062 and for anti-HER2 antibody-drug conjugates such as DS-8201, to enhance their therapeutic potential. Despite the therapeutic potential of antibody-drug conjugates such as DS-8201 and DS-1062 as monotherapy or in combination with a checkpoint inhibitor, and the therapeutic potential of bispecific checkpoint inhibitors, a need remains for improved therapeutic compositions and methods that can enhance efficacy of the existing cancer treating agents, increase durability of therapeutic response, improve tolerance to patients, reduce dose-dependent toxicity, and / or provide an alternative treatment of cancers exhibiting resistance or refractoriness to a previous cancer treatment. More specifically, there remains a need to identify further partnering combinations with antibody-drug conjugates, particularly with anti-TROP2 antibody-drug conjugates such as DS-1062 and with anti-HER2 antibody-drug conjugates such as DS-8201, to enhance their therapeutic potential. Therefore, it is desired to provide a medicine and treatment which can obtain a superior antitumor effect in the treatment of cancers, such as enhanced efficacy, increased durability of therapeutic response and / or reduced dose-dependent toxicity. [Summary of Disclosure] The present disclosure provides a pharmaceutical product which exhibits an excellent antitumor effect in the treatment of cancers, through administration of an antibody-drug conjugate, in particular an anti-TROP2 antibody-drug conjugate or an anti-HER2 antibody-drug conjugate, in combination with an anti-PD-1 / TIM-3 bispecific binding protein. The present disclosure also provides a therapeutic use and method wherein the antibody-drug conjugate and the bispecific binding protein are administered in combination to a subject. Specifically, the present disclosure relates to the following [1] to

[0070] : [1] a pharmaceutical product comprising an antibody-drug conjugate and an anti-PD-1 / TIM-3 bispecific binding protein for administration in combination, wherein the antibody-drug conjugate is an antibody-drug conjugate in which a drug-linker represented by the following formula: wherein A represents the connecting position to an antibody, is conjugated to an anti-TROP2 or anti-HER2 antibody, via a thioether bond; [2] the pharmaceutical product according to [1], wherein the drug-linker is conjugated to an anti-TROP2 antibody; [3] the pharmaceutical product according to [2], wherein the anti-TROP2 antibody is an antibody comprising a heavy chain comprising CDRH1 consisting of an amino acid sequence represented by SEQ ID NO: 3, CDRH2 consisting of an amino acid sequence represented by SEQ ID NO: 4 and CDRH3 consisting of an amino acid sequence represented by SEQ ID NO: 5, and a light chain comprising CDRL1 consisting of an amino acid sequence represented by SEQ ID NO: 6, CDRL2 consisting of an amino acid sequence represented by SEQ ID NO: 7 and CDRL3 consisting of an amino acid sequence represented by SEQ ID NO: 8; [4] the pharmaceutical product according to [3], wherein the anti-TROP2 antibody is an antibody comprising a heavy chain comprising a heavy chain variable region consisting of an amino acid sequence represented by SEQ ID NO: 9 and a light chain comprising a light chain variable region consisting of an amino acid sequence represented by SEQ ID NO: 10; [5] the pharmaceutical product according to [3] or [4], wherein the anti-TROP2 antibody is an antibody comprising a heavy chain consisting of an amino acid sequence represented by SEQ ID NO: 12 and a light chain consisting of an amino acid sequence represented by SEQ ID NO: 13; [6] the pharmaceutical product according to [5], wherein the anti-TROP2 antibody lacks a lysine residue at the carboxyl terminus of the heavy chain; [7] the pharmaceutical product according to any one of [2] to [6], wherein the average number of units of the drug-linker conjugated per antibody molecule in the antibody-drug conjugate is in the range of from 3.5 to 4.5; [8] the pharmaceutical product according to [7], wherein the anti-TROP2 antibody-drug conjugate is datopotamab deruxtecan (DS-1062); [9] the pharmaceutical product according to [1], wherein the drug-linker is conjugated to an anti-HER2 antibody;

[0010] the pharmaceutical product according to [9], wherein the anti-HER2 antibody is an antibody comprising a heavy chain comprising CDRH1 consisting of an amino acid sequence represented by SEQ ID NO: 16, CDRH2 consisting of an amino acid sequence represented by SEQ ID NO: 17 and CDRH3 consisting of an amino acid sequence represented by SEQ ID NO: 18, and a light chain comprising CDRL1 consisting of an amino acid sequence represented by SEQ ID NO: 19, CDRL2 consisting of an amino acid sequence consisting of amino acid residues 1 to 3 of SEQ ID NO: 20 and CDRL3 consisting of an amino acid sequence represented by SEQ ID NO: 21;

[0011] the pharmaceutical product according to

[0010] , wherein the anti-HER2 antibody is an antibody comprising a heavy chain comprising a heavy chain variable region consisting of an amino acid sequence represented by SEQ ID NO: 22 and a light chain comprising a light chain variable region consisting of an amino acid sequence represented by SEQ ID NO: 23;

[0012] the pharmaceutical product according to

[0011] , wherein the anti-HER2 antibody is an antibody comprising a heavy chain consisting of an amino acid sequence represented by SEQ ID NO: 14 and a light chain consisting of an amino acid sequence represented by SEQ ID NO: 15;

[0013] the pharmaceutical product according to

[0011] , wherein the anti-HER2 antibody is an antibody comprising a heavy chain consisting of an amino acid sequence represented by SEQ ID NO: 24 and a light chain consisting of an amino acid sequence represented by SEQ ID NO: 15;

[0014] the pharmaceutical product according to any one of [9] to

[0013] , wherein the average number of units of the drug-linker conjugated per anti-HER2 antibody molecule in the antibody-drug conjugate is in the range of from 7 to 8;

[0015] the pharmaceutical product according to

[0014] , wherein the anti-HER2 antibody-drug conjugate is trastuzumab deruxtecan (DS-8201);

[0016] the pharmaceutical product according to any one of [1] to

[0015] , wherein the anti-PD-1 / TIM-3 bispecific binding protein has a TIM-3 binding domain that nk`^dad^\ggt ]di_n oj oc` @^@^^ \i_ AB gjjkn ja oc` immunoglobulin variable (IgV) domain of TIM-3 (SEQ ID NO: 45);

[0017] the pharmaceutical product according to any one of [1] to

[0016] , wherein the anti-PD-1 / TIM-3 bispecific binding protein has a TIM-3 binding domain that specifically binds to epitopes on the IgV domain of TIM-3 (SEQ ID NO: 45) and the epitopes comprise N12, L47, R52, D53, V54, N55, Y56, W57, W62, L63, N64, G65, D66, F67, R68, K69, D71, T75, and E77;

[0018] the pharmaceutical product according to any one of [1] to

[0017] , wherein the anti-PD-1 / TIM-3 bispecific binding protein has a TIM-3 binding domain that comprises a first set of CDRs: CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 comprising the amino acid sequences of SEQ ID NOs: 35, 36, 37, 38, 39 and 40, or 35, 36, 37, 38, 39 and 45, respectively; and a PD-1 binding domain that comprises a second set of CDRs: CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 comprising the amino acid sequences of SEQ ID NOs: 25, 26, 27, 28, 29, and 30, respectively;

[0019] the pharmaceutical product according to any one of [1] to

[0018] , wherein the anti-PD-1 / TIM-3 bispecific binding protein has a TIM-3 binding domain that comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 41 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 43, and has a PD-1 binding domain that comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 31, and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 33;

[0020] the pharmaceutical product according to any one of [1] to

[0018] , wherein the anti-PD-1 / TIM-3 bispecific binding protein has a TIM-3 binding domain that comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 42 and a light chain comprising the amino acid sequence of SEQ ID NO: 43, and has a PD-1 binding domain that comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 32 and a light chain comprising the amino acid sequence of SEQ ID NO: 34;

[0021] the pharmaceutical product according to any one of [1] to

[0020] , wherein the anti-PD-1 / TIM-3 bispecific binding protein is an antibody;

[0022] the pharmaceutical product according to

[0021] , wherein the antibody is an IgG antibody;

[0023] the pharmaceutical product according to

[0021] , wherein the antibody is an IgG1 antibody;

[0024] the pharmaceutical product according to

[0022] or

[0023] , wherein the antibody is human or humanized;

[0025] the pharmaceutical product according to any one of

[0021] to

[0024] , wherein the bispecific antibody is monovalent;

[0026] the pharmaceutical product according to any one of [1] to

[0025] , wherein the anti-PD-1 / TIM-3 bispecific binding protein is a DuetMab;

[0027] the pharmaceutical product according to any one of [1] to

[0026] , wherein the anti-PD-1 / TIM-3 bispecific binding protein comprises an Fc region that is aglycosylated;

[0028] the pharmaceutical product according to any one of [1] to

[0026] , wherein the anti-PD-1 / TIM-3 bispecific binding protein comprises an Fc region that is deglycosylated;

[0029] the pharmaceutical product according to any one of [1] to

[0026] , wherein the anti-PD-1 / TIM-3 bispecific binding protein comprises an Fc region that has reduced fucosylation or is afucosylated;

[0030] the pharmaceutical product according to any one of [1] to

[0029] , wherein the anti-PD-1 / TIM-3 bispecific binding protein is ^>WA6678^ jm ^sabestomig^;

[0031] the pharmaceutical product according to any one of [1] to

[0030] wherein the product is a composition comprising the antibody-drug conjugate and the anti-PD- 1 / TIM-3 bispecific binding protein, for simultaneous administration;

[0032] the pharmaceutical product according to any one of [1] to

[0030] wherein the product is a combined preparation comprising the antibody-drug conjugate and the anti-PD- 1 / TIM-3 bispecific binding protein, for sequential or separate simultaneous administration;

[0033] the pharmaceutical product according to any one of [1] to

[0032] , wherein the product is for treating cancer;

[0034] the pharmaceutical product according to

[0033] , wherein the cancer is at least one selected from the group consisting of breast cancer, lung cancer, colorectal cancer, gastric cancer, esophageal cancer, head-and-neck cancer, esophagogastric junction adenocarcinoma, biliary tract cancer, Paget's disease, pancreatic cancer, ovarian cancer, uterine carcinosarcoma, urothelial cancer, prostate cancer, bladder cancer, endometrial cancer, gastrointestinal stromal tumor, digestive tract stromal tumor, uterine cervix cancer, squamous cell carcinoma, peritoneal cancer, liver cancer, hepatocellular cancer, corpus uteri carcinoma, kidney cancer, vulval cancer, thyroid cancer, penis cancer, leukemia, malignant lymphoma, plasmacytoma, myeloma, glioblastoma multiforme, osteosarcoma, sarcoma, and melanoma, cervical cancer, uterine cancer, testicular cancer, and renal cell carcinoma;

[0035] the pharmaceutical product according to

[0034] , wherein the cancer is lung cancer;

[0036] the pharmaceutical product according to

[0035] , wherein the lung cancer is non-small cell lung cancer;

[0037] the pharmaceutical product according to

[0034] , wherein the cancer is colorectal cancer;

[0038] the pharmaceutical product according to

[0034] , wherein the cancer is breast cancer;

[0039] the pharmaceutical product according to

[0038] , wherein the breast cancer is HER2 positive breast cancer;

[0040] the pharmaceutical product according to

[0038] , wherein the breast cancer is HER2 low breast cancer;

[0041] the pharmaceutical product according to

[0038] , wherein the breast cancer is triple negative breast cancer;

[0042] the pharmaceutical product according to

[0038] , wherein the breast cancer is hormone receptor (HR)- positive, HER2-negative breast cancer;

[0043] the pharmaceutical product according to

[0034] , wherein the cancer is gastric cancer;

[0044] the pharmaceutical product according to

[0034] , wherein the cancer is pancreatic cancer;

[0045] the pharmaceutical product according to

[0034] , wherein the cancer is ovarian cancer;

[0046] the pharmaceutical product according to

[0034] , wherein the cancer is prostate cancer;

[0047] the pharmaceutical product according to

[0034] , wherein the cancer is kidney cancer;

[0048] the pharmaceutical product according to

[0034] , wherein the cancer is bladder cancer;

[0049] the pharmaceutical product according to

[0034] , wherein the cancer is endometrial cancer;

[0050] the pharmaceutical product according to

[0034] , wherein the cancer is biliary tract cancer;

[0051] an antibody-drug conjugate for use, in combination with an anti-PD-1 / TIM-3 bispecific binding protein, in the treatment of cancer in a subject, wherein the antibody-drug conjugate and the anti-PD-1 / TIM-3 bispecific binding protein are as defined in any one of [1] to

[0030] ;

[0052] the antibody-drug conjugate for the use according to

[0051] , wherein the cancer is as defined in any one of

[0034] to

[0050] ;

[0053] the antibody-drug conjugate for the use according to

[0051] or

[0052] , wherein the use comprises administration of the antibody-drug conjugate and the anti-PD-1 / TIM-3 bispecific binding protein sequentially;

[0054] the antibody-drug conjugate for the use according to

[0051] or

[0052] , wherein the use comprises administration of the antibody-drug conjugate and the anti-PD-1 / TIM-3 bispecific binding protein separately and simultaneously;

[0055] the antibody-drug conjugate for the use according to any one of

[0051] to

[0054] , wherein the anti-PD-1 / TIM-3 bispecific binding protein is to be administered at a dose of about 750 mg or about 1500 mg;

[0056] the antibody-drug conjugate for the use according to

[0055] , wherein the anti-PD-1 / TIM-3 bispecific binding protein is to be administered once per treatment cycle, wherein the treatment cycle is about three weeks;

[0057] the antibody-drug conjugate for the use according to any one of

[0051] to

[0056] , wherein the cancer is non-small cell lung cancer, and wherein the subject is treatment- naïve, or wherein the subject has CPI acquired resistance;

[0058] the antibody-drug conjugate for the use according to

[0057] wherein the subject has any PD-L1 status;

[0059] the antibody-drug conjugate for the use according

[0058] , wherein the subject has a PD-L1 status of 1% to 49%, or wherein the subject has a PD-L1 status of less than 1%;

[0060] the antibody-drug conjugate for the use according to any one of

[0051] to

[0059] , wherein the subject is without actionable genomic alterations;

[0061] a method of treating cancer comprising administering an antibody-drug conjugate and an anti-PD-1 / TIM-3 bispecific binding protein as defined in any one of [1] to

[0030] in combination to a subject in need thereof;

[0062] the method according to

[0061] , wherein the cancer is as defined in any one of

[0034] to

[0050] ;

[0063] the method according to

[0061] or

[0062] , wherein the antibody-drug conjugate and the anti-PD-1 / TIM-3 bispecific binding protein are administered sequentially;

[0064] the method according to

[0061] or

[0062] , wherein the antibody-drug conjugate and the anti-PD-1 / TIM-3 bispecific binding protein are administered separately and simultaneously;

[0065] the method according to any one of

[0061] to

[0064] , wherein the anti-PD-1 / TIM-3 bispecific binding protein is administered at a dose of about 750 mg or about 1500 mg;

[0066] the method according to

[0065] , wherein the anti-PD- 1 / TIM-3 bispecific binding protein is administered once per treatment cycle, wherein the treatment cycle is about three weeks;

[0067] the method according to any one of

[0061] to

[0066] , wherein the cancer is non-small cell lung cancer, and wherein the subject is treatment-naïve, or wherein the subject has CPI acquired resistance;

[0068] the method according to

[0067] wherein the subject has any PD-L1 status;

[0069] the method according

[0068] , wherein the subject has a PD-L1 status of 1% to 49%, or wherein the subject has a PD-L1 status of less than 1%; and

[0070] the method according to any one of

[0061] to

[0069] , wherein the subject is without actionable genomic alterations. [Advantageous Effects of Disclosure] The present disclosure provides a pharmaceutical product comprising a specified antibody-drug conjugate, having an antitumor drug conjugated to an antibody (in particular an anti-TROP2 or anti-HER2 antibody) via a linker structure, and an anti-PD-1 / TIM-3 bispecific binding protein, for administration in combination, and a therapeutic use and method wherein the antibody-drug conjugate and the bispecific binding protein are administered in combination to a subject. Thus, the present disclosure provide a medicine and treatment which can obtain a superior antitumor effect in the treatment of cancers. [Brief Description of Drawings] [anti-TROP2 antibody]: Figure 1 is a diagram showing the amino acid sequence of a heavy chain of an anti-TROP2 antibody (SEQ ID NO: 1). Figure 2 is a diagram showing the amino acid sequence of a light chain of an anti-TROP2 antibody (SEQ ID NO: 2). Figure 3 is a diagram showing the amino acid sequence of a heavy chain CDRH1 (SEQ ID NO: 3 [= amino acid residues 50 to 54 of SEQ ID NO: 1]). Figure 4 is a diagram showing the amino acid sequence of a heavy chain CDRH2 (SEQ ID NO: 4 [= amino acid residues 69 to 85 of SEQ ID NO: 1]). Figure 5 is a diagram showing the amino acid sequence of a heavy chain CDRH3 (SEQ ID NO: 5 [= amino acid residues 118 to 129 of SEQ ID NO: 1]). Figure 6 is a diagram showing the amino acid sequence of a light chain CDRL1 (SEQ ID NO: 6 [= amino acid residues 44 to 54 of SEQ ID NO: 2]). Figure 7 is a diagram showing the amino acid sequence of a light chain CDRL2 (SEQ ID NO: 7 [= amino acid residues 70 to 76 of SEQ ID NO: 2]). Figure 8 is a diagram showing the amino acid sequence of a light chain CDRL3 (SEQ ID NO: 8 [= amino acid residues 109 to 117 of SEQ ID NO: 2]). Figure 9 is a diagram showing the amino acid sequence of a heavy chain variable region (SEQ ID NO: 9 [= amino acid residues 20 to 140 of SEQ ID NO: 1]). Figure 10 is a diagram showing the amino acid sequence of a light chain variable region (SEQ ID NO: 10 [= amino acid residues 21 to 129 of SEQ ID NO: 2]). Figure 11 is a diagram showing the amino acid sequence of a heavy chain (SEQ ID NO: 11 [= amino acid residues 20 to 469 of SEQ ID NO: 1]). [anti-HER2 antibody]: Figure 12 is a diagram showing the amino acid sequence of a heavy chain of an anti-HER2 antibody (SEQ ID NO: 14). Figure 13 is a diagram showing the amino acid sequence of a light chain of an anti-HER2 antibody (SEQ ID NO: 15). Figure 14 is a diagram showing the amino acid sequence of a heavy chain CDRH1 (SEQ ID NO: 16 [= amino acid residues 26 to 33 of SEQ ID NO: 14]). Figure 15 is a diagram showing the amino acid sequence of a heavy chain CDRH2 (SEQ ID NO: 17 [= amino acid residues 51 to 58 of SEQ ID NO: 14]). Figure 16 is a diagram showing the amino acid sequence of a heavy chain CDRH3 (SEQ ID NO: 18 [= amino acid residues 97 to 109 of SEQ ID NO: 14]). Figure 17 is a diagram showing the amino acid sequence of a light chain CDRL1 (SEQ ID NO: 19 [= amino acid residues 27 to 32 of SEQ ID NO: 15]). Figure 18 is a diagram showing an amino acid sequence comprising the amino acid sequence of a light chain CDRL2 (SAS) (SEQ ID NO: 20 [= amino acid residues 50 to 56 of SEQ ID NO: 15]). Figure 19 is a diagram showing the amino acid sequence of a light chain CDRL3 (SEQ ID NO: 21 [= amino acid residues 89 to 97 of SEQ ID NO: 15]). Figure 20 is a diagram showing the amino acid sequence of a heavy chain variable region (SEQ ID NO: 22 [= amino acid residues 1 to 120 of SEQ ID NO: 14]). Figure 21 is a diagram showing the amino acid sequence of a light chain variable region (SEQ ID NO: 23 [= amino acid residues 1 to 107 of SEQ ID NO: 15]). Figure 22 is a diagram showing the amino acid sequence of a heavy chain (SEQ ID NO: 24 [= amino acid residues 1 to 449 of SEQ ID NO: 14]). [anti-PD-1 / TIM-3 bispecific binding protein]: Figure 23 is a diagram showing the amino acid sequence of AZD7789 anti-PD1 heavy chain CDRH1 (SEQ ID NO: 24). Figure 24 is a diagram showing the amino acid sequence of AZD7789 anti-PD1 heavy chain CDRH2 (SEQ ID NO: 26) Figure 25 is a diagram showing the amino acid sequence of AZD7789 anti-PD1 heavy chain CDRH3 (SEQ ID NO: 27). Figure 26 is a diagram showing the amino acid sequence of AZD7789 anti-PD1 light chain CDRL1 (SEQ ID NO: 28). Figure 27 is a diagram showing the amino acid sequence of AZD7789 anti-PD1 light chain CDRL2 (SEQ ID NO: 29). Figure 28 is a diagram showing the amino acid sequence of AZD7789 anti-PD1 light chain CDRL3 (SEQ ID NO: 30). Figure 29 is a diagram showing the amino acid sequence of AZD7789 anti-PD1 heavy chain variable region (SEQ ID NO: 31). Figure 30 is a diagram showing the amino acid sequence of AZD7789 anti-PD1 heavy chain (SEQ ID NO: 32). Figure 31 is a diagram showing the amino acid sequence of AZD7789 anti-PD1 light chain variable region (SEQ ID NO: 33). Figure 32 is a diagram showing the amino acid sequence of AZD7789 anti-PD1 light chain (SEQ ID NO: 34). Figure 33 is a diagram showing the amino acid sequence of AZD7789 anti-TIM-3 heavy chain CDRH1 (SEQ ID NO: 35). Figure 34 is a diagram showing the amino acid sequence of AZD7789 anti-TIM-3 heavy chain CDRH2 (SEQ ID NO: 36). Figure 35 is a diagram showing the amino acid sequence of AZD7789 anti-TIM-3 heavy chain CDRH3 (SEQ ID NO: 37). Figure 36 is a diagram showing the amino acid sequence of AZD7789 anti-TIM-3 heavy chain CDRL1 (SEQ ID NO: 38). Figure 37 is a diagram showing the amino acid sequence of AZD7789 anti-TIM-3 heavy chain CDRL2 (SEQ ID NO: 39). Figure 38 is a diagram showing the amino acid sequence of AZD7789 anti-TIM-3 heavy chain CDRL3 (SEQ ID NO: 40). Figure 39 is a diagram showing the amino acid sequence of AZD7789 anti-TIM-3 heavy chain variable region (SEQ ID NO: 41). Figure 40 is a diagram showing the amino acid sequence of AZD7789 anti-TIM-3 heavy chain (SEQ ID NO: 42). Figure 41 is a diagram showing the amino acid sequence of AZD7789 anti-TIM-3 light chain variable region (SEQ ID NO: 43). Figure 42 is a diagram showing the amino acid sequence of AZD7789 anti-TIM-3 light chain (SEQ ID NO: 44). Figure 43 is a diagram showing the amino acid sequence of human TIM-3 IgV domain (SEQ ID NO: 45). [Experimental]: Figures 44 and 45 represent graphs showing tumor cell cytolytic activities of DS-1062, AZD7789 and their combination, in a tumor-immune cell co-culture model. Figures 46 and 47 represent graphs showing anti-tumor activities of DS-8201, AZD7789 and their combination, in humanized mice. Figure 48 represents graphs showing pharmacodynamic changes associated with DS-8201 alone or in combination with AZD7789, in humanized mice. [Detailed Description] In order that the present disclosure can be more readily understood, certain terms are first defined. Additional definitions are set forth throughout the detailed description. Unless defined otherwise, 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 is related. For example, the Concise Dictionary of Biomedicine and Molecular Biology, Juo, Pei-Show, 2nd ed., 2002, CRC Press; The Dictionary of Cell and Molecular Biology, 3rd ed., 1999, Academic Press; and the Oxford Dictionary Of Biochemistry And Molecular Biology, Revised, 2000, Oxford University Press, provide one of skill with a general dictionary of many of the terms used in this disclosure. Unless otherwise required by context, singular terms shall include pluralities and plural terms shall include the singular. Units, prefixes, and symbols are denoted in their Système International de Unites (SI) accepted form. Numeric ranges are inclusive of the numbers defining the range. It is understood that wherever aspects are described herein with the language "comprising", otherwise analogous aspects described in terms of "consisting of" and / or "consisting essentially of" are also provided. The terms "inhibit" and "inhibition" can refer to a decrease of about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% or 100% in biological activity. Cellular proliferation can be assayed using art recognized techniques which measure rate of cell division, and / or the fraction of cells within a cell population undergoing cell division, and / or rate of cell loss from a cell population due to terminal differentiation or cell death (e.g., thymidine incorporation). The term "subject" refers to any animal (e.g., a mammal), including, but not limited to humans, non-human primates, rodents, and the like, which is to be the recipient of a particular treatment. Typically, the terms "subject" and "patient" are used interchangeably herein in reference to a human subject. The term "pharmaceutical product" refers to a preparation which is in such form as to permit the biological activity of the active ingredients, either as a composition containing all the active ingredients (for simultaneous administration), or as a combination of separate compositions (a combined preparation) each containing at least one but not all of the active ingredients (for administration sequentially or simultaneously), and which contains no additional components which are unacceptably toxic to a subject to which the product would be administered. Such product can be sterile. ?t ^ndhpgo\i`jpn \_hdidnom\odji^ dn h`\io that the active ingredients are administered at the same odh`- ?t ^n`lp`iod\g \_hdidnom\odji^ dn h`\io oc\o oc` active ingredients are administered one after the other, in either order, at a time interval between the individual administrations. The time interval can be, for example, less than 24 hours; in another example, less than 6 hours; in another example, less than 2 hours. Terms such as "treating" or "treatment" or "to treat" or "alleviating" or "to alleviate" refer to both (1) therapeutic measures that cure, slow down, lessen symptoms of, and / or halt progression of a diagnosed pathologic condition or disorder and (2) prophylactic or preventative measures that prevent and / or slow the development of a targeted pathologic condition or disorder. Thus, those in need of treatment include those already with the disorder; those prone to have the disorder; and those in whom the disorder is to be prevented. In certain aspects, a subject is successfully "treated" for cancer according to the methods of the present disclosure if the patient shows, e.g., total, partial, or transient remission of a certain type of cancer. The terms "cancer", "tumor", "cancerous", and "malignant" refer to or describe the physiological condition in mammals that is typically characterized by unregulated cell growth. Examples of cancers include but are not limited to, breast cancer, lung cancer, colorectal cancer, gastric cancer, esophageal cancer, head-and-neck cancer, esophagogastric junction adenocarcinoma, biliary tract cancer, Paget's disease, pancreatic cancer, ovarian cancer, uterine carcinosarcoma, urothelial cancer, prostate cancer, bladder cancer, endometrial cancer, gastrointestinal stromal tumor, digestive tract stromal tumor, uterine cervix cancer, squamous cell carcinoma, peritoneal cancer, liver cancer, hepatocellular cancer, corpus uteri carcinoma, kidney cancer, vulval cancer, thyroid cancer, penis cancer, leukemia, malignant lymphoma, plasmacytoma, myeloma, glioblastoma multiforme, osteosarcoma, sarcoma, melanoma, cervical cancer, uterine cancer, testicular cancer, and renal cell carcinoma. Cancers include hematological malignancies such as acute myeloid leukemia, multiple myeloma, chronic lymphocytic leukemia, _daapn` g\mb` ? ^`gg gthkcjh\+ ?pmfdoo^n gthphoma, follicular lymphoma and solid tumors such as breast cancer, lung cancer, neuroblastoma and colon cancer. The term "cytotoxic drug" as used herein is defined broadly and refers to a substance that inhibits or prevents the function of cells and / or causes destruction of cells (cell death), and / or exerts anti- neoplastic / anti-proliferative effects. For example, a cytotoxic drug prevents directly or indirectly the development, maturation, or spread of neoplastic tumor cells. The term includes agents that cause a cytostatic effect only. The term includes chemotherapeutic agents as specified below. The term "chemotherapeutic agent" is a subset of the term "cytotoxic drug" comprising natural or synthetic chemical compounds. In accordance with the methods or uses of the present disclosure, compounds of the present disclosure may be administered to a patient to promote a positive therapeutic response with respect to cancer. The term "positive therapeutic response" with respect to cancer treatment refers to an improvement in the symptoms associated with the disease. For example, an improvement in the disease can be characterized as a complete response. The term "complete response" refers to an absence of clinically detectable disease with normalization of any previous test results. Alternatively, an improvement in the disease can be categorized as being a partial response. A "positive therapeutic response" encompasses a reduction or inhibition of the progression and / or duration of cancer, the reduction or amelioration of the severity of cancer, and / or the amelioration of one or more symptoms thereof resulting from the administration of compounds of the present disclosure. In specific aspects, such terms refer to one, two or three or more results following the administration of compounds of the instant disclosure: (1) a stabilization, reduction or elimination of the cancer cell population; (2) a stabilization or reduction in cancer growth; (3) an impairment in the formation of cancer; (4) eradication, removal, or control of primary, regional and / or metastatic cancer; (5) a reduction in mortality; (6) an increase in disease-free, relapse-free, progression-free, and / or overall survival, duration, or rate; (7) an increase in the response rate, the durability of response, or number of patients who respond or are in remission; (8) a decrease in hospitalization rate, (9) a decrease in hospitalization lengths, (10) the size of the cancer is maintained and does not increase or increases by less than 10%, or less than 5%, or less than 4%, or less than 2%, and (11) an increase in the number of patients in remission. (12) a decrease in the number of adjuvant therapies (e.g., chemotherapy or hormonal therapy) that would otherwise be required to treat the cancer. Clinical response can be assessed using screening techniques such as PET, magnetic resonance imaging (MRI) scan, x-radiographic imaging, computed tomographic (CT) scan, flow cytometry or fluorescence-activated cell sorter (FACS) analysis, histology, gross pathology, and blood chemistry, including but not limited to changes detectable by ELISA, RIA, chromatography, and the like. In addition to these positive therapeutic responses, the subject undergoing therapy can experience the beneficial effect of an improvement in the symptoms associated with the disease. The term "antibody" as used herein refers to a protein that is capable of recognizing and specifically binding to an antigen. Ordinary or conventional mammalian antibodies comprise a tetramer, which is typically composed of two identical pairs of polypeptide chains, each pair consisting of one "light" chain (typically having a molecular weight of about 25 kDa) and one "heavy" chain (typically having a molecular weight of about 50-70 kDa). The terms "heavy chain" and "light chain", as used herein, refer to any immunoglobulin polypeptide having sufficient variable domain sequence to confer specificity for a target antigen. The amino- terminal portion of each light and heavy chain typically includes a variable domain of about 100 to 110 or more amino acids that typically is responsible for antigen recognition. As pn`_ c`m`di+ oc` o`mhn ^q\md\]g` m`bdji^ jm ^q\md\]g` _jh\di^ \m` pn`_ dio`m^c\ib`\]gt \i_ \m` common in the art. The carboxyl-terminal portion of each chain typically defines a constant domain responsible for effector function. Thus, in a naturally occurring antibody, a full-length heavy chain immunoglobulin polypeptide includes a variable domain (VH) and three constant domains (CH1, CH2, and CH3) and a hinge region between CH1and CH2, wherein the VH domain is at the amino-terminus of the polypeptide and the CH3domain is at the carboxyl-terminus, and a full-length light chain immunoglobulin polypeptide includes a variable domain (VL) and a constant domain (CL), wherein the VLdomain is at the amino-terminus of the polypeptide and the CLdomain is at the carboxyl-terminus. Those of skill in the art, however, would appreciate that the locations of the domains in a naturally occurring antibody can be modified in certain antibody-like binding protein formats without a loss of antigen-binding capability. Classes of human light chains are termed kappa and lambda light chains. Within full-length light and heavy chains, the variable and constant domains typically are joined by a "J" region of about 12 or more amino acids, with the heavy chain also including a "D" region of about 10 more amino acids. The variable regions of each light / heavy chain pair typically form an antigen-binding site. The variable domains of naturally occurring antibodies typically exhibit the same general structure of relatively conserved framework regions (FR) joined by three hypervariable regions, also called complementarity determining regions or CDRs. The CDRs from the two chains of each pair typically are aligned by the framework regions, which may enable binding to a specific epitope. From the amino-terminus to the carboxyl-terminus, both light and heavy chain variable domains typically comprise the domains FR1, CDR1, FR2, CDR2, FR3, CDR3, and FR4. The term "antibody fragment" refers to a portion of an intact or full-length chain or an antibody, generally the target binding or variable region. Examples of antibody fragments include, but are not limited to, Fab, Fab', F(ab')2and Fvfragments. As used herein, the term "functional fragment" is generally synonymous with "antibody fragment", and with respect to antibodies, can refer to antibody fragments such as Fv, Fab, F(ab')2. Reference to the numbering of amino acid residues described herein is performed according to the EU numbering system (also described in Kabat et al, Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD. (1991)). > ^hjij^gji\g^ \iod]j_t jm \iodb`i-binding fragment thereof refers to a homogeneous antibody or antigen- binding fragment population involved in the highly specific binding of a single antigenic determinant, or epitope. This is in contrast to polyclonal antibodies that typically include different antibodies directed against different antigenic determinants. The term ^hjij^gji\g^ \iod]j_t jm \iodb`i-binding fragment thereof encompasses both intact and full-length monoclonal antibodies as well as antibody fragments (such as Fab, C\]^+ C'\]^(1+ Cq(+ ndibg` ^c\di 'n^Cq( hpo\ion+ apndji proteins comprising an antibody portion, and any other modified immunoglobulin molecule comprising an antigen m`^jbidodji ndo`- Cpmoc`mhjm`+ ^hjij^gji\g^ \iod]j_t jm antigen-binding fragment thereof refers to such antibodies and antigen-binding fragments thereof made in manner including but not limited to by hybridoma, phage selection, recombinant expression, and transgenic animals. The term "human antibody", as used herein, includes antibodies having variable and constant regions substantially corresponding to human germline immunoglobulin sequences. In some aspects, human antibodies are produced in non-human mammals, including, but not limited to, rodents, such as mice and rats, and lagomorphs, such as rabbits. In other aspects, human antibodies are produced in hybridoma cells. In still other aspects, human antibodies are produced recombinantly. In some aspects, the bispecific binding protein is a human or humanized antibody. The term "antigen" or "target antigen" as used herein refers to a molecule or a portion of a molecule that is capable of being recognized by and bound by binding proteins of the disclosure. The target antigen is capable of being used in an animal to produce antibodies capable of binding to an epitope of that antigen. A target antigen may have one or more epitopes. The term "epitope" as used herein refers to a localized region or structural element of an antigen that is recognized and bound by a binding protein, such as an antibody or antigen-binding fragment thereof, of the disclosure. More precisely, the epitope is the specific structure that is bound by the CDRs of the binding protein. Epitopes can comprise protein structural elements, carbohydrates or even portions of lipid structures found in membranes. A binding protein is said to specifically bind an antigen when it preferentially recognizes its antigen target in a complex mixture of proteins and / or macromolecules. The term "specifically binds" refers to a binding protein that specifically binds to a molecule or a fragment thereof (e.g., antigen). A binding protein that specifically binds a molecule or a fragment thereof may bind to other molecules with lower affinity as determined by, for example, immunoassays, BIAcore, or other assays known in the art. In particular, antibodies or fragments that specifically bind to at least one molecule or a fragment thereof can compete off molecules that bind non- specifically. The present disclosure specifically encompasses antibodies with multiple specificities (e.g., an antibody with specificity for two or more discrete antigens. For example, a bispecific binding protein can bind to two adjacent epitopes on a single target antigen, or can bind to two different antigens. The term "antigen binding site" as used herein refers to a site created on the surface of a binding protein of the disclosure where an antigen or an epitope on an antigen is bound. The antigen binding site of the binding protein is typically described by reference to the loop structures created by complementarity determining regions (CDRs) of the binding protein. Qc` o`mh ^^cdh`md^^ \iod]j_d`n jm \iodb`i-binding fragments thereof refers to antibodies or antigen-binding fragments thereof wherein the amino acid sequence is derived from two or more species. Typically, the variable region of both light and heavy chains corresponds to the variable region of antibodies or antigen-binding fragments thereof derived from one species of mammals (e.g. mouse, rat, rabbit, etc.) with the desired specificity, affinity, and capability while the constant regions are homologous to the sequences in antibodies or antigen-binding fragments thereof derived from another (usually human) to avoid eliciting an immune response in that species. Qc` o`mh ^cph\idu`_^ \iod]j_t jm \iodb`i-binding fragment thereof refers to forms of non-human (e.g. murine) antibodies or antigen-binding fragments that are specific immunoglobulin chains, chimeric immunoglobulins, or fragments thereof that contain minimal non-human (e.g., murine) sequences. Typically, humanized antibodies or antigen-binding fragments thereof are human immunoglobulins in which residues from the complementary determining region (CDR) are replaced by residues from the CDR of a non-human species (e.g. mouse, rat, rabbit, hamster) that have the desired specificity, affinity, and ^\k\]dgdot '^@AO bm\ao`_^( 'Gji`n `o \g-+ K\opm` 2109411- 525 (1986); Riechmann et al., Nature 332:323-327 (1988); Verhoeyen et al., Science 239:1534-1536 (1988)). In some instances, certain Fv framework region (FR) residues of a human immunoglobulin are replaced with the corresponding residues in an antibody or fragment from a non-human species that has the desired specificity, affinity, and capability. The humanized antibody or antigen-binding fragment thereof can be further modified by the substitution of additional residues either in the Fv framework region and / or within the non-human CDR residues to refine and optimize antibody or antigen-binding fragment thereof specificity, affinity, and / or capability. In general, the humanized antibody or antigen-binding fragment thereof will comprise variable domains containing all or substantially all of the CDR regions that correspond to the non-human immunoglobulin whereas all or substantially all of the FR regions are those of a human immunoglobulin consensus sequence. The humanized antibody or antigen-binding fragment thereof can also comprise at least a portion of an immunoglobulin constant region or domain (Fc), typically that of a human immunoglobulin. Examples of methods used to generate humanized antibodies are described in U.S. Pat. 5,225,539; Roguska et al., Proc. Natl. Acad. Sci., USA, 91(3):969-973 (1994), and Roguska et al., Protein Eng. 9(10):895-904 (1996). In some aspects of the present _dn^gjnpm`+ \ ^cph\idu`_ \iod]j_t^ dn \ m`npma\^`_ antibody. Qc` o`mh ^cph\i^ \iod]j_t jm \iodb`i-binding fragment thereof means an antibody or antigen-binding fragment thereof having an amino acid sequence derived from a human immunoglobulin gene locus, where such antibody or antigen-binding fragment is made using any technique known in the art. This definition of a human antibody or antigen-binding fragment thereof includes intact or full-length antibodies and fragments thereof. ^?di_dib \aadidot^ b`i`m\ggt m`a`mn oj oc` nom`iboc ja the sum total of non-covalent interactions between a single binding site of a molecule (e.g., an antibody or antigen-binding fragment thereof) and its binding partner (e.g., an antigen). Unless indicated otherwise, as used c`m`di+ ^]di_dib \aadidot^ m`a`mn oj diomdind^ ]di_dib affinity which reflects a 1:1 interaction between members of a binding pair (e.g., antibody or antigen-binding fragment thereof and antigen). The affinity of a molecule X for its partner Y can generally be represented by the dissociation constant (KD). Affinity can be measured and / or expressed using techniques known in the art, including, but not limited to, equilibrium dissociation constant (KD), and equilibrium association constant (KA). The KD is calculated from the quotient of koff / kon, whereas KA is calculated from the quotient of koff / kon. Konrefers to the association rate constant of, e.g., an antibody or antigen-binding fragment thereof to an antigen, and koffrefers to the dissociation of, e.g., an antibody or antigen-binding fragment thereof from an antigen. The konand koffcan be determined by techniques known to one of ordinary skill in the art, such as BIAcore® or KinExA. An epitope can be, for example, contiguous amino acids of a polypeptide (linear or contiguous epitope) or an epitope can, for example, come together from two or more non-contiguous regions of a polypeptide or polypeptides (conformational, non-linear, discontinuous, or non-contiguous epitope). In some aspects of the present disclosure, the epitope to which an antibody or antigen-binding fragment thereof specifically binds can be determined by, e.g., NMR spectroscopy, X-ray diffraction crystallography studies, ELISA assays, hydrogen / deuterium exchange coupled with mass spectrometry (e.g., liquid chromatography electrospray mass spectrometry), array-based oligo-peptide scanning assays, and / or mutagenesis mapping (e.g., site-directed mutagenesis mapping). For X-ray crystallography, crystallization can be accomplished using any of the known methods in the art (e.g., Giegé R et al., (1994) Acta Crystallogr D Biol Crystallogr 50(Pt 4): 339-350; McPherson A (1990) Eur J Biochem 189: 1-23; Chayen NE (1997) Structure 5: 1269-1274; McPherson A (1976) J Biol Chem 251: 6300-6303). Antibody / antigen-binding fragment thereof:antigen crystals can be studied using well known X-ray diffraction techniques and can be refined using computer software such as X-PLOR (Yale University, 1992, distributed by Molecular Simulations, Inc.; see, e.g., Meth Enzymol (1985) volumes 114 & 115, eds Wyckoff HW et al.,; U.S. 2004 / 0014194), and BUSTER (Bricogne G (1993) Acta Crystallogr D Biol Crystallogr 49(Pt 1): 37-60; Bricogne G (1997) Meth Enzymol 276A: 361-423, ed Carter CW; Roversi P et al., (2000) Acta Crystallogr D Biol Crystallogr 56(Pt 10): 1316-1323). Mutagenesis mapping studies can be accomplished using any method known to one of skill in the art. See, e.g., Champe M et al., (1995) J Biol Chem 270: 1388-1394 and Cunningham BC & Wells JA (1989) Science 244: 1081-1085 for a description of mutagenesis techniques, including alanine scanning mutagenesis techniques. >i \iod]j_t oc\o ^]di_n oj oc` n\h` `kdojk`^ \n \ reference antibody refers to an antibody that binds to the same amino acid residues as the reference antibody. The ability of an antibody to bind to the same epitope as a reference antibody can determined by a hydrogen / deuterium exchange assay (see Coales et al. Rapid Commun. Mass Spectrom. 2009; 23: 639^647) or x-ray crystallography. >i \iod]j_t dn n\d_ oj ^^jhk`ododq`gt dicd]do^ jm ^^mjnn ^jhk`o`^ rdoc ]di_dib ja \ m`a`m`i^` \iod]j_t oj \ given epitope if it preferentially binds to that epitope or an overlapping epitope to the extent that it blocks, to some degree, binding of the reference antibody to the epitope. Competitive inhibition can be determined by any method known in the art, for example, competition ELISA assays. An antibody can be said to competitively inhibit binding of the reference antibody to a given epitope by at least 90%, at least 80%, at least 70%, at least 60%, or at least 50%. A polypeptide, antibody, polynucleotide, vector, ^`gg+ jm ^jhkjndodji rcd^c dn ^dnjg\o`_^ dn \ polypeptide, antibody, polynucleotide, vector, cell, or composition which is in a form not found in nature. Isolated polypeptides, antibodies, polynucleotides, vectors, cell or compositions include those which have been purified to a degree that they are no longer in a form in which they are found in nature. In some aspects of the present disclosure, an antibody, polynucleotide, vector, cell, or composition which is isolated is np]no\iod\ggt kpm`- >n pn`_ c`m`di+ ^np]no\iod\ggt kpm`^ refers to material which is at least 50% pure (i.e., free from contaminants), at least 90% pure, at least 95% pure, at least 98% pure, or at least 99% pure. Qc` o`mhn ^kjgtk`kod_`+^ ^k`kod_`+^ \i_ ^kmjo`di^ are used interchangeably herein to refer to polymers of amino acids of any length. The polymer can be linear or branched, it can comprise modified amino acids, and it can be interrupted by non-amino acids. The terms also encompass an amino acid polymer that has been modified naturally or by intervention; for example, disulfide bond formation, glycosylation, lipidation, acetylation, phosphorylation, or any other manipulation or modification, such as conjugation with a labeling component. Also included within the definition are, for example, polypeptides containing one or more analogs of an amino acid (including, for example, unnatural amino acids, etc.), as well as other modifications known in the art. It is understood that, because the polypeptides of this disclosure are based upon antibodies, in some aspects of the present disclosure, the polypeptides can occur as single chains or associated chains. [Description of Embodiments] Hereinafter, specific modes for carrying out the present disclosure are described. The embodiments described below are given merely for illustrating one example of a typical embodiment of the present disclosure and are not intended to limit the scope of the present disclosure. 1. Antibody-drug conjugate The antibody-drug conjugate used in the present disclosure is an antibody-drug conjugate in which a drug- linker represented by the following formula: wherein A represents the connecting position to an antibody, is conjugated to an antibody, in particular an anti-TROP2 or anti-HER2 antibody, via a thioether bond. In the present disclosure, the partial structure consisting of a linker and a drug in the antibody-drug conjugate is referred to as a "drug-linker". The drug- linker is connected to a thiol group (in other words, the sulfur atom of a cysteine residue) formed at an interchain disulfide bond site (two sites between heavy chains, and two sites between a heavy chain and a light chain) in the antibody. The drug-linker of the present disclosure includes exatecan (IUPAC name: (1S,9S)-1-amino-9-ethyl-5-fluoro- 1,2,3,9,12,15-hexahydro-9-hydroxy-4-methyl-10H,13H- benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin- 10,13-dione, (also expressed as chemical name: (1S,9S)-1- amino-9-ethyl-5-fluoro-2,3-dihydro-9-hydroxy-4-methyl- 1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2- b]quinolin-10,13(9H,15H)-dione)), which is a topoisomerase I inhibitor, as a component. Exatecan is a camptothecin derivative having an antitumor effect, represented by the following formula: The antibody-drug conjugate used in the present disclosure can be also represented by the following formula: Here, the drug-linker is conjugated to an antibody '^>iod]j_t-^(+ in particular an anti-TROP2 or anti-HER2 antibody, via a thioether bond. The meaning of n is the same as that of what is called the average number of conjugated drug molecules (DAR; Drug-to-Antibody Ratio), and indicates the average number of units of the drug- linker conjugated per antibody molecule. After migrating into cancer cells, the antibody-drug conjugate used in the present disclosure is cleaved at the linker portion to release a compound represented by the following formula: 2. Antibody in antibody-drug conjugate The antibody in the antibody-drug conjugate used in the present disclosure is an anti-TROP2 or anti-HER2 antibody, and may be derived from any species, for example, from a human, a rat, a mouse, or a rabbit. In cases when the antibody is derived from species other than human species, it is, for example, chimerized or humanized using a well-known technique. The antibody may be a polyclonal antibody or a monoclonal antibody and is, for example, a monoclonal antibody. The antibody in the antibody-drug conjugate used in the present disclosure is an antibody, for example, having a characteristic of being capable of targeting cancer cells, and is, for example, an antibody possessing, for example, a property of recognizing a cancer cell, a property of binding to a cancer cell, a property of internalizing in a cancer cell, and / or cytocidal activity against cancer cells. The binding activity of the antibody against cancer cells can be confirmed using flow cytometry. The internalization of the antibody into cancer cells can be confirmed using (1) an assay of visualizing an antibody incorporated in cells under a fluorescence microscope using a secondary antibody (fluorescently labeled) binding to the therapeutic antibody (Cell Death and Differentiation (2008) 15, 751-761), (2) an assay of measuring a fluorescence intensity incorporated in cells using a secondary antibody (fluorescently labeled) binding to the therapeutic antibody (Molecular Biology of the Cell, Vol. 15, 5268-5282, December 2004), or (3) a Mab-ZAP assay using an immunotoxin binding to the therapeutic antibody wherein the toxin is released upon incorporation into cells to inhibit cell growth (Bio Techniques 28: 162-165, January 2000). As the immunotoxin, a recombinant complex protein of a diphtheria toxin catalytic domain and protein G may be used. The antitumor activity of the antibody can be confirmed in vitro by determining inhibitory activity against cell growth. For example, a cancer cell line overexpressing a target protein for the antibody is cultured, and the antibody is added at varying concentrations into the culture system to determine inhibitory activity against focus formation, colony formation, and spheroid growth. The antitumor activity can be confirmed in vivo, for example, by administering the antibody to a nude mouse with a transplanted cancer cell line highly expressing the target protein, and determining change in the cancer cell. Since the compound conjugated in the antibody-drug conjugate exerts an antitumor effect, in one embodiment, the antibody itself should have an antitumor effect. For the purpose of specifically and selectively exerting the cytotoxic activity of the antitumor compound against cancer cells, in one embodiment, the antibody should have the property of internalizing to migrate into cancer cells. The anti-TROP2 or anti-HER2 antibody in the antibody-drug conjugate used in the present disclosure can be obtained by a procedure known in the art. For example, the antibody of the present disclosure can be obtained using a method routinely carried out in the art, which involves immunizing animals with an antigenic polypeptide and collecting and purifying antibodies produced in vivo. The origin of the antigen is not limited to humans, and the animals may be immunized with an antigen derived from a non-human animal such as a mouse, a rat and the like. In this case, the cross- reactivity of antibodies binding to the obtained heterologous antigen with human antigens can be tested to screen for an antibody applicable to a human disease. Alternatively, antibody-producing cells which produce antibodies against the antigen are fused with myeloma cells according to a method known in the art (e.g., Kohler and Milstein, Nature (1975) 256, p. 495- 497; and Kennet, R. ed., Monoclonal Antibodies, p. 365- 367, Plenum Press, N.Y. (1980)) to establish hybridomas, from which monoclonal antibodies can in turn be obtained. The antigen can be obtained by genetically engineering host cells to produce a gene encoding the antigenic protein. Specifically, vectors that permit expression of the antigen gene are prepared and transferred to host cells so that the gene is expressed. The antigen thus expressed can be purified. The antibody can also be obtained by a method of immunizing animals with the above-described genetically engineered antigen- expressing cells or a cell line expressing the antigen. The anti-TROP2 or anti-HER2 antibody in the antibody-drug conjugate used the present disclosure is, for example, a recombinant antibody obtained by artificial modification for the purpose of decreasing heterologous antigenicity to humans such as a chimeric antibody or a humanized antibody, or is, for example, an antibody having only the gene sequence of an antibody derived from a human, that is, a human antibody. These antibodies can be produced using a known method. As the chimeric antibody, an antibody in which antibody variable and constant regions are derived from different species, for example, a chimeric antibody in which a mouse- or rat-derived antibody variable region is connected to a human-derived antibody constant region can be exemplified (Proc. Natl. Acad. Sci. USA, 81, 6851- 6855, (1984)). As the humanized antibody, an antibody obtained by integrating only the complementarity determining region (CDR) of a heterologous antibody into a human-derived antibody (Nature (1986) 321, pp. 522-525), and an antibody obtained by grafting a part of the amino acid residues of the framework of a heterologous antibody as well as the CDR sequence of the heterologous antibody to a human antibody by a CDR-grafting method (WO90 / 07861), and an antibody humanized using a gene conversion mutagenesis strategy (U.S. Patent No. 5821337) can be exemplified. As the human antibody, an antibody generated by using a human antibody-producing mouse having a human chromosome fragment including genes of a heavy chain and light chain of a human antibody (see Tomizuka, K. et al., Nature Genetics (1997) 16, p.133-143; Kuroiwa, Y. et. al., Nucl. Acids Res. (1998) 26, p.3447-3448; Yoshida, H. et. al., Animal Cell Technology: Basic and Applied Aspects vol.10, p.69-73 (Kitagawa, Y., Matsuda, T. and Iijima, S. eds.), Kluwer Academic Publishers, 1999; Tomizuka, K. et. al., Proc. Natl. Acad. Sci. USA (2000) 97, p.722-727, etc.) can be exemplified. As an alternative, an antibody obtained by phage display, the antibody being selected from a human antibody library (see Wormstone, I. M. et. al, Investigative Ophthalmology & Visual Science. (2002)43 (7), p.2301-2308; Carmen, S. et. al., Briefings in Functional Genomics and Proteomics (2002), 1(2), p.189-203; Siriwardena, D. et. al., Ophthalmology (2002) 109(3), p.427-431, etc.) can be exemplified. In the antibody in the antibody-drug conjugate used in present disclosure, modified variants of the antibody are also included. The modified variant refers to a variant obtained by subjecting the antibody according to the present disclosure to chemical or biological modification. Examples of the chemically modified variant include variants including a linkage of a chemical moiety to an amino acid skeleton, variants including a linkage of a chemical moiety to an N-linked or O-linked carbohydrate chain, etc. Examples of the biologically modified variant include variants obtained by post-translational modification (such as N-linked or O-linked glycosylation, N- or C-terminal processing, deamidation, isomerization of aspartic acid, or oxidation of methionine), and variants in which a methionine residue has been added to the N terminus by being expressed in a prokaryotic host cell. Further, an antibody labeled so as to enable the detection or isolation of the antibody or an antigen according to the present disclosure, for example, an enzyme-labeled antibody, a fluorescence-labeled antibody, and an affinity-labeled antibody are also included in the meaning of the modified variant. Such a modified variant of the antibody according to the present disclosure is useful for improving the stability and blood retention of the antibody, reducing the antigenicity thereof, detecting or isolating an antibody or an antigen, and so on. Further, by regulating the modification of a glycan which is linked to the antibody according to the present disclosure (glycosylation, defucosylation, etc.), it is possible to enhance antibody-dependent cellular cytotoxic activity. As the technique for regulating the modification of a glycan of antibodies, those disclosed in WO99 / 54342, WO00 / 61739, WO02 / 31140, WO2007 / 133855, WO2013 / 120066, etc. are known. However, the technique is not limited thereto. In the anti-TROP2 or anti-HER2 antibody according to the present disclosure, antibodies in which the modification of a glycan is regulated are also included. It is known that a lysine residue at the carboxyl terminus of the heavy chain of an antibody produced in a cultured mammalian cell is deleted (Journal of Chromatography A, 705: 129-134 (1995)), and it is also known that two amino acid residues (glycine and lysine) at the carboxyl terminus of the heavy chain of an antibody produced in a cultured mammalian cell are deleted and a proline residue newly located at the carboxyl terminus is amidated (Analytical Biochemistry, 360: 75-83 (2007)). However, such deletion and modification of the heavy chain sequence do not affect the antigen-binding affinity and the effector function (the activation of complement, antibody-dependent cellular cytotoxicity, etc.) of the antibody. Therefore, in the anti-TROP2 or anti-HER2 antibody according to the present disclosure, antibodies subjected to such modification and functional fragments of the antibody are also included, and deletion variants in which one or two amino acids have been deleted at the carboxyl terminus of the heavy chain, variants obtained by amidation of deletion variants (for example, a heavy chain in which the carboxyl terminal proline residue has been amidated), and the like are also included. The type of deletion variant having a deletion at the carboxyl terminus of the heavy chain of the antibody according to the present disclosure is not limited to the above variants as long as the antigen-binding affinity and the effector function are conserved. The two heavy chains constituting the antibody according to the present disclosure may be of one type selected from the group consisting of a full- length heavy chain and the above-described deletion variant, or may be of two types in combination selected therefrom. The ratio of the amount of each deletion variant can be affected by the type of cultured mammalian cells which produce the antibody according to the present disclosure and the culture conditions; however, an antibody in which one amino acid residue at the carboxyl terminus has been deleted in both of the two heavy chains in the antibody according to the present disclosure can be exemplified. As isotypes of the anti-TROP2 or anti-HER2 antibody according to the present disclosure, for example, IgG (IgG1, IgG2, IgG3, IgG4) can be exemplified, and IgG1 can be exemplified. In the present disclosure, the term "anti-TROP2 antibody" refers to an antibody which binds specifically to TROP2 (TACSTD2: Tumor-associated calcium signal transducer 2; EGP-1), and, for example, has an activity of internalization in TROP2-expressing cells by binding to TROP2. Examples of the anti-TROP2 antibody include hTINA1- H1L1 (WO2015 / 098099), and datopotamab can be exemplified. In the present disclosure, the term "anti-HER2 antibody" refers to an antibody which specifically binds to HER2 (Human Epidermal Growth Factor Receptor Type 2; ErbB-2), and, for example, has an activity of internalizing in HER2-expressing cells by binding to HER2. Examples of the anti-HER2 antibody include trastuzumab (U.S. Patent No. 5821337) and pertuzumab (WO01 / 00245), and trastuzumab can be exemplified. 3. Production of antibody-drug conjugate A drug-linker intermediate for use in production of the antibody-drug conjugate according to the present disclosure is represented by the following formula: The drug-linker intermediate can be expressed as the chemical name N-[6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1- yl)hexanoyl]glycylglycyl-L-phenylalanyl-N-[(2-{[(1S,9S)- 9-ethyl-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo- 2,3,9,10,13,15-hexahydro-1H,12H- benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1- yl]amino}-2-oxoethoxy)methyl]glycinamide, and can be produced with reference to descriptions in WO2014 / 057687, WO2015 / 098099, WO2019 / 044947 and so on. The antibody-drug conjugate used in the present disclosure can be produced by reacting the above- described drug-linker intermediate and an anti-TROP2 or anti-HER2 antibody having a thiol group (also referred to as a sulfhydryl group). An anti-TROP2 or anti-HER2 antibody having a sulfhydryl group can be obtained by a method well known in the art (Hermanson, G. T, Bioconjugate Techniques, pp. 56-136, pp. 456-493, Academic Press (1996)). For example, by using 0.3 to 3 molar equivalents of a reducing agent such as tris(2-carboxyethyl)phosphine hydrochloride (TCEP) per interchain disulfide within the antibody and reacting with the antibody in a buffer solution containing a chelating agent such as ethylenediamine tetraacetic acid (EDTA), an anti-TROP2 or anti-HER2 antibody having a sulfhydryl group with partially or completely reduced interchain disulfides within the antibody can be obtained. Further, by using 2 to 20 molar equivalents of the drug-linker intermediate per anti-TROP2 or anti-HER2 antibody having a sulfhydryl group, an antibody-drug conjugate in which 2 to 8 drug molecules are conjugated per antibody molecule can be produced. The average number of conjugated drug molecules per anti-TROP2 or anti-HER2 antibody molecule of the antibody-drug conjugate produced can be determined, for example, by a method of calculation based on measurement of UV absorbance for the antibody-drug conjugate and the conjugation precursor thereof at two wavelengths of 280 nm and 370 nm (UV method), or a method of calculation based on quantification through HPLC measurement for fragments obtained by treating the antibody-drug conjugate with a reducing agent (HPLC method). Conjugation between the anti-TROP2 or anti-HER2 antibody and the drug-linker intermediate and calculation of the average number of conjugated drug molecules per antibody molecule of the antibody-drug conjugate can be performed with reference to descriptions in WO2014 / 057687, WO2015 / 098099, WO2017 / 002776, WO2022 / 014698 and so on. In the present disclosure, the term "anti-TROP2 antibody-drug conjugate" refers to an antibody-drug conjugate such that the antibody in the antibody-drug conjugate according to the disclosure is an anti-TROP2 antibody. The anti-TROP2 antibody is, for example, an antibody comprising a heavy chain comprising CDRH1 consisting of an amino acid sequence represented by SEQ ID NO: 3 [= an amino acid sequence consisting of amino acid residues 50 to 54 of SEQ ID NO: 1], CDRH2 consisting of an amino acid sequence represented by SEQ ID NO: 4 [= an amino acid sequence consisting of amino acid residues 69 to 85 of SEQ ID NO: 1], and CDRH3 consisting of an amino acid sequence represented by SEQ ID NO: 5 [= an amino acid sequence consisting of amino acid residues 118 to 129 of SEQ ID NO: 1], and a light chain comprising CDRL1 consisting of an amino acid sequence represented by SEQ ID NO: 6 [= an amino acid sequence consisting of amino acid residues 44 to 54 of SEQ ID NO: 2], CDRL2 consisting of an amino acid sequence represented by SEQ ID NO: 7 [= an amino acid sequence consisting of amino acid residues 70 to 76 of SEQ ID NO: 2], and CDRL3 consisting of an amino acid sequence represented by SEQ ID NO: 8 [= an amino acid sequence consisting of amino acid residues 109 to 117 of SEQ ID NO: 2]. In one embodiment, anti-TROP2 antibody is an antibody comprising a heavy chain comprising a heavy chain variable region consisting of an amino acid sequence represented by SEQ ID NO: 9 [= an amino acid sequence consisting of amino acid residues 20 to 140 of SEQ ID NO: 1], and a light chain comprising a light chain variable region consisting of an amino acid sequence represented by SEQ ID NO: 10 [= an amino acid sequence consisting of amino acid residues 21 to 129 of SEQ ID NO: 2]. In another embodiment, an antibody comprising a heavy chain consisting of an amino acid sequence represented by SEQ ID NO: 12 [= an amino acid sequence consisting of amino acid residues 20 to 470 of SEQ ID NO: 1] and a light chain consisting of an amino acid sequence represented by SEQ ID NO: 13 [= amino acid residues 21 to 234 of SEQ ID NO: 2], or an antibody comprising a heavy chain consisting of an amino acid sequence represented by SEQ ID NO: 11 [= an amino acid sequence consisting of amino acid residues 20 to 469 of SEQ ID NO: 1] and a light chain consisting of an amino acid sequence represented by SEQ ID NO: 13 [= amino acid residues 21 to 234 of SEQ ID NO: 2]. The average number of units of the drug-linker conjugated per antibody molecule in the anti-TROP2 antibody-drug conjugate is 2 to 8, or 3 to 5, or 3.5 to 4.5, or about 4. The anti-TROP2 antibody-drug conjugate can be produced with reference to descriptions in WO2015 / 098099, WO2017 / 002776 and WO2022 / 014698. In certain embodiments, the anti-TROP2 antibody-drug conjugate is datopotamab deruxtecan (DS-1062). In the present disclosure, the term "anti-HER2 antibody-drug conjugate" refers to an antibody-drug conjugate such that the antibody in the antibody-drug conjugate according to the present disclosure is an anti- HER2 antibody. The anti-HER2 antibody is, for example, an antibody comprising a heavy chain comprising CDRH1 consisting of an amino acid sequence consisting of amino acid residues 26 to 33 of SEQ ID NO: 14, CDRH2 consisting of an amino acid sequence consisting of amino acid residues 51 to 58 of SEQ ID NO: 14 and CDRH3 consisting of an amino acid sequence consisting of amino acid residues 97 to 109 of SEQ ID NO: 14, and a light chain comprising CDRL1 consisting of an amino acid sequence consisting of amino acid residues 27 to 32 of SEQ ID NO: 15, CDRL2 consisting of an amino acid sequence consisting of amino acid residues 50 to 52 of SEQ ID NO: 15 and CDRL3 consisting of an amino acid sequence consisting of amino acid residues 89 to 97 of SEQ ID NO: 15, and in another example, an antibody comprising a heavy chain comprising a heavy chain variable region consisting of an amino acid sequence consisting of amino acid residues 1 to 120 of SEQ ID NO: 14 and a light chain comprising a light chain variable region consisting of an amino acid sequence consisting of amino acid residues 1 to 107 of SEQ ID NO: 15, and in another example, an antibody comprising a heavy chain consisting of an amino acid sequence represented by SEQ ID NO: 14 and a light chain consisting of the amino acid sequence represented by SEQ ID NO: 15, or an antibody comprising a heavy chain consisting of amino acid residues 1 to 449 of SEQ ID NO: 14 and a light chain consisting of an amino acid sequence consisting of all amino acid residues 1 to 214 of SEQ ID NO: 15. The average number of units of the drug-linker conjugated per antibody molecule in the anti-HER2 antibody-drug conjugate is 2 to 8, or 3 to 8, or 7 to 8, or 7.5 to 8, or about 8. The anti-HER2 antibody-drug conjugate used in the present disclosure can be produced with reference to descriptions in WO2015 / 115091 and so on. In certain embodiments, the anti-HER2 antibody-drug conjugate is trastuzumab deruxtecan (DS-8201). 4. Anti-PD-1 / TIM-3 bispecific binding protein As used herein, bispecific binding proteins have binding specificities for at least two independent antigens (or targets) or different epitopes within the same antigen. Exemplary bispecific binding proteins may bind to two different epitopes of a target, or may bind two different targets. Other such binding proteins may combine a first target binding site with a second binding site for another target. In some aspects, the binding protein is a bispecific antibody+ oc` o`mh ^]dnk`^dad^ \iod]j_d`n^ m`a`mmdib oj \iod]j_d`n oc\o ]di_ oj orj different epitopes. The epitopes can be on the same target antigen or can be on different target antigens. In some aspects, bispecific antibodies provide synergistic therapeutic effects derived from targeting two antigens simultaneously, with the administration of a single manufactured molecule. In some aspects, the antibodies provided herein are monovalent bispecific antibodies (MBab). The monovalent bispecific antibody scaffolds described herein provide a superior platform for the generation of bispecific antibodies that fulfill all the benefits associated with bispecific antibodies while reducing the potential therapeutic risks mentioned above due to their monovalent nature. Furthermore, the MBabs provided herein are readily expressed, stable, and are likely to have low immunogenicity. As used herein, the term "monovalent bispecific", which may be abbreviated "MBab", refers to bispecific antibodies, where each arm can specifically bind to a different target antigen, and for a given pair of different target antigens (A and B), the MBab can bind to one of each. In certain aspects, monovalent bispecific antibodies can specifically bind to two independent antigens (or targets) or two independent epitopes on the same antigen. Typically, monovalent bispecific antibodies comprise two different variable regions. In some aspects, the binding affinity for the two independent antigens is about the same. In some aspects, the binding affinities for the two independent antigens are different. The bispecific binding protein comprises a first binding domain that specifically binds to PD-1, and a second binding domain that specifically binds to TIM-3. As used herein, the terms ^MA-0^+ ^Mmjbm\hh`_ A`\oc 0^ and ^Mmjbm\hh`_ @`gg A`\oc 0^ \m` pn`_ interchangeably. The complete PD-1 sequence can be found under NCBI Reference Sequence: NG_012110.1. Programmed Death 0 '^MA-0^( dn \i \kkmjsdh\o`gt 20 fA otk` F membrane protein member of the extended CD28 / CTLA-4 family of T cell regulators (see, Ishida, Y. et al. (1992) Induced Expression Of PD-1, A Novel Member Of The Immunoglobulin Gene Superfamily, Upon Programmed Cell A`\oc+^ BJ?L G- 0092776-3895. PD-1 is expressed on activated T cells, B cells, and monocytes (Agata, Y. et \g- '0885( ^Bskm`nndji ja oc` MA-1 Antigen on the Surface ja Podhpg\o`_ Jjpn` Q \i_ ? Ithkcj^to`n+^ Fio- Fhhpijg- 8(5):765-772; Martin-Lmju^j+ K- `o \g- '1 / / 6( ^Ficd]dojmt Costimulation and Anti-Qphjm Fhhpidot+^ P`hdi- @\i^`m Biol. 17(4):288-298). PD-1 is a receptor responsible for down-regulation of the immune system following activation by binding of PDL-1 or PDL-2 (Martin-Orozco, N. et al. '1 / / 6( ^Ficd]dojmt @jnodhpg\odji \i_ >iod-Tumor Fhhpidot+^ P`hdi- @\i^`m ?djg- 06'3(9177-298) and functions as a cell death inducer (Ishida, Y. et al. '0881( ^Fi_p^`_ Bskm`nnion of PD-1, A Novel Member of The Immunoglobulin Gene Superfamily, Upon Programmed Cell A`\oc+^ BJ?L G- 009 2776-3895; Subudhi, S. K. et al. '1 / / 4( ^Qc` ?\g\i^` ja Fhhpi` O`nkjin`n9 @jnodhpg\odji S`mn` @jdicd]dodji+^ G- Jjg`^- J`_- 729 082-202). This process is exploited in many tumors via the over- expression of PD-L1, leading to a suppressed immune response. PD-1 is a well-validated target for immune mediated therapy in oncology, with positive results from clinical trials in the treatment of melanoma and non-small cell lung cancers (NSCLC), among others. Antagonistic inhibition of the PD-1 / PD-L1 interaction increases T-cell activation, enhancing recognition and elimination of tumour cells by the host immune system. The use of anti- PD-1 antibodies to treat infections and tumors and enhance an adaptive immune response has been proposed (see, U.S. Pat. Nos. 7,521,051; 7,563,869; 7,595,048). >n pn`_ c`m`di+ oc` o`mhn ^Q-cell immunoglobulin and mucin domain containing protein-2^ \i_ ^QFJ-2^ \m` pn`_ interchangeably, and include variants, isoforms, species homologs of human TIM-3. TIM-3 is a Type I cell-surface glycoprotein that comprises an N-terminal immunoglobulin (Ig)-like domain, a mucin domain with O-linked glycosylations and with N-linked glycosylations close to the membrane, a single transmembrane domain, and a cytoplasmic region with tyrosine phosphorylation motif(s). TIM-3 is a member of the T cell / transmembrane, immunoglobulin, and mucin (TIM) gene family. The amino acid sequence of the IgV domain of human TIM-3 is: SEVEYRAEVGQNAYLPCFYTPAAPGNLVPVCWGKGACPVFECGNVVLRTDERDVNYW TSRYWLNGDFRKGDVSLTIENVTLADSGIYCCRIQIPGIMNDEKFNLKLVIK (SEQ ID NO: 45). The T-cell inhibitory receptor TIM-3 plays a role in regulating antitumor immunity as it is expressed on IFN-gamma producing CD4+ helper 1 (Th1) and CD8+ T cytotoxic1 (Tc1) T cells. It was initially identified as a T-cell inhibitory receptor, acting as an immune checkpoint receptor that functions specifically to limit the duration and magnitude of Th1 and Tc1 T-cell responses. Further research has identified that the TIM-3 pathway may cooperate with the PD-1 pathway to promote the development of a severe dysfunctional phenotype in CD8+ T cells in cancer. It has also been expressed in regulatory T cells (Treg) in certain cancers. TIM-3 is also expressed on cells of the innate immune system including mouse mast cells, subpopulations of macrophages and dendritic cells (DCs), NK and NKT cells, and human monocytes, and on murine primary bronchial epithelial cell lines. TIM-3 can generate an inhibitory signal resulting in apoptosis of Th1 and Tc1 cells, and can mediate phagocytosis of apoptotic cells and cross- presentation of antigen. The crystal structure of the IgV domain of TIM-3 shows the presence of two anti-parallel ^ nc``on+ rcd^c are tethered by a disulfide bond. Two additional disulfide bonds formed by four non-canonical cysteines no\]dgdu` oc` FbS _jh\di \i_ m`jmd`io \ @@^ gjjk ojr\m_ \ CD gjjk oc`m`]t ajmhdib \ ^^g`ao^ nomp^opm` oc\o dn thought to be involved in ligand binding, and is not ajpi_ di joc`m FbPC h`h]`mn- Fino`\_+ ocdn ^^g`ao^ assembly is the signature structure that is identified in all TIM family proteins including TIM-1 and TIM-4. The engagement of the IgV domain by appropriate ligands has been found to be important for the immune-modulatory role of TIM-3, and instrumental for induction of peripheral tolerance and suppression of anti-tumor immunity. The @^@^ gjjk ja QFJ-3 involves amino acids after beta strand @^ \i_ ]`ajm` ]`o\ nom\i_ @^+ ajm `s\hkge, from amino acids 50 to 54. The DE loop consists of amino acids from 53 oj 62+ rcdg` oc` @@^ gjjk \i_ CD gjjk ^jhkmdn` \hdij acids 35 to 43 and 92 to 99, respectively. TIM-3 has several known ligands, such as galectin-9, phosphatidylserine, CEACAM1 and HMGB1. Galectin-9 is an S-type lectin with two distinct carbohydrate recognition domains joined by a long flexible linker, and has an enhanced affinity for larger poly-N-acetyllactosamine- containing structures. Galectin-9 does not have a signal sequence and is localized in the cytoplasm. However, it can be secreted and exerts its function by binding to glycoproteins on the target cell surface via their carbohydrate chains (Freeman G J et al., Immunol Rev. 2010 Can; 235(1): 172-89). Both human and mouse TIM-3 have been shown to be receptors for phosphatidylserine, based on binding studies, mutagenesis, and a co-crystal structure, and it has been shown that TIM-3-expressing cells bound and / or engulfed apoptotic cells expressing phosphatidylserine. Interaction of TIM-3 with phosphatidylserine does not exclude an interaction with galectin-9 as the binding sites have been found to be on opposite sides of the IgV domain. In view of the involvement the TIM-3 pathway in key immune cell populations that are immunosuppressed in some cancers, it represents an attractive candidate for immuno-oncology therapy. See, Anderson, A. C., Cancer Immunol Res., (2014) 2:393-398; and Ferris, R. L., et al., J Immunol. (2014) 193:1525-1530. >n pn`_ c`m`di+ oc` o`mh ^>WA6678^ m`a`mn oo an anti-TIM-3 / PD-1 bispecific antibody that comprises first heavy chain comprising the amino acid sequence of SEQ ID NO: 42, a first light chain comprising the amino acid sequence of SEQ ID NO: 44 and a second heavy chain comprising the amino acid sequence of SEQ ID NO: 32, and a second light chain comprising the amino acid sequence of SEQ ID NO: 34. AZD7789 is disclosed in US Patent No. 11,279,759, which is incorporated herein by reference in its entirety. AZD7789 is a monovalent bispecific humanized immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that specifically binds TIM-3 and PD-1, and targets a unique TIM-3 epitope. AZD7789 was constructed on the backbone of the DuetMab molecule. The DuetMab design is described in Mazor et al., MAbs. 7(2): 377^389, (2015 Mar-Apr 2015), which is hereby incorporated by reference di don `iodm`ot- Qc` ^Ap`oJ\]+^ _`ndbi di^gp_`n fij]n- into-holes (KIH) technology for heterodimerization of 2 distinct heavy chains and increases the efficiency of cognate heavy and light chain pairing by replacing the native disulfide bond in one of the CH1-CL interfaces with an engineered disulfide bond. AZD7789 includes a knob mutation in the heavy chain comprising a variable region that binds to TIM-3 and the hole mutation in the heavy chain comprising a variable region that binds to PD-1. In some aspects of the present disclosure, the anti- PD-1 / TIM-3 bispecific binding protein has a TIM-3 binding _jh\di oc\o nk`^dad^\ggt ]di_n oj oc` @^@^^ \i_ AB gjjkn of the immunoglobulin variable (IgV) domain of TIM-3. In some aspects of the present disclosure, the anti- PD-1 / TIM-3 bispecific binding protein has a TIM-3 binding domain specifically binds to epitopes on the IgV domain of TIM-3 (SEQ ID NO: 45) and the epitopes comprises N12, L47, R52, D53, V54, N55, Y56, W57, W62, L63, N64, G65, D66, F67, R68, K69, D71, T75, and E77 of TIM-3. In some aspects of the present disclosure, the bispecific binding protein is an anti-PD-1 / TIM-3 bispecific antibody or antigen-binding fragment thereof that specifically binds to human TIM-3 and human PD-1 and comprises the CDRs of the AZD7789 antibody. In some aspects of the present disclosure, the anti- PD-1 / TIM-3 bispecific binding protein has a TIM-3 binding domain that comprises a first set of CDRs: CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 comprising the amino acid sequences of SEQ ID NOs: 35, 36, 37, 38, 39 and 40, or 35, 36, 37, 38, 39 and 45, respectively; and a PD-1 binding domain that comprises a second set of CDRs: CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 comprising the amino acid sequences of SEQ ID NOs: 25, 26, 27, 28, 29, and 30, respectively. In some aspects of the present disclosure, the anti- PD-1 / TIM-3 bispecific binding protein has a TIM-3 binding domain that comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 41 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 43, and a PD-1 binding domain that comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 31, and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 33. In some aspects of the present disclosure, the anti- PD-1 / TIM-3 bispecific binding protein has a TIM-3 binding domain that comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 42 and a light chain comprising the amino acid sequence of SEQ ID NO: 44, and a PD-1 binding domain that comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 32 and a light chain comprising the amino acid sequence of SEQ ID NO: 34. In some aspects of the present disclosure, the anti- PD-1 / TIM-3 bispecific binding protein is an antibody. In some aspects of the present disclosure, the anti- PD-1 / TIM-3 bispecific binding protein is an IgG antibody. In some aspects of the present disclosure, the anti-PD- 1 / TIM-3 bispecific binding protein is an IgG1 antibody. In some aspects of the present disclosure, the anti- PD-1 / TIM-3 bispecific binding protein is a humanized antibody. In some aspects of the present disclosure, the anti- PD-1 / TIM-3 bispecific binding protein is monovalent. In some aspects of the present disclosure, the anti- PD-1 / TIM-3 bispecific binding protein is a DuetMab. In some aspects, the TIM-3 binding protein of the bispecific binding protein comprises an aglycosylated Fc region. In some aspects, the TIM-3 binding protein comprises a deglycosylated Fc region. In some aspects, the TIM-3 binding protein comprises an Fc region which has reduced fucosylation or is afucosylated. In certain embodiments, the anti-PD-1 / TIM-3 bispecific antibody is AZD7789 or sabestomig. Anti-PD-1 / TIM-3 bispecific antibodies including AZD7789 may be produced by methods as disclosed in WO2017 / 193032 and WO2022 / 221245. 5. Combination of antibody-drug conjugate and anti-PD- 1 / TIM-3 bispecific binding protein In a first combination embodiment of the disclosure, the antibody-drug conjugate which is combined with the anti-PD-1 / TIM-3 bispecific binding protein is an antibody-drug conjugate in which the antibody is an anti- TROP2 antibody. In an embodiment of the first combination embodiment described above, the anti-TROP2 antibody comprises a heavy chain comprising CDRH1 consisting of an amino acid sequence represented by SEQ ID NO: 3 [= amino acid residues 50 to 54 of SEQ ID NO: 1], CDRH2 consisting of an amino acid sequence represented by SEQ ID NO: 4 [= amino acid residues 69 to 85 of SEQ ID NO: 1] and CDRH3 consisting of an amino acid sequence represented by SEQ ID NO: 5 [= amino acid residues 118 to 129 of SEQ ID NO: 1], and a light chain comprising CDRL1 consisting of an amino acid sequence represented by SEQ ID NO: 6 [= amino acid residues 44 to 54 of SEQ ID NO: 2], CDRL2 consisting of an amino acid sequence represented by SEQ ID NO: 7 [= amino acid residues 70 to 76 of SEQ ID NO: 2] and CDRL3 consisting of an amino acid sequence represented by SEQ ID NO: 8 [= amino acid residues 109 to 117 of SEQ ID NO: 2]. In another embodiment of the first combination embodiment described above, the anti-TROP2 antibody comprises a heavy chain comprising a heavy chain variable region consisting of an amino acid sequence represented by SEQ ID NO: 9 [= amino acid residues 20 to 140 of SEQ ID NO: 1] and a light chain comprising a light chain variable region consisting of an amino acid sequence represented by SEQ ID NO: 10 [= amino acid residues 21 to 129 of SEQ ID NO: 2]. In another embodiment of the first combination embodiment described above, the anti-TROP2 antibody comprises a heavy chain consisting of an amino acid sequence represented by SEQ ID NO: 12 [= amino acid residues 20 to 470 of SEQ ID NO: 1] and a light chain consisting of an amino acid sequence represented by SEQ ID NO: 13 [= amino acid residues 21 to 234 of SEQ ID NO: 2]. In another embodiment of the first combination embodiment described above, the anti-TROP2 antibody comprises a heavy chain consisting of an amino acid sequence represented by SEQ ID NO: 11 [= amino acid residues 20 to 469 of SEQ ID NO: 1] and a light chain consisting of an amino acid sequence represented by SEQ ID NO: 13 [= amino acid residues 21 to 234 of SEQ ID NO: 2]. In another embodiment of the first combination embodiment described above, the anti-TROP2 antibody is datopotamab deruxtecan (DS-1062). In a second combination embodiment of the disclosure, the antibody-drug conjugate which is combined with the anti-PD-1 / TIM-3 bispecific binding protein is an antibody-drug conjugate in which the antibody is an anti- HER2 antibody. In an embodiment of the second combination embodiment described above, the anti-HER2 antibody comprises a heavy chain comprising CDRH1 consisting of an amino acid sequence represented by SEQ ID NO: 16, CDRH2 consisting of an amino acid sequence represented by SEQ ID NO: 17 and CDRH3 consisting of an amino acid sequence represented by SEQ ID NO: 18, and a light chain comprising CDRL1 consisting of an amino acid sequence represented by SEQ ID NO: 19, CDRL2 consisting of an amino acid sequence consisting of amino acid residues 1 to 3 of SEQ ID NO: 20 and CDRL3 consisting of an amino acid sequence represented by SEQ ID NO: 21. In another embodiment of the second combination embodiment described above, the anti-HER2 antibody comprises a heavy chain comprising a heavy chain variable region consisting of an amino acid sequence represented by SEQ ID NO: 22 and a light chain comprising a light chain variable region consisting of an amino acid sequence represented by SEQ ID NO: 23. In another embodiment of the second combination embodiment described above, the anti-HER2 antibody comprises a heavy chain consisting of an amino acid sequence represented by SEQ ID NO: 14 and a light chain consisting of an amino acid sequence represented by SEQ ID NO: 15. In another embodiment of the second combination embodiment described above, the anti-HER2 antibody comprises a heavy chain consisting of an amino acid sequence represented by SEQ ID NO: 24 and a light chain consisting of an amino acid sequence represented by SEQ ID NO: 15. In another embodiment of the second combination embodiment described above, the anti-HER2 antibody is trastuzumab deruxtecan (DS-8201). In a particular embodiment of the first combination embodiment described above, the anti-TROP2 antibody-drug conjugate is datopotamab deruxtecan (DS-1062) and the anti-PD-1 / TIM-3 bispecific binding protein is AZD7789. In a particular embodiment of the second combination embodiment described above, the anti-HER2 antibody-drug conjugate is trastuzumab deruxtecan (DS-8201) and the anti-PD-1 / TIM-3 bispecific binding protein is AZD7789, also known as Sabestomig. In some aspects of the above combination embodiments, the antibody-drug conjugate and / or the anti- PD-1 / TIM-3 bispecific binding protein are administered in further combination with one or more chemotherapeutic agents. 6. Therapeutic combined use and method Described in the following are a pharmaceutical product and a therapeutic use and method wherein the anti-TROP2 or anti-HER2 antibody-drug conjugate and the anti-PD-1 / TIM-3 bispecific binding protein according to the present disclosure are administered in combination. The pharmaceutical product and therapeutic use and method of the present disclosure may be characterized in that the antibody-drug conjugate and the anti-PD-1 / TIM-3 bispecific binding protein are separately contained as active components in different formulations, and are administered simultaneously or at different times, or characterized in that the antibody-drug conjugate and the anti-PD-1 / TIM-3 bispecific binding protein are contained as active components in a single formulation and administered. In the pharmaceutical product and therapeutic method of the present disclosure, a single anti-PD-1 / TIM-3 bispecific binding protein used in the present disclosure can be administered in combination with the antibody-drug conjugate, or two or more different anti-PD-1 / TIM-3 bispecific binding proteins can be administered in combination with the antibody-drug conjugate. The presence or absence of tumor markers such as TROP2 or HER2 tumor markers can be determined, for example, by collecting tumor tissue from a cancer patient to prepare a formalin-fixed, paraffin-embedded (FFPE) specimen and subjecting the specimen to a test for gene products (proteins), for example, with an immunohistochemical (IHC) method, a flow cytometer, or Western blotting, or to a test for gene transcription, for example, with an in situ hybridization (ISH) method, a quantitative PCR method (q-PCR), or microarray analysis, or by collecting cell-free circulating tumor DNA (ctDNA) from a cancer patient and subjecting the ctDNA to a test with a method such as next-generation sequencing (NGS). The pharmaceutical product and therapeutic method of the present disclosure, when comprising anti-HER2 antibody-drug conjugate, can be used for HER2-expressing cancer, which may be HER2-overexpressing cancer (high or moderate) or may be HER2 low-expressing cancer. In the present disclosure, the term "HER2- overexpressing cancer" is not particularly limited as long as it is recognized as HER2-overexpressing cancer by those skilled in the art. Certain examples of the HER2- overexpressing cancer can include cancer given a score of 3+ for the expression of HER2 in an IHC method, and cancer given a score of 2+ for the expression of HER2 in an IHC method and determined as positive for the expression of HER2 in an in situ hybridization method (ISH). The in situ hybridization method of the present disclosure includes a fluorescence in situ hybridization method (FISH) and a dual color in situ hybridization method (DISH). In the present disclosure, the term "HER2 low- expressing cancer" is not particularly limited as long as it is recognized as HER2 low-expressing cancer by those skilled in the art. Certain examples of the HER2 low- expressing cancer can include cancer given a score of 2+ for the expression of HER2 in an IHC method and determined as negative for the expression of HER2 in an in situ hybridization method, and cancer given a score of 1+ for the expression of HER2 in an IHC method. The method for scoring the degree of HER2 expression by the IHC method, or the method for determining positivity or negativity to HER2 expression by the in situ hybridization method is not particularly limited as long as it is recognized by those skilled in the art. Examples of the method can include a method described in the 4th edition of the guidelines for HER2 testing, breast cancer (developed by the Japanese Pathology Board for Optimal Use of HER2 for Breast Cancer). The cancer, particularly in regard to the treatment of breast cancer, may be HER2-overexpressing (high or moderate) or low-expressing breast cancer, or triple- negative breast cancer, and / or may have a HER2 status score of IHC 3+, IHC 2+, IHC 1+ or IHC >0 and <1+. The pharmaceutical product and therapeutic method of the present disclosure can be used for a mammal, for example for a human. The antitumor effect of the pharmaceutical product and therapeutic method of the present disclosure can be confirmed by transplanting cancer cells to a test subject animal to prepare a model and measuring reduction in tumor volume or life-prolonging effect by application of the pharmaceutical product and therapeutic method of the present disclosure. And then, the effect of combined use of the antibody-drug conjugate used in the present disclosure and a bispecific binding protein can be confirmed by comparing antitumor effect with single administration of the antibody-drug conjugate used in the present disclosure and that of the bispecific binding protein. The antitumor effect of the pharmaceutical product and therapeutic method of the present disclosure can be confirmed in a clinical trial using any of an evaluation method with Response Evaluation Criteria in Solid Tumors (RECIST), a WHO evaluation method, a Macdonald evaluation method, body weight measurement, and other approaches, and can be determined on the basis of indexes of complete response (CR), partial response (PR); progressive disease (PD), objective response rate (ORR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and so on. By using the above methods, the superiority in antitumor effect of the pharmaceutical product and therapeutic method of the present disclosure to existing pharmaceutical products and therapeutic methods for cancer treatment can be confirmed. The pharmaceutical product and therapeutic method of the present disclosure can delay development of cancer cells, inhibit growth thereof, and further kill cancer cells. These effects can allow cancer patients to be free from symptoms caused by cancer or achieve improvement in quality of life (QOL) of cancer patients and attain a therapeutic effect by sustaining the lives of the cancer patients. Even if the pharmaceutical product and therapeutic method of the present disclosure do not accomplish killing cancer cells, they can achieve higher QOL of cancer patients while achieving longer-term survival, by inhibiting or controlling the growth of cancer cells. The pharmaceutical product of the present disclosure can be expected to exert a therapeutic effect by application as systemic therapy to patients, and additionally, by local application to cancer tissues. The pharmaceutical product and therapeutic method of the present disclosure, in another aspect, provides for use as an adjuct in cancer therapy with ionizing radiation or other chemotherapeutic agents. For example, in the treatment of cancer, the treatment may comprise administering to a subject in need of treatment a therapeutically effective amount of the pharmaceutical product, simultaneously or sequentially with ionizing radiation or other chemotherapeutic agents. The pharmaceutical product and therapeutic method of the present disclosure can be used as adjuvant chemotherapy combined with surgery operation. The pharmaceutical product of the present disclosure may be administered for the purpose of reducing tumor size before surgical operation (referred to as preoperative adjuvant chemotherapy or neoadjuvant therapy), or may be administered for the purpose of preventing recurrence of tumor after surgical operation (referred to as postoperative adjuvant chemotherapy or adjuvant therapy). In some embodiments, the cancer cells may have a BRCA1 and / or a BRCA2 deficient phenotype i.e. BRCA1 and / or BRCA2 activity is reduced or abolished in the cancer cells. Cancer cells with this phenotype may be deficient in BRCA1 and / or BRCA2, i.e. expression and / or activity of BRCA1 and / or BRCA2 may be reduced or abolished in the cancer cells, for example by means of mutation or polymorphism in the encoding nucleic acid, or by means of amplification, mutation or polymorphism in a gene encoding a regulatory factor, for example the EMSY gene which encodes a BRCA2 regulatory factor (Hughes- Davies, et al., Cell, 115, 523-535). BRCA1 and BRCA2 are known tumour suppressors whose wild-type alleles are frequently lost in tumours of heterozygous carriers (Jasin M., Oncogene, 21(58), 8981-93 (2002); Tutt, et al., Trends Mol Med., 8 (12), 571-6, (2002)). The association of BRCA1 and / or BRCA2 mutations with breast cancer is well-characterised in the art (Radice, P.J., Exp Clin Cancer Res., 21(3 Suppl), 9-12 (2002)). Amplification of the EMSY gene, which encodes a BRCA2 binding factor, is also known to be associated with breast and ovarian cancer. Carriers of mutations in BRCA1 and / or BRCA2 are also at elevated risk of certain cancers, including breast, ovary, pancreas, prostate, hematological, gastrointestinal and lung cancer. In some embodiments, the individual is heterozygous for one or more variations, such as mutations and polymorphisms, in BRCA1 and / or BRCA2 or a regulator thereof. The detection of variation in BRCA1 and BRCA2 is well-known in the art and is described, for example in EP 699 754, EP 705 903, Neuhausen, S.L. and Ostrander, E.A., Genet. Test, 1, 75- 83 (1992); Chappnis, P.O. and Foulkes, W.O., Cancer Treat Res, 107, 29-59 (2002); Janatova M., et al., Neoplasma, 50(4), 246-505 (2003); Jancarkova, N., Ceska Gynekol., 68{1), 11-6 (2003)). Determination of amplification of the BRCA2 binding factor EMSY is described in Hughes- Davies, et al., Cell, 115, 523-535). Mutations and polymorphisms associated with cancer may be detected at the nucleic acid level by detecting the presence of a variant nucleic acid sequence or at the protein level by detecting the presence of a variant (i.e. a mutant or allelic variant) polypeptide. The pharmaceutical product of the present disclosure can be administered containing at least one pharmaceutically suitable ingredient. Pharmaceutically suitable ingredients can be suitably selected and applied from formulation additives or the like that are generally used in the art, in accordance with the dosage, administration concentration, or the like of the antibody-drug conjugate and the bispecific binding protein used in the present disclosure. The antibody- drug conjugate used in the present disclosure can be administered, for example, as a pharmaceutical product containing a buffer such as histidine buffer, a vehicle such as sucrose and trehalose, and a surfactant such as Polysorbates 80 and 20. The antibody-drug conjugate used in the pharmaceutical product of the present disclosure can be used as an injection, can be, for example, used as an aqueous injection or a lyophilized injection, and can be, for example, used as a lyophilized injection. In the case that the pharmaceutical product containing the antibody-drug conjugate used in the present disclosure is an aqueous injection, the aqueous injection can be diluted with a suitable diluent and then given as an intravenous infusion. Examples of the diluent can include dextrose solution and physiological saline, dextrose solution can be exemplified in one embodiment, and 5% dextrose solution can be exemplified in another embodiment. In the case that the pharmaceutical product of the present disclosure is a lyophilized injection, a required amount of the lyophilized injection dissolved in advance in water for injection can be diluted with a suitable diluent and then given as an intravenous infusion. Examples of the diluent can include dextrose solution and physiological saline, dextrose solution can be exemplified in one embodiment, and 5% dextrose solution can be exemplified in another embodiment. Examples of the administration route applicable to administration of the pharmaceutical product of the present disclosure can include intravenous, intradermal, subcutaneous, intramuscular, and intraperitoneal routes. In one embodiment, the administration route is intravenous. The size of the dose required for the therapeutic treatment of a particular disease state will necessarily be varied depending on the subject treated, the route of administration and the severity of the illness being treated. For further information on routes of administration and dosage regimes, reference may be made to Chapter 25.3 in Volume 5 of Comprehensive Medicinal Chemistry (Corwin Hansch; Chairman of Editorial Board), Pergamon Press 1990. The anti-TROP2 antibody-drug conjugate used in the present disclosure can be administered to a human once at intervals of 1 to 180 days, and can be, for example, administered once a week, once every 2 weeks, once every 3 weeks, or once every 4 weeks, and can be once every 3 weeks in one specific example. Also, the antibody-drug conjugate used in the present disclosure can be administered at a dose of about 0.001 to 100 mg / kg, and can be administered at a dose of 0.8 to 12.4 mg / kg. For example, the anti-TROP2 antibody-drug conjugate can be administered once every 3 weeks at a dose of 0.27 mg / kg, 0.5 mg / kg, 1.0 mg / kg, 2.0 mg / kg, 4.0 mg / kg, 6.0 mg / kg, or 8.0 mg / kg, and can be administered once every 3 weeks at a dose of 4.0 or 6.0 mg / kg in one specific example. The anti-HER2 antibody-drug conjugate used in the present disclosure can be administered to a human with intervals of 1 to 180 days, can be administered with intervals of a week, two weeks, three weeks, or four weeks, and can be administered with intervals of three weeks in one specific example. The anti-HER2 antibody- drug conjugate used in the present disclosure can be administered in a dose of about 0.001 to 100 mg / kg per administration, and can be administered in a dose of 0.8 to 12.4 mg / kg per administration. For example, the anti- HER2 antibody-drug conjugate can be administered once every three weeks at a dose of 0.8 mg / kg, 1.6 mg / kg, 3.2 mg / kg, 5.4 mg / kg, 6.4 mg / kg, 7.4 mg / kg, or 8 mg / kg, and can be administered once every three weeks at a dose of 5.4 mg / kg or 6.4 mg / kg in one specific example. The bispecific binding protein may be administered in a suitable dose by any suitable route of administration. In some aspects, AZD7789 or an antigen-binding fragment thereof is administered to the subject in a dose of about 750 mg or about 1500 mg. In some aspects, the dose for administration is about 1500 mg. In some aspects, the dose for administration is about 750 mg. In some aspects, a dose of AZD7789 or an antigen- binding fragment thereof is administered to the subject once per treatment cycle. In some aspects, a treatment cycle is three weeks. In some aspects, a dose of AZD7789 or an antigen-binding fragment thereof is administered every three weeks for about 12 months, about 24 months, about 36 months, or about 48 months. In some aspects, sabestomig and datopotamab deruxtecan are administered to a subject with non-small cell lung cancer, wherein sabestomig is administered at a dose of 750 mg or 1500 mg. In some aspects, sabestomig and datopotamab deruxtecan are administered to a subject with non-small cell lung cancer, wherein the subject has been previously treated with a checkpoint inhibitor (CPI), or wherein the subject is treatment-naïve, and wherein sabestomig is administered at a dose of 750 mg or 1500 mg. In some aspects, sabestomig and datopotamab deruxtecan are administered to a subject with non-small cell lung cancer, wherein the subject has been previously treated with a checkpoint inhibitor (CPI), and wherein sabestomig is administered at a dose of 750 mg or 1500 mg, and wherein the subject with non-small cell lung cancer has CPI acquired resistance. In some aspects, the CPI acquired resistance is defined as exposure greater than or equal to 4 months on anti-PD-1 / PD-L1 monotherapy (and greater than or equal to 2 cycles) or greater than or equal to 6 months to anti-PD-1 / PD-L1 plus chemotherapy. In some aspects, the subject with non-small cell lung cancer has any PD-L1 status. In some aspects, the subject with non-small cell lung cancer has a PD-L1 status of less than 1%. In some aspects, the subject with non-small cell lung cancer has a PD-L1 status of greater than 1%. In some aspects, the subject with non-small cell lung cancer has a PD-L1 status of greater than or equal to 50%. In some aspects, the subject with non-small cell lung cancer has a PD-L1 status of 1% to 49%. In some aspects, the PD-L1 status is determined by methods known in the art, for example, the Ventana PD-L1 (SP263) assay. In some aspects, the non-small cell lung cancer subject is without actionable genomic alterations (i.e., alterations in genes with approved therapies, such as epidermal growth factor receptor [EGFR], anaplastic lymphoma kinase [ALK], ROS proto-oncogene 1 [ROS1], neurotrophic tyrosine receptor kinase [NTRK], proto- oncogene B raf [BRAF], rearranged during transfection [RET], mesenchymal-epithelial transition factor [MET] or other actionable driver kinases). In some aspects, the bispecific binding protein, antibody or antigen-binding fragment thereof is administered in combination with one or more chemotherapeutic agents. In some aspects, the chemotherapeutic agent is carboplatin. In some aspects, the carboplatin is administered for up to four cycles. In some aspects, the bispecific binding proteins disclosed herein may be formulated with a pharmaceutically acceptable carrier, excipient, or stabilizer, as pharmaceutical compositions. In certain aspects, such pharmaceutical compositions are suitable for administration to a human or non-human animal via any one or more routes of administration using methods known in the art. The term "pharmaceutically acceptable carrier" means one or more non-toxic materials that do not interfere with the effectiveness of the biological activity of the active ingredients. Such preparations may routinely contain salts, buffering agents, preservatives, compatible carriers, and optionally other therapeutic agents. Such pharmaceutically acceptable preparations may also contain compatible solid or liquid fillers, diluents or encapsulating substances which are suitable for administration into a human. Other contemplated carriers, excipients, and / or additives, which may be utilized in the formulations described herein include, for example, flavoring agents, antimicrobial agents, sweeteners, antioxidants, antistatic agents, lipids, protein excipients such as serum albumin, gelatin, casein, salt- forming counterions such as sodium, and the like. These and additional known pharmaceutical carriers, excipients, and / or additives suitable for use in the formulations described herein are known in the art, for example, as listed in "Remington: The Science & Practice of Pharmacy", 2lst ed., Lippincott Williams & Wilkins, (2005), and in the "Physician's Desk Reference", 60th ed., Medical Economics, Montvale, N.J. (2005). Pharmaceutically acceptable carriers can be selected that are suitable for the mode of administration, solubility, and / or stability desired or required. In some aspects, therapeutic compositions can be formulated for particular routes of administration, such as oral, nasal, pulmonary, topical (including buccal and sublingual), rectal, vaginal, and / or parenteral administration. The terms "parenteral administration" and "administered parenterally" as used herein refer to modes of administration other than enteral and topical administration, usually by injection, and includes, without limitation, intravenous, intramuscular, intraarterial, intrathecal, intracapsular, intraorbital, intracardiac, intradermal, intraperitoneal, transtracheal, subcutaneous, subcuticular, intraarticular, subcapsular, subarachnoid, intraspinal, epidural and intrasternal injection, and infusion. Formulations of the disclosure that are suitable for topical or transdermal administration include powders, sprays, ointments, pastes, creams, lotions, gels, solutions, patches, and inhalants. The antibodies and other actives may be mixed under sterile conditions with a pharmaceutically acceptable carrier, and with any preservatives, buffers, or propellants which may be required (see, e.g., U.S. Patent Nos. 7,378,110; 7,258,873; and 7,135,180; U.S. Patent Application Publication Nos. 2004 / 0042972 and 2004 / 0042971). The formulations can be presented in unit dosage form and can be prepared by any method known in the art of pharmacy. Actual dosage levels of the active ingredients in the pharmaceutical compositions of the present disclosure may be varied so as to obtain an amount of the active ingredient which is effective to achieve the desired therapeutic response for a particular patient, composition, and mode of administration, without being toxic to the patient (e.g., "a therapeutically effective amount"). The selected dosage level will depend upon a variety of pharmacokinetic factors including the activity of the particular compositions employed, the route of administration, the time of administration, the rate of excretion of the particular compound being employed, the duration of the treatment, other drugs, compounds and / or materials used in combination with the particular compositions employed, the age, sex, weight, condition, general health and prior medical history of the patient being treated, and like factors well known in the medical arts. These dosages may be administered daily, weekly, biweekly, monthly, or less frequently, for example, biannually, depending on dosage, method of administration, disorder or symptoms to be treated, and individual subject characteristics. Dosages can also be administered via continuous infusion (such as through a pump). The administered dose may also depend on the route of administration. For example, subcutaneous administration may require a higher dosage than intravenous administration. As noted above, any commonly used dosing regimen (e.g., 1-10 mg / kg administered by injection or infusion daily or twice a week) may be adapted and suitable in the methods relating to treating human cancer patients. [Examples] The present disclosure is specifically described in view of the examples shown below. However, the present disclosure is not limited to these. Further, it is by no means to be interpreted in a limited way. Example 1A: Production of anti-TROP2 antibody-drug conjugate (DS-1062) In accordance with a production method described in WO2015 / 098099, WO2017 / 002776 and WO2022 / 014698 and using an anti-TROP2 antibody (an antibody comprising a heavy chain consisting of an amino acid sequence represented by SEQ ID NO: 12 [= amino acid residues 20 to 470 of SEQ ID NO: 1] and a light chain consisting of an amino acid sequence represented by SEQ ID NO: 13 [= amino acid residues 21 to 234 of SEQ ID NO: 2]), an anti-TROP2 antibody-drug conjugate in which a drug-linker represented by the following formula: wherein A represents the connecting position to an antibody, is conjugated to the anti-TROP2 antibody via a thioether bond was produced (DS-1062: datopotamab deruxtecan). The DAR of the antibody-drug conjugate is 4.0. Example 1B: Production of anti-HER2 antibody-drug conjugate (DS-8201) In accordance with a production method described in WO2015 / 115091 and using an anti-HER2 antibody (an antibody comprising a heavy chain consisting of an amino acid sequence represented by SEQ ID NO: 24 (amino acid residues 1 to 449 of SEQ ID NO: 14) and a light chain consisting of an amino acid sequence consisting of all amino acid residues 1 to 214 of SEQ ID NO: 15), an anti- HER2 antibody-drug conjugate in which a drug-linker represented by the following formula: wherein A represents the connecting position to an antibody, is conjugated to the anti-HER2 antibody via a thioether bond was produced (DS-8201: trastuzumab deruxtecan). The DAR of the antibody-drug conjugate is 7.7 or 7.8. Example 2: Production of anti-PD-1 / TIM-3 bispecific antibody (AZD7789) AZD7789, an anti-PD-1 / TIM-3 bispecific antibody, may be produced in accordance with methods disclosed in WO2017 / 193032, WO2022 / 221245 and Mazor et al., MAbs. 7(2): 377^389, (2015 Mar-Apr 2015). Example 3: Antitumor test: In vitro study in tumor- immune cell co-culture model Combination of antibody-drug conjugate DS-1062 with AZD7789. A co-culture assay system was developed which utilized melanoma antigen Melan A (MART-1) reactive T cells and PC9 lung adenocarcinoma cells engineered to express both the MART-1 antigen and Green Fluorescent Protein (GFP). Briefly, PC9-MART1-GFP cells were harvested from cell culture flasks using trypsin, washed once with complete RPMI media, resuspended and added to each well of 96 well clear bottom, opaque walled optical plates for 24 hours at 37°C in 5% CO2\n k`m oc` h\ipa\^opm`m^n dinomp^odjin- The anti-PD-1 / TIM3 bispecific antibody (AZD7789) was used at 10 µg / mL concentration. DS-1062 was used at 10 µg / ml. Treatments were added alone or in combination to wells immediately before rested, antigen-specific CD8+ T cells were added at effector to target (E:T) ratio of 1:1 (effector T cells to target tumor cells). Tumor cell lysis was evaluated utilizing the Sartorius Incucyte Live Cell Analysis System whereby loss of GFP signal intensity was used as a surrogate marker for cell death. Tumor cell death and percent cytolysis were measured 5 days after T cell addition by image analysis of GFP intensity per well. Activities of DS-1062, AZD7789 and their combination in the tumor-immune cell co-culture model are as shown in Figs. 44 and 45. Statistical significance for the indicated comparisons in Fig. 45 is denoted as ** p < 0.01. Results: As seen in Figs. 44 and 45, AZD7789 and DS-1062 enhanced T cell mediated cytolysis of PC9-MART1 tumor cells as monotherapies. The highest degree of tumor cell cytolysis was reached with the combination of AZD7789 and DS-1062. Accordingly, DS-1062 combined with AZD7789 enhanced in vitro T-cell mediated killing of tumor cells in the tumor-immune cell co-culture model. Example 4: A Phase 1b, Multicenter, 2-Part, Open-Label Study of Datopotamab Deruxtecan (Dato-DXd) in Combination with Immunotherapy with or without Carboplatin in Participants with Advanced or Metastatic Non-Small Cell Lung Cancer (Tropion-Lung04). Study Population: Participants with advanced or metastatic non-small cell lung cancer (NSCLC) without actionable genomic alterations (i.e., alterations in genes with approved therapies, such as epidermal growth factor receptor [EGFR], anaplastic lymphoma kinase [ALK], ROS proto- oncogene 1 [ROS1], neurotrophic tyrosine receptor kinase [NTRK], proto-oncogene B raf [BRAF], rearranged during transfection [RET], mesenchymal-epithelial transition factor [MET] or other actionable driver kinases). Participants with non-actionable driver kinase alterations with no targeted treatment available should be considered for the study. Cohorts Cohorts 12 and 13 (Parts 1 and 2) will enrol participants of any PD-L1 status with checkpoint inhibitor(CPI)-acquired resistance after 1 or 2 prior lines of systemic therapy for advanced or metastatic NSCLC, of which at least one prior line of therapy should have contained an approved anti-PD-1 / PD-L1. Cohort 14 will enrol participants of any PD-L1 status who have not received prior systemic anticancer therapy for advanced or metastatic NSCLC (treatment- naïve). Study Design: This is a multicenter, open-label, multiple-dose and regimen Phase 1b study of Dato-DXd in combination with immunotherapy (AZD7789 [sabestomig]), with or without up to 4 cycles of carboplatin in participants with advanced or metastatic NSCLC without actionable genomic alterations (i.e., alterations in genes with approved therapies, such as EGFR, ALK, ROS1, NTRK, BRAF, RET, MET, or other actionable driver kinases). Participants with non-actionable driver kinase alterations with no targeted treatment available or tumors that harbor KRAS mutations should be considered for the study. The primary objective is to assess the safety and tolerability of Dato-DXd in combination with immunotherapy with or without up to 4 cycles of carboplatin in participants with advanced or metastatic NSCLC. The study population is described in above. Two dose levels of Dato-DXd (4 mg / kg and 6 mg / kg) will be studied in combination with AZD7789 [750 or 1500 mg]) with or without up to 4 cycles of carboplatin in the study cohorts: Cohort 12: 6 mg / kg Dato-DXd in combination with 1500 mg AZD7789 Q3W in participants with CPI-acquired resistant NSCLC; Cohort 13: 4 mg / kg Dato-DXd in combination with 1500 mg AZD7789 Q3W or 6 mg / kg Dato-DXd in combination with 750 mg AZD7789 Q3W in participants with CPI-acquired resistant NSCLC (triggered only if de-escalation is required); Cohort 14: 4 or 6 mg / kg Dato-DXd in combination with 750 or 1500 mg AZD7789 Q3W in participants with treatment- naïve NSCLC. The dose of Dato-DXd and AZD7789 will be that deemed tolerated in CPI-acquired resistant participants from Cohorts 12 or 13. Cohorts 12 and 13 will enrol participants who have acquired resistance to CPI after 1 or 2 prior lines of systemic therapy for advanced or metastatic NSCLC. Cohorts 12 and 13 will recruit participants of any PD-L1 status, including 12 to 20 participants with PD-L1<1%. Cohort 14 will recruit participants of any PD-L1 status, including approximately 20 participants PD-L1 1% to 49%. Objectives, Outcome Measures, and Endpoints: Safety and tolerability, efficacy (e.g., Objective Response Rate, Duration of Response, Disease Control Rate, Progression Free Survival, Time to Response, Best percentage change in the SoD of measurable tumors, Overal Survival, Pharmacokinetic profile, and Immunogenicity of combination treatment with Dato-DXd and Sabestomig, with or without up to 4 cycles of carboplatin will be assessed. Example 5: Antitumor test: In vivo study in humanized mice Combination of antibody-drug conjugate DS-8201 with AZD7789. Female immunocompromised NOD.Cg-Prkdcscid Il2rgtm1Wjl / SzJ (NSG) mice were engrafted with CD34+cord blood stem cells at Jackson Laboratories. At 12 weeks post engraftment, humanized mice were acquired and allowed a 7-day acclimation period. At 14 weeks post engraftment, 1e6 Caki-1 cells were injected subcutaneously into the right flank. Tumor volume was measured two times per week using electronic callipers and calculated using the formula (width2×length) / 2. For efficacy assessment, treatment was initiated when tumors reached an average volume of 125 mm3. For assessment of tumoral pharmacodynamic (PD) changes by flow cytometry, treatment was initiated when tumors reached an average volume of 250 mm3. Mice were randomly assigned, based on tumor size and cord blood donor, to the treatment groups shown in Table 1. Table 1 Treatment Dose Route of Dosing (mg / kg) administration schedule Vehicle - IV Day 1 DS-8201 10 IV Day 1 AZD7789 10 IP Day 1, 4, 8, 11 DS-8201 10 IV Day 1 AZD7789 10 IP Day 1, 4, 8, 11 Formulation of DS-8201 at 10 mg / kg Dosing solutions of DS-8201 (batch HA306) were prepared by diluting DS-8201 stock (20.1 mg / mL) in vehicle (25mM histidine buffer, 9% Sucrose, pH 5.5) to 2 mg / mL, before administration via intravenous (IV) injection at a dosing volume of 5 mL / kg. Formulation of AZD7789 at 10 mg / kg Dosing solutions of AZD7789 (batch SP22-031) were prepared by diluting stock (50.3 mg / mL) in PBS to 2 mg / mL, before administration via intraperitoneal (IP) injection at a dosing volume of 5 mL / kg. Flow cytometric staining Tumors were resected and dissociated into a single cell suspension using Miltenyi human tumor dissociation kit. Single-cell suspensions were counted on Cellaca MX High- throughput Automated Cell Counter and plated at 1e6-2e6 cells per sample in a 96 well v-bottom plate. Cells were stained with Live / Dead Blue for 30 minutes at room temperature, followed by mouse and human Fc block for 10 minutes at room temperature. Full stain extracellular master mix was applied for 30 minutes on ice, and then cells were stored in fixation buffer overnight at 4°C. Plates were washed with staining buffer (PBS + 2% BSA) after each staining step. The following morning, permeabilization buffer was added for 30 minutes on ice. Human and mouse Fc block steps were repeated, and the intracellular master mix was applied for 30 minutes on ice. After a final wash with staining buffer, samples r`m` m`npnk`i_`_ di 01 / ^I C>@P ]paa`m- Mg\o`n r`m` filtered and run on Cytek Aurora System. Tumor growth rates were calculated for each animal based ji adoodib `\^c ophjm^n bmjroc curve to an exponential model log10 (tumor volume) = a + b · time + error, where a and b are parameters that correspond to the log initial volume and growth rate, respectively. Statistical significance of differences in tumor growth rates between groups was evaluated using a Mann Whitney U test. For differences in pharmacodynamics by flow cytometry, an Ordinary One-Way ANOVA was performed. P-values are m`kjmo`_ \n ajggjrn: k ^ / - / 4 'in+ ijo ndbidad^\io(: )+ k < 0.05; **, p < 0.01; ***, p <0.001; ****, p < 0.0001. Results: Humanized Caki-1-tumor bearing mice were treated with DS- 8201 and AZD7789 as single agents, and in combination, as outlined in Table 1. Enhanced tumor growth rate inhibition versus vehicle was observed with combination DS-8201 + AZD7789 (107.7%) compared to single agent DS- 8201 (5.5%) or AZD7789 (18.7%), as seen from the results shown in Figure 46 (tumor volume over time (±SEM)), Figure 47 (tumor growth rates (±SEM)), and Table 2. Table 2 Growth Growth rate inh p-value Treatment rate ibition (Mann-Whitne an vs. Veh y U medi icle (%) test vs. Vehicle) Vehicle 0.0185 0.0 N / A DS-8201 0.0131 5.5 1.000 AZD7789 0.0034 18.7 0.6905 DS-8201 AZD7789 -0.0026 107.7 0.0556 Pharmacodynamic changes Caki-1 cells were implanted subcutaneously into the right flank of CD34+cord blood engrafted NSG mice and treated with DS-8201 at 10mg / kg alone, or in combination with 10mg / kg AZD7789, according to dose schedule outlined in Table 1. 8 days after the initiation of treatment, tumors were collected and pharmacodynamic changes assessed via flow cytometry. As seen from the results shown in Figure 48, whole tumors taken 8 days post treatment initiation revealed a significant increase in tumor infiltrating CD8+T cells with the DS-8201 + AZD7789 combination compared to monotherapy AZD7789. Trends for an increased proportion of activated (CD69+), proliferating (ki67+), and effector (granzyme B+) CD8+T cells was also observed with the combination of DS-8201 and AZD7789 compared to other groups. Additionally, an increased abundance of NK (CD56+) cells was seen with the combination. In the myeloid compartment (CD33+cells), granzyme B expression was significantly increased compared to monotherapy DS- 8201. The foregoing written specification is considered to be sufficient to enable one skilled in the art to practice the embodiments. The foregoing description and Examples detail certain embodiments and describe the best mode contemplated by the inventors. It will be appreciated, however, that no matter how detailed the foregoing may appear in text, the embodiments may be practiced in many ways and the claims include any equivalents thereof. Free Text of Sequence Listing SEQ ID NO: 1 - Amino acid sequence of a heavy chain of anti-TROP2 antibody SEQ ID NO: 2 - Amino acid sequence of a light chain of anti-TROP2 antibody SEQ ID NO: 3 - Amino acid sequence of a heavy chain CDRH1 [= amino acid residues 50 to 54 of SEQ ID NO: 1] SEQ ID NO: 4 - Amino acid sequence of a heavy chain CDRH2 [= amino acid residues 69 to 85 of SEQ ID NO: 1] SEQ ID NO: 5 - Amino acid sequence of a heavy chain CDRH3 [= amino acid residues 118 to 129 of SEQ ID NO: 1] SEQ ID NO: 6 - Amino acid sequence of a light chain CDRL1 [= amino acid residues 44 to 54 of SEQ ID NO: 2] SEQ ID NO: 7 - Amino acid sequence of a light chain CDRL2 [= amino acid residues 70 to 76 of SEQ ID NO: 2] SEQ ID NO: 8 - Amino acid sequence of a light chain CDRL3 [= amino acid residues 109 to 117 of SEQ ID NO: 2] SEQ ID NO: 9 - Amino acid sequence of a heavy chain variable region [= amino acid residues 20 to 140 of SEQ ID NO: 1] SEQ ID NO: 10 - Amino acid sequence of a light chain variable region [= amino acid residues 21 to 129 of SEQ ID NO: 2] SEQ ID NO: 11 - Amino acid sequence of a heavy chain [= amino acid residues 20 to 469 of SEQ ID NO: 1] SEQ ID NO: 12 - Amino acid sequence of a heavy chain [= amino acid residues 20 to 470 of SEQ ID NO: 1] SEQ ID NO: 13 - Amino acid sequence of a light chain [= amino acid residues 21 to 234 of SEQ ID NO: 2] SEQ ID NO: 14 - Amino acid sequence of a heavy chain of an anti-HER2 antibody SEQ ID NO: 15 - Amino acid sequence of a light chain of an anti-HER2 antibody SEQ ID NO: 16 - Amino acid sequence of a heavy chain CDRH1 [= amino acid residues 26 to 33 of SEQ ID NO: 14] SEQ ID NO: 17 - Amino acid sequence of a heavy chain CDRH2 [= amino acid residues 51 to 58 of SEQ ID NO: 14] SEQ ID NO: 18 - Amino acid sequence of a heavy chain CDRH3 [= amino acid residues 97 to 109 of SEQ ID NO: 14] SEQ ID NO: 19 - Amino acid sequence of a light chain CDRL1 [= amino acid residues 27 to 32 of SEQ ID NO: 15] SEQ ID NO: 20 - Amino acid sequence comprising amino acid sequence of a light chain CDRL2 (SAS) [= amino acid residues 50 to 56 of SEQ ID NO: 15] SEQ ID NO: 21 - Amino acid sequence of a light chain CDRL3 [= amino acid residues 89 to 97 of SEQ ID NO: 15] SEQ ID NO: 22 - Amino acid sequence of a heavy chain variable region [= amino acid residues 1 to 120 of SEQ ID NO: 14] SEQ ID NO: 23 - Amino acid sequence of a light chain variable region [= amino acid residues 1 to 107 of SEQ ID NO: 15] SEQ ID NO: 24 - Amino acid sequence of a heavy chain [= amino acid residues 1 to 449 of SEQ ID NO: 14] SEQ ID NO: 25 - Amino acid sequence of an anti-PD1 heavy chain CDRH1 of anti-PD-1 / TIM-3 bispecific antibody SEQ ID NO: 26 - Amino acid sequence of an anti-PD1 heavy chain CDRH2 of anti-PD-1 / TIM-3 bispecific antibody SEQ ID NO: 27 - Amino acid sequence of an anti-PD1 heavy chain CDRH3 of anti-PD-1 / TIM-3 bispecific antibody SEQ ID NO: 28 - Amino acid sequence of an anti-PD1 light chain CDRL1 of anti-PD-1 / TIM-3 bispecific antibody SEQ ID NO: 29 - Amino acid sequence of an anti-PD1 light chain CDRL2 of anti-PD-1 / TIM-3 bispecific antibody SEQ ID NO: 30 - Amino acid sequence of an anti-PD1 light chain CDRL3 of anti-PD-1 / TIM-3 bispecific antibody SEQ ID NO: 31 - Amino acid sequence of an anti-PD1 heavy chain variable region of anti-PD-1 / TIM-3 bispecific antibody SEQ ID NO: 32 - Amino acid sequence of an anti-PD1 heavy chain of anti-PD-1 / TIM-3 bispecific antibody SEQ ID NO: 33 - Amino acid sequence of an anti-PD1 light chain variable region of anti-PD-1 / TIM-3 bispecific antibody SEQ ID NO: 34 - Amino acid sequence of an anti-PD1 light chain of anti-PD-1 / TIM-3 bispecific antibody SEQ ID NO: 35 - Amino acid sequence of an anti-TIM-3 heavy chain CDRH1 of anti-PD-1 / TIM-3 bispecific antibody SEQ ID NO: 36 - Amino acid sequence of an anti-TIM-3 heavy chain CDRH2 of anti-PD-1 / TIM-3 bispecific antibody SEQ ID NO: 37 - Amino acid sequence of an anti-TIM-3 heavy chain CDRH3 of anti-PD-1 / TIM-3 bispecific antibody SEQ ID NO: 38 - Amino acid sequence of an anti-TIM-3 light chain CDRL1 of anti-PD-1 / TIM-3 bispecific antibody SEQ ID NO: 39 - Amino acid sequence of an anti-TIM-3 light chain CDRL2 of anti-PD-1 / TIM-3 bispecific antibody SEQ ID NO: 40 - Amino acid sequence of an anti-TIM-3 light chain CDRL3 of anti-PD-1 / TIM-3 bispecific antibody SEQ ID NO: 41 - Amino acid sequence of an anti-TIM-3 heavy chain variable region of anti-PD-1 / TIM-3 bispecific antibody SEQ ID NO: 42 - Amino acid sequence of an anti-TIM-3 heavy chain of anti-PD-1 / TIM-3 bispecific antibody SEQ ID NO: 43 - Amino acid sequence of an anti-TIM-3 light chain variable region of anti-PD-1 / TIM-3 bispecific antibody SEQ ID NO: 44 - Amino acid sequence of an anti-TIM-3 light chain of anti-PD-1 / TIM-3 bispecific antibody SEQ ID NO: 45 - Amino acid sequence of human TIM-3 IgV

Claims

CLAIMS 1. A pharmaceutical product comprising an antibody-drug conjugate and an anti-PD-1 / TIM-3 bispecific binding protein for administration in combination, wherein the antibody-drug conjugate is an antibody-drug conjugate in which a drug-linker represented by the following formula:wherein A represents the connecting position to an antibody, is conjugated to an anti-TROP2 or anti-HER2 antibody via a thioether bond.

2. The pharmaceutical product according to claim 1, wherein the drug-linker is conjugated to an anti-TROP2 antibody.

3. The pharmaceutical product according to claim 2, wherein the anti-TROP2 antibody is an antibody comprising a heavy chain comprising CDRH1 consisting of an amino acid sequence represented by SEQ ID NO: 3, CDRH2 consisting of an amino acid sequence represented by SEQ ID NO: 4 and CDRH3 consisting of an amino acid sequence represented by SEQ ID NO: 5, and a light chain comprisingCDRL1 consisting of an amino acid sequence represented by SEQ ID NO: 6, CDRL2 consisting of an amino acid sequence represented by SEQ ID NO: 7 and CDRL3 consisting of an amino acid sequence represented by SEQ ID NO:

8.

4. The pharmaceutical product according to claim 3, wherein the anti-TROP2 antibody is an antibody comprising a heavy chain comprising a heavy chain variable region consisting of an amino acid sequence represented by SEQ ID NO: 9 and a light chain comprising a light chain variable region consisting of an amino acid sequence represented by SEQ ID NO:

10.

5. The pharmaceutical product according to claim 3 or 4, wherein the anti-TROP2 antibody is an antibody comprising a heavy chain consisting of an amino acid sequence represented by SEQ ID NO: 12 and a light chain consisting of an amino acid sequence represented by SEQ ID NO:

13.

6. The pharmaceutical product according to claim 5, wherein the anti-TROP2 antibody lacks a lysine residue at the carboxyl terminus of the heavy chain.

7. The pharmaceutical product according to any one of claims 1 to 6, wherein the average number of units of the drug-linker conjugated per antibody molecule in the antibody-drug conjugate is in the range of from 3.5 to 4.

5.

8. The pharmaceutical product according to claim 7, wherein the anti-TROP2 antibody-drug conjugate is datopotamab deruxtecan (DS-1062).

9. The pharmaceutical product according to claim 1, wherein the drug-linker is conjugated to an anti-HER2 antibody.

10. The pharmaceutical product according to claim 9, wherein the anti-HER2 antibody is an antibody comprising a heavy chain comprising CDRH1 consisting of an amino acid sequence represented by SEQ ID NO: 16, CDRH2 consisting of an amino acid sequence represented by SEQ ID NO: 17 and CDRH3 consisting of an amino acid sequence represented by SEQ ID NO: 18, and a light chain comprising CDRL1 consisting of an amino acid sequence represented by SEQ ID NO: 19, CDRL2 consisting of an amino acid sequence consisting of amino acid residues 1 to 3 of SEQ ID NO: 20 and CDRL3 consisting of an amino acid sequence represented by SEQ ID NO:

21.

11. The pharmaceutical product according to claim 10, wherein the anti-HER2 antibody is an antibody comprising a heavy chain comprising a heavy chain variable region consisting of an amino acid sequence represented by SEQ ID NO: 22 and a light chain comprising a light chain variable region consisting of an amino acid sequence represented by SEQ ID NO:

23.

12. The pharmaceutical product according to claim 11, wherein the anti-HER2 antibody is an antibody comprising a heavy chain consisting of an amino acid sequence represented by SEQ ID NO: 14 and a light chain consisting of an amino acid sequence represented by SEQ ID NO: 15.

13. The pharmaceutical product according to claim 11, wherein the anti-HER2 antibody is an antibody comprising a heavy chain consisting of an amino acid sequence represented by SEQ ID NO: 24 and a light chain consisting of an amino acid sequence represented by SEQ ID NO:

15.

14. The pharmaceutical product according to any one of claims 9 to 13, wherein the average number of units of the drug-linker conjugated per anti-HER2 antibody molecule in the antibody-drug conjugate is in the range of from 7 to 8.

15. The pharmaceutical product according to claim 14, wherein the anti-HER2 antibody-drug conjugate is trastuzumab deruxtecan (DS-8201).

16. The pharmaceutical product according to any one of claims 1 to 15, wherein the anti-PD-1 / TIM-3 bispecific binding protein has a TIM-3 binding domain that specifically binds to oc` @^@^^ \i_ AB gjjkn ja oc` immunoglobulin variable (IgV) domain of TIM-3 (SEQ ID NO: 45).

17. The pharmaceutical product according to any one of claims 1 to 16, wherein the anti-PD-1 / TIM-3 bispecific binding protein has a TIM-3 binding domain that specifically binds to epitopes on the IgV domain of TIM-3 (SEQ ID NO: 45) and the epitopes comprise N12, L47, R52, D53, V54, N55, Y56, W57, W62, L63, N64, G65, D66, F67, R68, K69, D71, T75, and E77.

18. The pharmaceutical product according to any one of claims 1 to 17, wherein the anti-PD-1 / TIM-3 bispecificbinding protein has a TIM-3 binding domain that comprises a first set of CDRs: CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 comprising the amino acid sequences of SEQ ID NOs: 35, 36, 37, 38, 39 and 40, or 35, 36, 37, 38, 39 and 45, respectively; and a PD-1 binding domain that comprises a second set of CDRs: CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 comprising the amino acid sequences of SEQ ID NOs: 25, 26, 27, 28, 29, and 30, respectively.

19. The pharmaceutical product according to any one of claims 1 to 18, wherein the anti-PD-1 / TIM-3 bispecific binding protein has a TIM-3 binding domain that comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 41 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 43, and has a PD-1 binding domain that comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 31, and a light chain variable domain comprising the amino acid sequence of SEQ ID NO:

33.

20. The pharmaceutical product according to any one of claims 1 to 18, wherein the anti-PD-1 / TIM-3 bispecific binding protein has a TIM-3 binding domain that comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 42 and a light chain comprising the amino acid sequence of SEQ ID NO: 44, and has a PD-1 binding domain that comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 32 and a light chain comprising the amino acid sequence of SEQ ID NO: 34.

21. The pharmaceutical product according to any one of claims 1 to 20, wherein the anti-PD-1 / TIM-3 bispecific binding protein is an antibody.

22. The pharmaceutical product according to claim 21, wherein the antibody is an IgG antibody.

23. The pharmaceutical product according to claim 21, wherein the antibody is an IgG1 antibody.

24. The pharmaceutical product according to claim 22 or 23, wherein the antibody is human or humanized.

25. The pharmaceutical product according to any one of claims 21 to 24, wherein the bispecific antibody is monovalent.

26. The pharmaceutical product according to any one of claims 1 to 25, wherein the anti-PD-1 / TIM-3 bispecific binding protein is a DuetMab.

27. The pharmaceutical product according to any one of claims 1 to 26, wherein the anti-PD-1 / TIM-3 bispecific binding protein comprises an Fc region that is aglycosylated.

28. The pharmaceutical product according to any one of claims 1 to 26, wherein the anti-PD-1 / TIM-3 bispecific binding protein comprises an Fc region that is deglycosylated.

29. The pharmaceutical product according to any one of claims 1 to 26, wherein the anti-PD-1 / TIM-3 bispecific binding protein comprises an Fc region that has reduced fucosylation or is afucosylated.

30. The pharmaceutical product according to any one of claims 1 to 29, wherein the anti-PD-1 / TIM-3 bispecific binding protein is ^>WA6678^.

31. The pharmaceutical product according to any one of claims 1 to 30 wherein the product is a composition comprising the antibody-drug conjugate and the anti-PD- 1 / TIM-3 bispecific binding protein, for simultaneous administration.

32. The pharmaceutical product according to any one of claims 1 to 30 wherein the product is a combined preparation comprising the antibody-drug conjugate and the anti-PD-1 / TIM-3 bispecific binding protein, for sequential or separate simultaneous administration.

33. The pharmaceutical product according to any one of claims 1 to 32, wherein the product is for treating cancer.

34. The pharmaceutical product according to claim 33, wherein the cancer is at least one selected from the group consisting of breast cancer, lung cancer, colorectal cancer, gastric cancer, esophageal cancer, head-and-neck cancer, esophagogastric junction adenocarcinoma, biliary tract cancer, Paget's disease, pancreatic cancer, ovarian cancer, uterine carcinosarcoma, urothelial cancer, prostate cancer, bladder cancer, endometrial cancer, gastrointestinal stromal tumor, digestive tract stromal tumor, uterine cervix cancer, squamous cell carcinoma, peritoneal cancer, liver cancer, hepatocellular cancer, corpus utericarcinoma, kidney cancer, vulval cancer, thyroid cancer, penis cancer, leukemia, malignant lymphoma, plasmacytoma, myeloma, glioblastoma multiforme, osteosarcoma, sarcoma, and melanoma, cervical cancer, uterine cancer, testicular cancer, and renal cell carcinoma.

35. The pharmaceutical product according to claim 34, wherein the cancer is lung cancer.

36. The pharmaceutical product according to claim 35, wherein the lung cancer is non-small cell lung cancer.

37. The pharmaceutical product according to claim 34, wherein the cancer is colorectal cancer.

38. The pharmaceutical product according to claim 34, wherein the cancer is breast cancer.

39. The pharmaceutical product according to claim 38, wherein the breast cancer is HER2 positive breast cancer.

40. The pharmaceutical product according to claim 38, wherein the breast cancer is HER2 low breast cancer.

41. The pharmaceutical product according to claim 38, wherein the breast cancer is triple negative breast cancer.

42. The pharmaceutical product according to claim 38, wherein the breast cancer is hormone receptor (HR)- positive, HER2-negative breast cancer.

43. The pharmaceutical product according to claim 34, wherein the cancer is gastric cancer.

44. The pharmaceutical product according to claim 34, wherein the cancer is pancreatic cancer.

45. The pharmaceutical product according to claim 34, wherein the cancer is ovarian cancer.

46. The pharmaceutical product according to claim 34, wherein the cancer is prostate cancer.

47. The pharmaceutical product according to claim 34, wherein the cancer is kidney cancer.

48. The pharmaceutical product according to claim 34, wherein the cancer is bladder cancer.

49. The pharmaceutical product according to claim 34, wherein the cancer is endometrial cancer.

50. The pharmaceutical product according to claim 34, wherein the cancer is biliary tract cancer.

51. An antibody-drug conjugate for use, in combination with an anti-PD-1 / TIM-3 bispecific binding protein, in the treatment of cancer in a subject, wherein the antibody-drug conjugate and the anti-PD-1 / TIM-3 bispecific binding protein are as defined in any one of claims 1 to 30.

52. The antibody-drug conjugate for the use according to claim 51, wherein the cancer is as defined in any one of claims 34 to 50.

53. The antibody-drug conjugate for the use according to claim 51 or 52, wherein the use comprises administration of the antibody-drug conjugate and the anti-PD-1 / TIM-3 bispecific binding protein sequentially.

54. The antibody-drug conjugate for the use according to claim 51 or 52, wherein the use comprises administrationof the antibody-drug conjugate and the anti-PD-1 / TIM-3 bispecific binding protein separately and simultaneously.

55. The antibody-drug conjugate for the use according to any one of claims 51 to 54, wherein the anti-PD-1 / TIM-3 bispecific binding protein is to be administered at a dose of about 750 mg or about 1500 mg.

56. The antibody-drug conjugate for the use according to claim 55, wherein the anti-PD-1 / TIM-3 bispecific binding protein is to be administered once per treatment cycle, wherein the treatment cycle is about three weeks.

57. The antibody-drug conjugate for the use according to any one of claims 51 to 56, wherein the cancer is non- small cell lung cancer, and wherein the subject is treatment-naïve, or wherein the subject has CPI acquired resistance.

58. The antibody-drug conjugate for the use according to claim 57 wherein the subject has any PD-L1 status.

59. The antibody-drug conjugate for the use according claim 58, wherein the subject has a PD-L1 status of 1% to 49%, or wherein the subject has a PD-L1 status of less than 1%.

60. The antibody-drug conjugate for the use according to any one of claims 51 to 59, wherein the subject is without actionable genomic alterations.

61. A method of treating cancer comprising administering an antibody-drug conjugate and an anti-PD-1 / TIM-3 bispecific binding protein as defined in any one ofclaims 1 to 30 in combination to a subject in need thereof.

62. The method according to claim 61, wherein the cancer is as defined in any one of claims 34 to 50.

63. The method according to claim 61 or 62, wherein the antibody-drug conjugate and the anti-PD-1 / TIM-3 bispecific binding protein are administered sequentially.

64. The method according to claim 61 or 62, wherein the antibody-drug conjugate and the anti-PD-1 / TIM-3 bispecific binding protein are administered separately and simultaneously.

65. The method according to any one of claims 61 to 64, wherein the anti-PD-1 / TIM-3 bispecific binding protein is administered at a dose of about 750 mg or about 1500 mg.

66. The method according to claim 65, wherein the anti- PD-1 / TIM-3 bispecific binding protein is administered once per treatment cycle, wherein the treatment cycle is about three weeks.

67. The method according to any one of claims 61 to 66, wherein the cancer is non-small cell lung cancer, and wherein the subject is treatment-naïve, or wherein the subject has CPI acquired resistance.

68. The method according to claim 67 wherein the subject has any PD-L1 status.

69. The method according claim 68, wherein the subject has a PD-L1 status of 1% to 49%, or wherein the subject has a PD-L1 status of less than 1%.

70. The method according to any one of claims 61 to 69, wherein the subject is without actionable genomic alterations.

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