Combination treatment of prostate cancer

Abstract

Compositions and methods for the treatment of cancer, in particular prostate cancer, are described. According to certain embodiments, a method of treating cancer in a patient comprises administering to the patient a combination of a therapeutically effective amount of a bispecific antibody that bind to kallikrein related peptidase 2 (hK2) and cluster determinant 3 (CD3) and an antibody drug conjugate (ADC) targeting prostate specific membrane antigen (PSMA).

Description

Attorney Docket No: 065768.12729 / 219WO1JBI6963WOPCT1COMBINATION TREATMENT OF PROSTATE CANCERCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to U.S. Provisional Application No. 63 / 735,419 filed on December 18, 2024, and U.S. Provisional Application No. 63 / 790,817 filed on April 18, 2025, the disclosures of each of which are hereby incorporated by reference in their entireties.SEQUENCE LISTING

[0002] The instant application contains a Sequence Listing which has been submitted electronically in XML format and is hereby incorporated by reference in its entirety. The XML copy, created on December 4, 2025, is named JBI6963PCT.xml and is 25.9 KB in size.TECHICAL FIELD

[0003] The disclosure provided herein relates to methods of treating prostate cancer using bispecific antibodies that bind to kallikrein related peptidase 2 (hK2) and cluster determinant 3 (CD3) in combination with an antibody drug conjugate (ADC) targeting prostate specific membrane antigen (PSMA).BACKGROUND

[0004] Prostate cancer (PC) is the second most frequently diagnosed cancer and the sixth leading cause of cancer death in males, accounting for 14% (903,500) of the total new cancer cases and 6% (258,400) of the total cancer deaths in males worldwide. Historically, androgen depletion therapy (ADT) has been the standard of care for patients with metastatic prostate cancer. With these agents, overall survival has improved from the previously reported range of 6 to 10 months to 18 to 24 months. However, most prostate cancer patients will experience disease progression on antiandrogen or androgen synthesis inhibitor therapy within 13 to 20 months.

[0005] In the advanced form of prostate cancer, it becomes metastatic and spreads beyond the prostate to other parts of the body. With metastatic Castration-Resistant Prostate Cancer (mCRPC), hormone therapy no longer stops cancer growth. End stage PC (castration-resistant prostate cancer) currently has no curative treatment option.

[0006] There remains a need, therefore, for novel therapeutic options, such as new dosage and treatment regimens that have an optimal benefit-risk profile in the treatment of prostate cancer, more specifically mCRPC.SUMMARY OF THE INVENTION

[0007] Provided herein is a method of treating prostate cancer, preferably advanced prostate cancer, more preferably metastatic castration-resistant prostate cancer (mCRPC), in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of an antibody drug conjugate (ADC) targeting prostate-specific membrane antigen (PSMA) at a first treatment dose, and a therapeutically effective amount of an anti-hK2 / anti-CD3 bispecific antibody at a treatment dose, wherein: a. the ADC comprises an anti-PSMA antibody conjugated to a drug-linker, wherein the conjugation occurs via para-acetyl phenylalanine (pAF) incorporated in the heavy chain sequence of the antibody, wherein the anti-PSMA antibody comprising a heavy chain (HC) of SEQ ID NO: 1 and a light chain (LC) of SEQ ID NO: 2, in which the pAF is incorporated at the HC position Al 14 according to Kabat numbering (i.e., the A, which is at position 116 in the amino acid sequence of SEQ ID NO: 1), and wherein the druglinker is amberstatin269 (AS269), which has the following structure:b. the anti-hK2 / anti-CD3 bispecific antibody comprises a first antigen binding domain that binds specifically to hK2, and a second antigen binding domain that binds specifically to CD3, wherein: i. the first domain comprises a first heavy chain variable region (VH1) of SEQ ID NO: 9 and a first light chain variable region (VL1) of SEQ ID NO: 10; and ii. the second domain comprises a second heavy chain variable region (VH2) of SEQ ID NO: 21 and a second light chain variable region (VL2) of SEQ ID NO:

[0008] The anti-PSMA antibody, which is comprised in the ADC, typically comprises two heavy chains and two light chains. One non-natural amino acid para-acetyl-L-phenylalanine (pAF) is incorporated into each heavy chain at position 114 according to Kabat numbering (i.e., the A, which is at position 116 in the amino acid sequence of SEQ ID NO: 1). The drug-linker is conjugated to each said pAF (DAR=2), via an oxime linkage. Hence, once conjugated to the anti- PSMA antibody, the H2N-O- end of the drug-linker is =N-O-. A pAF conjugated to the H2N-O- end of the drug-linker has the following structure:

[0009] The anti-PSMA ADC advantageously is ARX517 (cf. Skidmore et al. 2024, Mol. Cancer Ther. 23(12): 1842-1853 herein incorporated by reference; cf. US 12,059,473 B2 herein incorporated by reference).

[0010] In some embodiments, the first domain of the anti-hK2 / anti-CD3 bispecific antibody comprises a Fab and the second domain of the anti-hK2 / anti-CD3 bispecific antibody comprises an scFv. In some embodiments, the anti-hK2 / anti-CD3 antibody comprises a first heavy chain (HC1), a first light chain (LC1) and a second heavy chain (HC2) having amino acid sequences at least 90% identical to SEQ ID NO: 13, SEQ ID NO: 14 and SEQ ID NO: 26 respectively; preferably, the HC1, LC1 and HC2 comprise the amino acid sequences of SEQ ID NO: 13, SEQ ID NO: 14 and SEQ ID NO: 26, respectively. In some embodiments, the treatment dose of the anti-hK2 / anti- CD3 bi specific antibody is about 300 mg, per administration.

[0011] In some embodiments, the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody is administered at a flat dose.

[0012] In some embodiments, the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody is initially administered on a day, which is after the day of administration of the first treatment dose of the ADC, or on a day, which is before the day of administration of the first treatment dose of the ADC, for example on a day, which is after the day of administration of the first treatment dose of the ADC.

[0013] In some embodiments, the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody is initially administered on a day within 19-23 days, such as 19, 20, 21, 22, or 23 days, preferably 21 days, after the administration of the first treatment dose of the ADC. In some embodiments, the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody is subsequently administered once every 5 to 7 weeks, for example, once every 5, 6 or 7 weeks, preferably once every six weeks, after the initial administration of the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody.

[0014] In some embodiments, the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody is intravenously administered, for example, by intravenous (IV) infusion over a period of about 30 minutes to one hour for each administration, such as over a period of about 30 minutes or a period of about one hour for each administration.

[0015] In some embodiments, the method further comprises administering to the human patient one or more step-up doses (for example, one or two step-up doses) of the anti-hK2 / anti-CD3 bispecific antibody, wherein the one or more step-up doses are administered after the administration of the first treatment dose of the ADC and prior to the initial administration of the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody and wherein the one or more step-up doses are not higher than the treatment dose. In some embodiments, the more than one step-up doses of the anti-hK2 / anti-CD3 bispecific antibody are administered at ascending doses.

[0016] In some embodiments, the method comprises administering to the patient a first step-up dose of the anti-hK2 / anti-CD3 bispecific antibody of about 2 mg to about 5 mg per administration, for example about 2 mg, about 2.5 mg, about 3 mg, about 3.5 mg, about 4 mg, about 4.5 mg or about 5 mg, per administration, preferably about 3.5 mg per administration. In some embodiments, the first step-up dose is administered on a day within 5-9 days, such as 5, 6, 7, 8, or 9 days, preferably 7 days, after the first treatment dose of the ADC is administered.

[0017] In some embodiments, the method further comprises administering to the patient a second step-up dose of the anti-hK2 / anti-CD3 bispecific antibody of about 15 mg to about 25 mg per administration, for example about 15 mg, about 16 mg, about 17 mg, about 18 mg, about 19 mg, about 20 mg, about 21 mg, about 22 mg, about 23 mg, about 24 mg, or about 25 mg, per administration, preferably about 18 mg per administration. In some embodiments, the second step- up dose of the anti-hK2 / anti-CD3 bispecific antibody is administered on a day within 12-16 days, such as 12, 13, 14, 15 or 16 days, preferably 14 days, after the first treatment dose of the ADC is administered.

[0018] In some embodiments, the ADC is administered at the first treatment dose of 2.0 mg / kg or lower, such as 1.9-1.4 mg / kg or 1.7-1.4 mg / kg, e.g., 2.0 mg / kg, 1.7 mg / kg or 1.4 mg / kg.

[0019] In some embodiments, the ADC is administered at a first treatment of 1.4 mg / kg.

[0020] In some embodiments, the ADC is administered at a first treatment dose of 2.0 mg / kg.

[0021] In some embodiments, the method further comprises administering to the patient a second treatment dose of the ADC. For example, the second treatment dose of the ADC is administered: i. on a day within 19-44 days, such as on a day within 19-23 days or 40-44 days, for example 19, 20, 21, 22, or 23 days, preferably 21 days or 40, 41, 42, 43 or 44 days, preferably 41 days, after the administration of the first treatment dose of the ADC; or ii. on a day within 2 to 7 weeks, such as 2, 3, 4, 5, 6 or 7 weeks, for example 3 weeks or 6 weeks, after the administration of the first treatment dose of the ADC.

[0022] In some embodiments, the second treatment dose of the ADC is administered on a day within 19-23 days, such as 19, 20, 21, 22, or 23 days, preferably 21 days, after the first treatment dose of ADC is administered. In some embodiments, the method further comprises administering to the patient a subsequent treatment dose of the ADC once every 2 to 7 weeks, such as once every2, 3, 4, 5, 6 or 7 weeks, after the administration of the second treatment dose of the ADC. In some embodiments, the subsequent treatment dose of the ADC is administered once every 3 weeks for 2,3, or 4 doses and followed by once every 6 weeks.

[0023] In some embodiments, the second treatment dose of the ADC is administered on a day within 40-44 days, such as 40, 41, 42, 43 or 44 days, preferably 41 days, after the first treatment dose of ADC is administered. In some embodiments, the method further comprises administering to the patient a subsequent treatment dose of the ADC once every 2 to 7 weeks, such as once every 2, 3, 4, 5, 6 or 7 weeks, after the administration of the second treatment dose of the ADC.

[0024] In some embodiments, the second treatment dose of the ADC is 1.4 mg / kg.

[0025] In some embodiments, the second treatment dose of the ADC is 2 mg / kg.

[0026] In some embodiments, the first treatment and second treatment dose of the ADC is 1.4 mg / kg.

[0027] In some embodiments, the first treatment and second treatment dose of the ADC is 2.0 mg / kg.

[0028] In some embodiments, the first treatment of the ADC is 2 mg / kg and the second treatment dose of the ADC is 1.4 mg / kg.

[0029] In some embodiments, the human patient is 18 years of age or older. In some embodiments, the prostate cancer is histologically confirmed adenocarcinoma of the prostate, as defined by Prostate Cancer Working Group 3 (PCWG3) criteria (Scher et al. 2016 Journal of Clinical Oncology 34(12): 1402-1418). In some embodiments, the prostate cancer is a prostate adenocarcinoma that does not comprise small cell carcinoma, carcinoid tumor, mixed NE carcinoma, or large cell NE carcinoma. In some embodiments, the patient has received orchiectomy or medical castration; or has not undergone orchiectomy and is receiving ongoing androgen deprivation therapy with a gonadotropin releasing hormone (GnRH) analog (agonist or antagonist) prior to being administered with the first dose of study drug (i.e., prior to being administered the first dose of PSMA ADC and of anti-hK2 / anti-CD3 bispecific antibody of the application). In some embodiments, the patient has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. In some embodiments, the patient has received prior treatment for mCRPC with at least one androgen receptor (AR)-targeted therapy (for example treatment with abiraterone acetate, apalutamide, enzalutamide, or darolutamide). In some embodiments, the patient has received no more than one or no previous taxane therapies, more specifically no more than one or no prior anti-prostate cancer chemotherapy (i.e., docetaxel, cabazitaxel, cisplatin, carboplatin, etoposide, etc.).

[0030] In some embodiments, the method provides a decrease in the serum Prostate-Specific Antigen (PSA) level of the patient, wherein the decrease is relative to the PSA level of the patient prior to the administration of the anti-hK2 / anti-CD3 bispecific antibody. In some embodiments, the method provides for no disease progression in the patient, wherein disease progression is assessed according to the Prostate Cancer Working Group 3 (PCWG3) Criteria (Scher et al. 2016 Journal of Clinical Oncology 34(12): 1402-1418)). In some embodiments, the method provides a Partial Response or better according to RECIST version 1.1 response criteria (Eisenhauer et al. 2009 European Journal of Cancer 45: 228-247) without evidence of bone progression according to PCWG3 in the patient. In some embodiments, the method provides radiographic progression free survival (rPFS). In some embodiments, Adverse Events of Grade 3 or higher (according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0) are observed in 20% or fewer of patients in a cohort of at least 20 patients, forexample 15% or fewer of patients in a cohort of at least 20 patients. Tn some embodiments, the method does not induce a Dose Limiting Toxicity (DLT) in the patient.

[0031] In another aspect, the application provides the anti-hK2 / anti-CD3 bispecific antibody for use in the method of treating prostate cancer, preferably advanced prostate cancer, more preferably mCRPC.

[0032] In another aspect, the application provides the ADC for use in the method of treating prostate cancer, preferably advanced prostate cancer, more preferably mCRPC.

[0033] In another aspect, the application provides the anti-hK2 / anti-CD3 bispecific antibody and the ADC for use in the method treating prostate cancer, preferably advanced prostate cancer, more preferably mCRPC.

[0034] In another aspect, the application provides a combination or functional association comprising the anti-hK2 / anti-CD3 bispecific antibody and the ADC.

[0035] In another aspect, the application provides the anti-hK2 / anti-CD3 bispecific antibody and the ADC as a combined preparation for simultaneous, separate or sequential use in prostate cancer therapy, more specifically in mCRPC therapy.

[0036] Further aspects, features and advantages of the present invention will be better appreciated upon a reading of the following detailed description of the invention and claims.BRIEF DESCRIPTION OF THE DRAWINGS

[0037] The foregoing and other objects, aspects, features, and advantages of exemplary embodiments will become more apparent and may be better understood by referring to the following description taken in conjunction with the accompanying drawings.

[0038] FIG. 1 shows the number (FIG. 1 A) and viability (FIG. IB) of hK2 expressing LNCaP cells are decreased when using the combination of a sub-efficacious dose of PSMA ADC and a dose range of hK2xCD3 bispecific antibody versus hK2xCD3 bispecific antibody alone.

[0039] FIG. 2 shows the number (FIG. 2A) and viability (FIG. 2B) of hK2 expressing LNCaP cells are decreased when using the combination of a sub-efficacious dose of hK2xCD3 bispecific antibody and a dose range of PSMA ADC versus the combination of PSMA ADC and a NullxCD3 bispecific antibody.DETAILED DESCRIPTION OF THE INVENTION

[0040] The disclosed methods may be understood more readily by reference to the following detailed description taken in connection with the accompanying figures, which form a part of this disclosure. It is to be understood that the disclosed methods are not limited to the specific methods described and / or shown herein, and that the terminology used herein is for the purpose of describing particular embodiments by way of example only and is not intended to be limiting of the claimed methods. All patents, published patent applications, and publications cited herein are incorporated by reference as if set forth fully herein.

[0041] Various terms relating to aspects of the description are used throughout the specification and claims. Such terms are to be given their ordinary meaning in the art unless otherwise indicated. Other specifically defined terms are to be construed in a manner consistent with the definitions provided herein.

[0042] As used in this specification and the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless the content clearly dictates otherwise. Thus, for example, reference to “a cell” includes a combination of two or more cells, and the like.

[0043] When a list is presented, unless stated otherwise, it is to be understood that each individual element of that list, and every combination of that list, is a separate embodiment. For example, a list of embodiments presented as “A, B, or C” is to be interpreted as including the embodiments, “A,” “B,” “C,” “A or B,” “A or C,” “B or C,” or “A, B, or C.”

[0044] Unless otherwise stated, any numerical values, such as a concentration or a concentration range described herein, are to be understood as being modified in all instances by the term “about.” Thus, a numerical value typically includes ± 10% of the recited value. For example, a concentration of 1 mg / mL includes 0.9 mg / mL to 1.1 mg / mL. Likewise, a concentration range of 1% to 10% (w / v) includes 0.9% (w / v) to 11% (w / v). As used herein, the use of a numerical range expressly includes all possible subranges, all individual numerical values within that range, including integers within such ranges and fractions of the values unless the context clearly indicates otherwise.

[0045] Unless otherwise indicated, the term “at least” preceding a series of elements is to be understood to refer to every element in the series. Those skilled in the art will recognize or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. Such equivalents are intended to be encompassed by the invention.

[0046] The transitional terms “comprising,” “consisting essentially of,” and “consisting of’ are intended to connote their generally accepted meanings in the patent vernacular; that is, (i) “comprising,” which is synonymous with “including,” “containing,” or “characterized by,” is inclusive or open-ended and does not exclude additional, unrecited elements or method steps; (ii) “consisting of’ excludes any element, step, or ingredient not specified in the claim; and (iii) “consisting essentially of’ limits the scope of a claim to the specified materials or steps “and those that do not materially affect the basic and novel character! stic(s)” of the claimed invention. Embodiments described in terms of the phrase “comprising” (or its equivalents) also provide as embodiments those independently described in terms of “consisting of’ and “consisting essentially of.”

[0047] It should also be understood that the terms “about,” “approximately,” “generally,” “substantially” and like terms, used herein when referring to a dimension or characteristic of a component of the preferred invention, indicate that the described dimension / characteristic is not a strict boundary or parameter and does not exclude minor variations therefrom that are functionally the same or similar, as would be understood by one having ordinary skill in the art. At a minimum, such references that include a numerical parameter would include variations that, using mathematical and industrial principles accepted in the art (e.g., rounding, measurement or other systematic errors, manufacturing tolerances, etc.), would not vary the least significant digit.

[0048] The terms “identical” or percent “identity,” in the context of two or more nucleic acids or polypeptide sequences (e.g., anti-KLK2 / anti-CD3 bispecific antibodies and polynucleotides that encode them, anti-KLK2 / anti-CD3 bispecific antibodies and polynucleotides that encode them, KLK2 polypeptides and KLK2 polynucleotides that encode them, CD3 polypeptides and CD3 polynucleotides that encode them), refer to two or more sequences or subsequences that are the same or have a specified percentage of amino acid residues or nucleotides that are the same, when compared and aligned for maximum correspondence, as measured using one of the following sequence comparison algorithms or by visual inspection.

[0049] For sequence comparison, typically one sequence acts as a reference sequence, to which test sequences are compared. When using a sequence comparison algorithm, test and reference sequences are input into a computer, subsequence coordinates are designated, if necessary, and sequence algorithm program parameters are designated. The sequence comparison algorithm thencalculates the percent sequence identity for the test sequence(s) relative to the reference sequence, based on the designated program parameters.

[0050] Optimal alignment of sequences for comparison can be conducted, e.g., by the local homology algorithm of Smith & Waterman, Adv. Appl. Math. 2:482 (1981), by the homology alignment algorithm of Needleman & Wunsch, J. Mol. Biol. 48:443 (1970), by the search for similarity method of Pearson & Lipman, Proc. Nat’l. Acad. Sci. USA 85:2444 (1988), by computerized implementations of these algorithms (GAP, BESTFIT, FASTA, and TFASTA in the Wisconsin Genetics Software Package, Genetics Computer Group, 575 Science Dr., Madison, WI), or by visual inspection (see generally, Current Protocols in Molecular Biology, F.M. Ausubel et al., eds., Current Protocols, a joint venture between Greene Publishing Associates, Inc. and John Wiley & Sons, Inc., (1995 Supplement) (Ausubel)).

[0051] Examples of algorithms that are suitable for determining percent sequence identity and sequence similarity are the BLAST and BLAST 2.0 algorithms, which are described in Altschul et al. (1990) J. Mol. Biol. 215: 403-410 and Altschul et al. (1997) Nucleic Acids Res. 25: 3389-3402, respectively.

[0052] A “host cell” refers to a vehicle that includes the necessary cellular components, e g., organelles, needed to express the polypeptides and constructs described herein from their corresponding nucleic acids. The nucleic acids may be included in nucleic acid vectors that can be introduced into the host cell by conventional techniques known in the art (e.g., transformation, transfection, electroporation, calcium phosphate precipitation, direct microinjection, infection, etc.). The choice of nucleic acid vectors depends in part on the host cells to be used. Generally, host cells are of either prokaryotic (e.g., bacterial) or eukaryotic (e.g., mammalian) origin.

[0053] “Antigen” refers to any molecule (e.g., protein, peptide, polysaccharide, glycoprotein, glycolipid, nucleic acid, portions thereof, or combinations thereof) capable of being bound by an antigen binding domain or a T-cell receptor capable of mediating an immune response. Exemplary immune responses include antibody production and activation of immune cells, such as T cells, B cells or NK cells. Antigens may be expressed by genes, synthetized, or purified from biological samples such as a tissue sample, a tumor sample, a cell or a fluid with other biological components, organisms, subunits of proteins / antigens, killed or inactivated whole cells or lysates.

[0054] “Antigen binding fragment” or “antigen binding domain” refers to a portion of the protein that binds an antigen. Antigen binding fragments may be synthetic, enzymatically obtainable orgenetically engineered polypeptides and include portions of an immunoglobulin that bind an antigen, such as the VH, the VL, the VH and the VL, Fab, Fab', F(ab')2, Fd and Fv fragments, domain antibodies (dAb) consisting of one VH domain or one VL domain, shark variable IgNAR domains, camelized VH domains, VHH domains, minimal recognition units consisting of the amino acid residues that mimic the CDRs of an antibody, such as FR3-CDR3-FR4 portions, the HCDR1, the HCDR2 and / or the HCDR3 and the LCDR1, the LCDR2 and / or the LCDR3, alternative scaffolds that bind an antigen, and multispecific proteins comprising the antigen binding fragments. Antigen binding fragments (such as VH and VL) may be linked together via a synthetic linker to form various types of single antibody designs where the VH / VL domains may pair intramolecularly, or intermolecularly in those cases when the VH and VL domains are expressed by separate single chains, to form a monovalent antigen binding domain, such as single chain Fv (scFv) or diabody. Antigen binding fragments may also be conjugated to other antibodies, proteins, antigen binding fragments or alternative scaffolds which may be monospecific or multispecific to engineer bispecific and multispecific proteins.

[0055] “Antibodies” is meant in a broad sense and includes immunoglobulin molecules including monoclonal antibodies including murine, human, humanized and chimeric monoclonal antibodies, antigen binding fragments, multispecific antibodies, such as bispecific, trispecific, tetraspecific, dimeric, tetrameric or multimeric antibodies, single chain antibodies, domain antibodies and any other modified configuration of the immunoglobulin molecule that comprises an antigen binding site of the required specificity. “Full length antibodies” are comprised of two heavy chains (HC) and two light chains (LC) inter-connected by disulfide bonds as well as multimers thereof (e.g. IgM). Each heavy chain is comprised of a heavy chain variable region (VH) and a heavy chain constant region (comprised of domains CHI, hinge, CH2 and CH3). Each light chain is comprised of a light chain variable region (VL) and a light chain constant region (CL). The VH and the VL regions may be further subdivided into regions of hypervariability, termed complementarity determining regions (CDR), interspersed with framework regions (FR). Each VH and VL is composed of three CDRs and four FR segments, arranged from amino-to- carboxy-terminus in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3 and FR4. Immunoglobulins may be assigned to five major classes, IgA, IgD, IgE, IgG and IgM, depending on the heavy chain constant domain amino acid sequence. IgA and IgG are further sub-classified as the isotypes IgAl, IgA2, IgGl, IgG2, IgG3 and IgG4. Antibody light chains of any vertebratespecies may be assigned to one of two clearly distinct types, namely kappa (K) and lambda (1), based on the amino acid sequences of their constant domains.

[0056] “Complementarity determining regions” (CDR) are antibody regions that bind an antigen. There are three CDRs in the VH (HCDR1, HCDR2, HCDR3) and three CDRs in the VL (LCDR1, LCDR2, LCDR3). CDRs may be defined using various delineations such as Kabat (Wu et al. (1970) J Exp Med 132: 211-50; Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, Md., 1991), Chothia (Chothia et al. (1987) J Mol Biol 196: 901-17), IMGT (Lefranc et al. (2003) Dev Comp Immunol 27: 55-77) and AbM (Martin and Thornton J Mol Biol 263: 800-15, 1996). The correspondence between the various delineations and variable region numbering is described (see e.g., Lefranc et al. (2003) Dev Comp Immunol 27: 55-77; Honegger and Pluckthun, J Mol Biol (2001) 309:657-70; International ImMunoGeneTics (IMGT) database). Available programs such as abYsis by UCL Business PLC may be used to delineate CDRs. The term “CDR”, “HCDR1”, “HCDR2”, “HCDR3”, “LCDR”, “LCDR2” and “LCDR3” as used herein includes CDRs defined by any of the methods described supra, Kabat, Chothia, IMGT or AbM, unless otherwise explicitly stated in the specification.

[0057] “Epitope” refers to a portion of an antigen to which an antibody specifically binds. Epitopes typically consist of chemically active (such as polar, non-polar or hydrophobic) surface groupings of moieties such as amino acids or polysaccharide side chains and may have specific three-dimensional structural characteristics, as well as specific charge characteristics. An epitope may be composed of contiguous and / or discontinuous amino acids that form a conformational spatial unit. For a discontinuous epitope, amino acids from differing portions of the linear sequence of the antigen come in close proximity in 3-dimensional space through the folding of the protein molecule. Antibody “epitope” depends on the methodology used to identify the epitope.

[0058] “Specifically binds,” “specific binding,” “specifically binding” or “binds” refer to a proteinaceous molecule binding to an antigen or an epitope within the antigen with greater affinity than for other antigens. Typically, the proteinaceous molecule binds to the antigen or the epitope within the antigen with an equilibrium dissociation constant (KD) of about 1 x 107M or less, for example about 5P 08M or less, about 1 * 1CT8M or less, about P I O9M or less, about P I O10M or less, about P I 0 " M or less, or about 1 x 1012M or less, typically with the KD that is at least one hundred fold less than its KD for binding to a non-specific antigen (e.g., BSA, casein).

[0059] “dAb” or “dAb fragment” refers to an antibody fragment composed of a VH domain (Ward et al., Nature 341:544 546 (1989)).

[0060] “Fab” or “Fab fragment” refers to an antibody fragment composed of VH, CHI, VL and CL domains.

[0061] “F(ab')2” or “F(ab')2 fragment” refers to an antibody fragment containing two Fab fragments connected by a disulfide bridge in the hinge region.

[0062] “Fd” or “Fd fragment” refers to an antibody fragment composed of VH and CHI domains.

[0063] “Fv” or “Fv fragment” refers to an antibody fragment composed of the VH and the VL domains from a single arm of the antibody. Fv fragments lack the constant regions of Fab (CHI and CL) regions. The VH and VL in Fv fragments are held together by non-covalent interactions.

[0064] “Fc” polypeptide” of a dimeric Fc refers to one of the two polypeptide forming the dimeric Fc domain. For example, an Fc polypeptide of a dimeric IgG FC comprises an IgG CH2 and an IgG CH3 constant domain sequence).

[0065] “Single chain Fv” or “scFv” refers to a fusion protein comprising at least one antibody fragment comprising a light chain variable region (VL) and at least one antibody fragment comprising a heavy chain variable region (VH), wherein the VL and the VH are contiguously linked via a polypeptide linker, and capable of being expressed as a single chain polypeptide. Unless specified, as used herein, a scFv may have the VL and VH variable regions in either order, e g., with respect to the N-terminal and C-terminal ends of the polypeptide, the scFv may comprise VL-linker-VH or may comprise VH-linker-VL. The scFv can be fused to an Fc to create a scFv-Fc wherein the scFv is fused to the IgG CH2 and IgG CH3 domain of the Fc via the hinge domain.

[0066] “Stapled single chain Fv”, “stapled scFv” or “spFv” refers to a scFv that comprises one or more disulfide bonds between the VH and the linker or the VL and the linker. Typically, the spFv may comprise one disulfide bond between the VH and the linker, and one disulfide bond between the VL and the linker, or two disulfide bonds between the VH and the linker and the VL and the linker. The spFv can be fused to an Fc to create a spFv-Fc wherein the spFv is fused to the IgG CH2 and IgG CH3 domain of the Fc via the hinge domain.

[0067] “(scFv)2” or “tandem scFv” or “bis-scFv” fragments refers to a fusion protein comprising two light chain variable region (VL) and two heavy chain variable region (VH), wherein the two VL and the two VH regions are contiguously linked via polypeptide linkers, and capable of beingexpressed as a single chain polypeptide. The two VL and two VH regions fused by peptide linkers form a bivalent molecule VLA-linker-VHA-linker-VLB-linker-VHB to form two binding sites, capable of binding two different antigens or epitopes concurrently.

[0068] “Full length antibody” is comprised of two heavy chains (HC) and two light chains (LC) inter-connected by disulfide bonds as well as multimers thereof (e.g. IgM). Each heavy chain is comprised of a heavy chain variable domain (VH) and a heavy chain constant domain, the heavy chain constant domain comprised of subdomains CHI, hinge, CH2 and CH3. Each light chain is comprised of a light chain variable domain (VL) and a light chain constant domain (CL). The VH and the VL may be further subdivided into regions of hypervariability, termed complementarity determining regions (CDR), interspersed with framework regions (FR). Each VH and VL is composed of three CDRs and four FR segments, arranged from amino-to-carboxy-terminus in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3 and FR4.

[0069] “Monoclonal antibody” refers to an antibody obtained from a substantially homogenous population of antibody molecules, i.e., the individual antibodies comprising the population are identical except for possible well-known alterations such as removal of C-terminal lysine from the antibody heavy chain or post-translational modifications such as amino acid isomerization or deamidation, methionine oxidation or asparagine or glutamine deamidation. Monoclonal antibodies typically bind one antigenic epitope. A bispecific monoclonal antibody binds two distinct antigenic epitopes. Monoclonal antibodies may have heterogeneous glycosylation within the antibody population. Monoclonal antibody may be monospecific or multispecific such as bispecific, monovalent, bivalent or multivalent.

[0070] “Multispecific” refers to a molecule, such as an antibody that specifically binds two or more distinct antigens or two or more distinct epitopes within the same antigen. Multispecific molecule may have cross-reactivity to other related antigens, for example to the same antigen from other species (homologs), such as human or monkey, for example Macaca fascicularis (cynomolgus, cyno) or Pan troglodytes, or may bind an epitope that is shared between two or more distinct antigens.

[0071] As used herein, the term “bispecific antibody” refers to an antibody that binds no more than two epitopes or two antigens. A bispecific antibody is characterized by a first variable heavy and light chain pair which has binding specificity for a first epitope (e.g., an epitope on a hK2 antigen) and a second variable heavy and light chain pair that has binding specificity for a secondepitope (e.g., an epitope on a T cell (e.g., CD3). As used herein, a “bispecific antibody” encompasses a bispecific antibody comprising one or more immunoglobulin (Ig) constant regions, as well as one or more bispecific antigen-binding fragments thereof.

[0072] Unless indicated otherwise, the numbering of amino acid residues in the antibody constant region throughout the specification is according to the EU index as described in Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, Md. (1991), unless otherwise explicitly stated.

[0073] In some embodiments, antibodies described herein can comprise mutations (e.g., amino acid substitutions, additions, and / or deletions) outside of the CDRs (e.g., in framework regions (FRs) or constant regions). An amino acid substitution, addition, and / or deletion can be a substitution, addition, and / or deletion of one or more amino acids (e.g., 1, 2, 3, 4, 5, 6, 7, 8, or more). An amino acid substitution, addition, and / or deletion can be a substitution, addition, and / or deletion of eight or fewer, seven or fewer, six or fewer, five or fewer, four or fewer, three or fewer, or two or fewer single amino acids. In some embodiments, antibodies described herein may include amino acid substitutions, additions, and / or deletions in the constant regions (e.g., Fc region) of the antibody that, e.g., lead to decreased effector function, e.g., decreased complementdependent cytolysis (CDC) antibody-dependent cell-mediated cytolysis (ADCC), antibodydependent cell-mediated phagocytosis (ADCP), and / or decreased B-cell killing. For many applications of therapeutic antibodies, Fc-mediated effector functions are not part of the mechanism of action. These Fc-mediated effector functions can be detrimental and potentially pose a safety risk by causing off-mechanism toxicity. Modifying effector functions can be achieved by engineering the Fc regions to reduce their binding to FcgRs or the complement factors. The binding of IgG to the activating (FcgRI, FcgRIIa, FcgRIIIa and FcgRIIIb) and inhibitory (FcgRIIb) FcgRs or the first component of complement (Clq) depends on residues located in the hinge region and the CH2 domain. Mutations can be introduced in IgGl, IgG2 and IgG4 to reduce or silence Fc functionalities. Silencing mutations can include, but are not limited to IgGl AA (F234A, L235A), IgG4 PAA (S228P, F234A, L235A), IgG2 AA (V234A, G237A), IgGl FEA (L234F, L235E or D265A), IgGl AAS (L234A, L235A, and D265S), or IgGl FES (L234F / L235E / P331 S). In some embodiments, the disclosed antibody or antigen-binding fragment thereof can contain the IgGl AA (L234A, L235A) mutations. In some embodiments, the disclosed antibody or antigen-binding fragment thereof can contain IgGl AAS (L234A, L235A, and D265S) mutations to eliminateeffector function. The disclosed antibodies or antigen-binding fragments thereof can comprise an Fc region with one or more of the following properties: (a) reduced effector function when compared to the parent Fc; (b) reduced affinity to FcyRI, FcyRIIa, FcyRIIb, FcyRIIIb and / or FcyRIIIa; (c) reduced affinity to FcyRI; (d) reduced affinity to FcyRIIa; (e) reduced affinity to FcyRIIb; (f) reduced affinity to FcyRIIIb; or (g) reduced affinity to FcyRIIIa.

[0074] In some embodiment, one or more mutations can be introduced into the CH3 domain of two heavy chains to favor formation of the heterodimer during co-transfection.“Heterodimerization” as used herein refers to an interaction of two heavy chains having nonidentical CH3 amino acid sequences. “Heterodimer” as used herein refers to an antibody having two heavy chains with non-identical CH3 amino acid sequences. The “knob-in-hole” strategy (see, e.g., PCT Publ. No. W02006 / 028936) can be used to generate full length bispecific antibodies. Briefly, selected amino acids forming the interface of the CH3 domains in human IgG can be mutated at positions affecting CH3 domain interactions to promote heterodimer formation. An amino acid with a small side chain (hole) is introduced into a heavy chain of an antibody specifically binding a first antigen and an amino acid with a large side chain (knob) is introduced into a heavy chain of an antibody specifically binding a second antigen. After co-expression of the two antibodies, a heterodimer is formed as a result of the preferential interaction of the heavy chain with a “hole” with the heavy chain with a “knob.” Exemplary CH3 substitution pairs forming a knob and a hole are (expressed as modified position in the first CH3 domain of the first heavy chain / modified position in the second CH3 domain of the second heavy chain): T366Y / F405A, T366W / F405W, F405W / Y407A, T394W / Y407T, T394S / Y407A, T366W / T394S, F405W / T394S and T366W / T366S L368A Y407V. For example, one heavy chain can feature a knob mutation: T366W while another heavy chain can feature the hole mutations: T366S, L368A, Y407V, and the knobs-into-holes mutations promote heterodimerization of the two heavy chains.

[0075] Other strategies such as promoting heavy chain heterodimerization using electrostatic interactions by substituting positively charged residues at one CH3 surface and negatively charged residues at a second CH3 surface can be used, as described in US Pat. Publ. No. US2010 / 0015133; US Pat. Publ. No. US2009 / 0182127; US Pat. Publ. No. US2010 / 028637; or US Pat. Publ. No. US2011 / 0123532. In other strategies, heterodimerization can be promoted by the following substitutions (expressed as modified position in the first CH3 domain of the first heavy chain / modified position in the second CH3 domain of the second heavy chain):L351 Y_F405AY407V / T394W, T3661_K392M_T394W / F405A_Y407V, T366L_K392M_T394W / F405A_Y407V, L351 Y_Y407A / T366A_K409F, L351 Y_Y407A / T366V K409F Y407A / T366A K409F, or T350V L351Y F405A Y407V / T350V_T366L_K392L_T394W as described in U.S. Pat. Publ. No. US2012 / 0149876 or U.S. Pat. Publ. No. US2013 / 0195849. For example, L351Y, F405A and Y407V mutations can be introduced into one immunoglobulin constant region, and T394W can be introduced into another immunoglobulin constant region, and the interaction of the L351Y, F405A and Y407V mutations in the first Ig constant region and T394W mutation in the second Ig constant region promotes heterodimerization of the two immunoglobulin constant regions.

[0076] “CD3” refers to an antigen which is expressed on T cells as part of the multimolecular T cell receptor (TCR) complex and which consists of a homodimer or heterodimer formed from the association of two or four receptor chains: CD3 epsilon, CD3 delta, CD3 zeta and CD3 gamma. All references to proteins, polypeptides and protein fragments herein are intended to refer to the human version of the respective protein, polypeptide or protein fragment unless explicitly specified as being from a non-human species. Thus, “CD3” means human CD3 unless specified as being from a non-human species, e.g., “mouse CD3” or “monkey CD3,” etc.

[0077] Throughout the specification, “CD3 -specific” or “specifically binds CD3” or “anti-CD3 antibody” refers to antibodies that bind specifically to a CD3 -epsilon polypeptide, including antibodies that bind specifically to the CD3 -epsilon extracellular domain (ECD). CD3-epsilon, together with CD3-gamma, -delta and -zeta, and the T-cell receptor alpha / beta and gamma / delta heterodimers, forms the T-cell receptor-CD3 complex. This complex plays an important role in coupling antigen recognition to several intracellular signal-transduction pathways. The CD3 complex mediates signal transduction, resulting in T cell activation and proliferation. CD3 is required for the immune response.

[0078] “Kallikrein related peptidase 2” or “KLK2” or “hK2” refers to a human protein which is also called kallikrein-2, grandular kallikrein 2, or HK2. hK2 is produced as a preproprotein and cleaved during proteolysis to generate active protease. All hK2 isoforms and variants are encompassed in “hK2”. The amino acid sequences of various isoforms are retrievable from public sources, such as GenBank accession numbers NP_005542.1, NP_001002231.1 and NP_001243009.

[0079] “Bispecific anti-hK2 / anti-CD3 antibody”, “hk2 / CD3 antibody”, “hk2xCD3 antibody,” “KLK2xCD3 antibody,” “anti-KLK2xCD3 antibody,” “anti-hK2 / anti-CD3 protein,” and the like, such as “hK2xCD3 bispecific antibody” or “anti-hK2 / anti-CD3 bispecific antibody”, refer to an antibody that binds KLK2 and CD3 and that comprises at least one binding domain specifically binding KLK2 and at least one binding domain specifically binding CD3. The domains specifically binding hK2 and CD3 are typically VH / VL pairs. The bispecific anti-hk2xCD3 antibody may be monovalent in terms of its binding to either KLK2 or CD3.

[0080] The term “conjugated antibody” or “conjugate” refers to an antibody covalently linked to one or more chemical moieties; and the term “conjugated Fc fusion protein” refers to an Fc fusion protein covalently linked to one or more chemical moieties. The chemical moiety that is covalently linked to an antibody or Fc fusion protein can include a linker, a reactive linker, an amine linker, a payload, a reactive payload, an amine payload and / or a reactive-linker-payload.

[0081] As used herein, the term “antibody-payload conjugate”, “reactive payload”, “conjugate” or “antibody drug conjugate” or “ADC” refers to an antibody, or fragment thereof, that have been chemically linked to cytotoxic or cytosolic drug / agent, toxins or radionuclides referred to herein as a “payload” and that are capable of binding tumor-specific or tumor-associated cell surface antigens. Typically, antibody drug conjugates (ADC) are formed by covalently linking anticancer drugs to mAbs through a stable linker system. For example, tumor cell killing may occur upon binding of the drug conjugate to a tumor cell and release or / and activation of the cytotoxic activity of the drug moiety. The selectivity afforded by drug conjugates minimizes toxicity to normal cells, thereby enhancing tolerability of the drug in the patient.

[0082] Any suitable payload known to those skilled in the art in view of the present disclosure can be used in the invention. The payload can be, for example, a drug / agent, a linker, a click reaction partner, etc. According to particular embodiments, the payload can be, for example, a cytotoxic agent, a cytostatic agent, a chemotherapeutic agent, a toxin, a radionuclide, a DNA, an RNA, an siRNA, a microRNA, a peptide nucleic acid, a non-natural amino acid, a peptide, an enzyme, a fluorescent tag, a biotin, a linker, or a first click reaction partner.

[0083] “Decrease,” “lower,” “lessen,” “reduce,” or “abate” refers generally to the ability of a test molecule to mediate a reduced response (i.e., downstream effect) when compared to the response mediated by a control or a vehicle. Decrease may be a statistically significant difference in the measured response between the test molecule and the control (or the vehicle), or a decrease in themeasured response, such as a decrease of about 1.1 , 1.2, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20 or 30 fold or more, such as 500, 600, 700, 800, 900 or 1000 fold or more (including all integers and decimal points in between and above 1, e.g., 1.5, 1.6, 1.7, 1.8, etc.).

[0084] “Enhance,” “promote,” “increase,” “expand” or “improve” refers generally to the ability of a test molecule to mediate a greater response (i.e., downstream effect) when compared to the response mediated by a control or a vehicle. Enhance may be a statistically significant difference in the measured response between the test molecule and control (or vehicle), or an increase in the measured response, such as an increase of about 1.1, 1.2, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20 or 30 fold or more, such as 500, 600, 700, 800, 900 or 1000 fold or more (including all integers and decimal points in between and above 1, e.g., 1.5, 1.6, 1.7, 1.8, etc.).

[0085] “Enhanced immune cell function” can be enhanced function of any type of immune cells, for example of T and / or NK cells, for example of T cells. The term function is understood in accordance with its ordinary meaning in the art. More particularly, it refers to:- tumor cell killing induced or mediated by immune cells (e.g., by T cells and / or NK cells, e.g., by T cells);- cytotoxicity induced or mediated by immune cells (e.g., by T cells and / or NK cells, e.g., by T cells);- activation of immune cells (e.g., of T cells and / or NK cells, e.g., of T cells); and- proliferation of immune cells (e.g., of T cells and / or NK cells, e.g., of T cells); preferably tumor cell killing induced or mediated by immune cells (e.g., by T cells and / or NK cells, e.g., by T cells).

[0086] “Combination” refers to a functional unity comprising two or more ingredients for simultaneous, sequential, or separate administration.

[0087] “In combination with” means that two or more therapeutic agents are be administered to a subject together in a mixture, concurrently as single agents or sequentially as single agents in any order.

[0088] “Pharmaceutical composition” refers to a composition that results from combining an active ingredient and a pharmaceutically acceptable carrier.

[0089] “Pharmaceutically acceptable carrier” or “excipient” refers to an ingredient in a pharmaceutical composition, other than the active ingredient, which is nontoxic to a subject. Exemplary pharmaceutically acceptable carriers are a buffer, stabilizer or preservative.

[0090] “Treat,” “treating” or “treatment” of a disease or disorder such as cancer refers to accomplishing one or more of the following: reducing the severity and / or duration of the disorder, inhibiting worsening of symptoms characteristic of the disorder being treated, limiting or preventing recurrence of the disorder in subjects that have previously had the disorder, or limiting or preventing recurrence of symptoms in subjects that were previously symptomatic for the disorder.

[0091] “Administer” or “administration” refers to the act of physically delivering a substance as it exists outside the body into a patient, by injection or otherwise, such as by mucosal, intradermal, intravenous, intramuscular, subcutaneous delivery, and / or any other method of physical delivery described herein or known in the art.

[0092] “Intravenous infusion” and “intravenous injection” are understood in accordance with their ordinary meaning in the field. “Intravenous infusion” refers to the administration of a treatment directly into a subject’s bloodstream through a vein, for example using a needle or catheter. An intravenous infusion can be delivered over a set period of time, ranging from minutes to several hours (by contrast to an IV injection, such as IV push injection). “Intravenous injection” typically refers to IV push injection.

[0093] “Prevent,” “preventing,” “prevention,” or “prophylaxis” of a disease or disorder means preventing that a disorder occurs in a subject.

[0094] “Relapsed” refers to the return of a disease or the signs and symptoms of a disease after a period of improvement after prior treatment with a therapeutic.

[0095] “Refractory” refers to a disease that does not respond to a treatment. A refractory disease can be resistant to a treatment before or at the beginning of the treatment, or a refractory disease can become resistant during a treatment.

[0096] “Therapeutically effective amount” or “effective amount” used interchangeably herein, refers to an amount effective, at dosages and for periods of time necessary, to achieve a desired therapeutic result. A therapeutically effective amount may vary according to factors such as the disease state, age, sex, and weight of the individual, and the ability of a therapeutic or a combination of therapeutics to elicit a desired response in the individual. Example indicators of an effective therapeutic or combination of therapeutics that include, for example, improved wellbeing of the patient, reduction of a tumor burden, arrested or slowed growth of a tumor, and / or absence of metastasis of cancer cells to other locations in the body. An “effective amount” can be a“combination dose”, a dosage amount of a drug product to be used when the drug product is administered to a subject with another drug product.

[0097] “Intravenous infusion” refers to the administration of a treatment directly into a subject’s bloodstream through a vein, for example using a needle or catheter. An intravenous infusion can be delivered over a set period of time, ranging from minutes to several hours.

[0098] “Treatment dose” refers to a dose of the active agent that is administered to a subject to treat a disease. A treatment dose may be administered at a regular dosing interval on a repetitive basis (e.g. weekly (i.e. once a week), once every 2 weeks, once every 3 weeks, once every 4 weeks, once every 5 weeks, once every 6 weeks etc.). A treatment dose may be preceded by one or more step-up doses.

[0099] “Step-up dose” refers to a dose of an active agent that is administered to a subject prior to a treatment dose. A step-up dose is lower than the treatment dose. A dosing regimen comprising one or more step-up doses followed by higher treatment doses may be considered a “priming” dose strategy.

[0100] “Flat dose” refers to a dose that is administered to a subject without correction for the subject’s specific body weight or body surface area. A flat dose, sometimes referred to as a fixed dose, is therefore provided as an absolute amount of the agent (e.g., mg drug), and not as a weightbased amount that accounts for the subject’s specific weight (e.g. pg / kg or pg drug per kg body weight). For example, a subject weighing 65kg may be administered the same flat dose in milligrams as a subject weighing 85kg. A flat dose may be administered according to a pre-defined class or category of body weight, but is not modified according to the subject’s specific weight. For example, a “Flat Dose A” may be administered if a patient is greater than a pre-defined threshold weight, whereas a different “Flat Dose B” may be administered if the patent is less than the pre-defined threshold weight.

[0101] “Weight-based dose” refers to when a dose, such as a treatment dose or a step-up dose, is determined using the body weight of the subject. Such dosages can, for example, be based on the mg / kg dosages provided above according to the following: dose (mg / kg) x body weight (e.g., 50 - 100 kg).

[0102] “Q6W” is understood in accordance with its ordinary meaning in the field and refers to a dose frequency of once every 6 weeks, or of once every 42 days + / - 3 days, more specifically once every 42 days.

[0103] Throughout the application, in the context of the timing for administering a dose of an ADC or an anti-hK2 / anti-CD3 bispecific antibody to a patient, the expressions “on Day X to Day Y” and “on a day within Day X to Day Y” shall have the same meaning, which explicitly encompasses administering the dose of the ADC or the anti-hK2 / anti-CD3 bispecific antibody to the patient on Day X, Day Y as well as any day between Day X and Day Y. Similar, the expressions “X-Y days” and “a day within X-Y days” prior to or after a stated event shall have the same meaning, which encompasses administering the dose of the ADC or the anti-hK2 / anti-CD3 bispecific antibody to the patient on a day of X days, Y days, or any days between X days and Y days, prior to or after the stated event. For example, if a stated event (e.g., administering to the patient the ADC at a first treatment dose) occurs on Day 1, an administration 7-14 days (or on a day within 7-14 days) after the stated event can be an administration on Day 8, Day 9, Day 10, Day 11, Day 12, Day 13, Day 14 or Day 15.

[0104] “Subject” includes any human or nonhuman animal. “Nonhuman animal” includes all vertebrates, e.g., mammals and non-mammals, such as nonhuman primates, sheep, dogs, cats, horses, cows, chickens, amphibians, reptiles, etc. The terms “subject” and “patient” can be used interchangeably herein.

[0105] “Cancer” refers to a broad group of various diseases characterized by the uncontrolled growth of abnormal cells in the body. Unregulated cell division and growth results in the formation of malignant tumors that invade neighboring tissues and may also metastasize to distant parts of the body through the lymphatic system or bloodstream. A “cancer” or “cancer tissue” can include a tumor.

[0106] “Tumor cell” or a “cancer cell” refers to a cancerous, pre-cancerous or transformed cell, either in vivo, ex vivo, or in tissue culture, that has spontaneous or induced phenotypic changes. These changes do not necessarily involve the uptake of new genetic material. Although transformation may arise from infection with a transforming virus and incorporation of new genomic nucleic acid, uptake of exogenous nucleic acid or it can also arise spontaneously or following exposure to a carcinogen, thereby mutating an endogenous gene. Transformation / cancer is exemplified by morphological changes, immortalization of cells, aberrant growth control, foci formation, proliferation, malignancy, modulation of tumor specific marker levels, invasiveness, tumor growth in suitable animal hosts such as nude mice, and the like, in vitro, in vivo, and ex vivo. 2.

[0107] As used herein, the term “adverse event” (AE) refers to any untoward medical occurrence in a patient administered a pharmaceutical product and which does not necessarily have a causal relationship with the treatment. According to some embodiments of the invention, AEs are rated on a 5-point scale of increasing severity using the following definitions according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0:• Grade 1 (mild): referring to an AE that is asymptomatic or has mild symptoms which are easily tolerated by the subject, which cause minimal discomfort and does not interfere with everyday activities.• Grade 2 (moderate): referring to an AE that is sufficiently discomforting to interfere with instrumental activities of daily living (such as preparing meals, shopping for groceries or clothes, using the telephone, managing money etc.) and intervention may be needed.• Grade 3 (severe): referring to an AE that is severe but not immediately life-threatening but is limiting to self-care activities of daily living (such as bathing, dressing, feeding self, using the toilet, taking medications etc.). Hospitalization of prolongation of hospitalization can occur.• Grade 4 (life threatening) referring to an AE that has life-threatening consequences and which requires urgent intervention• Grade 5: referring to death related to an AE.

[0108] Examples of AEs include Injection Site Reaction (ISR), fatigue, nausea, anemia, constipation, back pain, arthralgia and pyrexia (or fever). These AEs may be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0, published 27th November 2017 (which is available, for example at www_dctd.cancer.gov_research_ctep-trials_for-sites_adverse-events_ctcae-v5-5x7.pdf or https: / / ctep.cancer.gov / protocoldevelopment / electronic_applications / docs / ctcae_v5_quick_referen ce 5x7.pdf) and incorporated by reference herein. NCI-CTCAE is a standard classification and severity grading scale for adverse events in clinical trials and oncology settings.

[0109] Other examples of AE are Cytokine Release Syndrome (CRS) and immune effector cell- associated neurotoxicity syndrome (ICANS). These AEs may be graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) guidelines, which is incorporated by reference (Lee et al. ASTCT Consensus Grading for Cytokine Release Syndrome and NeurologicToxicity Associated with Immune Effector Cells. Biol Blood Marrow Transplant, 2019 Apr;25(4):625-638).

[0110] “Dose limiting toxicity” or “DLT” refers to side effects of a treatment that are serious enough to prevent an increase in dose or level of that treatment. The DLT evaluation period is typically defined as the first 21 days of receiving a treatment dose. Examples of DLTs are as follows:• Neutrophil count decreased (this includes either febrile neutropenia or Neutropenia of Grade 4 for 7 days or more);• Platelet count decreases leading to Grade 3 or higher thrombocytopenia with bleeding or any Grade 4 thrombocytopenia with duration 7 days or more;• Any non-hematological toxicity of Grade >3, with the following exceptions: o Grade 3 fatigue, asthenia, fever, or constipation, lasting less than 7 days with best supportive care; o Grade 3 nausea / vomiting or diarrhea lasting less than 72 hours with adequate antiemetic and other supportive care; o Grade 3 or higher hypertension that can be controlled by medical management in 7 days or less; o Grade 3 or higher alanine aminotransferase (ALT) or aspartate aminotransferase (AST) that resolves to Grade 1 or baseline within 7 days, unless criteria for Hy’s law are met; o Isolated Grade 3 or higher alkaline phosphatase or gamma-glutamyl transferase (GGT) increase that returns to Grade 1 or baseline within 7 days; o Grade 3 or higher lipase or amylase increase not associated with clinical or radiological evidence of pancreatitis; o Grade 3 or higher electrolyte abnormalities that last up to 72 hours, are not clinically complicated, and either resolve spontaneously or respond to conventional medical interventions; and / or o First occurrence of Grade 3 systemic administration-related reactions (sARR) or cytokine release syndrome (CRS).

[0111] Other examples of DLTs are as follows:• Neutrophil count decreased (this includes febrile neutropenia or Neutropenia of Grade 4 for 7 days or more);• Platelet count decreased (Grade 3 thrombocytopenia with clinically significant bleeding or Grade 4 thrombocytopenia with duration >7 days);• Non-hematologic Toxicity• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevation: any occurrence >8X upper limit of normal (ULN) or 5X ULN lasting > 14 days or criteria for Hy’s Law are met• Grade >3 non-hematological toxicity with the following exceptions: o Grade 3 fever o Grade 3 nausea / vomiting or diarrhea lasting <72 hours with adequate antiemetic and other supportive care o Grade >3 hypertension that can be controlled without more intensive medical management and lasts <6 hours o Isolated Grade >3 alkaline phosphatase or gamma-glutamyl transferase (GGT) increase that returns to Grade <1 or baseline in <7 days o Grade >3 lipase or amylase increase not associated with clinical or radiological evidence of pancreatitis o Grade >3 electrolyte or blood glucose abnormalities that last <72 hours, are not clinically complicated, and either resolve spontaneously or respond to conventional medical intervention o Any Grade 3 Adverse Event (AE) of tumor flare (defined as pain at sites of known or suspected tumor) that resolves to Grade <1 in <7 days) o Any Grade 3 infusion-related reaction (IRR) that recovers or is downgraded within 48 hours with medical management

[0112] In a general aspect the application relates to a method of treating prostate cancer, preferably advanced prostate cancer, more preferably metastatic castration-resistant prostate cancer (mCRPC), in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of an antibody drug conjugate (ADC) targeting prostate-specific membrane antigen (PSMA) [at a first treatment dose], and a therapeutically effective amount of an anti- hK2 / anti-CD3 bispecific antibody [at a treatment dose], wherein:a. the ADC comprises an anti-PSMA antibody conjugated to a drug-linker, wherein the conjugation occurs via para-acetyl phenylalanine (pAF) incorporated in the heavy chain sequence of the antibody, wherein the anti-PSMA antibody comprising a heavy chain (HC) of SEQ ID NO: 1 and a light chain (LC) of SEQ ID NO: 2, in which the pAF is incorporated at the HC position Al 14 according to Kabat numbering (i.e., the A, which is at position 116 in the amino acid sequence of SEQ ID NO: 1), and wherein the drug-linker (is amberstatin269 (AS269), which) has the following structure:b. the anti-hK2 / anti-CD3 bispecific antibody comprises a first antigen binding domain that binds specifically to hK2, and a second antigen binding domain that binds specifically to CD3, wherein: i. the first domain comprises a first heavy chain variable region (VH1) of SEQ ID NO: 9 and a first light chain variable region (VL1) of SEQ ID NO: 10; and ii. the second domain comprises a second heavy chain variable region (VH2) of SEQ ID NO: 21 and a second light chain variable region (VL2) of SEQ ID NO: 22.

[0113] The anti-PSMA antibody, which is comprised in the ADC, typically comprises two heavy chains and two light chains. One non-natural amino acid para-acetyl-L-phenylalanine (pAF) is incorporated into each heavy chain at position 114 according to Kabat numbering (i.e., the A, which is at position 116 in the amino acid sequence of SEQ ID NO: 1). A drug-linker is conjugated to each said pAF (DAR=2), via an oxime linkage. Hence, once conjugated to the anti-PSMA antibody, the H2N-O- end of the drug-linker is =N-O-. A pAF conjugated to the H2N-O- end of the drug-linker has the following structure:

[0114] The (anti-PSMA) ADC advantageously is ARX517.

[0115] In certain embodiments, the first domain of the anti-hK2 / anti-CD3 bispecific antibody comprises a Fab and the second domain of the anti-hK2 / anti-CD3 bispecific antibody comprises an scFv.

[0116] In certain embodiments, the scFv comprises, from the N-terminus to the C-terminus, VH2 -linker- VL2 or VL2-linker-VH2, and the linker comprises or consists of the amino acid sequence of SEQ ID NO: 23.

[0117] In some embodiments, the anti-hK2 / anti-CD3 antibody comprises a first heavy chain (HC1), a first light chain (LC1) and a second heavy chain (HC2) having amino acid sequences at least 90% identical to SEQ ID NO: 13, SEQ ID NO: 14 and SEQ ID NO: 26, respectively; preferably, the HC1, LC1 and HC2 comprise the amino acid sequences of SEQ ID NO: 13, SEQ ID NO: 14 and SEQ ID NO: 26, respectively.

[0118] In some embodiments, the anti-PSMA antibody, which is comprised in the ADC, comprises two heavy chains and two light chains, wherein each heavy chain comprises the pAF at position Al 14 according to Kabat numbering, and wherein the drug-linker is conjugated to each said pAF (i.e., DAR=2) via an oxime linkage.

[0119] In some embodiments, the treatment dose of the anti-hK2 / anti-CD3 bi specific antibody is about 300 mg, per administration.

[0120] In some embodiments, the treatment dose of the anti-hK2 / anti-CD3 bi specific antibody is administered at a flat dose.

[0121] In some embodiments, the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody is initially administered on a day, which is after the day of administration of the first treatment dose of the ADC, or on a day, which is before the day of administration of the first treatment dose of the ADC, for example on a day, which is after the day of administration of the first treatment dose of the ADC.

[0122] In some embodiments, the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody is initially administered on a day within 19-23 days, such as 19, 20, 21, 22, or 23 days, preferably 21 days, after the administration of the first treatment dose of the ADC.

[0123] In some embodiments, the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody is subsequently administered once every 5 to 7 weeks, for example, once every 5, 6 or 7 weeks, preferably once every six weeks, after the initial administration of the treatment dose of the anti- hK2 / anti-CD3 bispecific antibody.

[0124] In some embodiments, the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody is intravenously administered, for example, by intravenous (IV) infusion, for example, via IV infusion over a period of about 30 minutes to one hour for each administration, such as over a period of about 30 minutes or a period of about one hour for each administration.

[0125] In certain embodiments, the treatment dose of the anti-hK2 / anti-CD3 bi specific antibody is intravenously administered, for example, by IV infusion, for example, via IV infusion over a period of about one hour for the initial administration, and by IV infusion over a period of about 30 minutes for any subsequent administration.

[0126] In some embodiments, the method does not comprise administering a step-up dose of the anti-hK2 / anti-CD3 bispecific antibody prior to the initial administration of the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody.

[0127] In some embodiments, the method further comprises administering to the (human) patient one or more step-up doses (for example, one or two step-up doses) of the anti-hK2 / anti- CD3 bispecific antibody, wherein the one or more step-up doses are administered prior to the initial administration of the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody and wherein the one or more step-up doses are not higher than the treatment dose.

[0128] In some embodiments, the method further comprises administering to the human patient one or more step-up doses (for example, one or two step-up doses) of the anti-hK2 / anti-CD3 bispecific antibody, wherein the one or more step-up doses are administered after the administration of the first treatment dose of the ADC and prior to the initial administration of the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody and wherein the one or more step-up doses are not higher than the treatment dose.

[0129] In certain embodiments, the one or more step-up doses of the anti-hK2 / anti-CD3 bispecific antibody are intravenously administered, for example via intravenous (IV) infusion.

[0130] In certain embodiments, one step-up dose of the anti-hK2 / anti-CD3 bispecific antibody is administered.

[0131] In certain embodiments, more than one step-up doses of the anti-hK2 / anti-CD3 bispecific antibody are administered.

[0132] In certain embodiments, the more than one step-up doses of the anti-hK2 / anti-CD3 bispecific antibody are administered at a flat dose.

[0133] In certain embodiments, the more than one step-up doses of the anti-hK2 / anti-CD3 bispecific antibody are administered at ascending doses.

[0134] In some embodiments, the method comprises administering to the patient a first step-up dose and a second step-up dose of the anti-hK2 / anti-CD3 bispecific antibody, wherein the first step-up dose is administered prior to the second step-up dose, and the second step-up dose is administered prior to the treatment dose.

[0135] In certain embodiments, the second step-up dose of the anti-hK2 / anti-CD3 bispecific antibody is greater than the first step-up dose.

[0136] In certain embodiments, the method comprises administering to the patient: i) the first step-up dose of the anti-hK2 / anti-CD3 bispecific antibody, ii) the second step-up dose of the anti-hK2 / anti-CD3 bispecific antibody; and iii) the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody, wherein the first step-up dose is administered once, and the second step-up dose is administered once.

[0137] In some embodiments, the method comprises administering to the patient a first step-up dose of the anti-hK2 / anti-CD3 bispecific antibody of about 2 mg to about 5 mg per administration, for example about 2 mg, about 2.5 mg, about 3 mg, about 3.5 mg, about 4 mg, about 4.5 mg or about 5 mg, per administration, preferably about 3.5 mg per administration.

[0138] In some embodiments, the first step-up dose of the anti-hK2 / anti-CD3 bispecific antibody is administered on a day within 5-9 days, such as 5, 6, 7, 8, or 9 days, preferably 7 days, after the first treatment dose of the ADC is administered.

[0139] In certain embodiments, the first step-up dose of the anti-hK2 / anti-CD3 bispecific antibody of about 3.5 mg per administration is administered 7 days after the first treatment dose of the ADC is administered.

[0140] In some embodiments, the method further comprises administering to the patient a second step-up dose of the anti-hK2 / anti-CD3 bispecific antibody of about 15 mg to about 25 mg per administration, for example about 15 mg, about 16 mg, about 17 mg, about 18 mg, about 19 mg, about 20 mg, about 21 mg, about 22 mg, about 23 mg, about 24 mg, or about 25 mg, per administration, preferably about 18 mg per administration.

[0141] In certain embodiments, the second step-up dose of the anti-hK2 / anti-CD3 bi specific antibody is administered on a day within 12-16 days, such as 12, 13, 14, 15 or 16 days, preferably 14 days, after the first treatment dose of the ADC is administered.

[0142] In certain embodiments, the second step-up dose of the anti-hK2 / anti-CD3 bi specific antibody of about 18 mg per administration is administered 14 days after the first treatment dose of the ADC is administered.

[0143] In some embodiments, the one or more step-up doses are administered on a day within 7-14 days, for example 7, 8, 9, 10, 11, 12, 13, or 14 days, prior to the initial administration of the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody.

[0144] In certain embodiments, the first step-up dose of the anti-hK2 / anti-CD3 bispecific antibody is administered 14 days prior to the initial administration of the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody.

[0145] In certain embodiments, the second step-up dose of the anti-hK2 / anti-CD3 bispecific antibody is administered 7 days prior to the initial administration of the treatment dose of the anti- hK2 / anti-CD3 bispecific antibody.

[0146] In some embodiments, the first step-up dose of the anti-hK2 / anti-CD3 bispecific antibody is administered via IV infusion.

[0147] In some embodiments, the second step-up dose of the anti-hK2 / anti-CD3 bispecific antibody is administered via IV infusion.

[0148] In some embodiments, the method comprises:(a) administering to the patient the ADC at a first treatment dose on Day 1 of the treatment;(b) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a first step-up dose of about 2-5 mg per administration on a day within Day 6 to Day 10 of the treatment;(c) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a second step-up dose of about 15-21 mg per administration on a day within Day 13 to Day 17 of the treatment;(d) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 250-350 mg per administration on a day within Day 20 to Day 24 of the treatment; and(e) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 250-350 mg per administration once every 5-7 weeks after step (d), wherein the first step-up dose, the second step-up dose and / or the treatment dose of the anti- hK2 / anti-CD3 bispecific antibody are intravenously administered, advantageously via IV infusion, for example, via IV infusion over a period of about 30 minutes for each administration (and wherein the ADC optionally is intravenously administered, for example via IV infusion, for example by IV infusion over a period of about 30 minutes to one hour for each administration).

[0149] Throughout the application, the expression “a day within Day X and Day Y” explicitly encompasses Day X, Day Y as well as any day between Day X and Day Y.

[0150] In some embodiments, the method comprises:(a) administering to the patient the ADC at a first treatment dose on Day 1 of the treatment;(b) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a first step-up dose of about 2-5 mg per administration on a day within Day 6 to Day 10 of the treatment;(c) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a second step-up dose of about 15-21 mg per administration on a day within Day 13 to Day 17 of the treatment;(d) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 250-350 mg per administration on a day within Day 20 to Day 24 of the treatment; and(e) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 250-350 mg per administration once every 5-7 weeks after step (d),wherein each of the first step-up dose, the second step-up dose and the treatment dose of the anti- hK2 / anti-CD3 bispecific antibody is intravenously administered, for example, via IV infusion, for example, via IV infusion over a period of about one hour for each administration (and wherein the ADC optionally is intravenously administered, for example via IV infusion).

[0151] In certain embodiments, the method comprises:(a) administering to the patient the ADC at the first treatment dose on Day 1 of the treatment;(b) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a first step-up dose of about 3.5 mg per administration on Day 8 of the treatment;(c) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a second step-up dose of about 18 mg per administration on Day 15 of the treatment;(d) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 300 mg per administration on Day 22 of the treatment; and(e) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 300 mg per administration once every 6 weeks after step (d), wherein the first step-up dose, the second step-up dose and the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody is intravenously administered, advantageously via IV infusion, for example, via IV infusion over a period of about 30 minutes for each administration (and wherein the ADC optionally is intravenously administered, for example via IV infusion).

[0152] In certain embodiments, the method comprises:(a) administering to the patient the ADC at the first treatment dose on Day 1 of the treatment;(b) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a first step-up dose of about 3.5 mg per administration on Day 8 of the treatment;(c) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a second step-up dose of about 18 mg per administration on Day 15 of the treatment;(d) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 300 mg per administration on Day 22 of the treatment; and(e) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 300 mg per administration once every 6 weeks after step (d), wherein the first step-up dose, the second step-up dose and the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody are intravenously administered, advantageously via IV infusion, for example, via IV infusion over a period of about one hour for each administration (and wherein the ADC optionally is intravenously administered, for example via IV infusion).

[0153] In some embodiments, the ADC is administered at the first treatment dose of 2.0 mg / kg or lower, such as 1.9-1.4 mg / kg or 1.7-1.4 mg / kg, e.g., 2.0 mg / kg, 1.7 mg / kg or 1.4 mg / kg.

[0154] In some embodiments, the ADC is administered at the first treatment dose of 1.4 mg / kg.

[0155] In some embodiments, the ADC is administered at the first treatment dose of 2.0 mg / kg.

[0156] In some embodiments, the method further comprises administering to the patient a second treatment dose of the ADC, for example a second treatment dose of the ADC:(a) on a day within 19-44 days, such as on a day within 19-23 days or 40-44 days, for example 19, 20, 21, 22, or 23 days, preferably 21 days or 40, 41, 42, 43 or 44 days, preferably 41 days, after the administration of the first treatment dose of the ADC; or(b) on a day within 2 to 7 weeks, such as 2, 3, 4, 5, 6 or 7 weeks, for example 3 weeks or 6 weeks, after the administration of the first treatment dose of the ADC.

[0157] In some embodiments, the method further comprises administering to the patient a second treatment dose of the ADC.

[0158] In certain embodiments, the second treatment dose of the ADC is the same dose as the first treatment dose of the ADC.

[0159] In certain embodiments, the second treatment dose of the ADC is 1.4 mg / kg.

[0160] In certain embodiments, the first and second treatment dose of the ADC is 1.4 mg / kg.

[0161] In certain embodiments, the first and second treatment dose of the ADC is 2.0 mg / kg.

[0162] In certain embodiments, the second treatment dose of the ADC is lower than the first treatment dose of the ADC but is higher than 1.4 mg / kg.

[0163] In some embodiments, the first treatment dose of the ADC is 2 mg / kg, and the second treatment dose of the ADC is 1.4 mg / kg.

[0164] In some embodiments, the second treatment dose of the ADC is administered on a day within 19-23 days, such as 19, 20, 21, 22, or 23 days, preferably 21 days, after the first treatment dose of ADC is administered.

[0165] In certain embodiments, the second treatment dose of the ADC is administered 21 days after the first treatment dose of ADC is administered.

[0166] In some embodiments, the second treatment dose of the ADC is administered on a day 40-44 days, such as 40, 41, 42, 43 or 44 days, preferably 42 days, after the first treatment dose of ADC is administered.

[0167] In some embodiments, the second treatment dose of the ADC is administered 4e days, after the first treatment dose of ADC is administered

[0168] In some embodiments, the method further comprises administering to the patient a subsequent treatment dose of the ADC after the administration of the second treatment dose of the ADC, for example a subsequent treatment dose of the ADC once every 2 to 7 weeks, such as once every 2, 3, 4, 5, 6 or 7 weeks, for example once every 3 weeks or once every 6 weeks, after the administration of the second treatment dose of the ADC.

[0169] In certain embodiments, the subsequent treatment dose of the ADC is administered once every 6 weeks.

[0170] In certain embodiments, the subsequent treatment dose of the ADC is administered once every 3 weeks.

[0171] In certain embodiments, the subsequent treatment dose of the ADC is administered once every 3 weeks for 2, 3, or 4 doses and followed by once every 6 weeks.

[0172] In some embodiments, the subsequent treatment dose of the ADC is administered once every 6 weeks for 2, 3, 4, 5 or 6 doses.

[0173] In some embodiments, the subsequent treatment dose of the ADC is administered once every 6 weeks for 2 subsequent treatment doses for a total of 4 treatment doses every 6 weeks (i.e., Q6W between treatment doses No. 1, No. 2, No. 3 and No. 4).

[0174] In some embodiments, the subsequent treatment dose of the ADC is administered once every 6 weeks for 3 subsequent treatment doses for a total of 5 treatment doses every 6 weeks (i.e., Q6W between treatment doses No. 1, No. 2, No. 3, No. 4 and No. 5).

[0175] In some embodiments, the subsequent treatment dose of the ADC is administered once every 6 weeks for 4 subsequent treatment doses for a total of 5 treatment doses every 6 weeks (i.e., Q6W between treatment doses No. 1, No. 2, No. 3, No. 4, and No. 6).

[0176] In some embodiments, the subsequent treatment dose of the ADC is administered once every 6 weeks for 5 subsequent treatment doses for a total of 5 treatment doses every 6 weeks (i.e., Q6W between treatment doses No. 1, No. 2, No. 3, No. 4, No. 5, No. 6, and No, 7).

[0177]

[0176] In some embodiments, the subsequent treatment dose of the ADC is administered once every 6 weeks for 6 subsequent treatment doses for a total of 5 treatment doses every 6 weeks (i.e., Q6W between treatment doses No. 1, No. 2, No. 3, No. 4, No. 5, No. 6, No, 7, and No. 8).

[0178] In some embodiments, the subsequent treatment dose of the ADC is administered once every 3 weeks for 2 doses.

[0179] In some embodiments, the method does not comprise administering more than 4 doses of the ADC.

[0180] In some embodiments, the method does not comprise administering more than 3 doses of the ADC .

[0181] In some embodiments, the method does not comprise administering more than 2 doses of the ADC .

[0182] In some embodiments, the subsequent treatment dose of the ADC is the same dose as the second treatment dose of the ADC.

[0183] In some embodiments, the subsequent treatment dose of the ADC is 1.4 mg / kg.

[0184] In some embodiments, the subsequent treatment dose of the ADC is 2.0 mg / kg.

[0185] In certain embodiments, the second and subsequent treatment dose of the ADC is 1.4 mg / kg.

[0186] In certain embodiments, the second and subsequent treatment dose of the ADC is 2.0 mg / kg.

[0187] In some embodiments, the subsequent treatment dose of the ADC is lower than the second treatment dose of the ADC but is higher than 1.4 mg / kg.

[0188] In some embodiments, the second treatment dose of the ADC is 2 mg / kg, and the subsequent treatment dose of the ADC is 1.4 mg / kg.

[0189] In some embodiments, the second treatment dose of the ADC is administered on a day 40-44 days, such as 40, 41, 42, 43 or 44 days, preferably 41 days, after the first treatment dose of ADC is administered.

[0190] In some embodiments, the second treatment dose of the ADC is administered 41 days after the first treatment dose of ADC is administered.

[0191] In some embodiments, the method further comprises administering to the patient a subsequent treatment dose of the ADC once every 2 to 7 weeks, such as once every 4, 5 or 6 weeks, after the administration of the second treatment dose of the ADC.

[0192] In some embodiments, the subsequent treatment dose of the ADC is administered once every 6 weeks.

[0193] In some embodiments, the subsequent treatment dose of the ADC is administered once every 3 weeks.

[0194] In some embodiments, the subsequent treatment dose of the ADC is the same dose as the second treatment dose of the ADC.

[0195] In some embodiments, the subsequent treatment dose of the ADC is lower than the second treatment dose of the ADC but is higher than 1.4 mg / kg.

[0196] In some embodiments, the first treatment dose, the second treatment dose, and / or the subsequent treatment dose of the ADC is intravenously administered, for example, by intravenous (IV) infusion over a period of about 30 minutes to one hour for each administration, such as over a period of about 30 minutes or a period of about one hour for each administration.

[0197] In some embodiments, the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody is intravenously administered, advantageously via IV infusion, for example, by IV infusion over a period of about one hour for the initial administration, and by IV infusion over a period of about 30 minutes for any subsequent administration.

[0198] In some embodiments, the method does not comprise administering a step-up dose of the ADC prior to the administration of the first treatment dose, the second treatment dose, and / or the subsequent treatment dose of the ADC.

[0199] In some embodiments, the method comprises:(a) administering to the patient the ADC at a first treatment dose on Day 1 of the treatment, wherein the first treatment dose is about 2.0 mg / kg;(b) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a first step-up dose of about 3.5 mg on a day within Day 6 to Day 10 of the treatment, for example on Day 8;(c) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a second step- up dose of about 18.5 mg on a day within Day 13 to Day 17 of the treatment, for example on Day 15;(d) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 300 mg on a day within Day 20 to Day 24 of the treatment, for example on Day 22;(e) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 300 mg per administration once every 6 weeks after the administering of step(f) administering to the patient a second treatment dose of the ADC on a day within Day 20 to Day 24 of the treatment, for example on Day 22, wherein the second treatment dose of the ADC is the same dose as the first treatment dose of the ADC;(g) administering to the patient a third and fourth treatment dose of the ADC once every 3 weeks after the administering of step (f), wherein the third and fourth treatment dose of the ADC is the same dose as the second treatment dose of the ADC.

[0200] In some embodiments, the total number of doses of the ADC does not exceed 4 doses.

[0201] In some embodiments, the method comprises:(a) administering to the patient the ADC at a first treatment dose on Day 1 of the treatment, wherein the first treatment dose is about 2.0 mg / kg;(b) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a first step-up dose of about 3.5 mg on a day within Day 6 to Day 10 of the treatment, for example on Day 8;(c) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a second step-up dose of about 18.5 mg on a day within Day 13 to Day 17 of the treatment, for example on Day 15;(d) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 300 mg on a day within Day 20 to Day 24 of the treatment, for example on Day 22;(e) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 300 mg per administration once every 6 weeks after the administering of step (d);(f) administering to the patient a second treatment dose of the ADC on a day within Day 40 to Day 44 of the treatment, for example on Day 43, wherein the second treatment dose of the ADC is the same dose as the first treatment dose of the ADC;(g) administering to the patient a subsequent treatment dose of the ADC once every 6 weeks after the administering of step (f), wherein the subsequent treatment dose of the ADC is the same dose as the second treatment dose of the ADC and the total number of doses of the ADC is 3 doses, 4 doses, 5 doses, 6 doses, 7 doses or 8 doses.

[0202] In some embodiments, the method comprises:(a) administering to the patient the ADC at a first treatment dose on Day 1 of the treatment, wherein the first treatment dose is about 2.0 mg / kg;(b) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a first step-up dose of about 3.5 mg on a day within Day 6 to Day 10 of the treatment, for example on Day 8;(c) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a second step-up dose of about 18.5 mg on a day within Day 13 to Day 17 of the treatment, for example on Day 15;(d) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 300 mg on a day within Day 20 to Day 24 of the treatment, for example on Day 22;(e) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 300 mg per administration once every 6 weeks after the administering of step (d);(f) administering to the patient a second treatment dose of the ADC on a day within Day 40 to Day 44 of the treatment, for example on Day 43, wherein the second treatment dose of the ADC is the same dose as the first treatment dose of the ADC.

[0203] In some of the embodiments, the first step-up dose, the second step-up dose and the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody are each intravenously administered, advantageously via IV infusion and the first treatment dose, the second treatment dose and the subsequent treatment dose of the ADC are each intravenously administered, for example, via IV infusion.

[0204] In certain embodiments, the method comprises:(a) administering to the patient the ADC at a first treatment dose on Day 1 of the treatment, wherein the first treatment dose is 2.0 mg / kg or lower, such as 1.9- 1.4 mg / kg or 1.7-1.4 mg / kg, e.g., 2.0 mg / kg, 1.7 mg / kg or 1.4 mg / kg;(b) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a first step-up dose of about 2-5 mg per administration on a day within Day 6 to Day 10 of the treatment;(c) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a second step-up dose of about 15-21 mg per administration on a day within Day 13 to Day 17 of the treatment;(d) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 250-350 mg per administration on a day within Day 20 to Day 24 of the treatment;(e) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 250-350 mg per administration once every 5-7 weeks after the administering of step (d),(f) administering to the patient a second treatment dose of the ADC on a day within Day 20 to Day 24 of the treatment, wherein the second treatment dose of the ADC is the same dose as the first treatment dose of the ADC, or the second treatment dose of the ADC is lower than the first treatment dose of the ADC but is higher than 1.4 mg / kg;(g) administering to the patient the ADC at a subsequent treatment dose once every 2 to 7 weeks, such as once every 3 weeks, once every 6 weeks, or once every 3 weeks for 2-4 doses and followed by once every 6 weeks, after the administering of step (f), wherein the subsequent treatment dose of the ADC is the same dose as thesecond treatment dose of the ADC, or the subsequent treatment dose of the ADC is lower than the second treatment dose of the ADC but is higher than 1.4 mg / kg; wherein, the first step-up dose, the second step-up dose and / or the treatment doses of the anti-hK2 / anti-CD3 bispecific antibody are intravenously administered, advantageously via IV infusion, for example, via IV infusion over a period of about 30 minutes for each administration; and wherein the first treatment dose, the second treatment dose and / or the subsequent treatment dose of the ADC is intravenously administered, for example, via IV infusion over a period of about 30 minutes for each administration.

[0205] In certain embodiments, the method comprises:(a) administering to the patient the ADC at a first treatment dose on Day 1 of the treatment, wherein the first treatment dose is 2.0 mg / kg or lower, such as 1.9- 1.4 mg / kg or 1.7-1.4 mg / kg, e.g., 2.0 mg / kg, 1.7 mg / kg or 1.4 mg / kg;(b) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a first step-up dose of about 2-5 mg per administration on a day within Day 6 to Day 10 of the treatment;(c) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a second step-up dose of about 15-21 mg per administration on day within Day 13 to Day 17 of the treatment;(d) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 250-350 mg per administration on a day within Day 20 to Day 24 of the treatment;(e) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 250-350 mg per administration once every 5-7 weeks after the administering of step (d),(f) administering to the patient a second treatment dose of the ADC on a day within Day 20 to Day 24 of the treatment, wherein the second treatment dose of the ADC is the same dose as the first treatment dose of the ADC, or the second treatment dose of the ADC is lower than the first treatment dose of the ADC but is higher than 1.4 mg / kg;(g) administering to the patient the ADC at a subsequent treatment dose once every 2 to 7 weeks, such as once every 3 weeks, once every 6 weeks, or once every 3 weeks for 2-4 doses and followed by once every 6 weeks, after the administering of step (f), wherein the subsequent treatment dose of the ADC is the same dose as the second treatment dose of the ADC, or the subsequent treatment dose of the ADC is lower than the second treatment dose of the ADC but is higher than 1.4 mg / kg; wherein, the first step-up dose, the second step-up dose and / or the treatment doses of the anti-hK2 / anti-CD3 bispecific antibody are intravenously administered, advantageously via IV infusion, for example, via IV infusion over a period of about one hour for each administration; and wherein the first treatment dose, the second treatment dose and / or the subsequent treatment dose of the ADC is intravenously administered, for example, via IV infusion over a period of about one hour for each administration.

[0206] In certain embodiments, the method comprises:(a) administering to the patient the ADC at a first treatment dose on Day 1 of the treatment, wherein the first treatment dose is 2.0 mg / kg, 1.7 mg / kg or 1.4 mg / kg;(b) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a first step-up dose of about 3.5 mg per administration on Day 8 of the treatment;(c) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a second step-up dose of about 18 mg per administration on Day 15 of the treatment;(d) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 300 mg per administration on Day 22 of the treatment;(e) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 300 mg per administration once every 6 weeks after the administering of step (d),(f) administering to the patient a second treatment dose of the ADC on Day 22 of the treatment, wherein the second treatment dose of the ADC is the same dose as the first treatment dose of the ADC, or the second treatment dose of the ADC is lower than the first treatment dose of the ADC but is higher than 1.4 mg / kg;(g) administering to the patient the ADC at a subsequent treatment dose once every 3 weeks, once every 6 weeks, or once every 3 weeks for 2-4 doses and followed byonce every 6 weeks, after the administering of step (f), wherein the subsequent treatment dose of the ADC is the same dose as the second treatment dose of the ADC, or the subsequent treatment dose of the ADC is lower than the second treatment dose of the ADC but is higher than 1.4 mg / kg; wherein the first step-up dose, the second step-up dose and / or the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody are intravenously administered, advantageously via IV infusion, for example, via IV infusion over a period of about 30 minutes for each administration; and wherein the first treatment dose, the second treatment dose and / or the subsequent treatment dose of the ADC is intravenously administered, for example, via IV infusion over a period of about 30 minutes for each administration.

[0207] In certain embodiments, the method comprises:(a) administering to the patient the ADC at a first treatment dose on Day 1 of the treatment, wherein the first treatment dose is 1.4 mg / kg;(b) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a first step-up dose of about 2-5 mg per administration on a day within Day 6 to Day 10 of the treatment;(c) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a second step-up dose of about 15-21 mg per administration on day within Day 13 to Day 17 of the treatment;(d) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 250-350 mg per administration on a day within Day 20 to Day 24 of the treatment;(e) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 250-350 mg per administration once every 5-7 weeks after the administering of step (d),(f) administering to the patient a second treatment dose of the ADC on a day within Day 20 to Day 24 of the treatment, wherein the second treatment dose of the ADC is 1.4 mg / kg;(g) administering to the patient the ADC at a subsequent treatment dose once every 3 weeks, after the administering of step (f), wherein the subsequent treatment dose of the ADC is 1.4 mg / kg; wherein, the first step-up dose, the second step-up dose and / or the treatment doses of the anti-hK2 / anti-CD3 bispecific antibody are intravenously administered, advantageously via IV infusion, for example, via IV infusion over a period of about one hour for each administration; and wherein the first treatment dose, the second treatment dose and / or the subsequent treatment dose of the ADC is intravenously administered, for example, via IV infusion over a period of about one hour for each administration.

[0208] In certain embodiments, the method comprises:(a) administering to the patient the ADC at a first treatment dose on Day 1 of the treatment, wherein the first treatment dose is 2.0 mg / kg;(b) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a first step-up dose of about 2-5 mg per administration on a day within Day 6 to Day 10 of the treatment;(c) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a second step-up dose of about 15-21 mg per administration on day within Day 13 to Day 17 of the treatment;(d) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 250-350 mg per administration on a day within Day 20 to Day 24 of the treatment;(e) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 250-350 mg per administration once every 5-7 weeks after the administering of step (d),(f) administering to the patient a second treatment dose of the ADC on a day within Day 20 to Day 24 of the treatment, wherein the second treatment dose of the ADC is 2.0 mg / kg;(g) administering to the patient the ADC at a subsequent treatment dose once every 3 weeks after the administering of step (f), wherein the subsequent treatment dose of the ADC is 2.0 mg / kg;wherein, the first step-up dose, the second step-up dose and / or the treatment doses of the anti-hK2 / anti-CD3 bispecific antibody are intravenously administered, advantageously via IV infusion, for example, via IV infusion over a period of about one hour for each administration; and wherein the first treatment dose, the second treatment dose and / or the subsequent treatment dose of the ADC is intravenously administered, for example, via IV infusion over a period of about one hour for each administration.

[0209] In certain embodiments, the method comprises:(a) administering to the patient the ADC at a first treatment dose on Day 1 of the treatment, wherein the first treatment dose is 2.0 mg / kg;(b) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a first step-up dose of about 2-5 mg per administration on a day within Day 6 to Day 10 of the treatment;(c) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a second step-up dose of about 15-21 mg per administration on day within Day 13 to Day 17 of the treatment;(d) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 250-350 mg per administration on a day within Day 20 to Day 24 of the treatment;(e) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 250-350 mg per administration once every 5-7 weeks after the administering of step (d),(f) administering to the patient a second treatment dose of the ADC on a day within Day 20 to Day 24 of the treatment, wherein the second treatment dose of the ADC is 2.0 mg / kg;(g) administering to the patient the ADC at a subsequent treatment dose once every 3 weeks after the administering of step (f), wherein the subsequent treatment dose of the ADC is 1.4 mg / kg; wherein, the first step-up dose, the second step-up dose and / or the treatment doses of the anti-hK2 / anti-CD3 bispecific antibody are intravenously administered, advantageously viaIV infusion, for example, via TV infusion over a period of about one hour for each administration; and wherein the first treatment dose, the second treatment dose and / or the subsequent treatment dose of the ADC is intravenously administered, for example, via IV infusion over a period of about one hour for each administration.

[0210] In certain embodiments, the method comprises:(a) administering to the patient the ADC at a first treatment dose on Day 1 of the treatment, wherein the first treatment dose is 2.0 mg / kg;(b) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a first step-up dose of about 2-5 mg per administration on a day within Day 6 to Day 10 of the treatment;(c) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a second step-up dose of about 15-21 mg per administration on day within Day 13 to Day 17 of the treatment;(d) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 250-350 mg per administration on a day within Day 20 to Day 24 of the treatment;(e) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 250-350 mg per administration once every 5-7 weeks after the administering of step (d),(f) administering to the patient a second treatment dose of the ADC on a day within Day 20 to Day 24 of the treatment, wherein the second treatment dose of the ADC is 1.4 mg / kg;(g) administering to the patient the ADC at a subsequent treatment dose once every 3 weeks after the administering of step (f), wherein the subsequent treatment dose of the ADC is 1.4 mg / kg; wherein, the first step-up dose, the second step-up dose and / or the treatment doses of the anti-hK2 / anti-CD3 bispecific antibody are intravenously administered, advantageously via IV infusion, for example, via IV infusion over a period of about one hour for each administration;and wherein the first treatment dose, the second treatment dose and / or the subsequent treatment dose of the ADC is intravenously administered, for example, via IV infusion over a period of about one hour for each administration.

[0211] In certain embodiments, the method comprises:(a) administering to the patient the ADC at a first treatment dose on Day 1 of the treatment, wherein the first treatment dose is 2.0 mg / kg, 1.7 mg / kg or 1.4 mg / kg;(b) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a first step-up dose of about 3.5 mg per administration on Day 8 of the treatment;(c) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a second step-up dose of about 18 mg per administration on Day 15 of the treatment;(d) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 300 mg per administration on Day 22 of the treatment;(e) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 300 mg per administration once every 6 weeks after the administering of step (d),(f) administering to the patient a second treatment dose of the ADC on Day 22 of the treatment, wherein the second treatment dose of the ADC is the same dose as the first treatment dose of the ADC, or the second treatment dose of the ADC is lower than the first treatment dose of the ADC but is higher than 1.4 mg / kg;(g) administering to the patient the ADC at a subsequent treatment dose once every 3 weeks, once every 6 weeks, or once every 3 weeks for 2-4 doses and followed by once every 6 weeks, after the administering of step (f), wherein the subsequent treatment dose of the ADC is the same dose as the second treatment dose of the ADC, or the subsequent treatment dose of the ADC is lower than the second treatment dose of the ADC but is higher than 1.4 mg / kg; wherein the first step-up dose, the second step-up dose and / or the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody are intravenously administered, advantageously via IV infusion, for example, via IV infusion over a period of about one hour for each administration; andwherein each of the first treatment dose, the second treatment dose and / or the subsequent treatment dose of the ADC is intravenously administered, for example, via IV infusion over a period of about one hour for each administration.

[0212] In some embodiments, the method comprises:(a) administering to the patient the ADC at a first treatment dose on Day 1 of the treatment, wherein the first treatment dose is 2.0 mg / kg or lower, such as 1.9- 1.4 mg / kg or 1.7-1.4 mg / kg, e.g., 2.0 mg / kg, 1.7 mg / kg or 1.4 mg / kg;(b) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a first step-up dose of about 2-5 mg per administration on a day within Day 6 to Day 10 of the treatment;(c) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a second step-up dose of about 15-21 mg per administration on a day within Day 13 to Day 17 of the treatment;(d) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 250-350 mg per administration on a day within Day 20 to Day 24 of the treatment;(e) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 250-350 mg per administration once every 5-7 weeks after the administering of step (d),(f) administering to the patient a second treatment dose of the ADC on a day within Day 40 to Day 44 of the treatment, wherein the second treatment dose of the ADC is the same dose as the first treatment dose of the ADC, or the second treatment dose of the ADC is lower than the first treatment dose of the ADC but is higher than 1.4 mg / kg;(g) administering to the patient the ADC at a subsequent treatment dose once every 5 to 7 weeks, such as once every 6 weeks after the administering of step (f), wherein the subsequent treatment dose of the ADC is the same dose as the second treatment dose of the ADC, or the subsequent treatment dose of the ADC is lower than the second treatment dose of the ADC but is higher than 1.4 mg / kg; wherein, the first step-up dose, the second step-up dose and / or the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody are intravenously administered, advantageously viaIV infusion, for example by IV infusion over a period of about 30 minutes to one hour for each administration; and wherein, the first treatment dose, the second treatment dose and / or the subsequent treatment dose of the ADC are intravenously administered, for example, via IV infusion, for example by IV infusion over a period of about 30 minutes to one hour for each administration.

[0213] In some embodiments, the method comprises:(a) administering to the patient the ADC at a first treatment dose on Day 1 of the treatment, wherein the first treatment dose is 2.0 mg / kg, 1.7 mg / kg or 1.4 mg / kg;(b) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a first step-up dose of about 3.5 mg per administration on Day 8 of the treatment;(c) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a second step-up dose of about 18 mg per administration on Day 15 of the treatment;(d) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 300 mg per administration on Day 22 of the treatment;(e) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 300 mg per administration once every 6 weeks after the administering of step (d),(f) administering to the patient a second treatment dose of the ADC on Day 42 of the treatment, wherein the second treatment dose of the ADC is the same dose as the first treatment dose of the ADC, or the second treatment dose of the ADC is lower than the first treatment dose of the ADC but is higher than 1.4 mg / kg;(g) administering to the patient the ADC at a subsequent treatment dose once every 6 weeks after the administering of step (f), wherein the subsequent treatment dose of the ADC is the same dose as the second treatment dose of the ADC, or the subsequent treatment dose of the ADC is lower than the second treatment dose of the ADC but is higher than 1.4 mg / kg; wherein the first step-up dose, the second step-up dose and / or the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody are intravenously administered, advantageously via IV infusion, for example by IV infusion over a period of about 30 minutes to one hour for each administration; andwherein the first treatment dose, the second treatment dose and / or the subsequent treatment dose of the ADC is intravenously administered, for example, via IV infusion, for example by IV infusion over a period of about 30 minutes to one hour for each administration.

[0214] In some embodiments, the method comprises:(a) administering to the patient the ADC at a first treatment dose on Day 1 of the treatment, wherein the first treatment dose is 1.4 mg / kg;(b) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a first step-up dose of about 3.5 mg per administration on Day 8 of the treatment;(c) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a second step-up dose of about 18 mg per administration on Day 15 of the treatment;(d) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 300 mg per administration on Day 22 of the treatment;(e) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 300 mg per administration once every 6 weeks after the administering of step (d),(f) administering to the patient a second treatment dose of the ADC on Day 42 of the treatment, wherein the second treatment dose of the ADC is the 1.4 mg / kg;(g) administering to the patient the ADC at a subsequent treatment dose once every 3 weeks after the administering of step (f), wherein the subsequent treatment dose of the ADC is 1.4 mg / kg; wherein the first step-up dose, the second step-up dose and / or the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody are intravenously administered, advantageously via IV infusion, for example by IV infusion over a period of about 30 minutes to one hour for each administration; and wherein the first treatment dose, the second treatment dose and / or the subsequent treatment dose of the ADC is intravenously administered, for example, via IV infusion, for example by IV infusion over a period of about 30 minutes to one hour for each administration.

[0215] In some embodiments, the method comprises:(a) administering to the patient the ADC at a first treatment dose on Day 1 of the treatment, wherein the first treatment dose is 2.0 mg / kg;(b) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a first step-up dose of about 3.5 mg per administration on Day 8 of the treatment;(c) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a second step-up dose of about 18 mg per administration on Day 15 of the treatment;(d) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 300 mg per administration on Day 22 of the treatment;(e) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 300 mg per administration once every 6 weeks after the administering of step (d),(f) administering to the patient a second treatment dose of the ADC on Day 42 of the treatment, wherein the second treatment dose of the ADC is the 2.0 mg / kg;(g) administering to the patient the ADC at a subsequent treatment dose once every 3 weeks after the administering of step (f), wherein the subsequent treatment dose of the ADC is 2.0 mg / kg; wherein the first step-up dose, the second step-up dose and / or the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody are intravenously administered, advantageously via IV infusion, for example by IV infusion over a period of about 30 minutes to one hour for each administration; and wherein the first treatment dose, the second treatment dose and / or the subsequent treatment dose of the ADC is intravenously administered, for example, via IV infusion, for example by IV infusion over a period of about 30 minutes to one hour for each administration.

[0216] In some embodiments, the method comprises:(a) administering to the patient the ADC at a first treatment dose on Day 1 of the treatment, wherein the first treatment dose is 2.0 mg / kg;(b) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a first step-up dose of about 3.5 mg per administration on Day 8 of the treatment;(c) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a second step-up dose of about 18 mg per administration on Day 15 of the treatment;(d) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 300 mg per administration on Day 22 of the treatment;(e) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 300 mg per administration once every 6 weeks after the administering of step (d),(f) administering to the patient a second treatment dose of the ADC on Day 42 of the treatment, wherein the second treatment dose of the ADC is the 2.0 mg / kg;(g) administering to the patient the ADC at a subsequent treatment dose once every 3 weeks after the administering of step (f), wherein the subsequent treatment dose of the ADC is 1.4 mg / kg; wherein the first step-up dose, the second step-up dose and / or the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody are intravenously administered, advantageously via IV infusion, for example by IV infusion over a period of about 30 minutes to one hour for each administration; and wherein the first treatment dose, the second treatment dose and / or the subsequent treatment dose of the ADC is intravenously administered, for example, via IV infusion, for example by IV infusion over a period of about 30 minutes to one hour for each administration.

[0217] In some embodiments, the method comprises:(a) administering to the patient the ADC at a first treatment dose on Day 1 of the treatment, wherein the first treatment dose is 2.0 mg / kg;(b) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a first step-up dose of about 3.5 mg per administration on Day 8 of the treatment;(c) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a second step-up dose of about 18 mg per administration on Day 15 of the treatment;(d) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 300 mg per administration on Day 22 of the treatment;(e) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 300 mg per administration once every 6 weeks after the administering of step (d),(f) administering to the patient a second treatment dose of the ADC on Day 42 of the treatment, wherein the second treatment dose of the ADC is the 1.4 mg / kg;(g) administering to the patient the ADC at a subsequent treatment dose once every 3 weeks after the administering of step (f), wherein the subsequent treatment dose of the ADC is 1.4 mg / kg; wherein the first step-up dose, the second step-up dose and / or the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody are intravenously administered, advantageously via IV infusion, for example by IV infusion over a period of about 30 minutes to one hour for each administration; and

[0218] wherein the first treatment dose, the second treatment dose and / or the subsequent treatment dose of the ADC is intravenously administered, for example, via IV infusion, for example by IV infusion over a period of about 30 minutes to one hour for each administration.

[0219] In some embodiments, the method comprises:(a) administering to the patient the ADC at a first treatment dose on Day 1 of the treatment, wherein the first treatment dose is 2.0 mg / kg;(b) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a first step-up dose of about 3.5 mg per administration on Day 8 of the treatment;(c) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a second step-up dose of about 18 mg per administration on Day 15 of the treatment;(d) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 300 mg per administration on Day 22 of the treatment;(e) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 300 mg per administration once every 6 weeks after the administering of step (d),(f) administering to the patient a subsequent treatment dose of the ADC once every 3 weeks for 3 doses after the administering of step (a), wherein the subsequent treatment dose of the ADC is 2.0 mg / kg; wherein the first step-up dose, the second step-up dose and / or the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody are intravenously administered, advantageously via IV infusion, for example by IV infusion over a period of about 30 minutes to one hour for each administration; and

[0220] wherein the first treatment dose, and / or the subsequent treatment dose of the ADC is intravenously administered, for example, via IV infusion, for example by IV infusion over a period of about 30 minutes to one hour for each administration.

[0221] In some embodiments, the method comprises:(a) administering to the patient the ADC at a first treatment dose on Day 1 of the treatment, wherein the first treatment dose is 2.0 mg / kg;(b) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a first step-up dose of about 3.5 mg per administration on Day 8 of the treatment;(c) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a second step-up dose of about 18 mg per administration on Day 15 of the treatment;(d) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 300 mg per administration on Day 22 of the treatment;(e) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 300 mg per administration once every 6 weeks after the administering of step (d);(f) administering to the patient a second treatment dose of the ADC on Day 43 and further administering subsequent treatment doses of the ADC once every 6 weeks after the administration of step (a), wherein the second and subsequent treatment doses of the ADC are 2 mg / kg and wherein the total number of doses of the ADC optionally is 3 doses, 4 doses, 5 doses, 6 doses, 7 doses or 8 doses; wherein the first step-up dose, the second step-up dose and the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody are intravenously administered, advantageously via IV infusion , for example by IV infusion over a period of about 30 minutes to one hour for each administration; and wherein the first treatment dose and the subsequent treatment dose of the ADC are intravenously administered, for example, via IV infusion, for example by IV infusion over a period of about 30 minutes to one hour for each administration.

[0222] In some embodiments, each of the first step-up dose, the second step-up dose and the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody is intravenously administered, advantageously via IV infusion, for example by IV infusion over a period of about 30 minutes to one hour for each administration.

[0223] In some embodiments, each of the first treatment dose, the second treatment dose and the subsequent treatment dose of the ADC is intravenously administered, for example, via IV infusion, for example by IV infusion over a period of about 30 minutes to one hour for each administration. In some embodiments, each of the first step-up dose, the second step-up dose and the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody, and each of the first treatment dose, the second treatment dose and the subsequent treatment dose of the ADC is intravenously administered, for example, via IV infusion, for example by IV infusion over a period of about 30 minutes to one hour for each administration.

[0224] In some embodiments, when the ADC and the anti-hK2 / anti-CD3 bispecific antibody are administered on the same day, the anti-hK2 / anti-CD3 bispecific antibody is administered at least one hour after the administration of the ADC.

[0225] In some embodiments, the patient has received one or more premedication independently selected from a glucocorticoid, an antihistamine and an antipyretic, more particularly the patient has received a glucocorticoid premedication, an antihistamine premedication and an antipyretic premedication prior to, but on the same day as the first administration of the anti-hK2 / anti-CD3 bispecific antibody.

[0226] In some embodiments, the patient has received one or more premedication independently selected from a glucocorticoid, an antihistamine and an antipyretic, more particularly the patient has received a glucocorticoid premedication, an antihistamine premedication and an antipyretic premedication prior to, but on the same day as the first administration of the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody.

[0227] In some embodiments, the method comprises administering one or more step-up dose(s) of 2-20 mg of the anti-hK2 / anti-CD3 bispecific antibody prior to the first treatment dose of the anti-hK2 / anti-CD3 bispecific antibody wherein, prior to, but on the same day as the administration of the one or more step-up dose(s) as well as prior to, but on the same day as the first administration of the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody, the patient has received one or more premedication independently selected from a glucocorticoid, an antihistamine and an antipyretic, more particularly the patient has received a glucocorticoid premedication, an antihistamine premedication and an antipyretic premedication.

[0228] In some embodiments, the one or more premedication is administered within 2 hours prior to the administration of the anti-hK2 / anti-CD3 bispecific antibody.

[0229] In some embodiments, the method comprises administering a first step-up dose of the anti-hK2 / anti-CD3 bispecific antibody and a second step-up dose of the anti-hK2 / anti-CD3 bispecific antibody prior to the first treatment dose of the anti-hK2 / anti-CD3 bispecific antibody, wherein, prior to but on the same day as the administration of the first step-up dose and the second step-up dose as well as prior to the first administration of the treatment dose of the anti-hK2 / anti- CD3 bispecific antibody, the patient has received at least one premedication independently selected from a glucocorticoid, an antihistamine and an antipyretic, more particularly the patient has received a glucocorticoid premedication, an antihistamine premedication and an antipyretic premedication.

[0230] In some embodiments, at least one premedication is administered within 2 hours prior to the first step-up dose, within 2 hours prior to the second step-up dose, and within 2 hours prior to the first administration of the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody.

[0231] In some embodiments, the method comprises administering a first step-up dose of 3.5 mg of the anti-hK2 / anti-CD3 bispecific antibody and a second step-up dose of 18 mg of the anti- hK2 / anti-CD3 bispecific antibody prior to the first treatment dose of the anti-hK2 / anti-CD3 bispecific antibody, wherein, prior to but on the same day as the administration of the first step-up dose and the second step-up dose as well as prior to the first administration of the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody, the patient has received at least one premedication independently selected from a glucocorticoid, an antihistamine and an antipyretic, more particularly the patient has received a glucocorticoid premedication, an antihistamine premedication and an antipyretic premedication.

[0232] In some embodiments, the first step-up dose is 3.5mg and the second step-up dose is 18mg.

[0233] In some embodiments, the first and second step-up doses are administered by intravenous infusion.

[0234] In some embodiments, the first step-up dose is administered 12-16 days, e.g., 14 days, or about 2 weeks before the first administration of the target dose, and wherein the second step-up dose is administered 5-9 days, e.g. 7 days, or about 1 week before the first administration of the target dose.

[0235] In some embodiments, the method does not comprise administering a premedication selected from a glucocorticoid, an antihistamine and an antipyretic, prior to the second as well as prior to any further administration of the KLK2xCD3 antibody.

[0236] In some embodiments, the glucocorticoid premedication is dexamethasone.

[0237] In some embodiments, the glucocorticoid premedication is 16mg or 8 mg per dose of dexamethasone by intravenous or oral administration.

[0238] In some embodiments, the anti -histamine premedication is diphenhydramine.

[0239] In some embodiments, the anti -histamine premedication is 50mg per dose of diphenhydramine by intravenous or oral administration.

[0240] In some embodiments, the antipyretic premedication is paracetamol or acetaminophen.

[0241] In some embodiments, the antipyretic premedication is 650 mg to 1,000 mg per dose of paracetamol or acetaminophen by intravenous or oral administration.

[0242] In some embodiments, the patient has received an anti-histamine medication on the day before, on the same day as and on the day after the administration of ADC.

[0243] In some embodiments, the anti-histamine medication is diphenhydramine.

[0244] In some embodiments, the anti-histamine medication is 50 mg per dose of diphenhydramine by intravenous administration.

[0245] In some embodiments, the patient has received an nonsteroidal anti-inflammatory medication on the day before, on the same day as and on the day after the administration of ADC.

[0246] In some embodiments, the nonsteroidal anti-inflammatory medication is indomethacin, ibuprofen, or naproxen sodium.

[0247] In some embodiments, the nonsteroidal anti-inflammatory medication is 25 mg per dose indomethacin, 600 mg per dose ibuprofen, or 500 mg per dose naproxen sodium by intravenous or oral administration.

[0248] In some embodiments, the nonsteroidal anti-inflammatory medication is 25 mg per dose indomethacin, 600 mg per dose ibuprofen, or 500 mg per dose naproxen sodium by intravenous or oral administration 2 hours before and 8 hours after the administration of the ADC.

[0249] In some embodiments, the human patient is 18 years of age or older.

[0250] In some embodiments, the prostate cancer is histologically confirmed adenocarcinoma of the prostate, as defined by Prostate Cancer Working Group 3 (PCWG3) criteria (Scher et al. 2016 Journal of Clinical Oncology 34(12): 1402-1418).

[0251] In some embodiments, the prostate cancer is a prostate adenocarcinoma that does not comprise small cell carcinoma, carcinoid tumor, mixed NE carcinoma, or large cell NE carcinoma.

[0252] In some embodiments, the prostate cancer is mCRPC.

[0253] In some embodiments, the patient has a PSA level of at least 2 ng / ml at screening.

[0254] In some embodiments, the patient has measurable or evaluable prostate cancer disease

[0255] In some embodiments, the patient has: a. received orchiectomy or medical castration; or b. has not undergone orchiectomy and is receiving ongoing androgen deprivation therapy with a gonadotropin releasing hormone (GnRH) analog (agonist or antagonist) prior to being administered with the first dose of study drug (i.e., prior to being administered the first dose of PSMA ADC and of anti-hK2 / anti- CD3 bispecific antibody of the application).

[0256] In some embodiments, the patient has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

[0257] In some embodiments, the patient has received prior treatment for mCRPC with at least one androgen receptor (AR)-targeted therapy (for example treatment with abiraterone acetate, apalutamide, enzalutamide, or darolutamide).

[0258] In some embodiments, the patient has received no more than one or no previous taxane therapies, more specifically no more than one or no prior anti-prostate cancer chemotherapy (i.e., docetaxel, cabazitaxel, cisplatin, carboplatin, etoposide, etc ).

[0259] In some embodiments, the patient has not received prior taxane regimen.

[0260] In some embodiments, the patient has not received prior taxane regimen for the treatment of mCRPC.

[0261] In some embodiments, the patient has received no prior taxane therapy for the treatment of mCRPC as well as no prior 177-Lu-PSMA radionuclide therapy (specifically, no prior pluvicto therapy) for the treatment of mCRPC.

[0262] In some embodiments, the patient has received only one prior taxane therapy for the treatment of mCRPC and has received no prior 177-Lu-PSMA radionuclide therapy (specifically, no prior pluvicto therapy) for the treatment of mCRPC.

[0263] In some embodiments, the patient has received only one prior taxane therapy for the treatment of mCRPC and has received prior 177-Lu-PSMA radionuclide therapy (specifically, prior pluvicto therapy) for the treatment of mCRPC.

[0264] In some embodiments, the patient has received no prior taxane therapy for the treatment of mCRPC, but has received prior 177-Lu-PSMA radionuclide therapy (specifically, prior pluvicto therapy) for the treatment of mCRPC.

[0265] In some embodiments, the patient has 1 and only 1 prior taxane regimen.

[0266] In some embodiments, the patient has received prior 177-Lu-PSMA radionuclide therapy.

[0267] In some embodiments, the patient has received prior PSMA radioligand therapy.

[0268] In some embodiments, the patient has not received prior PSMA radioligand therapy.

[0269]

[0261] In some embodiments, the patient has received no more than one or no taxane therapy for the treatment of mCRPC, specifically no more than one or no docetaxel therapy for the treatment of mCRPC and no more than one or no cabazitaxel therapy for the treatment of mCRPC.

[0270]

[0261] In some embodiments, the patient has received prior treatment with an androgen receptor pathway inhibitor (ARI) for the treatment of prostate cancer, for example at least one prior prostate cancer treatment with abiraterone acetate, apalutamide, enzalutamide or darolutamide.

[0271] In some embodiments, the patient has an estimated glomerular filtration rate (eGFR) >40 mL / min, based on the Modified Diet in Renal Disease (MDRD) 4-variable formula.

[0272] In some embodiments, the patient has an AST (aspartate aminotransferase) <2.5 x ULN (upper limit of normal), ALT (alanine aminotransferase) <2.5 x ULN, or Total bilirubin <1.5 x ULN.

[0273] In some embodiments, the patient has hemoglobin value > 9.0 g / dL independent of transfusion within 7 days or growth factors within 3 weeks prior to the start of the treatment method.

[0274] In some embodiments, the patient has neutrophils value > 1.5 x 109 / L independent of transfusion within 7 days or growth factors within 3 weeks prior to the start of the treatment method.

[0275] In some embodiments, the patient has platelets value > 100 x 109 / L independent of transfusion within 7 days or growth factors within 3 weeks prior to the start of the treatment method.

[0276] In some embodiments, the patient does not have an active autoimmune disease that requires systemic immunosuppressive medications within the 12 months prior to signing consent.

[0277] In some embodiments, the patient does not have toxicity related to prior anticancer therapy that has not returned to Grade <1 or baseline levels (except for alopecia and vitiligo).

[0278] In some embodiments, the patient does not have Grade 2 or higher peripheral sensory or motor neuropathy within 28 days prior to signing consent or for Part 2 any symptomatic peripheral sensory or motor neuropathy including Grade 1.

[0279] In some embodiments, the patient has not received solid organ or bone marrow transplantation.

[0280] In some embodiments, the patient does not have any known allergies, hypersensitivity, or intolerance to any of the components of anti-hk2 / anti-CD3 bispecific antibody or ADC.

[0281] In some embodiments, the patient does not have any of the following within 6 months prior to signature of informed consent: a. Myocardial infarction, b. Severe or unstable angina, c. Clinically significant ventricular arrhythmias, d. Congestive heart failure (New York Heart Association [NYHA] class II to IV), e. Transient ischemic attack, and f. Cerebrovascular accident.

[0282] In some embodiments, the patient does not have a history of interstitial lung disease (ILD) or pneumonitis within 12 months of enrollment, or other clinically significant pulmonary compromise, particularly a requirement for supplemental oxygen use to maintain adequate oxygenation.

[0283] In some embodiments, the patient does not have clinically significant ocular infections or chronic corneal disorders, including confluent superficial keratitis, cornea epithelial defect, corneal ulcer or stromal opacity.

[0284] In some embodiments, the patient did not have major surgery or significant trauma within 30 days before the start of the method of treatment or has not recovered from surgery.

[0285] In some embodiments, the patient does not have major surgery planned during the time the participant is receiving the treatment.

[0286] In some embodiments, the patient did not an active infection or condition that requires treatment with systemic antibiotics within 7 days prior to start of the method of treatment.

[0287] In some embodiments, the patient did not have venous thromboembolic events (eg, pulmonary embolism) within 1 month prior to start of the method of treatment.

[0288] In some embodiments, the patient did not have Leptomeningeal disease or brain metastases, with the exception of participants with definitively, locally treated brain metastases that are clinically stable and asymptomatic>2 weeks, and who are off corticosteroid treatment for at least 2 weeks prior to the start of the method of treatment.

[0289] In some embodiments, the patient did not receive immunosuppressive doses of systemic medications, such as glucocorticoids (doses >10 mg / day prednisone or equivalent) within 3 days prior to start of the method of treatment at the exception of a single course of glucocorticoids as prophylaxis for imaging contrast.

[0290] In some embodiments, the patient has not received or planned to receive any live, attenuated vaccine within 4 weeks prior to the start of the method of treatment or within 4 weeks after the last dose of the method of treatment.

[0291] In some embodiments, the patient has not received treatment with any anti-cancer or investigational agents within 14 days prior to the start of the method of treatment; specific requirements for certain anti-cancer therapies are as follows:(a) Any T-cell redirecting treatment (eg, CD3-directed bispecific or CAR-T therapy) within 90 days prior to the start of the method of treatment of the application (i.e., prior to being administered the first dose of PSMA ADC and of anti-hK2 / anti-CD3 bispecific antibody of the application).(b) Immune checkpoint inhibitors within 6 weeks prior to the first dose of study treatment(c) Radium (Ra) 223 dichloride within 28 days prior to the first dose of study treatment(d) Any prior treatment with KLK2 -targeted therapy(e) Any prior PSMA-targeting therapy (ie, patients who received PSMA-targeting radioconjugates are excluded) [Parts 2A and 2B only]. Prior PSMA RLT is allowed in Part 1 and required for Part 2C and Part 2D but last dose must be >3 months prior to the first dose of study treatment.(f) Any prior ADCs with microtubule inhibitor payloads (eg, auristatins, maytansinoids, tubulysins).

[0292] In some embodiments, the patient has no known positive test result for human immunodeficiency virus (unless stable on antiretroviral therapy with undetectable viral load and CD4 count above 200 cells / mm3).

[0293] In some embodiments, the patient does not have active hepatitis B or C virus infection according to local laboratory range.

[0294] In some embodiments, the patient does not have any known history of or suspicion for history of clinically significant liver disease including viral or non-viral hepatitis, fatty liver disease, or hepatic fibrosis requires discussion with the sponsor.

[0295] In some embodiments, the patient does not have any serious underlying medical conditions or other issue that would impair the ability of the participant to receive or tolerate the planned treatment at the investigational site to understand the informed consent, or any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (e.g., compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.

[0257] In some embodiments, the patient does not have triplicate average QTc interval corrected using Fridericia’s formula (QTcF)>470 msec.

[0296] In some embodiments, the patient has received a pre-medication prior to the administration of the hk2xCD3 antibody, wherein the premedication is a. a glucocorticoid i. 16 mgs of Dexamethasone or equivalent prior to the step-up doses and the first treatment dose of the hk2xCD3 antibody; or ii. 16 mgs of Dexamethasone followed by 8 mgs Dexamethasone for cases of Grade >2 CRS or IRR due to hk2xCD3 antibody b. an antihistamine such as 50 mgs of Diphenhydramine or equivalent prior to step-up doses and treatment doses of the hK2xCD3 antibody; and / or c. an antipyretic such as Paracetamol / acetaminophen (650 to 1,000 mg) or equivalent prior to all doses of hK2xCD3 antibody.

[0297] In some embodiments, the pre-medication is administered within 2 hours prior to the administration of the hK2xCD3 antibody.

[0298] In some embodiments, the patient has received a pre-medication prior to the administration of the PSMA ADC, wherein the premedication is a. an antihistamine such as 50 mgs of Diphenhydramine or equivalent in cases of IRR due to the PSMA ADC b. nonsteroidal anti-inflammatory drugs such as 25 mg indomethacin or a comparable dose, 600 mg ibuprofen, or 500 mg naproxen sodium in case of PSMA ADC infusion-related flu-like symptoms.

[0299] In some embodiments, the nonsteroidal anti-inflammatory drug is administered 2 hours before and 8 hours after the start of each PSMA ADC infusion

[0300] In some embodiments, the method provides a decrease in the serum Prostate-Specific Antigen (PSA) level of the patient, wherein the decrease is relative to the PSA level of the patient prior to the administration of the anti-hK2 / anti-CD3 bispecific antibody.

[0301] In some embodiments, the PSA level decreases by 50% or more compared to the PSA level of the patient prior to the administration of the anti-hK2 / anti-CD3 bispecific antibody.

[0302] In some embodiments, the method provides for no disease progression in the patient, wherein disease progression is assessed according to the Prostate Cancer Working Group 3 (PCWG3) Criteria (Scher et al. 2016 Journal of Clinical Oncology 34(12): 1402-1418)).

[0303] In some embodiments, the method provides a Partial Response or better according to RECIST version 1.1 response criteria (Eisenhauer et al. 2009 European Journal of Cancer 45: 228- 247) without evidence of bone progression according to PCWG3 in the patient.

[0304] In some embodiments, the method provides radiographic progression free survival (rPFS).

[0305] In some embodiments, no Adverse Event of Grade 3 or higher (according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0) is observed in the patient.

[0306] In some embodiments, Adverse Events of Grade 3 or higher (according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0) are observed in 20% or fewer of patients in a cohort of at least 20 patients, for example 15% or fewer of patients in a cohort of at least 20 patients.

[0307] In some embodiments, the method does not induce a Dose Limiting Toxicity (DLT) in the patient.

[0308] In another general aspect, the application relates to the anti-hK2 / anti-CD3 bispecific antibody of any one of the preceding embodiments for use in the method of any one of the preceding embodiments.

[0309] In another general aspect, the application relates to the ADC of any one of the preceding embodiments for use in the method of any one of the preceding embodiments.

[0310] In another general aspect, the application relates to the anti-hK2 / anti-CD3 bispecific antibody of any one of the preceding embodiments and the ADC of any one of the preceding embodiments for use in the method of any one of the preceding embodiments.

[0311] In another general aspect, the application relates to a combination or functional association comprising the anti-hK2 / anti-CD3 bispecific antibody of any one of the preceding embodiments and the ADC of any one of the preceding embodiments.

[0312] In a final general aspect, the application relates to the anti-hK2 / anti-CD3 bispecific antibody of any one of the preceding embodiments and the ADC of any one of the preceding embodiments as a combined preparation for simultaneous, separate or sequential use in prostate cancer therapy, more specifically in mCRPC therapy.SUBJECT MATTER DESCRIBED IN THE APPLICATION1. A method of treating prostate cancer, preferably advanced prostate cancer, more preferably metastatic castration-resistant prostate cancer (mCRPC), in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of an antibody drug conjugate (ADC) targeting prostate-specific membrane antigen (PSMA) [at a first treatment dose], and a therapeutically effective amount of an anti-hK2 / anti-CD3 bispecific antibody [at a treatment dose], wherein: a. the ADC comprises an anti-PSMA antibody conjugated to a drug-linker, wherein the conjugation occurs via para-acetyl phenylalanine (pAF) incorporated in the heavy chain sequence of the antibody, wherein the anti- PSMA antibody comprising a heavy chain (HC) of SEQ ID NO: 1 and a light chain (LC) of SEQ ID NO: 2, in which the pAF is incorporated at the HC position Al 14 according to Kabat numbering (i.e., the A, which is at position 116 in the amino acid sequence of SEQ ID NO: 1), and wherein the drug-linker (amberstatin269 (AS269), which) has the following structure:b. the anti-hK2 / anti-CD3 bispecific antibody comprises a first antigen binding domain that binds specifically to hK2, and a second antigen binding domain that binds specifically to CD3, wherein: i. the first domain comprises a first heavy chain variable region (VH1 ) of SEQ ID NO: 9 and a first light chain variable region (VL1) of SEQ ID NO: 10; and ii. the second domain comprises a second heavy chain variable region (VH2) of SEQ ID NO: 21 and a second light chain variable region (VL2) of SEQ ID NO: 22. The method of embodiment 1, wherein the first domain of the anti-hK2 / anti-CD3 bi specific antibody comprises a Fab and the second domain of the anti-hK2 / anti-CD3 bispecific antibody comprises an scFv. The method of embodiment 2, wherein the scFv comprises, from the N-terminus to the C- terminus, VH2-linker-VL2 or VL2-linker-VH2, and the linker comprises or consists of the amino acid sequence of SEQ ID NO: 23. The method of any one of the foregoing embodiments, wherein the anti-hK2 / anti-CD3 antibody comprises a first heavy chain (HC1), a first light chain (LC1) and a second heavy chain (HC2) having amino acid sequences at least 90% identical to SEQ ID NO: 13, SEQ ID NO: 14 and SEQ ID NO: 26, respectively; preferably, the HC1, LC1 and HC2 comprise the amino acid sequences of SEQ ID NO: 13, SEQ ID NO: 14 and SEQ ID NO: 26, respectively. The method of any one of embodiments 1-4, wherein the anti-PSMA antibody, which is comprised in the ADC, comprises two heavy chains and two light chains, wherein each heavy chain comprises the pAF at position Al 14 according to Kabat numbering, wherein the druglinker is conjugated to each said pAF (i.e., DAR=2) via an oxime linkage. The method of any one of embodiments 1-5, wherein the ADC is ARX517. The method of any one of the foregoing embodiments, wherein the treatment dose of the anti- hK2 / anti-CD3 bispecific antibody is about 300 mg, per administration.The method of any one of the foregoing embodiments, wherein the treatment dose of the anti- hK2 / anti-CD3 bispecific antibody is administered at a flat dose. The method of any one of the foregoing embodiments, wherein the treatment dose of the anti- hK2 / anti-CD3 bispecific antibody is initially administered on a day, which is after the day of administration of the first treatment dose of the ADC, or on a day, which is before the day of administration of the first treatment dose of the ADC, for example on a day, which is after the day of administration of the first treatment dose of the ADC. The method of any one of the foregoing embodiments, wherein the treatment dose of the anti- hK2 / anti-CD3 bispecific antibody is initially administered on a day within 19-23 days, such as 19, 20, 21, 22, or 23 days, preferably 21 days, after the administration of the first treatment dose of the ADC. The method of any one of the foregoing embodiments, wherein the treatment dose of the anti- hK2 / anti-CD3 bispecific antibody is subsequently administered once every 5 to 7 weeks, for example, once every 5, 6 or 7 weeks, preferably once every six weeks, after the initial administration of the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody. The method of any one of the foregoing embodiments, wherein the treatment dose of the anti- hK2 / anti-CD3 bispecific antibody is intravenously administered, advantageously by intravenous (IV) infusion, for example by IV infusion over a period of about 30 minutes to one hour for each administration, such as over a period of about 30 minutes or a period of about one hour for each administration. The method of embodiment 12, wherein the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody is intravenously administered, advantageously by IV infusion, for example by IV infusion over a period of about one hour for the initial administration, and by IV infusion over a period of about 30 minutes for any subsequent administration. The method of any one of the foregoing embodiments, wherein the method does not comprise administering a step-up dose of the anti-hK2 / anti-CD3 bispecific antibody prior to the initial administration of the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody. The method of any one of embodiments 1-13, further comprising administering to the human patient one or more step-up doses (for example, one or two step-up doses) of the anti-hK2 / anti- CD3 bispecific antibody, wherein the one or more step-up doses are administered after the administration of the first treatment dose of the ADC and prior to the initial administration ofthe treatment dose of the anti-hK2 / anti-CD3 bispecific antibody and wherein the one or more step-up doses are not higher than the treatment dose. The method of embodiment 15, wherein the one or more step-up doses of the anti-hK2 / anti- CD3 bispecific antibody are intravenously administered, for example via intravenous (IV) infusion. The method of embodiment 15 or 16, wherein one step-up dose of the anti-hK2 / anti-CD3 bispecific antibody is administered. The method of embodiment 15 or 16, wherein more than one step-up doses of the anti- hK2 / anti-CD3 bispecific antibody are administered. The method of embodiment 18, wherein the more than one step-up doses of the anti-hK2 / anti- CD3 bispecific antibody are administered at a flat dose. The method of embodiment 18, wherein the more than one step-up doses of the anti-hK2 / anti- CD3 bispecific antibody are administered at ascending doses. The method of any one of embodiments 18-20, wherein the method comprises administering to the patient a first step-up dose and a second step-up dose of the anti-hK2 / anti-CD3 bispecific antibody, wherein the first step-up dose is administered prior to the second step-up dose, and the second step-up dose is administered prior to the treatment dose. The method of embodiment 21, wherein the second step-up dose of the anti-hK2 / anti-CD3 bispecific antibody is greater than the first step-up dose. The method of embodiment 21 or 22, wherein the method comprises administering to the patient: i) the first step-up dose of the anti-hK2 / anti-CD3 bispecific antibody, ii) the second step-up dose of the anti-hK2 / anti-CD3 bispecific antibody; and iii) the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody, wherein the first step-up dose is administered once, and the second step-up dose is administered once. The method of any one of embodiments 18-23, wherein the method comprises administering to the patient a first step-up dose of the anti-hK2 / anti-CD3 bispecific antibody of about 2 mg to about 5 mg per administration, for example about 2 mg, about 2.5 mg, about 3 mg, about 3.5 mg, about 4 mg, about 4.5 mg or about 5 mg, per administration, preferably about 3.5 mg per administration.The method of any one of embodiments 18-24, wherein the first step-up dose is administered on a day within 5-9 days, such as 5, 6, 7, 8, or 9 days, preferably 7 days, after the first treatment dose of the ADC is administered. The method of embodiment 25, wherein the first step-up dose of the anti-hK2 / anti-CD3 bispecific antibody of about 3.5 mg per administration is administered 7 days after the first treatment dose of the ADC is administered. The method of any one of embodiments 18-26, wherein the method further comprises administering to the patient a second step-up dose of the anti-hK2 / anti-CD3 bispecific antibody of about 15 mg to about 25 mg per administration, for example about 15 mg, about 16 mg, about 17 mg, about 18 mg, about 19 mg, about 20 mg, about 21 mg, about 22 mg, about 23 mg, about 24 mg, or about 25 mg, per administration, preferably about 18 mg per administration. The method of embodiment 27, wherein the second step-up dose of the anti-hK2 / anti-CD3 bispecific antibody is administered on a day within 12-16 days, such as 12, 13, 14, 15 or 16 days, preferably 14 days, after the first treatment dose of the ADC is administered. The method of embodiment 28, wherein the second step-up dose of the anti-hK2 / anti-CD3 bispecific antibody of about 18 mg per administration is administered 14 days after the first treatment dose of the ADC is administered. The method of any one of embodiments 15-29, wherein the one or more step-up doses are administered on a day within 7-14 days, for example 7, 8, 9, 10, 11, 12, 13, or 14 days, prior to the initial administration of the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody. The method of embodiment 30, wherein the first step-up dose of the anti-hK2 / anti-CD3 bispecific antibody is administered 14 days prior to the initial administration of the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody. The method of embodiment 30 or 31, wherein the second step-up dose of the anti-hK2 / anti- CD3 bispecific antibody is administered 7 days prior to the initial administration of the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody. The method of any one of embodiments 15-32, wherein the first step-up dose of the anti- hK2 / anti-CD3 bispecific antibody is administered via IV infusion. The method of any one of embodiments 18-33, wherein the second step-up dose of the anti- hK2 / anti-CD3 bispecific antibody is administered via IV infusion. The method of any one of embodiments 1-34, comprising:(a) administering to the patient the ADC at a first treatment dose on Day 1 of the treatment;(b) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a first step-up dose of about 2-5 mg per administration on a day within Day 6 to Day 10 of the treatment;(c) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a second step-up dose of about 15-21 mg per administration on a day within Day 13 to Day 17 of the treatment;(d) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 250-350 mg per administration on a day within Day 20 to Day 24 of the treatment; and(e) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 250-350 mg per administration once every 5-7 weeks after step (d), wherein, each of the first step-up dose, the second step-up dose and the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody is intravenously administered, advantageously via IV infusion, for example by IV infusion over a period of about 30 minutes to one hour for each administration. method of embodiment 35, comprising:(a) administering to the patient the ADC at the first treatment dose on Day 1 of the treatment;(b) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a first step-up dose of about 3.5 mg per administration on Day 8 of the treatment;(c) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a second step-up dose of about 18 mg per administration on Day 15 of the treatment;(d) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 300 mg per administration on Day 22 of the treatment; and(e) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 300 mg per administration once every 6 weeks after step (d),wherein each of the first step-up dose, the second step-up dose and the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody is intravenously administered, advantageously via IV infusion, for example by IV infusion over a period of about 30 minutes to one hour for each administration. The method of any one of the foregoing embodiments, wherein the ADC is administered at the first treatment dose of 2.0 mg / kg or lower, such as 1.9-1.4 mg / kg or 1.7-1.4 mg / kg, e.g., 2.0 mg / kg, 1.7 mg / kg or 1.4 mg / kg. The method of embodiment 37, wherein the ADC is administered at the first treatment dose of 1.4 mg / kg. The method of embodiment 37, wherein the ADC is administered at the first treatment dose of 2.0 mg / kg The method of any one of the foregoing embodiments, further comprising administering to the patient a second treatment dose of the ADC, for example a second treatment dose of the ADC: i. on a day within 19-44 days, such as on a day within 19-23 days or 40-44 days, for example 19, 20, 21, 22, or 23 days, preferably 21 days or 40, 41, 42, 43 or 44 days, preferably 41 days, after the administration of the first treatment dose of the ADC; or ii. on a day within 2 to 7 weeks, such as 2, 3, 4, 5, 6 or 7 weeks, for example 3 weeks or 6 weeks, after the administration of the first treatment dose of the ADC. The method of embodiment 40, wherein the second treatment dose of the ADC is the same dose as the first treatment dose of the ADC. The method of embodiment 41, wherein first and second treatment dose of the ADC is 1.4 mg / kg. The method of embodiment 41, wherein first and second treatment dose of the ADC is 2.0 mg / kg. The method of embodiment 40, wherein the second treatment dose of the ADC is lower than the first treatment dose of the ADC but is higher than 1.4 mg / kg. The method of embodiment 40, wherein the first treatment dose is 2 mg / kg and the second treatment dose is 1.4 mg / kg.The method of any one of embodiments 40-45, wherein the second treatment dose of the ADC is administered on a day within 19-23 days, such as 19, 20, 21, 22, or 23 days, preferably 21 days, after the first treatment dose of ADC is administered. The method of embodiment 46, wherein the second treatment dose of the ADC is administered 21 days after the first treatment dose of ADC is administered. The method of any one of the foregoing embodiments, further comprising administering to the patient a subsequent treatment dose of the ADC after the administration of the second treatment dose of the ADC, for example a subsequent treatment dose of the ADC once every 2 to 7 weeks, such as once every 2, 3, 4, 5, 6 or 7 weeks, for example once every 3 weeks or once every 6 weeks, after the administration of the second treatment dose of the ADC. The method of embodiment 48, wherein the subsequent treatment dose of the ADC is administered once every 6 weeks. The method of embodiment 48, wherein the subsequent treatment dose of the ADC is administered once every 3 weeks. The method of embodiment 48, wherein the subsequent treatment dose of the ADC is administered once every 3 weeks for 2, 3, or 4 doses and followed by once every 6 weeks. The method of any one of embodiments 48-51, wherein the subsequent treatment dose of the ADC is the same dose as the second treatment dose of the ADC. The method of embodiment 52, wherein the second treatment dose and the subsequent treatment dose of the ADC is 1.4 mg / kg. The method of embodiment 52, wherein the second dose and the subsequent treatment dose of the ADC is 2.0 mg / kg. The method of any one of embodiments 48-51 wherein the subsequent treatment dose of the ADC is lower than the second treatment dose of the ADC but is higher than 1.4 mg / kg. The method of any one of embodiments 48-51 wherein the second treatment dose of the ADC is 2 mg / kg and the subsequent treatment dose of the ADC is 1.4 mg / kg. The method of any one of embodiments 48-51, wherein the second treatment dose of the ADC is administered 40-44 days, such as 40, 41, 42, 43 or 44 days, preferably 41 days, after the first treatment dose of ADC is administered. The method of embodiment 53, wherein the second treatment dose of the ADC is administered 41 days after the first treatment dose of ADC is administered.The method of any one of embodiments 57-58, further comprising administering to the patient a subsequent treatment dose of the ADC once every 2 to 7 weeks, such as once every 4, 5 or 6 weeks, after the administration of the second treatment dose of the ADC. The method of embodiment 59, wherein the subsequent treatment dose of the ADC is administered once every 6 weeks. The method of embodiment 59, wherein the subsequent treatment dose of the ADC is administered once every 3 weeks. The method of any one of embodiments 59-61, wherein the subsequent treatment dose of the ADC is the same dose as the second treatment dose of the ADC. The method of embodiment 62, wherein the second treatment dose and the subsequent treatment dose of the ADC is 1.4 mg / kg. The method of embodiment 62, wherein the second treatment dose and the subsequent treatment dose of the ADC is 2.0 mg / kg. The method of any one of embodiments 59-61, wherein the subsequent treatment dose of the ADC is lower than the second treatment dose of the ADC but is higher than 1.4 mg / kg. The method of any one of embodiments 59-61, wherein the second treatment dose is 2mg / kg and the subsequent treatment dose of the ADC is 1.4 mg / kg. The method of any one of the foregoing embodiments, wherein each of the first treatment dose, the second treatment dose, and / or the subsequent treatment dose of the ADC is intravenously administered, for example, by intravenous (IV) infusion over a period of about 30 minutes to one hour for each administration, such as over a period of about 30 minutes or a period of about one hour for each administration. The method of any one of the foregoing embodiments, wherein the treatment dose of the anti- hK2 / anti-CD3 bispecific antibody is intravenously administered, for example, by IV infusion over a period of about one hour for the initial administration, and by IV infusion over a period of about 30 minutes for any subsequent administration. The method of any one of the foregoing embodiments, wherein the method does not comprise administering a step-up dose of the ADC prior to the administration of the first treatment dose, the second treatment dose, and / or the subsequent treatment dose of the ADC. The method of any one of embodiments 37-56 and 67-69, comprising:(a) administering to the patient the ADC at a first treatment dose on Day 1 of the treatment, wherein the first treatment dose is 2.0 mg / kg or lower, such as 1.9- 1.4 mg / kg or 1.7-1.4 mg / kg, e.g., 2.0 mg / kg, 1.7 mg / kg or 1.4 mg / kg;(b) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a first step-up dose of about 2-5 mg per administration on a day within Day 6 to Day 10 of the treatment;(c) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a second step-up dose of about 15-21 mg per administration on a day within Day 13 to Day 17 of the treatment;(d) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 250-350 mg per administration on a day within Day 20 to Day 24 of the treatment;(e) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 250-350 mg per administration once every 5-7 weeks after the administering of step (d),(f) administering to the patient a second treatment dose of the ADC on a day within Day 20 to Day 24 of the treatment, wherein the second treatment dose of the ADC is the same dose as the first treatment dose of the ADC, or the second treatment dose of the ADC is lower than the first treatment dose of the ADC but is higher than 1.4 mg / kg;(g) administering to the patient the ADC at a subsequent treatment dose once every 2 to 7 weeks, such as once every 3 weeks, once every 6 weeks, or once every 3 weeks for 2-4 doses and followed by once every 6 weeks, after the administering of step (f), wherein the subsequent treatment dose of the ADC is the same dose as the second treatment dose of the ADC, or the subsequent treatment dose of the ADC is lower than the second treatment dose of the ADC but is higher than 1.4 mg / kg; wherein, each of the first step-up dose, the second step-up dose and the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody is intravenously administered, advantageously via IV infusion for example by IV infusion over a period of about 30 minutes to one hour for each administration; andwherein, each of the first treatment dose, the second treatment dose and the subsequent treatment dose of the ADC is intravenously administered, for example, via IV infusion over a period of about 30 minutes to one hour for each administration. method of embodiment 70, comprising:(a) administering to the patient the ADC at a first treatment dose on Day 1 of the treatment, wherein the first treatment dose is 2.0 mg / kg, 1.7 mg / kg or 1.4 mg / kg;(b) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a first step-up dose of about 3.5 mg per administration on Day 8 of the treatment;(c) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a second step-up dose of about 18 mg per administration on Day 15 of the treatment;(d) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 300 mg per administration on Day 22 of the treatment;(e) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 300 mg per administration once every 6 weeks after the administering of step (d),(f) administering to the patient a second treatment dose of the ADC on Day 22 of the treatment, wherein the second treatment dose of the ADC is the same dose as the first treatment dose of the ADC, or the second treatment dose of the ADC is lower than the first treatment dose of the ADC but is higher than 1.4 mg / kg;(g) administering to the patient the ADC at a subsequent treatment dose once every 3 weeks, once every 6 weeks, or once every 3 weeks for 2-4 doses and followed by once every 6 weeks, after the administering of step (f), wherein the subsequent treatment dose of the ADC is the same dose as the second treatment dose of the ADC, or the subsequent treatment dose of the ADC is lower than the second treatment dose of the ADC but is higher than 1.4 mg / kg; wherein each of the first step-up dose, the second step-up dose and the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody is intravenously administered, advantageously via IV infusion for example by IV infusion over a period of about 30 minutes to one hour for each administration; andwherein each of the first treatment dose, the second treatment dose and the subsequent treatment dose of the ADC is intravenously administered, for example, via IV infusion over a period of about 30 minutes to one hour for each administration. method of any one of embodiments 37-45 and 57-69, comprising:(a) administering to the patient the ADC at a first treatment dose on Day 1 of the treatment, wherein the first treatment dose is 2.0 mg / kg or lower, such as 1.9-1.4 mg / kg or 1.7-1.4 mg / kg, e.g., 2.0 mg / kg, 1.7 mg / kg or 1.4 mg / kg;(b) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a first step-up dose of about 2-5 mg per administration on a day within Day 6 to Day 10 of the treatment;(c) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a second step-up dose of about 15-21 mg per administration on a day within Day 13 to Day 17 of the treatment;(d) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 250-350 mg per administration on a day within Day 20 to Day 24 of the treatment;(e) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 250-350 mg per administration once every 5-7 weeks after the administering of step (d),(f) administering to the patient a second treatment dose of the ADC on a day within Day 40 to Day 44 of the treatment, wherein the second treatment dose of the ADC is the same dose as the first treatment dose of the ADC, or the second treatment dose of the ADC is lower than the first treatment dose of the ADC but is higher than 1.4 mg / kg;(g) administering to the patient the ADC at a subsequent treatment dose once every 5 to 7 weeks, such as once every 6 weeks after the administering of step (f), wherein the subsequent treatment dose of the ADC is the same dose as the second treatment dose of the ADC, or the subsequent treatment dose of the ADC is lower than the second treatment dose of the ADC but is higher than 1.4 mg / kg; wherein, the first step-up dose, the second step-up dose and the treatment dose of the anti- hK2 / anti-CD3 bispecific antibody are intravenously administered, advantageously via IVinfusion, for example by IV infusion over a period of about 30 minutes to one hour for each administration; and wherein, each of the first treatment dose, the second treatment dose and the subsequent treatment dose of the ADC is intravenously administered, for example, via IV infusion, for example by IV infusion over a period of about 30 minutes to one hour for each administration. method of embodiment 72, comprising:(a) administering to the patient the ADC at a first treatment dose on Day 1 of the treatment, wherein the first treatment dose is 2.0 mg / kg, 1.7 mg / kg or 1.4 mg / kg;(b) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a first step-up dose of about 3.5 mg per administration on Day 8 of the treatment;(c) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a second step-up dose of about 18 mg per administration on Day 15 of the treatment;(d) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 300 mg per administration on Day 22 of the treatment;(e) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 300 mg per administration once every 6 weeks after the administering of step (d),(f) administering to the patient a second treatment dose of the ADC on Day 42 of the treatment, wherein the second treatment dose of the ADC is the same dose as the first treatment dose of the ADC, or the second treatment dose of the ADC is lower than the first treatment dose of the ADC but is higher than 1.4 mg / kg;(g) administering to the patient the ADC at a subsequent treatment dose once every 6 weeks after the administering of step (f), wherein the subsequent treatment dose of the ADC is the same dose as the second treatment dose of the ADC, or the subsequent treatment dose of the ADC is lower than the second treatment dose of the ADC but is higher than 1.4 mg / kg; wherein each of the first step-up dose, the second step-up dose and the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody is intravenously administered, advantageously via IV infusion, for example by IV infusion over a period of about 30 minutes to one hour for each administration; andwherein each of the first treatment dose, the second treatment dose and the subsequent treatment dose of the ADC is intravenously administered, for example, via IV infusion, for example by IV infusion over a period of about 30 minutes to one hour for each administration. method of anyone of the forgoing embodiments comprising(a) administering to the patient the ADC at a first treatment dose on Day 1 of the treatment, wherein the first treatment dose is 1.4 mg / kg;(b) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a first step-up dose of about 2-5 mg per administration on a day within Day 6 to Day 10 of the treatment;(c) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a second step-up dose of about 15-21 mg per administration on day within Day 13 to Day 17 of the treatment;(d) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 250-350 mg per administration on a day within Day 20 to Day 24 of the treatment;(e) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 250-350 mg per administration once every 5-7 weeks after the administering of step (d),(f) administering to the patient a second treatment dose of the ADC on a day within Day 20 to Day 24 of the treatment, wherein the second treatment dose of the ADC is 1.4 mg / kg;(g) administering to the patient the ADC at a subsequent treatment dose once every 3 weeks, after the administering of step (f), wherein the subsequent treatment dose of the ADC is 1.4 mg / kg; wherein, the first step-up dose, the second step-up dose and / or the treatment doses of the anti-hK2 / anti-CD3 bispecific antibody are intravenously administered, advantageously via IV infusion, for example, via IV infusion over a period of about one hour for each administration;and wherein the first treatment dose, the second treatment dose and / or the subsequent treatment dose of the ADC is intravenously administered, for example, via IV infusion over a period of about one hour for each administration. method of anyone of the forgoing embodiments comprising:(a) administering to the patient the ADC at a first treatment dose on Day 1 of the treatment, wherein the first treatment dose is 2.0 mg / kg;(b) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a first step-up dose of about 2-5 mg per administration on a day within Day 6 to Day 10 of the treatment;(c) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a second step-up dose of about 15-21 mg per administration on day within Day 13 to Day 17 of the treatment;(d) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 250-350 mg per administration on a day within Day 20 to Day 24 of the treatment;(e) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 250-350 mg per administration once every 5-7 weeks after the administering of step (d),(f) administering to the patient a second treatment dose of the ADC on a day within Day 20 to Day 24 of the treatment, wherein the second treatment dose of the ADC is 2.0 mg / kg;(g) administering to the patient the ADC at a subsequent treatment dose once every 3 weeks after the administering of step (f), wherein the subsequent treatment dose of the ADC is 2.0 mg / kg; wherein, the first step-up dose, the second step-up dose and / or the treatment doses of the anti-hK2 / anti-CD3 bispecific antibody are intravenously administered, advantageously via IV infusion, for example, via IV infusion over a period of about one hour for each administration; and wherein the first treatment dose, the second treatment dose and / or the subsequent treatment dose of the ADC is intravenously administered, for example, via IV infusion over a period of about one hour for each administration.method of anyone of the forgoing embodiments comprising:(a) administering to the patient the ADC at a first treatment dose on Day 1 of the treatment, wherein the first treatment dose is 2.0 mg / kg;(b) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a first step-up dose of about 2-5 mg per administration on a day within Day 6 to Day 10 of the treatment;(c) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a second step-up dose of about 15-21 mg per administration on day within Day 13 to Day 17 of the treatment;(d) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 250-350 mg per administration on a day within Day 20 to Day 24 of the treatment;(e) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 250-350 mg per administration once every 5-7 weeks after the administering of step (d),(f) administering to the patient a second treatment dose of the ADC on a day within Day 20 to Day 24 of the treatment, wherein the second treatment dose of the ADC is 2.0 mg / kg;(g) administering to the patient the ADC at a subsequent treatment dose once every 3 weeks after the administering of step (f), wherein the subsequent treatment dose of the ADC is 1.4 mg / kg; wherein, the first step-up dose, the second step-up dose and / or the treatment doses of the anti-hK2 / anti-CD3 bispecific antibody are intravenously administered, advantageously via IV infusion, for example, via IV infusion over a period of about one hour for each administration; and wherein the first treatment dose, the second treatment dose and / or the subsequent treatment dose of the ADC is intravenously administered, for example, via IV infusion over a period of about one hour for each administration. method of anyone of the forgoing embodiments comprising:(a) administering to the patient the ADC at a first treatment dose on Day 1 of the treatment, wherein the first treatment dose is 2.0 mg / kg;(b) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a first step-up dose of about 2-5 mg per administration on a day within Day 6 to Day 10 of the treatment;(c) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a second step-up dose of about 15-21 mg per administration on day within Day 13 to Day 17 of the treatment;(d) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 250-350 mg per administration on a day within Day 20 to Day 24 of the treatment;(e) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 250-350 mg per administration once every 5-7 weeks after the administering of step (d),(f) administering to the patient a second treatment dose of the ADC on a day within Day 20 to Day 24 of the treatment, wherein the second treatment dose of the ADC is 1.4 mg / kg;(g) administering to the patient the ADC at a subsequent treatment dose once every 3 weeks after the administering of step (f), wherein the subsequent treatment dose of the ADC is 1.4 mg / kg; wherein, the first step-up dose, the second step-up dose and / or the treatment doses of the anti-hK2 / anti-CD3 bispecific antibody are intravenously administered, advantageously via IV infusion, for example, via IV infusion over a period of about one hour for each administration; and wherein the first treatment dose, the second treatment dose and / or the subsequent treatment dose of the ADC is intravenously administered, for example, via IV infusion over a period of about one hour for each administration.78. The method of any one of the foregoing embodiments, wherein when the ADC and the anti- hK2 / anti-CD3 bispecific antibody are administered on the same day, the anti-hK2 / anti-CD3 bi specific antibody is administered at least one hour after the administration of the ADC.79. The method of any one of the foregoing embodiments, wherein the human patient is 18 years of age or older.80. The method of any one of the foregoing embodiments, wherein the prostate cancer is histologically confirmed adenocarcinoma of the prostate, as defined by Prostate Cancer Working Group 3 (PCWG3) criteria (Scher et al. 2016 Journal of Clinical Oncology 34(12): 1402-1418).81. The method of any one of the preceding embodiments, wherein the prostate cancer is a prostate adenocarcinoma that does not comprise small cell carcinoma, carcinoid tumor, mixed NE carcinoma, or large cell NE carcinoma.82. The method of any one of the preceding embodiments, wherein the patient has: a. received orchiectomy or medical castration; or b. has not undergone orchiectomy and is receiving ongoing androgen deprivation therapy with a gonadotropin releasing hormone (GnRH) analog (agonist or antagonist) prior to being administered with the first dose of study drug (i.e., prior to being administered the first dose of PSMA ADC and of anti-hK2 / anti-CD3 bispecific antibody of the application).83. The method of any one of the preceding embodiments, wherein the patient has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.84. The method of any one of the preceding embodiments, wherein the patient has received prior treatment for mCRPC with at least one androgen receptor (AR)-targeted therapy (for example treatment with abiraterone acetate, apalutamide, enzalutamide, or darolutamide).85. The method of any one of the preceding embodiments, wherein the patient has received no more than one or no previous taxane therapies, more specifically no more than one or no prior antiprostate cancer chemotherapy (i.e., docetaxel, cabazitaxel, cisplatin, carboplatin, etoposide, etc ).86. The method of any one of the preceding embodiments, wherein the patient has received prior 177-Lu-PSMA radionuclide therapy.87. The method of any one of the preceding embodiments, wherein the method provides a decrease in the serum Prostate-Specific Antigen (PSA) level of the patient, wherein the decrease is relative to the PSA level of the patient prior to the administration of the anti-hK2 / anti-CD3 bispecific antibody.88. The method of any one of the preceding embodiments, wherein the PSA level decreases by 50% or more compared to the PSA level of the patient prior to the administration of the anti- hK2 / anti-CD3 bispecific antibody.89. The method of any one of the preceding embodiments, wherein the method provides for no disease progression in the patient, wherein disease progression is assessed according to theProstate Cancer Working Group 3 (PCWG3) Criteria (Scher et al. 2016 Journal of Clinical Oncology 34(12): 1402-1418)).90. The method of any one of the preceding embodiments, wherein the method provides a Partial Response or better according to RECIST version 1.1 response criteria (Eisenhauer et al. 2009 European Journal of Cancer 45: 228-247) without evidence of bone progression according to PCWG3 in the patient.91. The method of any one of the preceding embodiments, wherein the method provides radiographic progression free survival (rPFS).92. The method of any one of the preceding embodiments, wherein no Adverse Event of Grade 3 or higher (according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0) is observed in the patient.93. The method of any one of the preceding embodiments, wherein Adverse Events of Grade 3 or higher (according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0) are observed in 20% or fewer of patients in a cohort of at least 20 patients, for example 15% or fewer of patients in a cohort of at least 20 patients.94. The method of any one of the preceding embodiments, wherein the method does not induce a Dose Limiting Toxicity (DLT) in the patient.95. The method of any one of the preceding embodiments, wherein the anti-hK2 / anti-CD3 bispecific antibody is pasritamig.96. The anti-hK2 / anti-CD3 bispecific antibody of any one of the preceding embodiments for use in the method of any one of the preceding embodiments.97. The ADC of any one of the preceding embodiments for use in the method of any one of the preceding embodiments.98. The anti-hK2 / anti-CD3 bispecific antibody of any one of the preceding embodiments and the ADC of any one of the preceding embodiments for use in the method of any one of the preceding embodiments.99. A combination or functional association comprising the anti-hK2 / anti-CD3 bispecific antibody of any one of the preceding embodiments and the ADC of any one of the preceding embodiments.100. The anti-hK2 / anti-CD3 bispecific antibody of any one of the preceding embodiments and the ADC of any one of the preceding embodiments as a combined preparation for simultaneous, separate or sequential use in prostate cancer therapy, more specifically in mCRPC therapy.SUBJECT MATTER DESCRIBED IN THE APPLICATION A method of treating prostate cancer, preferably advanced prostate cancer, more preferably metastatic castration-resistant prostate cancer (mCRPC), in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of an antibody drug conjugate (ADC) targeting prostate-specific membrane antigen (PSMA) at a first treatment dose, and a therapeutically effective amount of an anti-hK2 / anti-CD3 bispecific antibody at a treatment dose, wherein: a. the ADC comprises an anti-PSMA antibody conjugated to a drug-linker, wherein the conjugation occurs via para-acetyl phenylalanine (pAF) incorporated in the heavy chain sequence of the antibody, wherein the anti-PSMA antibody comprises a heavy chain (HC) of SEQ ID NO: 1 and a light chain (LC) of SEQ ID NO: 2, in which the pAF is incorporated at the HC position Al 14 according to Kabat numbering, and wherein the drug-linker has the following structure:b. the anti-hK2 / anti-CD3 bispecific antibody comprises a first antigen binding domain that binds specifically to hK2, and a second antigen binding domain that binds specifically to CD3, wherein: i. the first domain comprises a first heavy chain variable region (VH1) of SEQ ID NO: 9 and a first light chain variable region (VL1) of SEQ ID NO: 10; and ii. the second domain comprises a second heavy chain variable region (VH2) of SEQ ID NO: 21 and a second light chain variable region (VL2) of SEQ ID NO: 22. The method of embodiment 1, wherein the first domain of the anti-hK2 / anti-CD3 bi specific antibody comprises a Fab and the second domain of the anti-hK2 / anti-CD3 bispecific antibody comprises an scFv.The method of embodiment 2, wherein the scFv comprises, from the N-terminus to the C- terminus, VH2-linker-VL2 or VL2-linker-VH2, and the linker comprises or consists of the amino acid sequence of SEQ ID NO: 23. The method of any one of the foregoing embodiments, wherein the anti-hK2 / anti-CD3 antibody comprises a first heavy chain (HC1), a first light chain (LC1) and a second heavy chain (HC2) having amino acid sequences at least 90% identical to SEQ ID NO: 13, SEQ ID NO: 14 and SEQ ID NO: 26, respectively; preferably, the HC1, LC1 and HC2 comprise the amino acid sequences of SEQ ID NO: 13, SEQ ID NO: 14 and SEQ ID NO: 26, respectively. The method of any one of embodiments 1-4, wherein the anti-PSMA antibody, which is comprised in the ADC, comprises two heavy chains and two light chains, wherein each heavy chain comprises the pAF at position Al 14 according to Kabat numbering, and wherein the drug-linker is conjugated to each said pAF (i.e., DAR=2) via an oxime linkage. The method of any one of the foregoing embodiments, wherein the treatment dose of the anti- hK2 / anti-CD3 bispecific antibody is about 300 mg, per administration. The method of any one of the foregoing embodiments, wherein the treatment dose of the anti- hK2 / anti-CD3 bispecific antibody is administered at a flat dose. The method of any one of the foregoing embodiments, wherein the treatment dose of the anti- hK2 / anti-CD3 bispecific antibody is initially administered on a day, which is after the day of administration of the first treatment dose of the ADC, or on a day, which is before the day of administration of the first treatment dose of the ADC, for example on a day, which is after the day of administration of the first treatment dose of the ADC. The method of any one of the foregoing embodiments, wherein the treatment dose of the anti- hK2 / anti-CD3 bispecific antibody is initially administered on a day within 19-23 days, such as 19, 20, 21, 22, or 23 days, preferably 21 days, after the administration of the first treatment dose of the ADC. The method of any one of the foregoing embodiments, wherein the treatment dose of the anti- hK2 / anti-CD3 bispecific antibody is subsequently administered once every 5 to 7 weeks, for example, once every 5, 6 or 7 weeks, preferably once every six weeks, after the initial administration of the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody. The method of any one of the foregoing embodiments, wherein the treatment dose of the anti- hK2 / anti-CD3 bispecific antibody is intravenously administered, for example, by intravenous(TV) infusion, for example by TV infusion over a period of about 30 minutes to one hour for each administration, such as over a period of about 30 minutes or a period of about one hour for each administration. The method of embodiment 10, wherein the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody is intravenously administered, for example, by TV infusion, for example by TV infusion over a period of about one hour for the initial administration, and by TV infusion over a period of about 30 minutes for any subsequent administration. The method of any one of the foregoing embodiments, wherein the method does not comprise administering a step-up dose of the anti-hK2 / anti-CD3 bispecific antibody prior to the initial administration of the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody. The method of any one of the preceding embodiments, further comprising administering to the patient one or more step-up doses (for example, one or two step-up doses) of the anti-hK2 / anti- CD3 bispecific antibody, wherein the one or more step-up doses are administered prior to the initial administration of the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody and wherein the one or more step-up doses are not higher than the treatment dose. The method of any one of the preceding embodiments, further comprising administering to the (human) patient one or more step-up doses (for example, one or two step-up doses) of the anti- hK2 / anti-CD3 bispecific antibody, wherein the one or more step-up doses are administered after the administration of the first treatment dose of the ADC and prior to the initial administration of the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody and wherein the one or more step-up doses are not higher than the treatment dose. The method of embodiment 14 or 15, wherein the one or more step-up doses of the anti- hK2 / anti-CD3 bispecific antibody are intravenously administered, for example via intravenous (TV) infusion. The method of any one of embodiments 14-16, wherein one step-up dose of the anti-hK2 / anti- CD3 bispecific antibody is administered. The method of any one of embodiments 14-16, wherein more than one step-up doses of the anti-hK2 / anti-CD3 bispecific antibody are administered. The method of embodiment 18, wherein the more than one step-up doses of the anti-hK2 / anti- CD3 bispecific antibody are administered at a flat dose.The method of embodiment 18 or 19, wherein the more than one step-up doses of the anti- hK2 / anti-CD3 bispecific antibody are administered at ascending doses. The method of any one of embodiments 18-20, wherein the method comprises administering to the patient a first step-up dose and a second step-up dose of the anti-hK2 / anti-CD3 bispecific antibody, wherein the first step-up dose is administered prior to the second step-up dose, and the second step-up dose is administered prior to the treatment dose. The method of embodiment 21, wherein the second step-up dose of the anti-hK2 / anti-CD3 bispecific antibody is greater than the first step-up dose. The method of embodiment 21 or 22, wherein the method comprises administering to the patient: i) the first step-up dose of the anti-hK2 / anti-CD3 bispecific antibody, ii) the second step-up dose of the anti-hK2 / anti-CD3 bispecific antibody; and iii) the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody, wherein the first step-up dose is administered once, and the second step-up dose is administered once. The method of any one of embodiments 18-23, wherein the method comprises administering to the patient a first step-up dose of the anti-hK2 / anti-CD3 bispecific antibody of about 2 mg to about 5 mg per administration, for example about 2 mg, about 2.5 mg, about 3 mg, about 3.5 mg, about 4 mg, about 4.5 mg or about 5 mg, per administration, preferably about 3.5 mg per administration. The method of any one of embodiments 18-24, wherein the first step-up dose is administered on a day within 5-9 days, such as 5, 6, 7, 8, or 9 days, preferably 7 days, after the first treatment dose of the ADC is administered. The method of embodiment 25, wherein the first step-up dose of the anti-hK2 / anti-CD3 bispecific antibody of about 3.5 mg per administration is administered 7 days after the first treatment dose of the ADC is administered. The method of any one of embodiments 18-26, wherein the method further comprises administering to the patient a second step-up dose of the anti-hK2 / anti-CD3 bi specific antibody of about 15 mg to about 25 mg per administration, for example about 15 mg, about 16 mg, about 17 mg, about 18 mg, about 19 mg, about 20 mg, about 21 mg, about 22 mg, about 23 mg, about 24 mg, or about 25 mg, per administration, preferably about 18 mg per administration.The method of embodiment 27, wherein the second step-up dose of the anti-hK2 / anti-CD3 bispecific antibody is administered on a day within 12-16 days, such as 12, 13, 14, 15 or 16 days, preferably 14 days, after the first treatment dose of the ADC is administered. The method of embodiment 28, wherein the second step-up dose of the anti-hK2 / anti-CD3 bispecific antibody of about 18 mg per administration is administered 14 days after the first treatment dose of the ADC is administered. The method of any one of embodiments 14-29, wherein the one or more step-up doses are administered on a day within 7-14 days, for example 7, 8, 9, 10, 11, 12, 13, or 14 days, prior to the initial administration of the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody. The method of embodiment 30, wherein the first step-up dose of the anti-hK2 / anti-CD3 bispecific antibody is administered 14 days prior to the initial administration of the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody. The method of embodiment 29 or 30, wherein the second step-up dose of the anti-hK2 / anti- CD3 bispecific antibody is administered 7 days prior to the initial administration of the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody. The method of any one of embodiments 14-32, wherein the first step-up dose of the anti- hK2 / anti-CD3 bispecific antibody is administered via IV infusion. The method of any one of embodiments 18-33, wherein the second step-up dose of the anti- hK2 / anti-CD3 bispecific antibody is administered via IV infusion. The method of any one of the preceding embodiments, comprising:(a) administering to the patient the ADC at a first treatment dose on Day 1 of the treatment;(b) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a first step-up dose of about 2 mg to 5 mg per administration on a day within Day 6 to Day 10 of the treatment;(c) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a second step-up dose of about 15 mg to 21 mg per administration on a day within Day 13 to Day 17 of the treatment;(d) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 250 mg to 350 mg per administration on a day within Day 20 to Day 24 of the treatment; and(e) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 250 mg to 350 mg per administration once every 5-7 weeks after step (d), wherein, each of the first step-up dose, the second step-up dose and the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody is intravenously administered, advantageously via IV infusion, for example via IV infusion over a period of about 30 minutes to one hour for each administration. The method of embodiment 35, comprising:(a) administering to the patient the ADC at the first treatment dose on Day 1 of the treatment;(b) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a first step-up dose of about 3.5 mg per administration on Day 8 of the treatment;(c) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a second step-up dose of about 18 mg per administration on Day 15 of the treatment;(d) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 300 mg per administration on Day 22 of the treatment; and(e) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 300 mg per administration once every 6 weeks after step (d), wherein each of the first step-up dose, the second step-up dose and the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody is intravenously administered, for example, via IV infusion, for example via IV infusion over a period of about 30 minutes to one hour for each administration. The method of any one of the foregoing embodiments, wherein the ADC is administered at the first treatment dose of 2.0 mg / kg or lower, such as 1.9-1.4 mg / kg or 1.7-1.4 mg / kg, e.g., 2.0 mg / kg, 1.7 mg / kg or 1.4 mg / kg. The method of embodiment 37, wherein the ADC is administered at the first treatment dose of 1.4 mg / kg. The method of embodiment 37, wherein the ADC is administered at the first treatment dose of 2.0 mg / kg.The method of any one of the foregoing embodiments, further comprising administering to the patient a second treatment dose of the ADC, for example a second treatment dose of the ADC:(a) on a day within 19-44 days, such as on a day within 19-23 days or 40-44 days, for example 19, 20, 21, 22, or 23 days, preferably 21 days, or 40, 41, 42, 43 or 44 days, preferably 41 days, after the administration of the first treatment dose of the ADC; or(b) on a day within 2 to 7 weeks, such as 2, 3, 4, 5, 6 or 7 weeks, for example 3 weeks or 6 weeks, after the administration of the first treatment dose of the ADC. The method of embodiment 40, wherein the second treatment dose of the ADC is the same dose as the first treatment dose of the ADC. The method of embodiment 41, wherein first and second treatment dose of the ADC is 1.4 mg / kg. The method of embodiment 41, wherein first and second treatment dose of the ADC is 2.0 mg / kg. The method of embodiment 40, wherein the second treatment dose of the ADC is lower than the first treatment dose of the ADC but is higher than 1.4 mg / kg. The method of embodiment 40, wherein the first treatment dose is 2 mg / kg and the second treatment dose is 1.4 mg / kg. The method of any one of embodiments 40-45, wherein the second treatment dose of the ADC is administered on a day within 19-23 days, such as 19, 20, 21, 22, or 23 days, preferably 21 days, after the first treatment dose of ADC is administered. The method of any one of embodiments 40-46, wherein the second treatment dose of the ADC is administered three weeks after the first treatment dose of ADC is administered. The method of any one of embodiments 40-45, wherein the second treatment dose of the ADC is administered on a day within 40-44 days, such as 40, 41, 42, 43 or 44 days, preferably 42 days, after the first treatment dose of ADC is administered. The method of any one of claims 40-45 and 48, wherein the second treatment dose of the ADC is administered six weeks after the first treatment dose of ADC is administered. The method of any one of embodiments 40-49, wherein the second treatment dose of the ADC is administered 21 or 41 days after the first treatment dose of ADC is administered.The method of any one of embodiments 40-50, further comprising administering to the patient a subsequent treatment dose of the ADC after the administration of the second treatment dose of the ADC, for example a subsequent treatment dose of the ADC once every 2 to 7 weeks, such as once every 2, 3, 4, 5, 6 or 7 weeks, for example once every 3 weeks or once every 6 weeks, after the administration of the second treatment dose of the ADC. The method of embodiment 51, wherein the subsequent treatment dose of the ADC is administered once every 6 weeks. The method of embodiment 51, wherein the subsequent treatment dose of the ADC is administered once every 3 weeks. The method of embodiment 51, wherein the subsequent treatment dose of the ADC is administered once every 6 weeks for 2 doses, 3 doses, 4 doses, 5 doses, 6 doses, 7 doses or 8 doses. The method of embodiment 51, wherein the subsequent treatment dose of the ADC is administered once every 3 weeks for 2 doses. The method of any one of the preceding embodiments, which does not comprise administering more than 4 doses of the ADC. The method of any one of embodiments 51-55, wherein the subsequent treatment dose of the ADC is the same dose as the second treatment dose of the ADC. The method of embodiment 57, wherein the second treatment dose and the subsequent treatment dose of the ADC is 1.4 mg / kg. The method of embodiment 57, wherein the second dose and the subsequent treatment dose of the ADC is 2.0 mg / kg. The method of any one of embodiments 51-55, wherein the subsequent treatment dose of the ADC is lower than the second treatment dose of the ADC but is higher than 1.4 mg / kg. The method of any one of embodiments 51-55, wherein the second treatment dose of the ADC is 2 mg / kg and the subsequent treatment dose of the ADC is 1.4 mg / kg. The method of any one of embodiments 51-55, wherein the second treatment dose of the ADC is administered on a day 40-44 days, such as 40, 41, 42, 43 or 44 days, preferably 41 days, after the first treatment dose of ADC is administered. The method of embodiment 62, wherein the second treatment dose of the ADC is administered 41 days after the first treatment dose of ADC is administered.The method of any one of embodiments 62-63, further comprising administering to the patient a subsequent treatment dose of the ADC once every 2 to 7 weeks, such as once every 4, 5 or 6 weeks, after the administration of the second treatment dose of the ADC. The method of embodiment 64, wherein the subsequent treatment dose of the ADC is administered once every 6 weeks. The method of embodiment 64, wherein the subsequent treatment dose of the ADC is administered once every 3 weeks. The method of any one of embodiments 64-66, wherein the subsequent treatment dose of the ADC is the same dose as the second treatment dose of the ADC. The method of embodiment 67, wherein the second treatment dose and the subsequent treatment dose of the ADC is 1.4 mg / kg. The method of embodiment 67, wherein the second treatment dose and the subsequent treatment dose of the ADC is 2.0 mg / kg. The method of any one of embodiments 64-66, wherein the subsequent treatment dose of the ADC is lower than the second treatment dose of the ADC but is higher than 1.4 mg / kg. The method of any one of embodiments 64-66, wherein the second treatment dose is 2mg / kg and the subsequent treatment dose of the ADC is 1.4 mg / kg. The method of any one of the foregoing embodiments, wherein each of the first treatment dose, the second treatment dose, and / or the subsequent treatment dose of the ADC is intravenously administered, for example, by intravenous (IV) infusion over a period of about 30 minutes to one hour for each administration, such as over a period of about 30 minutes or a period of about one hour for each administration. The method of any one of the foregoing embodiments, wherein the treatment dose of the anti- hK2 / anti-CD3 bispecific antibody is intravenously administered, advantageously via IV infusion, for example, by IV infusion over a period of about one hour for the initial administration, and by IV infusion over a period of about 30 minutes for any subsequent administration. The method of any one of the foregoing embodiments, wherein the method does not comprise administering a step-up dose of the ADC prior to the administration of the first treatment dose, the second treatment dose, and / or the subsequent treatment dose of the ADC. The method of any one of the preceding embodiments, comprising:(a) administering to the patient the ADC at a first treatment dose on Day 1 of the treatment, wherein the first treatment dose is about 2.0 mg / kg;(b) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a first step-up dose of about 3.5 mg on a day within Day 6 to Day 10 of the treatment, for example on Day 8;(c) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a second step-up dose of about 18.5 mg on a day within Day 13 to Day 17 of the treatment, for example on Day 15;(d) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 300 mg on a day within Day 20 to Day 24 of the treatment, for example on Day 22;(e) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 300 mg per administration once every 6 weeks after the administering of step (d);(f) administering to the patient a second treatment dose of the ADC on a day within Day 20 to Day 24 of the treatment, for example on Day 22, wherein the second treatment dose of the ADC is the same dose as the first treatment dose of the ADC; and(g) administering to the patient a third and fourth treatment dose of the ADC once every 3 weeks after the administering of step (f), wherein the third and fourth treatment dose of the ADC is the same dose as the second treatment dose of the ADC e method of embodiment 75, wherein the total number of doses of the ADC does not exceed doses. e method of any one of the preceding embodiments, comprising:(a) administering to the patient the ADC at a first treatment dose on Day 1 of the treatment, wherein the first treatment dose is about 2.0 mg / kg;(b) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a first step-up dose of about 3.5 mg on a day within Day 6 to Day 10 of the treatment, for example on Day 8;(c) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a second step-up dose of about 18.5 mg on a day within Day 13 to Day 17 of the treatment, for example on Day 15;(d) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 300 mg on a day within Day 20 to Day 24 of the treatment, for example on Day 22;(e) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 300 mg per administration once every 6 weeks after the administering of step (d);(f) administering to the patient a second treatment dose of the ADC on a day within Day 40 to Day 44 of the treatment, for example on Day 43, wherein the second treatment dose of the ADC is the same dose as the first treatment dose of the ADC;(g) administering to the patient one or more subsequent treatment dose(s) of the ADC once every 6 weeks after the administering of step (f), wherein the one or more subsequent treatment dose(s) of the ADC is (are) the same dose as the second treatment dose of the ADC, (and optionally wherein the total number of treatment doses of the ADC is 3 doses, 4 doses, 5 doses, 6 doses, 7 doses or 8 doses). The method of any one of embodiment 75-77, wherein, each of the first step-up dose, the second step-up dose and the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody is intravenously administered, advantageously via IV infusion; and wherein, each of the first treatment dose, the second treatment dose and the subsequent treatment dose of the ADC is intravenously administered, for example, via IV infusion. The method of any one of embodiments 38-61 and 72-74, comprising:(a) administering to the patient the ADC at a first treatment dose on Day 1 of the treatment, wherein the first treatment dose is 2.0 mg / kg or lower, such as 1.9- 1.4 mg / kg or 1.7-1.4 mg / kg, e.g., 2.0 mg / kg, 1.7 mg / kg or 1.4 mg / kg;(b) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a first step-up dose of about 2-5 mg per administration on a day within Day 6 to Day 10 of the treatment;(c) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a second step-up dose of about 15-21 mg per administration on a day within Day 13 to Day 17 of the treatment;(d) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 250-350 mg per administration on a day within Day 20 to Day 24 of the treatment;(e) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 250-350 mg per administration once every 5-7 weeks after the administering of step (d),(f) administering to the patient a second treatment dose of the ADC on a day within Day 20 to Day 24 of the treatment, wherein the second treatment dose of the ADC is the same dose as the first treatment dose of the ADC, or the second treatment dose of the ADC is lower than the first treatment dose of the ADC but is higher than 1.4 mg / kg;(g) administering to the patient the ADC at a subsequent treatment dose once every 2 to 7 weeks, such as once every 3 weeks, once every 6 weeks, or once every 3 weeks for 2-4 doses and followed by once every 6 weeks, after the administering of step (f), wherein the subsequent treatment dose of the ADC is the same dose as the second treatment dose of the ADC, or the subsequent treatment dose of the ADC is lower than the second treatment dose of the ADC but is higher than 1.4 mg / kg; wherein, each of the first step-up dose, the second step-up dose and the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody is intravenously administered, advantageously via IV infusion, for example by IV infusion over a period of about 30 minutes to one hour for each administration; and wherein, each of the first treatment dose, the second treatment dose and the subsequent treatment dose of the ADC is intravenously administered, for example, via IV infusion over a period of about 30 minutes to one hour for each administration. method of embodiment 79, comprising:(a) administering to the patient the ADC at a first treatment dose on Day 1 of the treatment, wherein the first treatment dose is 2.0 mg / kg, 1.7 mg / kg or 1.4 mg / kg;(b) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a first step-up dose of about 3.5 mg per administration on Day 8 of the treatment;(c) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a second step-up dose of about 18 mg per administration on Day 15 of the treatment;(d) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 300 mg per administration on Day 22 of the treatment;(e) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 300 mg per administration once every 6 weeks after the administering of step (d),(f) administering to the patient a second treatment dose of the ADC on Day 22 of the treatment, wherein the second treatment dose of the ADC is the same dose as the first treatment dose of the ADC, or the second treatment dose of the ADC is lower than the first treatment dose of the ADC but is higher than 1.4 mg / kg;(g) administering to the patient the ADC at a subsequent treatment dose once every 3 weeks, once every 6 weeks, or once every 3 weeks for 2-4 doses and followed by once every 6 weeks, after the administering of step (f), wherein the subsequent treatment dose of the ADC is the same dose as the second treatment dose of the ADC, or the subsequent treatment dose of the ADC is lower than the second treatment dose of the ADC but is higher than 1.4 mg / kg; wherein each of the first step-up dose, the second step-up dose and the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody is intravenously administered, advantageously via IV infusion, for example by IV infusion over a period of about 30 minutes to one hour for each administration; and wherein each of the first treatment dose, the second treatment dose and the subsequent treatment dose of the ADC is intravenously administered, for example, via IV infusion over a period of about 30 minutes to one hour for each administration. method of any one of embodiments 36-49 and 55-66, comprising:(a) administering to the patient the ADC at a first treatment dose on Day 1 of the treatment, wherein the first treatment dose is 2.0 mg / kg or lower, such as 1.9- 1.4 mg / kg or 1.7-1.4 mg / kg, e.g., 2.0 mg / kg, 1.7 mg / kg or 1.4 mg / kg;(b) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a first step-up dose of about 2-5 mg per administration on a day within Day 6 to Day 10 of the treatment;(c) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a second step-up dose of about 15-21 mg per administration on a day within Day 13 to Day 17 of the treatment;(d) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 250-350 mg per administration on a day within Day 20 to Day 24 of the treatment;(e) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 250-350 mg per administration once every 5-7 weeks after the administering of step (d),(f) administering to the patient a second treatment dose of the ADC on a day within Day 40 to Day 44 of the treatment, wherein the second treatment dose of the ADC is the same dose as the first treatment dose of the ADC, or the second treatment dose of the ADC is lower than the first treatment dose of the ADC but is higher than 1.4 mg / kg;(g) administering to the patient the ADC at a subsequent treatment dose once every 5 to 7 weeks, such as once every 6 weeks after the administering of step (f), wherein the subsequent treatment dose of the ADC is the same dose as the second treatment dose of the ADC, or the subsequent treatment dose of the ADC is lower than the second treatment dose of the ADC but is higher than 1.4 mg / kg; wherein, the first step-up dose, the second step-up dose and the treatment dose of the anti- hK2 / anti-CD3 bispecific antibody are intravenously administered, advantageously via IV infusion, for example by IV infusion over a period of about 30 minutes to one hour for each administration; and wherein, the first treatment dose, the second treatment dose and the subsequent treatment dose of the ADC are intravenously administered, for example, via IV infusion, for example by IV infusion over a period of about 30 minutes to one hour for each administration. method of embodiment 81, comprising:(a) administering to the patient the ADC at a first treatment dose on Day 1 of the treatment, wherein the first treatment dose is 2.0 mg / kg, 1.7 mg / kg or 1.4 mg / kg;(b) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a first step-up dose of about 3.5 mg per administration on Day 8 of the treatment;(c) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a second step-up dose of about 18 mg per administration on Day 15 of the treatment;(d) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 300 mg per administration on Day 22 of the treatment;(e) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 300 mg per administration once every 6 weeks after the administering of step (d),(f) administering to the patient a second treatment dose of the ADC on Day 42 of the treatment, wherein the second treatment dose of the ADC is the same dose as the first treatment dose of the ADC, or the second treatment dose of the ADC is lower than the first treatment dose of the ADC but is higher than 1.4 mg / kg;(g) administering to the patient the ADC at a subsequent treatment dose once every 6 weeks after the administering of step (f), wherein the subsequent treatment dose of the ADC is the same dose as the second treatment dose of the ADC, or the subsequent treatment dose of the ADC is lower than the second treatment dose of the ADC but is higher than 1.4 mg / kg; wherein the first step-up dose, the second step-up dose and the treatment dose of the anti- hK2 / anti-CD3 bispecific antibody are intravenously administered, advantageously via IV infusion , for example by IV infusion over a period of about 30 minutes to one hour for each administration; and wherein the first treatment dose, the second treatment dose and the subsequent treatment dose of the ADC are intravenously administered, for example, via IV infusion, for example by IV infusion over a period of about 30 minutes to one hour for each administration. method of anyone of the foregoing embodiments comprising(a) administering to the patient the ADC at a first treatment dose on Day 1 of the treatment, wherein the first treatment dose is 1.4 mg / kg;(b) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a first step-up dose of about 2-5 mg per administration on a day within Day 6 to Day 10 of the treatment;(c) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a second step-up dose of about 15-21 mg per administration on day within Day 13 to Day 17 of the treatment;(d) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 250-350 mg per administration on a day within Day 20 to Day 24 of the treatment;(e) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 250-350 mg per administration once every 5-7 weeks after the administering of step (d),(f) administering to the patient a second treatment dose of the ADC on a day within Day 20 to Day 24 of the treatment, wherein the second treatment dose of the ADC is 1.4 mg / kg;(g) administering to the patient the ADC at a subsequent treatment dose once every 3 weeks, after the administering of step (f), wherein the subsequent treatment dose of the ADC is 1.4 mg / kg; wherein, the first step-up dose, the second step-up dose and / or the treatment doses of the anti-hK2 / anti-CD3 bispecific antibody are intravenously administered, advantageously via IV infusion, for example, via IV infusion over a period of about one hour for each administration; and wherein the first treatment dose, the second treatment dose and / or the subsequent treatment dose of the ADC is intravenously administered, for example, via IV infusion over a period of about one hour for each administration. method of anyone of the foregoing embodiments comprising:(a) administering to the patient the ADC at a first treatment dose on Day 1 of the treatment, wherein the first treatment dose is 2.0 mg / kg;(b) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a first step-up dose of about 2-5 mg per administration on a day within Day 6 to Day 10 of the treatment;(c) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a second step-up dose of about 15-21 mg per administration on day within Day 13 to Day 17 of the treatment;(d) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 250-350 mg per administration on a day within Day 20 to Day 24 of the treatment;(e) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 250-350 mg per administration once every 5-7 weeks after the administering of step (d),(f) administering to the patient a second treatment dose of the ADC on a day within Day 20 to Day 24 of the treatment, wherein the second treatment dose of the ADC is 2.0 mg / kg;(g) administering to the patient the ADC at a subsequent treatment dose once every 3 weeks after the administering of step (f), wherein the subsequent treatment dose of the ADC is 2.0 mg / kg; wherein, the first step-up dose, the second step-up dose and / or the treatment doses of the anti-hK2 / anti-CD3 bispecific antibody are intravenously administered, advantageously via IV infusion, for example, via IV infusion over a period of about one hour for each administration; and wherein the first treatment dose, the second treatment dose and / or the subsequent treatment dose of the ADC is intravenously administered, for example, via IV infusion over a period of about one hour for each administration. method of anyone of the foregoing embodiments comprising:(a) administering to the patient the ADC at a first treatment dose on Day 1 of the treatment, wherein the first treatment dose is 2.0 mg / kg;(b) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a first step-up dose of about 2-5 mg per administration on a day within Day 6 to Day 10 of the treatment;(c) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a second step-up dose of about 15-21 mg per administration on day within Day 13 to Day 17 of the treatment;(d) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 250-350 mg per administration on a day within Day 20 to Day 24 of the treatment;(e) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 250-350 mg per administration once every 5-7 weeks after the administering of step (d),(f) administering to the patient a second treatment dose of the ADC on a day within Day 20 to Day 24 of the treatment, wherein the second treatment dose of the ADC is 2.0 mg / kg;(g) administering to the patient the ADC at a subsequent treatment dose once every 3 weeks after the administering of step (f), wherein the subsequent treatment dose of the ADC is 1.4 mg / kg; wherein, the first step-up dose, the second step-up dose and / or the treatment doses of the anti-hK2 / anti-CD3 bispecific antibody are intravenously administered, advantageously via IV infusion, for example, via IV infusion over a period of about one hour for each administration; and wherein the first treatment dose, the second treatment dose and / or the subsequent treatment dose of the ADC is intravenously administered, for example, via IV infusion over a period of about one hour for each administration. method of anyone of the foregoing embodiments comprising:(a) administering to the patient the ADC at a first treatment dose on Day 1 of the treatment, wherein the first treatment dose is 2.0 mg / kg;(b) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a first step-up dose of about 2-5 mg per administration on a day within Day 6 to Day 10 of the treatment;(c) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a second step-up dose of about 15-21 mg per administration on day within Day 13 to Day 17 of the treatment;(d) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 250-350 mg per administration on a day within Day 20 to Day 24 of the treatment;(e) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 250-350 mg per administration once every 5-7 weeks after the administering of step (d),(f) administering to the patient a second treatment dose of the ADC on a day within Day 20 to Day 24 of the treatment, wherein the second treatment dose of the ADC is 1.4 mg / kg;(g) administering to the patient the ADC at a subsequent treatment dose once every 3 weeks after the administering of step (f), wherein the subsequent treatment dose of the ADC is 1.4 mg / kg; wherein, the first step-up dose, the second step-up dose and / or the treatment doses of the anti-hK2 / anti-CD3 bispecific antibody are intravenously administered, advantageously via IV infusion, for example, via IV infusion over a period of about one hour for each administration; and wherein the first treatment dose, the second treatment dose and / or the subsequent treatment dose of the ADC is intravenously administered, for example, via IV infusion over a period of about one hour for each administration. method of any of the foregoing embodiments, comprising:(a) administering to the patient the ADC at a first treatment dose on Day 1 of the treatment, wherein the first treatment dose is 2.0 mg / kg;(b) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a first step-up dose of about 3.5 mg per administration on Day 8 of the treatment;(c) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a second step- up dose of about 18 mg per administration on Day 15 of the treatment;(d) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 300 mg per administration on Day 22 of the treatment;(e) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 300 mg per administration once every 6 weeks after the administering of step (d);(f) administering to the patient a subsequent treatment dose of the ADC once every 3 weeks for 3 doses after the administration of step (a), wherein the subsequent treatment dose of the ADC is 2 mg / kg;wherein the first step-up dose, the second step-up dose and the treatment dose of the anti- hK2 / anti-CD3 bispecific antibody are intravenously administered, advantageously via IV infusion , for example by IV infusion over a period of about 30 minutes to one hour for each administration; and wherein the first treatment dose and the subsequent treatment dose of the ADC are intravenously administered, for example, via IV infusion, for example by IV infusion over a period of about 30 minutes to one hour for each administration. method of any of the foregoing embodiments, comprising:(a) administering to the patient the ADC at a first treatment dose on Day 1 of the treatment, wherein the first treatment dose is 2.0 mg / kg;(b) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a first step-up dose of about 3.5 mg per administration on Day 8 of the treatment;(c) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a second step- up dose of about 18 mg per administration on Day 15 of the treatment;(d) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 300 mg per administration on Day 22 of the treatment;(e) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 300 mg per administration once every 6 weeks after the administering of step (d);(f) administering to the patient a second treatment dose of the ADC on Day 22 and further administering subsequent treatment doses of the ADC once every 6 weeks after the administration of step (a), wherein the second and subsequent treatment doses of the ADC are 2 mg / kg; wherein the first step-up dose, the second step-up dose and the treatment dose of the anti- hK2 / anti-CD3 bispecific antibody are intravenously administered, advantageously via IV infusion , for example by IV infusion over a period of about 30 minutes to one hour for each administration; and wherein the first treatment dose and the subsequent treatment dose of the ADC are intravenously administered, for example, via IV infusion, for example by IV infusion over a period of about 30 minutes to one hour for each administration.The method of any one of the foregoing embodiments, wherein when the ADC and the anti- hK2 / anti-CD3 bispecific antibody are administered on the same day, the anti-hK2 / anti-CD3 bispecific antibody is administered at least one hour after the administration of the ADC. The method of any one of the foregoing embodiments, wherein, prior to, but on the same day as the first administration of the anti-hK2 / anti-CD3 bispecific antibody, the patient has received one or more premedication independently selected from a glucocorticoid, an antihistamine and an antipyretic, more particularly the patient has received a glucocorticoid premedication, an antihistamine premedication and an antipyretic premedication. The method of any one of the foregoing embodiments, wherein, prior to, but on the same day as the first administration of the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody, the patient has received one or more premedication independently selected from a glucocorticoid, an antihistamine and an antipyretic, more particularly the patient has received a glucocorticoid premedication, an antihistamine premedication and an antipyretic premedication. The method of any one of the preceding embodiments, which comprises administering one or more step-up dose(s) of 2 to 20 mg of the anti-hK2 / anti-CD3 bispecific antibody prior to the first treatment dose of the anti-hK2 / anti-CD3 bispecific antibody, wherein, prior to, but on the same day as the administration of the one or more step-up dose(s) as well as prior to, but on the same day as the first administration of the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody, the patient has received one or more premedication independently selected from a glucocorticoid, an antihistamine and an antipyretic, more particularly the patient has received a glucocorticoid premedication, an antihistamine premedication and an antipyretic premedication. The method of any one of embodiments 90-92, wherein the one or more premedication is administered within 2 hours prior to the administration of the anti-hK2 / anti-CD3 bispecific antibody The method of any one of embodiments 1-93, which comprises administering a first step-up dose of the anti-hK2 / anti-CD3 bispecific antibody and a second step-up dose of the anti-hK2 / anti- CD3 bispecific antibody prior to the first treatment dose of the anti-hK2 / anti-CD3 bispecific antibody, and wherein, prior to but on the same day as the administration of the first step-up dose and the second step-up dose as well as prior to the first administration of the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody, the patient has received at least one premedication independently selected from a glucocorticoid, an antihistamine and an antipyretic, moreparticularly the patient has received a glucocorticoid premedication, an antihistamine premedication and an antipyretic premedication. The method of embodiment 94, wherein at least one premedication is administered within 2 hours prior to the first step-up dose, within 2 hours prior to the second step-up dose, and within 2 hours prior to the first administration of the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody. The method of any one of embodiments 94-95, wherein the first step-up dose is 3.5mg and the second step-up dose is 18mg. The method of any one of embodiments 94-96, wherein the first and second step-up doses are administered by intravenous infusion. The method of any one of embodiments 93-97, wherein the first step-up dose is administered 12-16 days, e.g., 14 days, or about 2 weeks before the first administration of the target dose, and wherein the second step-up dose is administered 5-9 days, e.g. 7 days, or about 1 week before the first administration of the target dose. The method of any one of the foregoing embodiments, which does not comprise administering a premedication selected from a glucocorticoid, an antihistamine and an antipyretic, prior to the second as well as prior to any further administration of the KLK2xCD3 antibody. . The method of any one of embodiments 90-99, wherein the glucocorticoid premedication is dexamethasone. . The method of any one of embodiments 90-99, wherein the glucocorticoid premedication is 16mg or 8 mg per dose of dexamethasone by intravenous or oral administration. . The method of any one of embodiments 90-101, wherein the anti -histamine premedication is diphenhydramine. . The method of any one of embodiments 90-102, wherein the anti -histamine premedication is 50mg per dose of diphenhydramine by intravenous or oral administration. . The method of any one of embodiments 90-103, wherein the antipyretic premedication is paracetamol or acetaminophen. . The method of any one of embodiments 90-104, wherein the antipyretic premedication is 650 mg to 1,000 mg per dose of paracetamol or acetaminophen by intravenous or oral administration.. The method of any one of the foregoing embodiments, wherein the patient has received an anti-histamine medication on the day before, on the same day as and on the day after the administration of ADC. . The method of embodiment 106, wherein the anti-histamine medication is diphenhydramine.. The method of embodiment 106 or 107, wherein the anti-histamine medication is 50 mg per dose of diphenhydramine by intravenous administration. . The method of any one of the foregoing embodiments, wherein the patient has received a nonsteroidal anti-inflammatory medication on the day before, on the same day as and on the day after the administration of ADC. . The method of embodiment 109, wherein the nonsteroidal anti-inflammatory medication is indomethacin, ibuprofen, or naproxen sodium. . The method of embodiment 109 or 110, wherein the nonsteroidal anti-inflammatory medication is 25 mg per dose indomethacin, 600 mg per dose ibuprofen, or 500 mg per dose naproxen sodium by intravenous or oral administration. . The method of any one of embodiments 109-111, wherein the nonsteroidal antiinflammatory medication is 25 mg per dose indomethacin, 600 mg per dose ibuprofen, or 500 mg per dose naproxen sodium by intravenous or oral administration 2 hours before and 8 hours after the administration of the ADC. . The method of any of the foregoing embodiments, wherein the (human) patient is 18 years of age or older. . The method of any one of the foregoing embodiments, wherein the prostate cancer is histologically confirmed adenocarcinoma of the prostate, as defined by Prostate Cancer Working Group 3 (PCWG3) criteria (Scher et al. 2016 Journal of Clinical Oncology 34(12): 1402-1418). . The method of any one of the preceding embodiments, wherein the prostate cancer is a prostate adenocarcinoma that does not comprise small cell carcinoma, carcinoid tumor, mixed neuroendocrine (NE) carcinoma, or large cell NE carcinoma. . The method of any one of the preceding embodiments, wherein the patient has: a. received orchiectomy or medical castration; or b. has not undergone orchiectomy and is receiving ongoing androgen deprivation therapy with a gonadotropin releasing hormone (GnRH) analog (agonist or antagonist) prior tobeing administered (with the first dose of anti-hK2 / anti-CD3 bispecific antibody, i.e., prior to being administered with) the method of treatment of any one of the preceding embodiments. . The method of any one of the preceding embodiments, wherein the patient has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. . The method of any one of the preceding embodiments, wherein the patient has received prior treatment for mCRPC with at least one androgen receptor (AR)-targeted therapy (for example treatment with abiraterone acetate, apalutamide, enzalutamide, or darolutamide).. The method of any one of the preceding embodiments, wherein the patient has received no more than one or no previous taxane therapies, more specifically no more than one or no prior anti-prostate cancer chemotherapy (i.e., docetaxel, cabazitaxel, cisplatin, carboplatin, etoposide, etc ). . The method of any one of embodiments 1-119, wherein the patient has received no prior taxane therapy for the treatment of mCRPC as well as no prior 177-Lu-PSMA radionuclide therapy (specifically, no prior pluvicto therapy) for the treatment of mCRPC. . The method of any one of embodiments 1-119, wherein the patient has received only one prior taxane therapy for the treatment of mCRPC and has received no prior 177-Lu-PSMA radionuclide therapy (specifically, no prior pluvicto therapy) for the treatment of mCRPC.. The method of any one of embodiments 1-119, wherein the patient has received only one prior taxane therapy for the treatment of mCRPC and has received prior 177-Lu-PSMA radionuclide therapy (specifically, prior pluvicto therapy) for the treatment of mCRPC. . The method of any one of embodiments 1-119, wherein the patient has received no prior taxane therapy for the treatment of mCRPC, but has received prior 177-Lu-PSMA radionuclide therapy (specifically, prior pluvicto therapy) for the treatment of mCRPC. . The method of any one of the embodiments 1-119, 120 and 121, wherein the patient has received prior PSMA radioligand therapy. . The method of any one of embodiments 1-119 and 122-124, wherein the patient has received prior 177-Lu-PSMA radionuclide therapy. . The method of any one of the preceding embodiments, wherein the patient has received no more than one or no taxane therapy for the treatment of mCRPC, specifically no more than oneor no docetaxel therapy for the treatment of mCRPC and no more than one or no cabazitaxel therapy for the treatment of mCRPC. . The method of any one of the preceding embodiments, wherein the patient has received prior treatment with an androgen receptor pathway inhibitor (ARPI) for the treatment of prostate cancer, for example at least one prior prostate cancer treatment with abiraterone acetate, apalutamide, enzalutamide or darolutamide. . The method of any one of the preceding embodiments, wherein the patient has an estimated glomerular filtration rate (eGFR) >40 mL / min, based on the Modified Diet in Renal Disease (MDRD) 4-variable formula. . The method of any one of the preceding embodiments, wherein the patient has an AST (aspartate aminotransferase) <2.5 x ULN (upper limit of normal), ALT (alanine aminotransferase) <2.5 x ULN, or Total bilirubin <1.5 x ULN. . The method of any one of the preceding embodiments, wherein the patient has hemoglobin value > 9.0 g / dL independent of transfusion within 7 days or growth factors within 3 weeks prior to the start of the treatment. . The method of any one of the preceding embodiments, wherein the patient has neutrophils value > 1.5 x 109 / L independent of transfusion within 7 days or growth factors within 3 weeks prior to the start of the method of any one of the preceding embodiments. . The method of any one of the preceding embodiments, wherein the patient has platelets value > 100 x 109 / L independent of transfusion within 7 days or growth factors within 3 weeks prior to the start of the treatment. . The method of any of the foregoing embodiments, wherein the patient does not have one or more, more particularly does not have any of the following:(1) Active autoimmune disease within the 12 months prior to signing consent that requires systemic immunosuppressive medications;(2) Toxicity related to prior anti cancer therapy that has not returned to Grade <1 or baseline levels (except for alopecia and vitiligo);(3) Grade 2 or higher peripheral sensory or motor neuropathy within 28 days prior to signing consent and for Part 2, any symptomatic peripheral sensory or motor neuropathy including Grade 1 ;(4) Solid organ or bone marrow transplantation;(5) Known allergies, hypersensitivity, or intolerance to any of the components of the hK2xCD3 antibody or the PSMA ADC;(6) Any of the following within 6 months prior to signature of informed consent: a. Myocardial infarction, b. Severe or unstable angina, c. Clinically significant ventricular arrhythmias, d. Congestive heart failure (New York Heart Association [NYHA] class II to IV), e. Transient ischemic attack, and f. Cerebrovascular accident;(7) History of interstitial lung disease (ILD) or pneumonitis within 12 months of enrollment, or other clinically significant pulmonary compromise, particularly a requirement for supplemental oxygen use to maintain adequate oxygenation;(8) Clinically significant ocular infections or chronic corneal disorders, including confluent superficial keratitis, cornea epithelial defect, corneal ulcer or stromal opacity.(9) Major surgery or had significant trauma within 30 days before the start of the method of treatment of any one of the preceding embodiments, or has not recovered from surgery;(10) Active infection or condition that requires treatment with systemic antibiotics within 7 days prior to the start of the method of treatment of any one of the preceding embodiments;(11) Venous thromboembolic events (eg, pulmonary embolism) within 1 month prior to the start of the method of treatment of any one of the preceding embodiments;.(12) Leptomeningeal disease or brain metastases, with the exception of participants with definitively, locally treated brain metastases that are clinically stable and asymptomatic>2 weeks, and who are off corticosteroid treatment for at least 2 weeks prior to the start of the method of treatment of any one of the preceding embodiments;(13) Received immunosuppressive doses of systemic medications, such as glucocorticoids (doses >10 mg / day prednisone or equivalent) within 3 days prior to the start of the method of treatment of any one of the preceding embodiments;(14) Received or plans to receive any live, attenuated vaccine within 4 weeks prior to the first dose of study treatment or within 4 weeks after the last dose of the method of treatment of any one of the preceding embodiments;(15) Treatment with any anti -cancer or investigational agents within 14 days prior to the start of the method of treatment of any one of the preceding embodiments as follows: a. Any T-cell redirecting treatment (eg, CD3-directed bispecific or CAR-T therapy) within 90 days prior to the start of the method of treatment of any one of the preceding embodiments; b. Immune checkpoint inhibitors within 6 weeks prior to the start of the method of treatment of any one of the preceding embodiments; c. Radium (Ra) 223 dichloride within 28 days prior to the start of the method of treatment of any one of the preceding embodiments; d. Any prior treatment with KLK2 -targeted therapy; e. Any prior ADCs with microtubule inhibitor payloads (e.g., auristatins, maytansinoids, tubulysins);(16) Known positive test result for human immunodeficiency virus;(17) Active hepatitis B or C virus infection according to local laboratory range; and(18) Triplicate average corrected QT (QTc) interval corrected using Fridericia’s formula (QTcF) > 470 msec. . The method of any one of the preceding embodiments, wherein the method provides a decrease in the serum Prostate-Specific Antigen (PSA) level of the patient, wherein the decrease is relative to the PSA level of the patient prior to the administration of the anti- hK2 / anti-CD3 bispecific antibody. . The method of any one of the preceding embodiments, wherein the PSA level decreases by 50% or more compared to the PSA level of the patient prior to the administration of the anti- hK2 / anti-CD3 bispecific antibody (PSA50). . The method of any one of the preceding embodiments, which provides for a higher probability of achieving PSA50, compared to probability of achieving PSA50 that would have been observed in a comparable treatment regimen with the anti-hK2 / anti-CD3 bispecific antibody in monotherapy (i.e., without administration of the ADC). . The method of embodiment 133, wherein the PSA50 probability is the percentage of patients having a PSA50 in a cohort of patients. The method of embodiment 133 or 134, wherein the PSA50 is the confirmed PSA50 (PSA50 confirmed by a second measurement taken at least three weeks after the first PSA55 measurement). . The method of any one of the preceding embodiments, wherein the method provides for no disease progression in the patient, wherein disease progression is assessed according to the Prostate Cancer Working Group 3 (PCWG3) Criteria (Scher et al. 2016 Journal of Clinical Oncology 34(12): 1402-1418)). . The method of any one of the preceding embodiments, wherein the method provides a Partial Response or better according to RECIST version 1.1 response criteria (Eisenhauer et al. 2009 European Journal of Cancer 45: 228-247) without evidence of bone progression according to PCWG3 in the patient. . The method of any one of the preceding embodiments, wherein the method provides radiographic progression free survival (rPFS). . The method of any one of the preceding embodiments, wherein no Adverse Event of Grade 3 or higher (according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0) is observed in the patient. . The method of any one of the preceding embodiments, wherein Adverse Events of Grade 3 or higher (according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0) are observed in 20% or fewer of patients in a cohort of at least 20 patients, for example 15% or fewer of patients in a cohort of at least 20 patients. . The method of any one of the preceding embodiments, wherein the method does not induce a Dose Limiting Toxicity (DLT) in the patient. . The method of any one of the preceding embodiments, wherein the anti-hK2 / anti-CD3 bispecific antibody is pasritamig. . The anti-hK2 / anti-CD3 bispecific antibody as defined in any one of the preceding embodiments for use in the method of any one of the preceding embodiments. . The ADC as defined in any one of the preceding embodiments for use in the method of any one of the preceding embodiments.148. The anti-hK2 / anti-CD3 bispecific antibody as defined in any one of the preceding embodiments and the ADC as defined in any one of the preceding embodiments for use in the method of any one of the preceding embodiments.149. A combination or functional association comprising the anti-hK2 / anti-CD3 bispecific antibody as defined in any one of the preceding embodiments and the ADC as defined in any one of the preceding embodiments.150. The anti-hK2 / anti-CD3 bispecific antibody as defined in any one of the preceding embodiments and the ADC as defined in any one of the preceding embodiments as a combined preparation for simultaneous, separate or sequential use in prostate cancer therapy, more specifically in mCRPC therapy.

[0313] Various embodiments or subject matter have been described. It will be understood that various modifications may be made without departing from the spirit and scope of the invention. Accordingly, the following examples are intended to illustrate but not limit the scope of inventions described in the claims.EXAMPLES

[0314] The following examples are provided to further describe some of the embodiments disclosed herein. The examples are intended to illustrate, not to limit, the disclosed embodiments.Example 1; Manufacture of the PSMA ADC

[0315] Antibodies can be purified using chromatography based methods, well known to one of ordinary skill in the art, that involve Protein A affinity capture and cation exchange polishing. The antibody harvested in the cell culture media is captured on a Protein A affinity column and eluted under acidic conditions. Antibody preparation is titrated to pH 5 and polished by running through a cation exchange column. Using post cation exchange the antibody can be buffer exchanged into conjugation buffer.

[0316] Humanized anti-PSMA antibody was conjugated to a MMAF toxin via a small hydrophilic (PEG) linker as described e.g., in US 12,059,473B2, which is herein incorporated by reference. The Heavy Chain (HC) and the Light Chain (LC) of the humanized anti-PSMA antibody (Ab) were as follows:HC SEQ ID NO: 1 QVQLVQSGAEVKKPGASVKVSCKASGYTFTEYTIHWVRQAPGQRLEWMGNINPNNGGT TYNQKFEDRVTITRDTSASTAYMELSSLRSEDTAVYYCAAGWNFDYWGQGTTLTVSSAS TKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFL FPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYR VVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN VFSCSVMHEALHNHYTQKSLSLSPGLC SEQ ID NO: 2 DIQLTQSPSFLSASVGDRVTITCKASQDVGTAVDWYQQKPGKAPKLLIYWASTRHTGVPS RFSGSGSGTEFTLTISSLQPEDFATYYCQQYNSYPLTFGGGTKVEIKRTVAAPSVFIFPPSDE QLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSK ADYEKHKVYACEVTHQGLS SPVTKSFNRGEC

[0317] The drug-payload linker covalently conjugates with the para-acetyl phenylalanine (pAF) in the anti-PSMA heavy chain (wherein the underlined “A” at position 116 in the amino acid sequence (position 114 according to the Kabat Numbering) is the non-natural amino acid pAF in each heavy chain) resulting in the formation of the anti-PSMA-ADC (DAR = 2). Please see ARX517 in Skidmore et al. August 22, 2024 Mol Cancer Ther. (doi: 10.1158 / 1535-7163.MCT-23- 0927. Online ahead of print), which is herein incorporated by reference. PSMA antibody is conjugated with the drug-payload linker by incubating at 28° C. in presence of 135 mM acetic hydrazide, acting as a catalyst. Unconjugated antibodies, unconjugated drug payload-linker, aggregates and impurities were removed by running the reaction mixture through a cation exchange chromatography column before exchanging the anti-PSMA ADC into formulation buffer (50 mM Histidine, 150 mM sodium chloride, 2.5% Trehalose pH 6). The antibody drug conjugate was eluted from the column under a salt gradient generating a monodisperse peak.Example 2: A Phase 1, Multicenter, Open-Label, Dose-Escalation, and Dose-Expansion Study to Evaluate the Safety, Pharmacokinetics, and Anti-Tumor Activity of the PSMA ADC inI l lSubjects With Metastatic Castration-Resistant Prostate Cancer Who Are Resistant or Refractory to Prior Standard Therapies

[0318] A first-in-human, Phase 1, multicenter, open-label study has been initiated to evaluate the safety, PK, PD, and preliminary anti-tumor activity of the PSMA ADC (of example 1) in adult subjects with mCRPC with serum testosterone level < 50 ng / dL at screening who are resistant or refractory to standard therapies. Phase la (dose-escalation) and Phase lb (dose-expansion) stages are designed to identify the MTD and / or RDDs.

[0319] Key Inclusion Criteria included:• Male subjects > 18 years at the first time of providing written informed consent.• Histologically confirmed prostate adenocarcinoma.• Documented metastatic disease and evidence of disease progression• Castration-resistant prostate cancer defined as surgical or medical castration with serum testosterone levels of < 50 ng / dL (1.73 nM) at Screening. For patients who have not undergone an orchiectomy, must be undergoing treatment with a luteinizing hormone-releasing hormone (LHRH) agonist or antagonist and must agree to continue such therapy while on study treatment.• Prior receipt of the following for metastatic prostate cancer: o at least two lines of treatment o at least two Food and Drug Administration (FDA)-approved therapies with at least one being a second-generation androgen receptor signaling inhibitor (e.g., abiraterone, darolutamide, apalutamide, or enzalutamide).• Adequate blood counts

[0320] The PSMA ADC was administered via IV infusion at different dosing frequencies (e.g., Q3W, Q4W)

[0321] Eights Cohorts have been implemented (Cohort 1 : 0.32 mg / kg; Cohort 2: 0.64 mg / kg; Cohort 3: 1.07 mg / kg; Cohort 4: 1.4 mg / kg; Cohort 5: 1.7 mg / kg; Cohort 6: 2.0 mg / kg; Cohort 7: 2.4 mg / kg; Cohort 8: 2.88 mg / kg)

[0322] The data collected up to September 5, 2023 showed that the PSMA ADC resulted in PSA declines and RECIST vl. l responses (RECIST Guidelines as described in Eisenhauer et al. 2009, EJC 228-247) without treatment-related Serious Adverse Events (SAEs)

[0323] Safety (Cohorts 1-8):• Most common Treatment Emergent Adverse Events (TRAE: Dry mouth, dry eye, and fatigue• All Grade 1-2 in severity• Higher frequency of these events with increasing dose• Most common Grade 3 TRAEs were lymphopenia and thrombocytopenia. As of Oct 2023, no TRAEs > Grade 3 were observed• No DLTs or SAEs as of Oct 2023

[0324] Efficacy (average of Cohorts 6-8): PSA50: 52% (12 / 23) [PSA50 referring to >50% decline in PSA value from baseline]Example 3; Manufacture of the hK2xCD3 bispecific antibody

[0325] The hK2xCD3 bispecific antibody (i.e. anti-hK2 / anti-CD3 bispecific antibody), (described in WO2021019389 and US 12,077,585) was made by Janssen Biotech, Inc. The hK2xCD3 bispecific antibody comprises a first domain that binds hK2 (KL2B30 in the format of a Fab) and a second domain that binds CD3 (CD3W245 in format of an scFv). The amino acid sequences of the hK2xCD3 bispecific antibody are shown in Table 1 and Table 2, respectively. CDR sequences are defined according to Kabat.

[0326] The hk2 binding domain is in Fab format. The CD3 binding domain is in scFv format. The scFv comprises a linker polypeptide (SEQ ID NO: 23; GGSEGKSSGSGSESKSTGGS) between the VL and the VH. The bispecific antibody is in an IgGl format. The VH of the hk2 binding domain is linked to a IgGl heavy chain constant region containing the following mutations: the Fc silencing mutations (L234A / L235A / D265S) and the T350V / T366L / K392L / T394W mutations designed to promote selective heterodimerization. The VL of the hk2 binding domain is linked to a IgGl light chain constant region. The scFv is linked to an IgGl heavy chain constant region containing the following mutations: the Fc silencing mutation (L234A / L235A / D265S) and the T350V / L351Y / F405A / Y407V mutations designed to promote selective heterodimerization. The bispecific antibody comprises a lysine (K477) at the C-terminus of both of the Fc domains (i.e. the HC1 and HC2 domains).Table 1. Sequences of the hK2 binding domain of the hK2xCD3 bispecific antibodyTable 2. Sequences of the CD3 binding domain of the hK2xCD3 bispecific antibodyExample 4: A Phase 1 Study of hK2xCD3 antibody for advanced prostate cancer

[0327] A FIH, dose-escalation Phase 1 trial has been initiated to evaluate the safety, PK, PD, and preliminary antitumor activity of the hK2xCD3 antibody of example 3 in mCRPC patients.

[0328] This study included males >18 years with histologically confirmed prostate adenocarcinoma who had >1 prior line of therapy. The hK2xCD3 antibody was escalated from 0.5 mg to 2000 mg for subcutaneous (SC) administration and from 150 mg to 900 mg for intravenous (IV) administration at dosing frequencies ranging from every week to every 6 weeks. The primary objectives were to determine safety and the recommended Phase 2 dose (RP2D) of the hK2xCD3 antibody. Secondary objectives included preliminary assessment of antitumor activity.

[0329] A RP2D was determined to be 3.5 mg (Day 1), 18 mg (Day 8), then 300 mg IV infusion every 6 weeks. As of October 7, 2024, 172 patients received at least one dose of the hK2xCD3 antibody. Most patients reported >1 related treatment-emergent adverse event (TRAE; Total, 139 / 172 [80.5%]; 63.9% IV; 92.2% SC). Grade >3 TRAEs occurred in 17 / 172 (9.8%) participants. One participant experienced protocol-defined dose-limiting toxicities. In the RP2D safety population (n=45), the most common TRAEs were infusion-related reactions (22.2%; Grade 1 / 2), fatigue (15.6%; Grade 1 / 2), and cytokine release syndrome (8.9%; all Grade 1). In the RP2D efficacy population (n=33), the median radiographic progression-free survival was 6.77 (95% CI 1.87, not evaluable) months.

[0330] The hK2xCD3 antibody was safely administered in an outpatient setting and was well tolerated. Preliminary antitumor activity was demonstrated, indicating proof of concept for hK2 as a target in advanced PC. Further development of the hK2xCD3 antibody is planned.Example 5; in vitro experiments on the hK2xCD3 antibody + PSMA ADC combination therapy

[0331] Generation of LNCaP-hK2-NLR cells

[0332] LNCaP cells were grown in RPMI 1640+l-glut+10%FBS. LNCaP cells (ATCC) were engineered to constitutively express KLK2 (NM_005551.5) driven by a CMV promoter with a C terminal 3X FLAG tag. Cloning and lentiviral particles were pLV[Exp]-Bsd- CMV>hK2[NM_005551.5] / 3xFLAG [Vector ID :VB230215-1719twt], Cells were selected with 5 pg / mL blasticidin, then LNCaP-hK2 cells were transduced with Incucyte® Nuclight Red Lentivirus (NLR; EFla, Bleo) (Sartorius Item # 4478) and selected with Zeocin to produce LNCaP-hK2-NLR cells for visualization by Incucyte assay.Cell Viability Assay (KLK2xCD3 Dose Curve)

[0333] LNCaP-KLK2-NLR cells (15,000 cells) were plated in a 96-well plate (Costar 3603) and after 24 hours, cells were treated with a dose range of hK2xCD3 (hK2xCD3 antibody of examples 3-4), starting at 50 nM with a five-fold dilution curve with or without 0.2 nM PSMA ADC (PSMA ADC of examples 1-2). Healthy, male donor peripheral blood mononuclear cells (PBMCs) were added at a ratio of 1 :2 effector to target (E:T) cells. The number of NucLight Red cells (LNCaP-KLK2-NLR) was assessed by Incucyte® assay over 6-7 days. For analysis, the area under the curve of the experiment duration for each condition (hK2xCD3 only or hK2xCD3+PSMA ADC) was calculated using GraphPad Prism 10, then normalized to its respective E:T only condition to obtain a viability percentage.Cell Viability Assay (PSMA ADC Dose Curve)

[0334] LNCaP-hK2-NLR cells (15,000 cells) were plated in a 96-well plate (Costar 3603) and after 24 hours, they were treated with a dose range of PSMA ADC, starting at 100 nM with a tenfold dilution plus either NullxCD3 or KLK2xCD3 (EC20 per donor). Healthy, male donor PBMCs were added at a ratio of 1 :2 effector to target (E:T) cells. The number of NucLight Red cells was assessed by Incucyte® assay over 6-7 days. For analysis, the area under the curve of the experiment duration for each condition (NullxCD3+PSMA ADC or hK2xCD3+PSMA ADC was calculated in GraphPad Prism 10, then normalized to its respective E:T only condition to obtain a viability percentage.Results

[0335] Using a sub-efficacious dose of PSMA ADC and a dose range of hK2xCD3, the combination of PSMA ADC and hK2xCD3 decreased cell viability more than hK2xCD3 alone (cf. FIG. 1A-1B).

[0336] Using a sub-efficacious dose of hK2xCD3 and a dose range of PSMA ADC, the combination of hK2xCD3 and PSMA ADC decreased cell viability more than the combination of PSMA ADC and NullxCD3 (cf. FIG. 2A-2B).Example 6: A Phase lb Study of the hK2xCD3 antibody (of Examples 3-4) in Combination with the PSMA ADC (of Examples 1-2) for Prostate Cancer

[0337] An interventional Phase lb study has been designed to evaluate the safety, tolerability, and preliminary antitumor activity of the hK2xCD3 antibody (of examples 3-4) in combination with the PSMA ADC (of examples 1-2) administered to patients with metastatic castrate resistant prostate cancer (mCRPC), more specifically to mCRPC patients following at least 1 prior line of therapy. The study is comprised of 2 parts: dose confirmation (Part 1) and dose expansion (Part 2).

[0338] hKL2xCD3 is dosed at 300 mg IV infusion Q6W with 2 step-up doses at 3.5 mg and 18 mg IV infusion. The PSMA ADC is dosed at 2.0 mg / kg IV infusion initially Q3W. Exploration of less-intense dosing schedule for the PSMA ADC, such as 1) Q3W for 4 doses, and then Q6W or 2) Q6W, is ongoing. In addition, exploration of a different dosing schedule (for example, hK2xCD3 and PSMA ADC administered utilizing a different schedule) may be implemented in this study.

[0339] Patients can be premedicated prior to each administration of the bispecific KLK2xCD3 antibody, e g., with glucocorticoid, antihistamine, and antipyretic pre-medi cation (e.g., within 2 hours prior to dosing)

[0340] The patients continue to receive study treatment until radiographic disease progression, unequivocal clinical progression, unacceptable toxicity, withdrawal of consent or lost to follow-up, whichever comes first. The end of study (study completion) is defined as the last assessment for the last participant in the study.

[0341] Inclusion criteria comprise:• be > 18 years of age• histologically confirmed adenocarcinoma of the prostate as defined by Prostate Cancer Working Group 3 (PCWG3). Adenocarcinoma with small cell or neuroendocrine (NE) features is permitted. However, small cell carcinoma, carcinoid tumor, mixed NE carcinoma, or large cell NE carcinoma is not allowed• prior orchiectomy or medical castration; or, for participants who have not undergone orchiectomy, must be receiving ongoing androgen deprivation therapy with a gonadotropin-releasing hormone (GnRH) analog (agonist or antagonist) prior to the first dose of study drug (i.e., prior to being administered the first dose of PSMA ADC and of anti-hK2 / anti-CD3 bispecific antibody of the application) and must continue this therapy throughout the treatment phase• eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1• Concerning any prior anti-cancer therapy, the patients:• may have received at least one line of novel AR-targeted therapy (ie, abiraterone acetate, apalutamide, enzalutamide, etc.);• may have received no more than one or no previous taxane regimen, more specifically no more than one or no prior anti-prostate cancer chemotherapy (ie, docetaxel, cabazitaxel, cisplatin, carboplatin, etoposide, etc.);• may have received prior 177-Lu-PSMA radionuclide therapy.Table 3. Objectives and EndpointsTable 4. Overall Study Design

[0342] Safety is being monitored during the Study, and clinical activity is assessed e.g., using the following evaluations: computed tomography (CT) scan of the chest, abdomen, and pelvis with contrast as clinically indicated; magnetic resonance imaging (MRI) may be substituted as clinically indicated (e.g., for sites not adequately imaged using CT). Additional evaluations include PSMA- PET scan, serum prostate-specific antigen (PSA) and whole-body bone scans (99mTc). Evaluation of treatment response is performed according to Prostate Cancer Working Group 3 (PCWG3) criteria and Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 to evaluate progression of soft tissue lesions (CT or MRI).Example 7; Results of the Phase 1, Multicenter, Open-Label, Dose-Escalation, and Dose- Expansion Study of PSMA ADC in Subjects with Metastatic Castration-Resistant Prostate Cancer Who Are Resistant or Refractory to Prior Standard Therapies

[0343] As of 15 October 2024 data cut off, a total of 133 participants with mCRPC have received at least 1 dose of PSMA ADC ranging from 0.32 to 4.5 mg / kg IV Q3W. Cohorts at 1.4 mg / kg (n=33), 2 mg / kg (n=34), 2.88 mg / kg (n=20), and 3.4 mg / kg (n=25) were expanded for further assessment of safety and efficacy. Preliminary safety findings based on treatment of the 133 participants have shown that PSMA ADC administered IV Q3W was generally well tolerated; no DLTs were reported over the dose range of 0.32 to 4.5 mg / kg evaluated to date in 10 dose cohorts. Overall, 97.1% of participants reported TRAEs and 33.1% reported Grade >3 treatment- related AEs. Treatment-related AEs reported in >10% of participants included dry eye (54.1%), dry mouth (51.9%), fatigue (32.3%), platelet count decreased / thrombocytopenia (16.5% / 9.8%), dysgeusia (21.8%), decreased appetite (20.3%), nausea (18.8%), neuropathy peripheral (15.8%), anemia (15.8%), vision blurred (15.0%), AST increased (14.3%), diarrhea (12.8%), and keratitis (10.5%). Treatment-related Grade >3 ADRs reported in >1 participant included platelet countdecreased / thrombocytopenia (6.0% / 4.5%), anemia (5.3%), peripheral neuropathy (5.3%), fatigue (3.8%), proteinuria (3.0%), nephrotic syndrome (1.5%), and dry eye (1.5%). Fourteen treatment- related SAEs have been reported in 9 participants of which 12 were Grade 3 severity, including peripheral neuropathy (4 participants [includes multiple preferred terms]), nephrotic syndrome (2 participants), and cardiac failure, acute kidney injury, muscular weakness, failure to thrive, fatigue, and labile hypertension (1 participant each), and 1 event of Grade 4 thrombocytopenia without signs and symptoms of bleeding. As of 15 October 2024, 3 cases of nephrotic syndrome (Grade 3, per CTCAE v5) were reported at PSMA ADC dose levels of 2.88 mg / kg Q3W or higher. No treatment-emergent Grade 3 or higher proteinuria or nephrotic syndrome cases have been reported at doses of 2.4 mg / kg Q3W or lower. At putative therapeutic doses >1.4 mg / kg, 36% (40 / 112) of participants experienced a >50% reduction in PSA and 13% (6 / 46) of evaluable participants had confirmed PR per RECIST vl .1.Example 8: A Phase lb Study of the hK2xCD3 antibody (of examples 3-4) in Combination with the PSMA ADC (of Examples 1-2) for Prostate Cancer

[0344] This is an open-label, multicenter, interventional, Phase lb study to evaluate the safety, tolerability, and preliminary antitumor activity of hK2xCD3 antibody (a T-cell Redirecting Agent Targeting Human Kallikrein 2 (KLK2); pasritamig) in combination with the PSMA ADC (an Antibody Drug Conjugate Targeting Prostate Specific Membrane Antigen) administered to adult participants with advanced prostate cancer following at least 1 prior line of therapy. The study is comprised of 2 parts: dose confirmation (Part 1) to first assess the overall safety of combining the two agents; dose expansion (Part 2) to continue assessing safety in addition to efficacy in participants after the RP2CD(s) of the combination has / have been established in Part 1. The IND of this study (which includes the Study Protocol) has been approved by FDA and the study has been initiated at different Clinical Sites.Number of participants

[0345] Approximately 110 participants (approximately 20 participants in Part 1 and up to 90 participants at the identified RP2CD(s) in Part 2) are treated in this 2-part study. The actual number of participants treated depends on the number of dose levels explored and the number of participants enrolled at each dose level.Treatment group and duration

[0346] Part 1 (dose confirmation) is designed to confirm the RP2CD(s) and regimen(s) of hK2xCD3 antibody and PSMA ADC in participants with advanced prostate cancer. During the dose confirmation phase, hK2xCD3 antibody is dosed at the treatment dose of 300 mg IV Q6W with 2 step-up doses at 3.5 mg and 18 mg IV administered 7 days apart as determined in Study of Example 4. PSMA ACD is dosed at 2 mg / kg IV or 1.4 mg / kg initially Q3W, a dose that was deemed both safe and tolerable in the study of Example 2. PSMA ADC may be administered at a first treatment dose IV, followed by a second treatment dose IV and a subsequent treatment dose IV, Q3W as shown in Table 5.Table 5. PSMA ADC study dose levels

[0347] Patients can be premedicated prior to each administration of the bispecific KLK2xCD3 antibody, e.g., with glucocorticoid, antihistamine, and antipyretic pre-medication (e.g., within 2 hours prior to dosing).

[0348] In Part 2, the provisional recommended Phase 2 combined dose (RP2CD(s)) / regimen(s) of hK2xCD3 antibody and PSMA ADC as determined in Part 1 is administered to additional participants with prostate cancer to confirm the safety and preliminary anti-tumor activity of hK2xCD3 antibody and PSMA ADC. Note that multiple doses or schedules may be evaluated, with each being tested in up to 30 participants. Taxane requirements apply to mCRPC setting and prior docetaxel for mHSPC is not counted unless disease progressed during docetaxel therapy. At least 1 of the following mCRPC expansion cohorts to further define the levels of activity in different disease settings may be enrolled:Part 2A: no prior taxane and no prior 177-Lu-PSMA radionuclide therapy Part 2B: 1 prior taxane and no prior 177-Lu-PSMA radionuclide therapy Part 2C: Must have received no more than 1 prior taxane regimen and received prior 177- Lu-PSMA radionuclide therapyTreatment dose strategy

[0349] Exploration of less frequent dosing schedules for PSMA ADC, such as 1) Q3W for 4 doses, and then Q6W or 2) Q6W, may be implemented in this study. In addition, exploration of a different dose schedule for the first combination dose of hK2xCD3 antibody and PSMA ADC may be implemented. Participants continue to receive study treatment until radiographic disease progression, unequivocal clinical progression, unacceptable toxicity, withdrawal of consent or lost to follow-up, whichever comes first. The end of study (study completion) is defined as the last assessment for the last participant in the study.

[0350] The DLT evaluation period begins on the day on when the participant has been exposed to both study drugs (i.e., prior to being administered the first dose of PSMA ADC and of anti- hK2 / anti-CD3 bispecific antibody of the application) and extends 21 days past the initial combination dose of study treatment (ie, from Step Up Cycle Day 8 to Cycle 1 Day 22 dose).

[0351] RP2CD(s) regimens may be identified such that maximal 27% of participants experience a DLT. DLT events include events such neutrophil count decreased, platelet count decreased, non-hematologic toxicity events (e.g., AST elevation, Grade 3 non-hematological toxicity), and Infusion-related Reactions.Objectives

[0352] The primary objective of this study is to identify the RP2CD(s), based on the safety and tolerability of hK2xCD3 bispecific antibody administered in combination with PSMA ADC by assessing the incidence and severity of adverse events (AEs), including dose limiting toxi cities (DLTs). A key secondary objective is to characterize the preliminary antitumor activity and provide a further understanding of the pharmacology of the hK2xCD3 antibody and PSMA ADC combination by assessing PK, immunogenicity, objective response rate, PSA response, radiographic progression-free survival (rPFS), and duration of response according to response criteria of Prostate Cancer Working Group 3 (PCWG3) and RECIST version 1.1.Primary Endpoints

[0353] Part 1 (Dose Finding): incidence of and severity of adverse events (AEs) / Dose limiting toxicology (DLTs)

[0354] Part 2 (Dose Expansion): incidence and severity of AEs.Secondary Endpoints

[0355] For the time-to-events endpoints (Time to response [TTR] and Duration of response [DOR]), participants with no on-study assessment or no baseline assessment are censored on the date of first dose.

[0356] Duration of response is calculated among responders (Partial response [PR] or better) from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease, as defined in the PCWG3 or RECIST vl.1 response criteria, or death due to any cause, whichever occurs first. For participants with a response (complete response [CR] or partial response [PR]) to treatment with disease that has not progressed and who are alive, data is censored at the last disease evaluation before the start of any subsequent anticancer therapy.

[0357] Time to response is defined for the responders as the time from the date of first dose of any study treatment to the date of first documented response.

[0358] Overall response rate (ORR) is defined as the proportion of participants who have a partial response (PR) or better according to the RECIST vl .1 response criteria without evidence of bone progression according to PCWG3. Response to treatment is evaluated by investigator.

[0359] PSA response rate is defined as the proportion of participants with a decline of prostatespecific antigen (PSA) of 50% or more from baseline. Confirmed PSA50 is defined as the proportion of participants retaining the decline of PSA more than 50% at least 3 weeks after the initial PSA50.

[0360] Radiographic progression-free survival (rPFS) is defined as the time from the date of first dose of hK2xCD3 antibody or the combination agent until the date of radiographic disease progression or death, whichever comes first. The evidence of disease progression is defined by:• Progression of soft tissue lesions measured by CT or MRI as defined in RECIST 1.1• Progression by bone lesions observed by bone scan and based on PCWG3. See Section 8.2.2 for more information.

[0361] The objectives and endpoints are summarized in Table 6.Table 6.Inclusion and Exclusion criteria

[0362] All participants must have a diagnosis of prostate cancer and satisfy the following inclusion and exclusion criteria:Inclusion criteria(1) Must be > 18 years of age(2) Have histologically confirmed adenocarcinoma of the prostate. Primary small cell carcinoma, carcinoid tumor, NE carcinoma, or large cell NE carcinoma arising in the prostate are not allowed; however, adenocarcinomas with NE features (e.g., IHC with both AR- and NE-marker positivity) are allowed.(3) Must have mCRPC.(4) PSA must measure at least 2 ng / mL at screening.(5) Measurable or evaluable disease.(6) Prior orchiectomy or medical castration; or, for participants who have not undergone orchiectomy, must be receiving ongoing androgen deprivation therapy with a GnRH analog (agonist or antagonist) prior to the first dose of study drug (i.e., prior to being administered the first dose of PSMA ADC and of anti-hK2 / anti-CD3 bispecific antibody of the application) and must continue this therapy throughout the treatment phase.(7) Can have a prior or concurrent second malignancy (other than the disease under study) which natural history or treatment is unlikely to interfere with any study endpoints of safety or the efficacy of the study treatment(s).(8) Prior therapy restrictions or requirements(a) Must have received at least 1 line of ARPI (ie, abiraterone acetate, apalutamide, enzalutamide, darolutamide).(b) For Part 2 A cohorts:(i) No prior taxane regimen(ii) No prior 177-Lu-PSMA radionuclide therapy(c ) Part 2B cohort:(i) Must have received no more than 1 prior taxane regimen(ii) No prior 177-Lu-PSMA radionuclide therapy(d) Part 2C cohort:(i) Must have received no more than 1 prior taxane regimen.(ii) Must have received prior 177-Lu-PSMA radionuclide therapy(9) Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1(10 Have an estimated glomerular filtration rate (eGFR) >40 mL / min, based on the Modified Diet in Renal Disease (MDRD) 4-variable formula.(12) 24-hour urine protein <lg / 24h. Note: 24h urine is only required at screening if urinalysis is >2+ on the dipstick.(13) Have the following Hepatic Function a. AST (aspartate aminotransferase): <2.5 x ULN (upper limit of normal), b. ALT (alanine aminotransferase): <2.5 x ULN c. Total bilirubin <1.5 x ULNd. Bilirubin in case of known congenital nonhemolytic hyperbilirubinemias such as Gilbert’s Syndrome: isolated total bilirubin < 1.5 x ULN with conjugated [direct] bilirubin < 3 x ULN(14) have the following Hematologic Values a. Hemoglobin: > 9.0 g / dL b. Neutrophils: > 1.5 x 109 / L; >1.0 x 109 / L if participant has a history of benign ethic neutropenia c. Platelets: > 100 x 109 / LExclusion criteria

[0363] Any potential participant who meets any of the following criteria may be excluded from participating in the study:(1) Active autoimmune disease within the 12 months prior to signing consent that requires systemic immunosuppressive medications. Exception: Participants with vitiligo or prior autoimmune thyroiditis that is currently euthyroid based on clinical symptoms and laboratory testing.(2) Toxicity related to prior anticancer therapy that has not returned to Grade <1 or baseline levels (except for alopecia and vitiligo).(3) Grade 2 or higher peripheral sensory or motor neuropathy within 28 days prior to signing consent.(4) Solid organ or bone marrow transplantation.(5) Known allergies, hypersensitivity, or intolerance to any of the components (eg, excipients) of hK2xCD3 antibody or PSMA ADC.(6) Any of the following within 6 months prior to signature of informed consent: a. Myocardial infarction b. Severe or unstable angina c. Clinically significant ventricular arrhythmias d. Congestive heart failure (New York Heart Association [NYHA] class II to IV) e. Transient ischemic attack f. Cerebrovascular accident(7) History of interstitial lung disease (ILD) or pneumonitis within 12 months of enrollment, or other clinically significant pulmonary compromise, particularly a requirement for supplemental oxygen use to maintain adequate oxygenation.(8) Clinically significant ocular infections or chronic corneal disorders, including confluent superficial keratitis, cornea epithelial defect, corneal ulcer or stromal opacity.(9) Had major surgery or had significant trauma within 30 days before first dose of study treatment or has not recovered from surgery. Must not have major surgery planned during the time the participant is receiving study treatment.(10) Active infection or condition that requires treatment with systemic antibiotics within 7 days prior to the first dose of study treatment. Antibiotic or antiviral prophylaxis is allowed.(11) Venous thromboembolic events (eg, pulmonary embolism) within 1 month prior to the first dose of study treatment. EXCEPTION: Uncomplicated (Grade <2) deep vein thrombosis is not considered exclusionary.(12) Participants with leptomeningeal disease or brain metastases, with the exception of participants with definitively, locally treated brain metastases that are clinically stable and asymptomatic>2 weeks, and who are off corticosteroid treatment for at least 2 weeks prior to first dose of study treatment.(13) Received immunosuppressive doses of systemic medications, such as glucocorticoids (doses >10 mg / day prednisone or equivalent) within 3 days prior to the first dose of study treatment. A single course of glucocorticoids is permitted as prophylaxis for imaging contrast (ie, for participants with allergies to contrast). If glucocorticoids were used to treat immune-related adverse events associated with prior therapy, >7 days must have elapsed since the last dose of corticosteroid.(14) Received or plans to receive any live, attenuated vaccine within 4 weeks prior to the first dose of study treatment or within 4 weeks after the last dose of study treatment. Live, attenuated influenza vaccines are permitted as late as 7 days prior to the first dose of study treatment. Non-live or non-replication-competent vaccines approved or authorized for emergency use (eg, COVID-19) by local health authorities are allowed.(15) Treatment with any anti -cancer or investigational agents within 14 days prior to the first dose of study treatment; specific requirements for certain anti-cancer therapies are as follows:• Any T-cell redirecting treatment (eg, CD3-directed bispecific or CAR-T therapy) within 90 days prior to the first dose of study treatment.• Immune checkpoint inhibitors within 6 weeks prior to the first dose of study treatment• Radium (Ra) 223 dichloride within 28 days prior to the first dose of study treatment• Any prior treatment with KLK2 -targeted therapy• Any prior PSMA-targeting therapy (ie, patients who received PSMA-targeting radioconjugates are excluded) [Parts 2A and 2B only. Prior 177-Lu-PSMA radionuclide therapy is allowed in Part 1 and required for Part 2C] but last dose must be >6 weeks prior to the first dose of study treatment.• Any prior ADCs with microtubule inhibitor payloads (eg, auristatins, maytansinoids, tubulysins).Efficacy evaluations

[0364] Clinical activity is assessed using CT scan of the chest, abdomen, and pelvis with contrast as clinically indicated; MRI may be substituted as clinically indicated (eg, for sites not adequately imaged using CT). Additional evaluations include serum PSA and whole-body bone scans (99mTc). Evaluation of treatment response is performed according to PCWG3 criteria and RECIST version 1.1 to evaluate progression of soft tissue lesions (CT or MRI).Safety evaluations

[0365] The safety of hK2xCD3 antibody in combination with PSMA ADC is assessed by physical examinations, vital signs, ECOG performance status, clinical laboratory tests, and AE monitoring, including DLTs. The severity of AEs is assessed using NCI-CTCAE, Version 5.0, except for CRS and associated CNS toxicity events (ie, ICANS events), which is graded according to the ASTCT guidelines.Example 9; Results of the Phase lb study of Examples 6-8

[0366] The First Patient for the study of Examples 6-8 was dosed on July 16, 2025; at the cutoff date of Z, W patients have been dosed.

[0367] Based on the preliminary results of Cohort 1 (n = 6 patients), a recommended phase 2 combination dosing regimen (RP2CD) has been determined, which is: the PSMA ADC at the dose of a. 2 mg / kg IV Q3W for a maximum of 4 doses (doses n°l, n°2, n°3 and n°4: 3 dose cycles), or b. 2mg / kg IV Q6W, which was deemed to be safe and tolerable in combination with pasritamig at 300mg Q6WIV infusion, i. with prior step-up dosing of pasritamig at 3.5mg on Day 8 and at 18mg on Day 15 (±2 days); ii. with the first target dose (first treatment dose) of pasritamig (300mg) administered atDay 22 (± 2 days), and iii. with the second and following target doses of pasritamig administered Q6W computed from the day of the first target dose (Q6W = 42 ± 3 days).

[0368] The administration of all step-up and target doses of pasritamig was via IV infusion.

[0369] The first target dose (first treatment dose) of the PSMA ADC was administered on Day 1; the second target dose of the PSMA ADC was administered on Day 22 (± 2 days), i.e., on the same day as the first target dose of pasritamig (first Combination Dose). The Q3W or Q6W frequency of administration of the PSMA ADC was computed starting from the day of administration of the first Combination Dose (Q3W = 21 ± 3 days; Q6W = 42 ± 3 days).

[0370] As of November 19, 2025, 8 patients were enrolled. No DLT was reported. Five out of the 7 patients had a PSA reduction more than 50% from baseline.Example 10: A Phase lb Study of the hK2xCD3 antibody (of Examples 3-4) in Combination with the PSMA ADC (of Examples 1-2) for Prostate CancerOverall design

[0371] This was an open-label, multicenter, interventional, Phase lb study to evaluate the safety, tolerability, and preliminary antitumor activity of hK2xCD3 antibody (a T-cell Redirecting Agent Targeting Human Kallikrein 2 (KLK2); pasritamig) in combination with the PSMA ADC (an Antibody Drug Conjugate Targeting Prostate Specific Membrane Antigen) administered toadult participants with mCRPC following at least 1 prior line of therapy. The study comprised of 2 parts: dose confirmation (Part 1) first assessed the overall safety of combining the two agents; Part 2 Expansion continued to assess safety in addition to efficacy in participants with mCRPC in 4 cohorts with and without prior taxane or PSMA radioligand therapy (RLT), after the recommended Phase 2 combination dosing regimen(s) (RP2CD(s)) of the combination were established in Part 1. The IND of this study (which includes the Study Protocol) has been approved by FDA and the study has been initiated at different Clinical Sites.Number of participants

[0372] Approximately 140 participants (approximately 20 participants in Part 1 and up to 120 participants in Part 2) were treated (or are scheduled to be treated) in this 2-part study. The First Patient for the study of Example 10 is scheduled to be dosed in December 2025.Treatment group and duration

[0373] hK2xCD3 antibody was dosed at the (hK2xCD3) RP2CD of example 9, i.e., at a treatment dose of 300 mg IV infusion Q6W with 2 step-up doses at 3.5 mg and 18 mg IV infusion; cf Example 9 above. The PSMA ADC was dosed at a RP2CD of example 9, more particularly at 2 mg / kg IV Q3W for a maximum of 4 doses (3 dose cycles), or at 2mg / kg IV infusion Q3W for the first and second doses of PSMA ADC followed by a third and subsequent doses at Q6W.

[0374] Participants continued to receive study treatment until radiographic disease progression, unequivocal clinical progression, unacceptable toxicity, withdrawal of consent or lost to follow-up, whichever comes first. The end of study (study completion) was defined as the last assessment for the last participant in the study.Part 1 (Dose Confirmation)

[0375] Part 1 (dose confirmation) was designed to confirm the RP2CD(s) of hK2xCD3 antibody and PSMA ADC in participants with mCRPC. During the dose confirmation phase, hK2xCD3 antibody and the PSMA ADC were dosed at a RP2CD of Example 9, more particularly at- 2 mg / kg IV of the PSMA ADC Q3W for a maximum of 4 doses (3 dose cycles),- with prior step-up dosing of pasritamig at 3.5mg on Day 8 and at 18mg on Day 15 (± 2 days);- with the first target dose (first treatment dose) of pasritamig (300mg) administered at Day22 (± 2 days), and- with the second and following target doses of pasritamig administered Q6W computed from the day of the first target dose (Q6W = 42 ± 3 days).

[0376] The administration of all step-up and target doses of pasritamig is via IV infusion.

[0377] The first target dose (first treatment dose) of the PSMA ADC has been administered on Day 1; the second target dose of the PSMA ADC has been administered on Day 22 (± 2 days), i.e., on the same day as the first target dose of pasritamig (first Combination Dose). The Q3W or Q6W frequency of administration of the PSMA ADC is computed starting from the day of administration of the first Combination Dose (Q3W = 21 ± 3 days; Q6W = 42 ± 3 days).Cohort EnrollmentTo assess safety and tolerability of the current dose level, a minimum of 3 DLT evaluable participants have been reviewed.Part 2 (Dose Expansion)

[0378] In Part 2, the RP2CD(s) of hK2xCD3 antibody and PSMA ADC as determined in Part 1 (cf. example 9 above) was administered to additional participants with mCRPC to confirm the safety and preliminary anti -tumor activity of hK2xCD3 antibody and PSMA ADC. At least 1 of the following mCRPC expansion cohorts to further define the levels of activity in different disease settings has been enrolled:Part 2A: no prior taxane and no prior PSMA radioligand therapy (PSMA RLT)Part 2B: 1 and only 1 prior taxane and no prior PSMA RLTPart 2C: 1 and only 1 prior taxane, and have received prior PSMA RLTPart 2D: no prior taxane, and have received prior PSMA RLT

[0379] Prior PSMA RLT typically refers to prior 177Lu PSMA radionuclide therapy, such as prior pluvicto therapy. “No prior taxane” refers to no prior taxane therapy for the treatment of mCRPC; for example, prior docetaxel for the treatment of mHSPC is not counted unless disease progressed during docetaxel therapy.Objectives

[0380] The primary objective of this study is to identify the RP2CD(s), based on the safety and tolerability of hk2xCD3 antibody administered in combination with PSMA ADC by assessing the incidence and severity of AEs, including DLTs. A key secondary objective is to characterize the preliminary antitumor activity and provide a further understanding of the pharmacology of the hK2xCD3 antibody and PSMA ADC combination by assessing PK, immunogenicity, objective response rate, PSA response, radiographic progression-free survival (rPFS), and duration of response according to response criteria of PCWG3 and RECIST version 1.1.The objectives and endpoints listed in Table 7 have been evaluated in this study.Table 7Study population

[0381] Screening for eligible participants was performed within 30 days before administration of the study treatment. The inclusion and exclusion criteria for enrolling participants in this study are described below.Inclusion criteria

[0382] Each potential participant must have satisfied all of the following criteria to be enrolled in the study:(1) Must be > 18 years of age at the time of informed consent(2) Have histologically confirmed adenocarcinoma of the prostate. Primary small cell carcinoma, carcinoid tumor, neuroendocrine (NE) carcinoma, or large cell NE carcinoma arising in the prostate are not allowed; however, adenocarcinomas with NE features (e.g., IHC with both AR- and NE-marker positivity) are allowed.(3) Must have mCRPC.(4) PSA must measure at least 2 ng / mL at screening.(5) Must have measurable or evaluable disease.(6) Prior orchiectomy or medical castration; or, for participants who have not undergone orchiectomy, must be receiving ongoing androgen deprivation therapy with a GnRH analog (agonist or antagonist) prior to the first dose of study drug (i.e., prior to being administered the first dose of PSMA ADC and of anti-hK2 / anti-CD3 bispecific antibody of the application) and must continue this therapy throughout the treatment phase.(7) Prior Malignancies - Can have a prior or concurrent second malignancy (other than the disease under study) which natural history or treatment is unlikely to interfere with any study endpoints of safety or the efficacy of the study treatment(s).(8) Prior Therapy Restrictions or Requirements(a) Must have received at least 1 line of ARPI (ie, abiraterone acetate, apalutamide, enzalutamide, darolutamide).(b) For Part 2: Taxane requirements noted below apply to the mCRPC setting and prior docetaxel for mHSPC is not counted unless disease progressed during docetaxel therapy. The following criteria apply to specific Part 2 cohorts:(i) Part 2A:• No prior taxane regimen• No prior PSMA radioligand therapy (RLT)(ii) Part 2B:• 1 and only 1 prior taxane regimen• No prior PSMA radioligand therapy (RLT)(iii) Part 2C:• 1 and only 1 prior taxane regimen.• Must have received prior PSMA radioligand therapy (RLT)(iv) Part 2D:• No prior taxane regimen• Must have received prior PSMA radioligand therapy (RLT)(10) Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1(11) Have an estimated glomerular filtration rate (eGFR) >40 mL / min, based on the ModifiedDiet in Renal Disease (MDRD) 4-variable formula.(12) Have 24-hour urine protein <lg / 24h. Note: 24h urine is only required at screening if urinalysis is >2+ on the dipstick.(13) Have the following hepatic function: a. AST (asparate aminotransferase): <2.5 x ULN (upper limit of normal) b. ALT (alanine aminotransferase): <2.5 x ULN (upper limit of normal) c. Total bilirubin: <1 .5 x ULN (upper limit of normal) d. Bilirubin in case of known congenital nonhemolytic hyperbilirubinemias such as Gilbert’s Syndrome: direct bilirubin < 1.5 x ULN (upper limit of normal)(14) Have the following hematologic values independent of transfusion within 7 days or growth factors within 3 weeks prior to the first dose of study treatment: a. Hemoglobin: > 9.0 g / dL b. Neutrophils: > 1.5 x 109 / L; Exception: Participants of certain ethnicities (eg, African,Middle Eastern, Caribbean) with a history of medically diagnosed benign ethnic neutropenia (>1 x 109 / L ANC) or who have at least 3 blood samples showing neutropenia (>1 x 109 / L ANC) at intervals of at least 2 weeks and with no other identifiable causes are eligible to enroll. c. Platelets: > 100 x 109 / LExclusion Criteria

[0383] Any potential participant who met any of the following criteria was excluded from participating in the study:(1) Active autoimmune disease within the 12 months prior to signing consent that requires systemic immunosuppressive medications. Exception: Participants with vitiligo or prior autoimmune thyroiditis that was currently euthyroid based on clinical symptoms and laboratory testing.(2) Toxicity related to prior anticancer therapy that has not returned to Grade <1 or baseline levels (except for alopecia and vitiligo).(3) Grade 2 or higher peripheral sensory or motor neuropathy within 28 days prior to signing consent. For Part 2 any symptomatic peripheral sensory or motor neuropathy including Grade 1.(4) Solid organ or bone marrow transplantation.(5) Known allergies, hypersensitivity, or intolerance to any of the components (eg, excipients) of hK2xCD3 antibody or PSMA ADC.(6) Any of the following within 6 months prior to signature of informed consent: a. Myocardial infarction b. Severe or unstable angina c. Clinically significant ventricular arrhythmias d. Congestive heart failure (New York Heart Association [NYHA] class II to IV) e. Transient ischemic attack f. Cerebrovascular accident(7) History of interstitial lung disease (ILD) or pneumonitis within 12 months of enrollment, or other clinically significant pulmonary compromise, particularly a requirement for supplemental oxygen use to maintain adequate oxygenation.(8) Clinically significant ocular infections or chronic corneal disorders, including confluent superficial keratitis, cornea epithelial defect, corneal ulcer or stromal opacity.(9) Major surgery or significant trauma within 30 days before first dose of study treatment or has not recovered from surgery. Must not have major surgery planned during the time the participant is receiving study treatment.(10) Active infection or condition that requires treatment with systemic antibiotics within 7 days prior to the first dose of study treatment. Antibiotic or antiviral prophylaxis is allowed.(1 1) Venous thromboembolic events (eg, pulmonary embolism) within 1 month prior to the first dose of study treatment. Exception: Uncomplicated (Grade <2) deep vein thrombosis is not considered exclusionary.(12) Brain and Central Nervous System Metastases - Participants with leptomeningeal disease or brain metastases, with the exception of participants with definitively, locally treated brain metastases that are clinically stable and asymptomatic>2 weeks, and who are off corticosteroid treatment for at least 2 weeks prior to first dose of study treatment.(13) Received immunosuppressive doses of systemic medications, such as glucocorticoids (doses >10 mg / day prednisone or equivalent) within 3 days prior to the first dose of study treatment. A single course of glucocorticoids is permitted as prophylaxis for imaging contrast (ie, for participants with allergies to contrast). If glucocorticoids were used to treat immune-related adverse events associated with prior therapy, >7 days must have elapsed since the last dose of corticosteroid.(14) Received or plans to receive any live, attenuated vaccine within 4 weeks prior to the first dose of study treatment or within 4 weeks after the last dose of study treatment. Live, attenuated influenza vaccines are permitted as late as 7 days prior to the first dose of study treatment. Non-live or non-replication-competent vaccines approved or authorized for emergency use (eg, COVID- 19) by local health authorities are allowed.(15) Treatment with any anti-cancer or investigational agents within 14 days prior to the first dose of study treatment; specific requirements for certain anti-cancer therapies are as follows:(a) Any T-cell redirecting treatment (eg, CD3-directed bispecific or CAR-T therapy) within 90 days prior to the first dose of study treatment.(b) Immune checkpoint inhibitors within 6 weeks prior to the first dose of study treatment(c) Radium (Ra) 223 dichloride within 28 days prior to the first dose of study treatment(d) Any prior treatment with KLK2 -targeted therapy(e) Any prior PSMA-targeting therapy (ie, patients who received PSMA-targeting radioconjugates are excluded) [Parts 2A and 2B only]. Prior PSMA RLT is allowed in Part 1 and required for Part 2C and Part 2D but last dose must be >3 months prior to the first dose of study treatment.(f) Any prior ADCs with microtubule inhibitor payloads (eg, auristatins, maytansinoids, tubulysins).(16) Known positive test result for human immunodeficiency virus (unless stable on antiretroviral therapy with undetectable viral load and CD4 count above 200 cells / mm3).(17) Active hepatitis B or C virus infection according to local laboratory range.(18) Any known history of or suspicion for history of clinically significant liver disease including viral or non-viral hepatitis, fatty liver disease, or hepatic fibrosis requires discussion with the sponsor.(19) Any serious underlying medical conditions or other issue that would impair the ability of the participant to receive or tolerate the planned treatment at the investigational site to understand the informed consent, or any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.(20) Triplicate average QTc interval corrected using Fridericia’s formula (QTcF)>470 msec.Pre-medications for hK2xCD3 antibody

[0384] Participants in this study were premedicated prior to each study treatment administration. All pre-medications were given within 2 hours prior to dosing. Premedications for hK2xCD3 antibody are noted in Table 8.Table 8.Pre-medications for PSMA ADC

[0385] If an IRR occurs during or after any infusion, premedication may be used for subsequent infusions as shown in Table 9.Table 9.Efficacy evaluation

[0386] Clinical activity was assessed using CT scan of the chest, abdomen, and pelvis with contrast as clinically indicated; MRI were substituted as clinically indicated (eg, for sites notadequately imaged using CT). Additional evaluations included serum PSA and whole-body bone scans (99mTc). Evaluation of treatment response was performed according to PCWG3 criteria and RECIST version 1.1 to evaluate progression of soft tissue lesions (CT or MRI).Safety evaluation

[0387] The safety of hK2xCD3 antibody in combination with PSMA ADC was assessed by physical examinations, vital signs, ECOG performance status, clinical laboratory tests, ECGs, and adverse events (AE) monitoring, including dose limiting toxicides (DLTs). Concomitant medication usage was recorded. The severity of AEs was assessed using NCI-CTCAE, Version 5.0, except for CRS and associated CNS toxicity events (i.e., ICANS events), which were graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) guidelines, and ocular events, which used the alternative scale provided in this protocolResult of trial

[0388] As of November 19, 2025, 8 patients were enrolled. No DLT was reported. Five out of the 7 patients had a PSA reduction more than 50% from baseline

Claims

CLAIMSWe claim:

1. A method of treating prostate cancer, in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of an antibody drug conjugate (ADC) targeting prostate-specific membrane antigen (PSMA) at a first treatment dose, and a therapeutically effective amount of an anti-hK2 / anti-CD3 bispecific antibody at a treatment dose, wherein: a. the ADC comprises an anti-PSMA antibody conjugated to a drug-linker, wherein the conjugation occurs via para-acetyl phenylalanine (pAF) incorporated in the heavy chain sequence of the antibody, wherein the anti-PSMA antibody comprises a heavy chain (HC) of SEQ ID NO: 1 and a light chain (LC) of SEQ ID NO: 2, in which the pAF is incorporated at the HC position Al 14 according to Kabat numbering, and wherein the drug-linker has the following structure:b. the anti-hK2 / anti-CD3 bispecific antibody comprises a first antigen binding domain that binds specifically to hK2, and a second antigen binding domain that binds specifically to CD3, wherein: i. the first domain comprises a first heavy chain variable region (VH1) of SEQ ID NO: 9 and a first light chain variable region (VL1) of SEQ ID NO: 10; and ii. the second domain comprises a second heavy chain variable region (VH2) of SEQ ID NO: 21 and a second light chain variable region (VL2) of SEQ ID NO: 22.

2. The method of claim 1, wherein the first domain of the anti-hK2 / anti-CD3 bispecific antibody comprises a Fab and the second domain of the anti-hK2 / anti-CD3 bispecific antibody comprises an scFv.

3. The method of claim 2, wherein the scFv comprises, from the N-terminus to the C-terminus, VH2 -linker- VL2 or VL2-linker-VH2, and the linker comprises or consists of the amino acid sequence of SEQ ID NO: 23.

4. The method of any one of the foregoing claims, wherein the anti-hK2 / anti-CD3 antibody comprises a first heavy chain (HC1), a first light chain (LC1) and a second heavy chain (HC2) having amino acid sequences at least 90% identical to SEQ ID NO: 13, SEQ ID NO: 14 and SEQ ID NO: 26, respectively; preferably, the HC1, LC1 and HC2 comprise the amino acid sequences of SEQ ID NO: 13, SEQ ID NO: 14 and SEQ ID NO: 26, respectively.

5. The method of any one of claims 1-4, wherein the anti-PSMA antibody, which is comprised in the ADC, comprises two heavy chains and two light chains, wherein each heavy chain comprises the pAF at position Al 14 according to Kabat numbering, and wherein the druglinker is conjugated to each said pAF (i.e., DAR=2) via an oxime linkage.

6. The method of any one of the foregoing claims, wherein the treatment dose of the anti- hK2 / anti-CD3 bispecific antibody is about 300 mg, per administration.

7. The method of any one of the foregoing claims, wherein the treatment dose of the anti- hK2 / anti-CD3 bispecific antibody is administered at a flat dose.

8. The method of any one of the foregoing claims, wherein the treatment dose of the anti- hK2 / anti-CD3 bispecific antibody is initially administered on a day within 19-23 days, such as 19, 20, 21, 22, or 23 days, preferably 21 days, after the administration of the first treatment dose of the ADC.

9. The method of any one of the foregoing claims, wherein the treatment dose of the anti- hK2 / anti-CD3 bispecific antibody is subsequently administered once every 5 to 7 weeks, for example, once every 5, 6 or 7 weeks, preferably once every six weeks, after the initial administration of the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody.

10. The method of any one of the foregoing claims, wherein the treatment dose of the anti- hK2 / anti-CD3 bispecific antibody is intravenously administered, for example, by intravenous (IV) infusion.

11. The method of any one of the preceding claims, further comprising administering to the patient one or more step-up doses (for example, one or two step-up doses) of the anti-hK2 / anti-CD3 bispecific antibody, wherein the one or more step-up doses are administered prior to the initial administration of the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody and wherein the one or more step-up doses are not higher than the treatment dose.

12. The method of any one of the preceding claims, further comprising administering to the patient one or more step-up doses (for example, one or two step-up doses) of the anti-hK2 / anti-CD3bi specific antibody, wherein the one or more step-up doses are administered after the administration of the first treatment dose of the ADC and prior to the initial administration of the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody and wherein the one or more step-up doses are not higher than the treatment dose.

13. The method of claim 11 or 12, wherein the one or more step-up doses of the anti-hK2 / anti-CD3 bispecific antibody are intravenously administered, for example via intravenous (IV) infusion.

14. The method of any one of claims 11-13, wherein the method comprises administering to the patient a first step-up dose and a second step-up dose of the anti-hK2 / anti-CD3 bispecific antibody, wherein the first step-up dose is administered prior to the second step-up dose, and the second step-up dose is administered prior to the treatment dose.

15. The method of claim 14, wherein the second step-up dose of the anti-hK2 / anti-CD3 bispecific antibody is greater than the first step-up dose.

16. The method of claim 14 or 15, wherein the method comprises administering to the patient: i) the first step-up dose of the anti-hK2 / anti-CD3 bispecific antibody, ii) the second step-up dose of the anti-hK2 / anti-CD3 bispecific antibody; and iii) the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody, wherein the first step-up dose is administered once, and the second step-up dose is administered once.

17. The method of any one of claims 14-16, wherein the method comprises administering to the patient a first step-up dose of the anti-hK2 / anti-CD3 bispecific antibody of about 3.5 mg per administration.

18. The method of any one of claims 14-17, wherein the first step-up dose is administered on a day within 5-9 days, such as 5, 6, 7, 8, or 9 days, preferably 7 days, after the first treatment dose of the ADC is administered.

19. The method of claim 18, wherein the first step-up dose of the anti-hK2 / anti-CD3 bispecific antibody of about 3.5 mg per administration is administered 7 days after the first treatment dose of the ADC is administered.

20. The method of any one of claims 17-19, wherein the method further comprises administering to the patient a second step-up dose of the anti-hK2 / anti-CD3 bispecific antibody of about 18 mg per administration.21 . The method of claim 20, wherein the second step-up dose of the anti-hK2 / anti-CD3 bispecific antibody is administered on a day within 12-16 days, such as 12, 13, 14, 15 or 16 days, preferably 14 days, after the first treatment dose of the ADC is administered.

22. The method of claim 21, wherein the second step-up dose of the anti-hK2 / anti-CD3 bispecific antibody of about 18 mg per administration is administered 14 days after the first treatment dose of the ADC is administered.

23. The method of claim 22, comprising:(a) administering to the patient the ADC at the first treatment dose on Day 1 of the treatment;(b) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a first step-up dose of about 3.5 mg per administration on Day 8 of the treatment;(c) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a second step-up dose of about 18 mg per administration on Day 15 of the treatment;(d) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 300 mg per administration on Day 22 of the treatment; and(e) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 300 mg per administration once every 6 weeks after step (d), wherein each of the first step-up dose, the second step-up dose and the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody is intravenously administered, for example, via IV infusion, for example via IV infusion over a period of about 30 minutes to one hour for each administration.

24. The method of claim 23, wherein the ADC is administered at the first treatment dose of 2.0 mg / kg.

25. The method of any one of the foregoing claims, further comprising administering to the patient a second treatment dose of the ADC, for example a second treatment dose of the ADC:(a) on a day within 19-44 days, such as on a day within 19-23 days or 40-44 days after the administration of the first treatment dose of the ADC; or(b) on a day within 2 to 7 weeks, such as 2, 3, 4, 5, 6 or 7 weeks, for example 3 weeks or 6 weeks, after the administration of the first treatment dose of the ADC.

26. The method of claim 25, wherein the second treatment dose of the ADC is the same dose as the first treatment dose of the ADC.

27. The method of claim 26, wherein first and second treatment dose of the ADC is 2.0 mg / kg.

28. The method of any one of claims 25-27, wherein the second treatment dose of the ADC is administered on a day within 19-23 days, such as 19, 20, 21, 22, or 23 days, preferably 21 days, after the first treatment dose of ADC is administered.

29. The method of any one of claims 25-28, wherein the second treatment dose of the ADC is administered three weeks after the first treatment dose of ADC is administered.

30. The method of any one of claims 25-27, wherein the second treatment dose of the ADC is administered on a day within 40-44 days, such as 40, 41, 42, 43 or 44 days, preferably 42 days, after the first treatment dose of ADC is administered.

31. The method of any one of claims 25-27 and 30, wherein the second treatment dose of the ADC is administered six weeks after the first treatment dose of ADC is administered.

32. The method of any one of claims 25-31, further comprising administering to the patient a subsequent treatment dose of the ADC after the administration of the second treatment dose of the ADC, for example a subsequent treatment dose of the ADC once every 2 to 7 weeks, such as once every 2, 3, 4, 5, 6 or 7 weeks, for example once every 3 weeks or once every 6 weeks, after the administration of the second treatment dose of the ADC.

33. The method of claim 32, wherein the subsequent treatment dose of the ADC is administered once every 6 weeks.

34. The method of claim 32, wherein the subsequent treatment dose of the ADC is administered once every 3 weeks.

35. The method of claim 34, wherein the subsequent treatment dose of the ADC is administered once every 3 weeks for 2 doses.

36. The method of any one of the preceding claims, which does not comprise administering more than 4 doses of the ADC.

37. The method of any one of claims 32-36, wherein the subsequent treatment dose of the ADC is the same dose as the second treatment dose of the ADC.

38. The method of claim 37, wherein the second dose and the subsequent treatment dose of the ADC is 2.0 mg / kg.

39. The method of any one of the foregoing claims, wherein each of the first treatment dose, the second treatment dose, and the subsequent treatment dose of the ADC is intravenously administered.

40. The method of any one of the preceding claims, comprising:(a) administering to the patient the ADC at a first treatment dose on Day 1 of the treatment, wherein the first treatment dose is about 2.0 mg / kg;(b) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a first step-up dose of about 3.5 mg on a day within Day 6 to Day 10 of the treatment, for example on Day 8;(c) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a second step-up dose of about 18.5 mg on a day within Day 13 to Day 17 of the treatment, for example on Day 15;(d) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 300 mg on a day within Day 20 to Day 24 of the treatment, for example on Day 22;(e) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 300 mg per administration once every 6 weeks after the administering of step (d);(f) administering to the patient a second treatment dose of the ADC on a day within Day 20 to Day 24 of the treatment, for example on Day 22, wherein the second treatment dose of the ADC is the same dose as the first treatment dose of the ADC; and(g) administering to the patient a third and fourth treatment dose of the ADC once every 3 weeks after the administering of step (f), wherein the third and fourth treatment dose of the ADC is the same dose as the second treatment dose of the ADC41. The method of claim 40, wherein the total number of doses of the ADC does not exceed 4 doses.

42. The method of any one of the preceding claims, comprising:(a) administering to the patient the ADC at a first treatment dose on Day 1 of the treatment, wherein the first treatment dose is about 2.0 mg / kg;(b) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a first step-up dose of about 3.5 mg on a day within Day 6 to Day 10 of the treatment, for example on Day 8;(c) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at a second step-up dose of about 18.5 mg on a day within Day 13 to Day 17 of the treatment, for example on Day 15;(d) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 300 mg on a day within Day 20 to Day 24 of the treatment, for example on Day 22;(e) administering to the patient the anti-hK2 / anti-CD3 bispecific antibody at the treatment dose of about 300 mg per administration once every 6 weeks after the administering of step (d);(f) administering to the patient a second treatment dose of the ADC on a day within Day 40 to Day 44 of the treatment, for example on Day 43, wherein the second treatment dose of the ADC is the same dose as the first treatment dose of the ADC;(g) administering to the patient one or more subsequent treatment dose(s) of the ADC once every 6 weeks after the administering of step (f), wherein the one or more subsequent treatment dose(s) of the ADC is (are) the same dose as the second treatment dose of the ADC.

43. The method of any one of claim 40-42, wherein, each of the first step-up dose, the second step- up dose and the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody is intravenously administered, advantageously via IV infusion; and wherein, each of the first treatment dose, the second treatment dose and the subsequent treatment dose of the ADC is intravenously administered, for example, via IV infusion.

44. The method of any one of the foregoing claims, wherein when the ADC and the anti-hK2 / anti- CD3 bispecific antibody are administered on the same day, the anti-hK2 / anti-CD3 bispecific antibody is administered at least one hour after the administration of the ADC.

45. The method of any one of the foregoing claims, wherein, prior to, but on the same day as the first administration of the anti-hK2 / anti-CD3 bispecific antibody, the patient has received one or more premedication independently selected from a glucocorticoid, an antihistamine and anantipyretic, more particularly the patient has received a glucocorticoid premedication, an antihistamine premedication and an antipyretic premedication.

46. The method of claim 45, wherein the one or more premedication is administered within 2 hours prior to the administration of the anti-hK2 / anti-CD3 bispecific antibody47. The method of any one of the preceding claims, which comprises administering a first step-up dose of the anti-hK2 / anti-CD3 bispecific antibody and a second step-up dose of the anti- hK2 / anti-CD3 bispecific antibody prior to the first treatment dose of the anti-hK2 / anti-CD3 bispecific antibody, and wherein, prior to but on the same day as the administration of the first step-up dose and the second step-up dose as well as prior to the first administration of the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody, the patient has received at least one premedication independently selected from a glucocorticoid, an antihistamine and an antipyretic, more particularly the patient has received a glucocorticoid premedication, an antihistamine premedication and an antipyretic premedication.

48. The method of claim 47, wherein at least one premedication is administered within 2 hours prior to the first step-up dose, within 2 hours prior to the second step-up dose, and within 2 hours prior to the first administration of the treatment dose of the anti-hK2 / anti-CD3 bispecific antibody.

49. The method of any one of the foregoing claims, wherein the patient has received an antihistamine medication on the day before, on the same day as and on the day after the administration of ADC.

50. The method of any one of the foregoing claims, wherein the patient has received a nonsteroidal anti-inflammatory medication on the day before, on the same day as and on the day after the administration of ADC.

51. The method of any of the foregoing claims, wherein the (human) patient is 18 years of age or older.

52. The method of any one of the foregoing claims, wherein the prostate cancer is histologically confirmed adenocarcinoma of the prostate, as defined by Prostate Cancer Working Group 3 (PCWG3) criteria (Scher et al. 2016 Journal of Clinical Oncology 34(12): 1402-1418).

53. The method of any one of the preceding claims, wherein the prostate cancer is a prostate adenocarcinoma that does not comprise small cell carcinoma, carcinoid tumor, mixed neuroendocrine (NE) carcinoma, or large cell NE carcinoma.

54. The method of any one of the preceding claims, wherein the patient has: a. received orchiectomy or medical castration; or b. has not undergone orchiectomy and is receiving ongoing androgen deprivation therapy with a gonadotropin releasing hormone (GnRH) analog (agonist or antagonist) prior to being administered with the method of treatment of any one of the preceding claims.

55. The method of any one of the preceding claims, wherein the patient has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

56. The method of any one of the preceding claims, wherein the patient has received no more than one or no previous taxane therapies, more specifically no more than one or no prior antiprostate cancer chemotherapy (i.e., docetaxel, cabazitaxel, cisplatin, carboplatin, etoposide, etc.).

57. The method of any one of claims 1-56, wherein the patient has received no prior taxane therapy for the treatment of mCRPC as well as no prior 177-Lu-PSMA radionuclide therapy (specifically, no prior pluvicto therapy) for the treatment of mCRPC.

58. The method of any one of claims 1-56, wherein the patient has received only one prior taxane therapy for the treatment of mCRPC and has received no prior 177-Lu-PSMA radionuclide therapy (specifically, no prior pluvicto therapy) for the treatment of mCRPC.

59. The method of any one of claims 1-56, wherein the patient has received only one prior taxane therapy for the treatment of mCRPC and has received prior 177-Lu-PSMA radionuclide therapy (specifically, prior pluvicto therapy) for the treatment of mCRPC.

60. The method of any one of claims 1-56, wherein the patient has received no prior taxane therapy for the treatment of mCRPC, but has received prior 177-Lu-PSMA radionuclide therapy (specifically, prior pluvicto therapy) for the treatment of mCRPC.

61. The method of any one of the claims 1-56 and 58-60, wherein the patient has received prior PSMA radioligand therapy.

62. The method of any one of claims 1-56 and 58-60, wherein the patient has received prior 177- Lu-PSMA radionuclide therapy.

63. The method of any one of the preceding claims, wherein the patient has received no more than one or no taxane therapy for the treatment of mCRPC, specifically no more than one or no docetaxel therapy for the treatment of mCRPC and no more than one or no cabazitaxel therapy for the treatment of mCRPC.

64. The method of any one of the preceding claims, wherein the patient has received prior treatment with an androgen receptor pathway inhibitor (ARPI) for the treatment of prostate cancer, for example at least one prior prostate cancer treatment with abiraterone acetate, apalutamide, enzalutamide or darolutamide.

65. The method of any one of the preceding claims, wherein the method provides a decrease in the serum Prostate-Specific Antigen (PSA) level of the patient, wherein the decrease is relative to the PSA level of the patient prior to the administration of the anti-hK2 / anti-CD3 bispecific antibody.

66. The method of any one of the preceding claims, wherein the PSA level decreases by 50% or more compared to the PSA level of the patient prior to the administration of the anti-hK2 / anti- CD3 bispecific antibody (PSA50).

67. The method of any one of the preceding claims, which provides for a higher probability of achieving PSA50, compared to what would have been observed in a comparable treatment regimen with the anti-hK2 / anti-CD3 bispecific antibody in monotherapy (i.e., without administration of the ADC).

68. The method of claim 67, wherein the PSA50 is the confirmed PSA50 (PSA50 confirmed by a second measurement taken at least three weeks after the first PSA55O measurement).

69. The method of any one of the preceding claims, wherein the method provides for no disease progression in the patient, wherein disease progression is assessed according to the Prostate Cancer Working Group 3 (PCWG3) Criteria (Scher et al. 2016 Journal of Clinical Oncology 34(12): 1402-1418)).

70. The method of any one of the preceding claims, wherein the method provides a Partial Response or better according to RECIST version 1.1 response criteria (Eisenhauer et al. 2009 European Journal of Cancer 45: 228-247) without evidence of bone progression according to PCWG3 in the patient.

71. The method of any one of the preceding claims, wherein the method provides radiographic progression free survival (rPFS).

72. The method of any one of the preceding claims, wherein no Adverse Event of Grade 3 or higher (according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCLCTCAE) version 5.0) is observed in the patient.

73. The method of any one of the preceding claims, wherein Adverse Events of Grade 3 or higher (according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0) are observed in 20% or fewer of patients in a cohort of at least 20 patients, for example 15% or fewer of patients in a cohort of at least 20 patients.

74. The method of any one of the preceding claims, wherein the method does not induce a Dose Limiting Toxicity (DLT) in the patient.

75. The method of any one of the preceding claims, wherein the anti-hK2 / anti-CD3 bispecific antibody is pasritamig.

76. The method of any one of the preceding claims, wherein the prostate cancer is metastatic castration-resistant prostate cancer (mCRPC).

77. The anti-hK2 / anti-CD3 bispecific antibody as defined in any one of the preceding claims for use in the method of any one of the preceding claims.

78. The ADC as defined in any one of the preceding claims for use in the method of any one of the preceding claims.

79. The anti-hK2 / anti-CD3 bispecific antibody as defined in any one of the preceding claims and the ADC as defined in any one of the preceding claims for use in the method of any one of the preceding claims.

80. A combination or functional association comprising the anti-hK2 / anti-CD3 bispecific antibody as defined in any one of the preceding claims and the ADC as defined in any one of the preceding claims.

81. The anti-hK2 / anti-CD3 bispecific antibody as defined in any one of the preceding claims and the ADC as defined in any one of the preceding claims as a combined preparation for simultaneous, separate or sequential use in prostate cancer therapy, more specifically in mCRPC therapy.

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