Combination of trispecific antibody targeting BCMA, GPRC5d and CD3, and pomalidomide for the treatment of multiple myeloma

Abstract

Embodiments described herein relate to methods of treating multiple myeloma in a subject in need thereof, comprising administering a therapeutically effective amount of a BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof, and pomalidomide, to the subject to treat the multiple myeloma.

Description

COMBINATION OF TRISPECIFIC ANTIBODY TARGETING BCMA, GPRC5D AND CD3, AND POMALIDOMIDE FOR THE TREATMENT OF MULTIPLE MYELOMACROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of United States Provisional Application Serial Numbers 63 / 706,358 filed on 11 October 2024, 63 / 738,238 filed on 23 December 2024, and 63 / 809,579 filed on 21 May 2025. The entire contents of the above-referenced application are incorporated by reference in their entirety.SEQUENCE LISTING instant application contains a Sequence Listing which has been submittedelectronically in XML file format and is hereby incorporated by reference in its entirety.Said XML copy, created on 6 October 2025, is named JBI6956WOPCTl_SL.xml and 66,425 bytes in size.TECHNICAL FIELD

[0003] The disclosure provided herein relates to methods of treating multiple myeloma using a trispecific antibodies or trispecific binding fragments thereof that bind B-cell maturation antigen (BCMA), G-protein coupled receptor, class C, group 5, member D (GPRC5D), and cluster determinant 3 (CD3) and pomalidomide.BACKGROUND

[0004] Multiple myeloma (MM) is a malignant plasma cell disorder that accounts for 10% of all hematologic cancers, making it the second most common hematological malignancy and responsible for 2% of cancer deaths. It often develops from asymptomatic precursor states like monoclonal gammopathy or smoldering MM, affecting about 3% of adults over 50. MM is a heterogeneous disease caused primarily by chromosomal translocations (e.g., t(l 1 ; 14), t(4;14), del(13)). It is more prevalent in men and twice as common in people of African descent.

[0005] The clinical manifestations arise from clonal expansion of bone marrow plasma cells, resulting in bone marrow infiltration, bone destruction, renal failure, andimmunodeficiency. As of 2006, the 5-year survival rate was 34%, and no curative treatments exist. Diagnosis is based on clonal plasma cells and end-organ damage, defined by the "CRAB" features: hypercalcemia, renal failure, anemia, and bone lesions.

[0006] BCMA (B-cell maturation antigen), a key target in MM, plays a role in plasma cell growth and survival. It binds to APRIL and BAFF ligands, activating pro-survival pathways. BCMA is highly expressed on malignant B cells, making it a prime therapeutic target, with several approved treatments including idecabtagene vicleucel and belantamab mafodotin. GPRC5D, another plasma cell target, shows promise for treating MM due to its restricted expression in plasma cells and malignant plasma cell correlation. Dual targeting of BCMA and GPRC5D improves tumor eradication and reduces the risk of tumor escape.

[0007] Although treatment options for MM, such as proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies, have improved over time, MM remains incurable, especially in elderly patients and those with refractory disease. Novel regimens, including combinations with pomalidomide, are needed to address treatment resistance and provide better outcomes for these patients.SUMMARY

[0008] Provided herein is a method of treating multiple myeloma in a subject in need thereof, comprising administering a therapeutically effective amount of BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof and pomalidomide, to the subject to treat the multiple myeloma, wherein theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered at a treatment dose of at least about 20 mg.

[0009] In one aspect, provided herein is a method of treating multiple myeloma in a subject in need thereof, comprising administering a therapeutically effective amount of a BCMA x GPRC5D x CD3 trispecific antibody or a trispecific binding fragment thereof and Pomalidomide, to the subject to treat the multiple myeloma, wherein the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered at a treatment dose of at least about 20 mg.24897-1598-5221.1

[0010] In another aspect, provided herein is a method of treating multiple myeloma in a subject in need thereof, comprising administering a therapeutically effective amount of a BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof and pomalidomide, to the subject to treat the multiple myeloma, wherein theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered at a treatment dose of about 20 mg and wherein the treatment dose is administered once every four weeks.

[0011] In another aspect, provided herein is a method of treating multiple myeloma in a subject in need thereof, comprising administering a therapeutically effective amount of a BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof and pomalidomide, to the subject to treat the multiple myeloma, wherein theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered at a treatment dose of about 50 mg and wherein the treatment dose is administered once every four weeks.

[0012] In another aspect, provided herein is a method of treating multiple myeloma in a subject in need thereof, comprising administering a therapeutically effective amount of a BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof and pomalidomide, to the subject to treat the multiple myeloma, wherein theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered at a treatment dose of about 100 mg and wherein the treatment dose is administered once every four weeks.

[0013] In another aspect, provided herein is a method of treating multiple myeloma in a subject in need thereof, comprising administering a therapeutically effective amount of a BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof and pomalidomide, to the subject to treat the multiple myeloma, wherein theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered at a treatment dose of about 200 mg and wherein the treatment dose is administered once every four weeks.34897-1598-5221.1

[0014] In another aspect, provided herein is a method of treating multiple myeloma in a subject in need thereof, comprising administering a therapeutically effective amount of a BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof and pomalidomide, to the subject to treat the multiple myeloma, wherein theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered at a treatment dose of about 300 mg and wherein the treatment dose is administered once every four weeks.

[0015] In some embodiments, the multiple myeloma is a relapsed or refractory form of multiple myeloma. In some embodiments, the multiple myeloma is a relapsed form of multiple myeloma. In some embodiments, the multiple myeloma is a refractory form of multiple myeloma.

[0016] In some embodiments of any of the methods provided herein, theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is the trispecific antibody formed from the amino acid chains having the sequences of SEQ ID Nos: 29, 30 and 31 (this molecule is also herein termed BGCB491; see also the structure in FIG. 10).

[0017] Provided herein is a method of treating multiple myeloma in a subject in need thereof, comprising administering a therapeutically effective amount of aBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof and pomalidomide, to the subject to treat the multiple myeloma, wherein the method comprises subcutaneous administration of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof once every four weeks at a treatment dose of about 20 mg, wherein the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is BGCB491, and wherein the subject is a human subject.

[0018] Provided herein is a method of treating multiple myeloma in a subject in need thereof, comprising administering a therapeutically effective amount of aBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof and pomalidomide, to the subject to treat the multiple myeloma, wherein the method comprises subcutaneous administration of the BCMA x GPRC5D x CD3 trispecific antibody or44897-1598-5221.1trispecific binding fragment thereof once every four weeks at a treatment dose of about 50 mg, wherein the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is BGCB491, and wherein the subject is a human subject.

[0019] Provided herein is a method of treating multiple myeloma in a subject in need thereof, comprising administering a therapeutically effective amount of aBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof and pomalidomide, to the subject to treat the multiple myeloma, wherein the method comprises subcutaneous administration of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof once every four weeks at a treatment dose of about 100 mg, wherein the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is BGCB491, and wherein the subject is a human subject.

[0020] Provided herein is a method of treating multiple myeloma in a subject in need thereof, comprising administering a therapeutically effective amount of aBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof and pomalidomide, to the subject to treat the multiple myeloma, wherein the method comprises subcutaneous administration of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof once every four weeks at a treatment dose of about 300 mg, wherein the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is BGCB491, and wherein the subject is a human subject.

[0021] The skilled person will understand that the described methods may be specified in medical use format, for example in the form of BCMA x GPRC5D x CD3 -trispecific antibodies and trispecific antigen-binding fragments and pomalidomide for use in the treatment of multiple myeloma. This skilled person will also understand that the methods may be specified in so-called Swiss form, for example in the form of the use of BCMA x GPRC5D x CD3 -trispecific antibodies and trispecific antigen-binding fragments and pomalidomide for the manufacture of a medicament for the treatment of multiple myeloma. This applies throughout the disclosure.BRIEF DESCRIPTION OF THE DRAWINGS54897-1598-5221.1

[0022] FIG. 1A, FIG. IB, and FIG. 1C show simultaneous treatment of BGCB491 with pomalidomide results in statistically significant decreased EC50 of H929 tumor cytotoxicity. CFSE-labeled H929 target cells and PBMCs of Donor 1 were co-cultured at a ratio of 3: 1 E:T in the presence of increasing concentrations of BGCB491and Pomalidomide for 72 hours. (FIG. 1A) Dose-response curve for cytotoxicity of H929 MM cell line assessed by flow cytometry. Each point represents the mean and error bars of the standard deviation of technical triplicates. (FIG. IB) Table detailing the EC50 values of BGCB491with increasing concentrations of pomalidomide and p-values compared to BGCB491 monotherapy. (FIG. 1C) Synergy analysis contour plot with increasing concentrations of BGCB491 along the x-axis and increasing concentrations of pomalidomide along the y-axis using Highest Single Agent (HSA) synergy model. Grey dots on the contour plot represent effect size which is the difference in mean observed effect and mean expected effect. Red indicates a call of antagonism while blue indicates a call of synergy.

[0023] FIG. 2A, FIG. 2B, and FIG. 2C show simultaneous treatment of BGCB491 with pomalidomide results in statistically significant decreased EC50 of H929 tumor cytotoxicity. CFSE-labeled H929 target cells and PBMCs of donor 2 were co-cultured at a ratio of 3: 1 E:T in the presence of increasing concentrations of BGCB491and pomalidomide for 72 hours. (FIG. 2A) Dose-response curve for cytotoxicity of H929 MM cell line assessed by flow cytometry. Each point represents the mean and error bars of the standard deviation of technical triplicates. (FIG. 2B) Table detailing the EC50 values of BGCB491with increasing concentrations of pomalidomide and p-values compared to BGCB491 monotherapy. (FIG. 2C) Synergy analysis contour plot with increasing concentrations of BGCB491 along the x-axis and increasing concentrations of pomalidomide along the y-axis using Highest Single Agent (HSA) synergy model. Grey dots on the contour plot represent effect size which is the difference in mean observed effect and mean expected effect. Red indicates a call of antagonism while blue indicates a call of synergy.64897-1598-5221.1

[0024] FIG. 3 A, FIG. 3B, and FIG. 3C show simultaneous treatment of BGCB491 with pomalidomide results in statistically significant decreased EC50 of H929 tumor cytotoxicity. CFSE-labeled H929 target cells and PBMCs of Donor 3 were co-cultured at a ratio of 3: 1 E:T in the presence of increasing concentrations of BGCB491and pomalidomide for 72 hours. (FIG. 3 A) Dose-response curve for cytotoxicity of H929 MM cell line assessed by flow cytometry. Each point represents the mean and error bars of the standard deviation of technical triplicates. (FIG. 3B) Table detailing the EC50 values of BGCB491with increasing concentrations of pomalidomide and p-values compared to BGCB491 monotherapy. (FIG. 3C) Synergy analysis contour plot with increasing concentrations of BGCB491 along the x-axis and increasing concentrations of pomalidomide along the y-axis using Highest Single Agent (HSA) synergy model. Grey dots on the contour plot represent effect size which is the difference in mean observed effect and mean expected effect. Red indicates a call of antagonism while blue indicates a call of synergy.

[0025] FIG. 4A, FIG. 4B, FIG. 4C, FIG. 4D, FIG. 4E, and FIG. 4F show simultaneous treatment of BGCB491 and pomalidomide enhances to variable degrees BGCB491- mediated T cell activation in H929 MM cells. CFSE-labeled H929 target cells and PBMCs of donor 1 were co-cultured at a ratio of 3:1 E:T in the presence of increasing concentrations of BGCB491 and pomalidomide for 72 hours. Flow cytometry assessment of (FIG. 4A) Frequency of CD3+ CD25+ T cells. (FIG. 4B) Synergy analysis contour plot with increasing concentrations of BGCB491 along the x-axis and increasing concentrations of pomalidomide along the y-axis using Highest Single Agent (HSA) synergy model for CD3+ CD25+. Grey dots on the contour plot represent effect size which is the difference in mean observed effect and mean expected effect. Red indicates a call of antagonism while blue indicates a call of synergy. (FIG. 4C) Table detailing the EC50 values of BGCB491 with increasing concentrations of pomalidomide and p-values compared to BGCB491 monotherapy for CD3+ CD25+. (FIG. 4D) Frequency of CD3+ HLADR+ T cells. (FIG. 4E) Synergy analysis contour plot with increasing concentrations of BGCB491 along the x-axis and increasing concentrations of pomalidomide along the y-axis using Highest74897-1598-5221.1Single Agent (HSA) synergy model for CD3+ HLADR+. Grey dots on the contour plot represent effect size which is the difference in mean observed effect and mean expected effect. Red indicates a call of antagonism while blue indicates a call of synergy. (FIG. 4F) Table detailing the ECso values of BGCB491 with increasing concentrations of pomalidomide and p-values compared to BGCB491 monotherapy for CD3+ HLADR+.

[0026] FIG. 5A, FIG. 5B, FIG. 5C, FIG. 5D, FIG. 5E, and FIG. 5F show simultaneous treatment of BGCB491 and pomalidomide enhances to variable degrees BGCB491- mediated T cell activation in H929 MM cells. CFSE-labeled H929 target cells and PBMCs of donor 2 were co-cultured at a ratio of 3 : 1 E: T in the presence of increasing concentrations of BGCB491 and Pomalidomide for 72 hours. Flow cytometry assessment of (FIG. 5A) Frequency of CD3+ CD25+ T cells. (FIG. 5B) Synergy analysis contour plot with increasing concentrations of BGCB491 along the x-axis and increasing concentrations of pomalidomide along the y-axis using Highest Single Agent (HSA) synergy model for CD3+ CD25+. Grey dots on the contour plot represent effect size which is the difference in mean observed effect and mean expected effect. Red indicates a call of antagonism while blue indicates a call of synergy. (FIG. 5C) Table detailing the EC50 values of BGCB491 with increasing concentrations of pomalidomide and p-values compared to BGCB491 monotherapy for CD3+ CD25+. (FIG. 5D) Frequency of CD3+ HLADR+ T cells. (FIG. 5E) Synergy analysis contour plot with increasing concentrations of BGCB491 along the x-axis and increasing concentrations of pomalidomide along the y-axis using Highest Single Agent (HSA) synergy model for CD3+ HLADR+. Grey dots on the contour plot represent effect size which is the difference in mean observed effect and mean expected effect. Red indicates a call of antagonism while blue indicates a call of synergy. (FIG. 5F) Table detailing the ECso values of BGCB491 with increasing concentrations of pomalidomide and p-values compared to BGCB491 monotherapy for CD3+ HLADR+.

[0027] FIG. 6A, FIG. 6B, FIG. 6C, FIG. 6D, FIG. 6E, and FIG. 6F show simultaneous treatment of BGCB491 and pomalidomide enhances to variable degrees BGCB491- mediated T cell activation in H929 MM cells. CFSE-labeled H929 target cells and PBMCs of donor 3 were co-cultured at a ratio of 3:1 E:T in the presence of increasing84897-1598-5221.1concentrations of BGCB491 and pomalidomide for 72 hours. Flow cytometry assessment of (FIG. 6A) Frequency of CD3+ CD25+ T cells. (FIG. 6B) Synergy analysis contour plot with increasing concentrations of BGCB491 along the x-axis and increasing concentrations of pomalidomide along the y-axis using Highest Single Agent (HSA) synergy model for CD3+ CD25+. Grey dots on the contour plot represent effect size which is the difference in mean observed effect and mean expected effect. Red indicates a call of antagonism while blue indicates a call of synergy. (FIG. 6C) Table detailing the EC50 values of BGCB491 with increasing concentrations of pomalidomide and p-values compared to BGCB491 monotherapy for CD3+ CD25+. (FIG. 6D) Frequency of CD3+ HLADR+ T cells. (FIG. 6E) Synergy analysis contour plot with increasing concentrations of BGCB491 along the x-axis and increasing concentrations of pomalidomide along the y-axis using Highest Single Agent (HSA) synergy model for CD3+ HLADR+. Grey dots on the contour plot represent effect size which is the difference in mean observed effect and mean expected effect. Red indicates a call of antagonism while blue indicates a call of synergy. (FIG. 6F) Table detailing the ECso values of BGCB491 with increasing concentrations of pomalidomide and p-values compared to BGCB491 monotherapy for CD3+ HLADR+.

[0028] FIG. 7A and FIG. 7B show simultaneous treatment of BGCB491 with pomalidomide results in statistically significant synergy of H929 tumor cytotoxicity. (FIG. 7A AND FIG. 7B) Synergy analysis contour plots with increasing concentrations of BGCB491 along the x-axis and increasing concentrations of pomalidomide along the y- axis using (FIG. 7A) Bliss Independence model and (FIG. 7B) Alternative Loewe Model. Blue shade indicates areas of synergy. Grey dots on the contour plot represent effect size which is the difference in mean observed effect and mean expected effect. Red indicates a call of antagonism while blue indicates a call of synergy.

[0029] FIG. 8A and FIG. 8B show simultaneous treatment of BGCB491 with pomalidomide results in statistically significant synergy of H929 tumor cytotoxicity. (FIG. 8A AND FIG. 8B) Synergy analysis contour plots with increasing concentrations of BGCB491 along the x-axis and increasing concentrations of pomalidomide along the y- axis using (FIG. 8A) Bliss Independence model and (FIG. 8B) Alternative Loewe Model.94897-1598-5221.1Blue shade indicates areas of synergy. Grey dots on the contour plot represent effect size which is the difference in mean observed effect and mean expected effect. Red indicates a call of antagonism while blue indicates a call of synergy.

[0030] FIG. 9A and FIG. 9B show simultaneous treatment of BGCB491 with pomalidomide results in statistically significant synergy of H929 tumor cytotoxicity. (FIG. 9A AND FIG. 9B) Synergy analysis contour plots with increasing concentrations of BGCB491 along the x-axis and increasing concentrations of pomalidomide along the y- axis using (FIG. 9A) Bliss Independence model and (FIG. 9B) Alternative Loewe Model. Blue shade indicates areas of synergy. Grey dots on the contour plot represent effect size which is the difference in mean observed effect and mean expected effect. Red indicates a call of antagonism while blue indicates a call of synergy.

[0031] FIG. 10 is a depiction of the BGCB491 trispecific antibody.

[0032] FIG. 11 is a schematic overview of the study plan for BGCB491 and pomalidomideDETAILED DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS

[0033] The disclosed methods can be understood more readily by reference to the following detailed description. 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 fourth fully herein.

[0034] Unless otherwise defined herein, technical and scientific terms used in the present description have the meanings that are commonly understood by those of ordinary skill in the art. For purposes of interpreting this specification, the following description of terms will apply and whenever appropriate, terms used in the singular will also include the plural and vice versa. In the event that any description of a term set forth conflicts with any104897-1598-5221.1document incorporated herein by reference, the description of the term set forth below shall control.

[0035] In an attempt to help the reader of the present application, the description has been separated in various paragraphs or sections. These separations are not considered as disconnecting the substance of a paragraph or section from the substance of another paragraph or section. To the contrary, the present description encompasses all the combinations of the various sections, paragraphs and sentences that can be contemplated.Definitions

[0036] 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.

[0037] 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.

[0038] The term “about” as used herein when referring to a measurable value such as an amount, a temporal duration, and the like, is meant to encompass variations of up to ±10% from the specified value, as such variations are appropriate to perform the disclosed methods. Unless otherwise indicated, all numbers expressing quantities of ingredients, properties such as molecular weight, reaction conditions, and so forth used in the specification and claims are to be understood as being modified in all instances by the term “about.” Accordingly, unless indicated to the contrary, the numerical parameters set forth in the following specification and attached claims are approximations that may vary depending upon the desired properties sought to be obtained by the present disclosure. At the very least, and not as an attempt to limit the application of the doctrine of equivalents to the scope of the claims, each numerical parameter should at least be construed in light of the number of reported significant digits and by applying ordinary rounding techniques.114897-1598-5221.1

[0039] Notwithstanding that the numerical ranges and parameters setting forth the broad scope of the disclosure are approximations, the numerical values set forth in the specific examples are reported as precisely as possible. Any numerical value, however, inherently contains certain errors necessarily resulting from the standard deviation found in their respective testing measurements.

[0040] The term “comprising” is intended to include examples encompassed by the terms “consisting essentially of’ and “consisting of’; similarly, the term “consisting essentially of’ is intended to include examples encompassed by the term “consisting of.” Unless the context clearly requires otherwise, throughout the description and the claims, the words “comprise”, “comprising”, and the like are to be construed in an inclusive sense as opposed to an exclusive or exhaustive sense; that is to say, in the sense of “including, but not limited to”.

[0041] “Isolated” means a biological component (such as a nucleic acid, peptide or protein) has been substantially separated, produced apart from, or purified away from other biological components of the organism in which the component naturally occurs, i.e., other chromosomal and extrachromosomal DNA and RNA, and proteins. Nucleic acids, peptides and proteins that have been “isolated” thus include nucleic acids and proteins purified by standard purification methods. “Isolated” nucleic acids, peptides and proteins can be part of a composition and still be isolated if such composition is not part of the native environment of the nucleic acid, peptide, or protein. The term also embraces nucleic acids, peptides and proteins prepared by recombinant expression in a host cell as well as chemically synthesized nucleic acids. An "isolated” antibody or antigen-binding fragment, as used herein, is intended to refer to an antibody or antigen-binding fragment which is substantially free of other antibodies or antigen-binding fragments having different antigenic specificities (for instance, an isolated antibody that specifically binds to BCMA is substantially free of antibodies that specifically bind antigens other than BCMA). An isolated antibody that specifically binds to an epitope, isoform or variant of BCMA or GPRC5D may, however, have cross-reactivity to other related antigens, for instance from other species (such as BCMA or GPRC5D species homologs).124897-1598-5221.1

[0042] “Polynucleotide,” synonymously referred to as “nucleic acid molecule,” “nucleotides” or “nucleic acids,” refers to any polyribonucleotide or polydeoxyribonucleotide, which may be unmodified RNA or DNA or modified RNA or DNA. “Polynucleotides” include, without limitation single- and double-stranded DNA, DNA that is a mixture of single- and double-stranded regions, single- and double-stranded RNA, and RNA that is mixture of single- and double-stranded regions, hybrid molecules comprising DNA and RNA that may be single-stranded or, more typically, double-stranded or a mixture of single- and double-stranded regions. In addition, “polynucleotide” refers to triple-stranded regions comprising RNA or DNA or both RNA and DNA. The term polynucleotide also includes DNAs or RNAs containing one or more modified bases and DNAs or RNAs with backbones modified for stability or for other reasons. “Modified” bases include, for example, tritylated bases and unusual bases such as inosine. A variety of modifications may be made to DNA and RNA; thus, “polynucleotide” embraces chemically, enzymatically or metabolically modified forms of polynucleotides as typically found in nature, as well as the chemical forms of DNA and RNA characteristic of viruses and cells. “Polynucleotide” also embraces relatively short nucleic acid chains, often referred to as oligonucleotides.

[0043] The meaning of “substantially the same” can differ depending on the context in which the term is used. Because of the natural sequence variation likely to exist among heavy and light chains and the genes encoding them, one would expect to find some level of variation within the amino acid sequences or the genes encoding the antibodies or antigen-binding fragments described herein, with little or no impact on their unique binding properties (e.g., specificity and affinity). Such an expectation is due in part to the degeneracy of the genetic code, as well as to the evolutionary success of conservative amino acid sequence variations, which do not appreciably alter the nature of the encoded protein. Accordingly, in the context of nucleic acid sequences, “substantially the same” means at least 65% identity between two or more sequences. Preferably, the term refers to at least 70% identity between two or more sequences, more preferably at least 75% identity, more preferably at least 80% identity, more preferably at least 85% identity, more134897-1598-5221.1preferably at least 90% identity, more preferably at least 91% identity, more preferably at least 92% identity, more preferably at least 93% identity, more preferably at least 94% identity, more preferably at least 95% identity, more preferably at least 96% identity, more preferably at least 97% identity, more preferably at least 98% identity, and more preferably at least 99% or greater identity. The percent identity between two sequences is a function of the number of identical positions shared by the sequences (i.e., % homology = # of identical positions / total # of positions x 100), taking into account the number of gaps, and the length of each gap, which need to be introduced for optimal alignment of the two sequences. The percent identity between two nucleotide or amino acid sequences may e.g. be determined using the algorithm of E. Meyers and W. Miller, Comput. Appl. Biosci 4, 11-17 (1988) which has been incorporated into the ALIGN program (version 2.0), using a P AMI 20 weight residue table, a gap length penalty of 12 and a gap penalty of 4. In addition, the percent identity between two amino acid sequences may be determined using the Needleman and Wunsch, J. Mol. Biol. 48, 444-453 (1970) algorithm.

[0044] The degree of variation that may occur within the amino acid sequence of a protein without having a substantial effect on protein function is much lower than that of a nucleic acid sequence, since the same degeneracy principles do not apply to amino acid sequences. Accordingly, in the context of an antibody or antigen-binding fragment, “substantially the same” means antibodies or antigen-binding fragments having 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the antibodies or antigen-binding fragments described. Other embodiments include antibodies, or antigen-binding fragments, that have framework, scaffold, or other non-binding regions that do not share significant identity with the antibodies and antigen-binding fragments described herein, but do incorporate one or more CDRs or other sequences needed to confer binding that are 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to such sequences described herein.

[0045] A “clone” is a population of cells derived from a single cell or common ancestor by mitosis. A “cell line” is a clone of a primary cell that is capable of stable growth in vitro for many generations. In some examples provided herein, cells are transformed by transfecting the cells with DNA.144897-1598-5221.1

[0046] The terms “express” and “produce” are used synonymously herein, and refer to the biosynthesis of a gene product. These terms encompass the transcription of a gene into RNA. These terms also encompass translation of RNA into one or more polypeptides, and further encompass all naturally occurring post-transcriptional and post-translational modifications. The expression or production of an antibody or antigen-binding fragment thereof may be within the cytoplasm of the cell, or into the extracellular milieu such as the growth medium of a cell culture.

[0047] The terms “treating” or “treatment” refer to any success or indicia of success in the attenuation or amelioration of an injury, pathology or condition, including any objective or subjective parameter such as abatement, remission, diminishing of symptoms or making the condition more tolerable to the patient, slowing in the rate of degeneration or decline, making the final point of degeneration less debilitating, improving a subject’s physical or mental well-being, or prolonging the length of survival. The treatment may be assessed by objective or subjective parameters; including the results of a physical examination, neurological examination, or psychiatric evaluations.

[0048] An "effective amount" or "therapeutically effective amount" refers to an amount effective, at dosages and for periods of time necessary, to achieve a desired therapeutic result. A therapeutically effective amount of a BCMA x GPRC5D x CD3 antibody may vary according to factors such as the disease state, age, sex, and weight of the individual, and the ability of the antibody to elicit a desired response in the individual. . A therapeutically effective amount of pomalidomide may vary according to factors such as the disease state, age, sex, and weight of the individual, and the ability of the antibody to elicit a desired response in the individual. A therapeutically effective amount is also one in which any toxic or detrimental effects of the antibody or antibody portion, or the pomalidomide, are outweighed by the therapeutically beneficial effects.

[0049] “Antibody” refers to all isotypes of immunoglobulins (IgG, IgA, IgE, IgM, IgD, and IgY) including various monomeric, polymeric and chimeric forms, unless otherwise specified. Specifically encompassed by the term “antibody” are polyclonal antibodies,154897-1598-5221.1monoclonal antibodies (mAbs), and antibody-like polypeptides, such as chimeric antibodies and humanized antibodies.

[0050] The term “antigen-binding arm” refers to a portion of an antibody that includes an antigen-binding domain that binds to an antigen (e.g., BCMA, GPRC5D, or CD3), and optionally includes one or more other antibody regions (e.g., Fc domain).

[0051] The term “antigen-binding fragment” refers to a fragment of the antigen-binding arm containing an antigen-binding domain. Antigen-binding fragments include those provided by any known technique, such as enzymatic cleavage, peptide synthesis, and recombinant techniques. Some antigen-binding fragments are composed of portions of intact antibodies that retain antigen-binding specificity of the parent antibody molecule. For example, antigen-binding fragments may comprise at least one variable region (either a heavy chain or light chain variable region) or one or more CDRs of an antibody known to bind a particular antigen. Examples of suitable antigen-binding fragments include, without limitation diabodies and single-chain molecules as well as Fab, F(ab’)2, Fc, Fabc, and Fv molecules, single chain (Sc) antibodies, individual antibody light chains, individual antibody heavy chains, chimeric fusions between antibody chains or CDRs and other proteins, protein scaffolds, heavy chain monomers or dimers, light chain monomers or dimers, dimers consisting of one heavy and one light chain, a monovalent fragment consisting of the VL, VH, CL and CHI domains, or a monovalent antibody as described in W02007059782, bivalent fragments comprising two Fab fragments linked by a disulfide bridge at the hinge region, a Fd fragment consisting essentially of the VH and CHI domains; a Fv fragment consisting essentially of the VL and VH domains of a single arm of an antibody, a dAb fragment (Ward et al., Nature 341, 544-546 (1989)), which consists essentially of a VH domain and also called domain antibodies (Holt et al; Trends Biotechnol. 2003 Nov.; 21(11):484-90); camelid or nanobodies (Revets et al; Expert Opin Biol Ther. 2005 Jan.; 5(1): 111-24); an isolated complementarity determining region (CDR), and the like; and trispecific antibodies formed from antibody fragments. All antibody isotypes may be used to produce antigen-binding fragments. Additionally, antigen-binding fragments may include non-antibody proteinaceous frameworks that may164897-1598-5221.1successfully incorporate polypeptide segments in an orientation that confers affinity for a given antigen of interest, such as protein scaffolds. Antigen-binding fragments may be recombinantly produced or produced by enzymatic or chemical cleavage of intact antibodies. The phrase “an antibody or antigen-binding fragment thereof’ may be used to denote that a given antigen-binding fragment incorporates one or more amino acid segments of the antibody referred to in the phrase.

[0052] The term “antigen-binding domain” refers to the proteinaceous structure of an antigen-binding arm that exhibits binding affinity for a particular antigen. This proteinaceous structure is mediated by the complementarity determining regions (CDRs) of the antigen-binding domain.

[0053] The terms “CDR”, and its plural “CDRs”, refer to a complementarity determining region (CDR) of which three make up the binding character of a light chain variable region (CDRL1, CDRL2 and CDRL3) and three make up the binding character of a heavy chain variable region (CDRH1, CDRH2 and CDRH3). CDRs contribute to the functional activity of an antibody molecule and are separated by amino acid sequences that comprise scaffolding or framework regions. The exact definitional CDR boundaries and lengths are subject to different classification and numbering systems. CDRs may therefore be referred to herein by Kabat, Chothia, AbM, contact or any other boundary definitions. Despite differing boundaries, each of these systems has some degree of overlap in what constitutes the so called “hypervariable regions” within the variable sequences. CDR definitions according to these systems may therefore differ in length and boundary areas with respect to the adjacent framework region. See for example Kabat et al., Sequences of Proteins of Immunological Interest, 5th ed. NIH Publication No. 91-3242 (1991); Chothia et al., “Canonical Structures For the Hypervariable Regions of Immunoglobulins,” J. Mol. Biol. 196:901 (1987); and MacCallum et al., “Antibody- Antigen Interactions: Contact Analysis and Binding Site Topography,” J. Mol. Biol. 262:732 (1996)), each of which is hereby incorporated by reference in its entirety.

[0054] Typically, CDRs form a loop structure that can be classified as a canonical structure. The term “canonical structure” refers to the main chain conformation that is174897-1598-5221.1adopted by the antigen binding (CDR) loops. From comparative structural studies, it has been found that five of the six antigen binding loops have only a limited repertoire of available conformations. Each canonical structure can be characterized by the torsion angles of the polypeptide backbone. Correspondent loops between antibodies may, therefore, have very similar three dimensional structures, despite high amino acid sequence variability in most parts of the loops (Chothia et al., “Canonical Structures For the Hypervariable Regions of Immunoglobulins,” J. Mol. Biol. 196:901 (1987); Chothia et al., “Conformations of Immunoglobulin Hypervariable Regions,” I 342:877 (1989); Martin and Thornton, “Structural Families in Loops of Homologous Proteins: Automatic Classification, Modelling and Application to Antibodies,” J. Mol. Biol. 263:800 (1996), each of which is incorporated by reference in its entirety). Furthermore, there is a relationship between the adopted loop structure and the amino acid sequences surrounding it. The conformation of a particular canonical class is determined by the length of the loop and the amino acid residues residing at key positions within the loop, as well as within the conserved framework (i.e., outside of the loop). Assignment to a particular canonical class can therefore be made based on the presence of these key amino acid residues.

[0055] The term "polypeptide" is used interchangeably with the term "protein" and in its broadest sense refers to a compound of two or more subunit amino acids, amino acid analogs or peptidomimetics. The subunits may be linked by peptide bonds. In another embodiment, the subunit may be linked by other bonds, e.g., ester, ether, etc. As used herein the term "amino acid" refers to either natural and / or unnatural or synthetic amino acids, including glycine and both the D and L optical isomers, amino acid analogs and peptidomimetics. A peptide of three or more amino acids is commonly called an oligopeptide if the peptide chain is short. If the peptide chain is long, the peptide is commonly called a polypeptide or a protein

[0056] As used herein the term “Fc” refers to the fragment crystallizable domain of an antibody, which comprises two constant heavy chain (CH) regions, CH2 and CH3. Herein, the amino acid residues of the Fc region are typically numbered according to the EU numbering scheme (Edelman, G.M. et al., Proc. Natl. Acad. USA, 63, 78-85 (1969).184897-1598-5221.1PMID: 5257969). These residues can be readily assigned according to alternative numbering schemes such as IMGT and Kabat (Kabat, E.A. et al., Sequences of proteins of immunological interest. 5th Edition - US Department of Health and Human Services, NIH publication n° 91-3242, pp 662,680,689 (1991)) numbering as would be readily appreciated by one skilled in the art. For example, L234 according to EU numbering may also be represented as L247 according to Kabat.

[0057] “Specifically binds” or “binds specifically” or derivatives thereof when used in the context of antibodies, or antibody fragments, represents binding via domains encoded by immunoglobulin genes or fragments of immunoglobulin genes to one or more epitopes of a protein of interest, without preferentially binding other molecules in a sample containing a mixed population of molecules. Typically, an antibody binds to a cognate antigen with a Ka of less than about 1x1 O'8M, as measured by a surface plasmon resonance assay or a cell-binding assay. Phrases such as “[antigen] -specific” antibody (e.g., BCMA-specific antibody) are meant to convey that the recited antibody specifically binds the recited antigen. Wherever the term “binds” is used herein it is intended that this encompasses “specifically binds” and the terms may be interchanged as desired.

[0058] As used herein, the term “chimeric” refers to an antibody, or antigen-binding fragment thereof, having at least some portion of at least one variable domain derived from the antibody amino acid sequence of a non-human mammal, a rodent, or a reptile, while the remaining portions of the antibody, or antigen-binding fragment thereof, are derived from a human.

[0059] A “vector” is a replicon, such as plasmid, phage, cosmid, or virus in which another nucleic acid segment may be operably inserted so as to bring about the replication or expression of the segment.

[0060] As used herein, the term "host cell" can be any type of cell, e.g., a primary cell, a cell in culture, or a cell from a cell line. In specific embodiments, the term "host cell" refers to a cell transfected with a nucleic acid molecule and the progeny or potential progeny of such a cell. Progeny of such a cell may not be identical to the parent cell transfected with the nucleic acid molecule, e.g., due to mutations or environmental194897-1598-5221.1influences that may occur in succeeding generations or integration of the nucleic acid molecule into the host cell genome. The terms “expression” and “production” are used synonymously herein, and refer to the biosynthesis of a gene product. These terms encompass the transcription of a gene into RNA. These terms also encompass translation of RNA into one or more polypeptides, and further encompass all naturally occurring post- transcriptional and post-translational modifications.

[0061] The term “subject” refers to human and non-human animals, including all vertebrates, e.g., mammals and non-mammals, such as non-human primates, mice, rabbits, sheep, dogs, cats, horses, cows, chickens, amphibians, and reptiles. In a certain embodiment of the described methods, the subject is a human.

[0062] The term “redirect” or “redirecting” as used herein refers to the ability of the BCMA x GPRC5D x CD3 antibody to traffic the activity of T cells effectively, from its inherent cognate specificity toward reactivity against GPRC5D and / or BCMA-expressing cells.

[0063] The term “sample” as used herein refers to a collection of similar fluids, cells, or tissues (e.g., surgically resected tumor tissue, biopsies, including fine needle aspiration), isolated from a subject, as well as fluids, cells, or tissues present within a subject. In some embodiments the sample is a biological fluid. Biological fluids are typically liquids at physiological temperatures and may include naturally occurring fluids present in, withdrawn from, expressed or otherwise extracted from a subject or biological source. Certain biological fluids derive from particular tissues, organs or localized regions and certain other biological fluids may be more globally or systemically situated in a subject or biological source. Examples of biological fluids include blood, serum and serosal fluids, plasma, lymph, urine, saliva, cystic fluid, tear drops, feces, sputum, mucosal secretions of the secretory tissues and organs, vaginal secretions, ascites fluids such as those associated with non-solid tumors, fluids of the pleural, pericardial, peritoneal, abdominal and other body cavities, fluids collected by bronchial lavage and the like. Biological fluids may also include liquid solutions contacted with a subject or biological source, for example, cell and organ culture medium including cell or organ conditioned medium, lavage fluids and the 204897-1598-5221.1like. The term “sample,” as used herein, encompasses materials removed from a subject or materials present in a subject. The relevant aspects of the disclosure may be performed in vitro based on isolated samples as required.

[0064] A “known standard” may be a solution having a known amount or concentration of GPRC5D and / or BCMA, where the solution may be a naturally occurring solution, such as a sample from a patient known to have early, moderate, late, progressive, or static cancer, or the solution may be a synthetic solution such as buffered water having a known amount of GPRC5D and / or BCMA diluted therein. The known standards, described herein may include GPRC5D and / or BCMA isolated from a subject, recombinant or purified GPRC5D and / or BCMA protein, or a value of GPRC5D and / or BCMA concentration associated with a disease condition.

[0065] The terms “B-cell maturation antigen” and "BCMA" as used herein include human B cell maturation antigen, also known as BCMA, CD269, and TNFRSF17 (UniProt Q02223), which is a member of the tumor necrosis receptor superfamily that is preferentially expressed in differentiated plasma cells. The extracellular domain of human BCMA consists, according to UniProt of amino acids 1 - 54 (or 5-51). The term "antibody against BCMA, anti-BCMA antibody" as used herein relates to an antibody specifically binding to BCMA.

[0066] The terms "G-protein coupled receptor family C group 5 member D" and "GPRC5D" specifically include the human GPRC5D protein, for example as described in GenBank Accession No. BC069341, NCBI Reference Sequence: NP_061124.1 and UniProtKB / Swiss-Prot Accession No. Q9NZD1 (see also Brauner-Osborne, H. et al. 2001, Biochim. Biophys. Acta 1518, 237-248).

[0067] The terms “cluster determinant 3” and “CD3” include the human CD3 protein multi-subunit complex. The CD3 protein multi-subunit complex is composed to 6 distinctive polypeptide chains. These include a CD3y chain (SwissProt P09693), a CD38 chain (SwissProt P04234), two CD3s chains (SwissProt P07766), and one CD3 chain homodimer (SwissProt 20963), and which is associated with the T cell receptor a and 0 chain. The term “CD3” includes any CD3 variant, isoform and species homolog which is 214897-1598-5221.1naturally expressed by cells (including T cells) or can be expressed on cells transfected with genes or cDNA encoding those polypeptides, unless noted.

[0068] A “BCMA x GPRC5D x CD3 antibody” is a trispecific antibody, which comprises three different antigen-binding arms, one of which binds to the antigen BCMA, one of which binds to the antigen GPRC5D, and one of which binds to CD3. The term "multispecific antibody" is used herein in the broadest sense and specifically covers an antibody that has polyepitopic specificity. Multispecific antibodies include, but are not limited to, an antibody comprising a heavy chain variable domain (VH) and a light chain variable domain (VL), where the VHVL unit has polyepitopic specificity, antibodies having two or more VL and VH domains where each VHVL unit binds to a different epitope, antibodies having two or more single variable domains with each single variable domain binding to a different epitope, full length antibodies, and antibodies comprising one or more antibody fragments as well as antibodies comprising antibody fragments that have been linked covalently or non-covalently.

[0069] A multispecific antibody can be a bispecific antibody, a trispecific antibody, diabody, or similar molecule (see for instance PNAS USA 90(14), 6444-8 (1993) for a description of diabodies). The bispecific antibodies, trispecific antibodies, diabodies, and the like, provided herein may bind any suitable target in addition to a portion of BCMA or GPRC5D. The term "bispecific antibody" is to be understood as an antibody having two different antigen-binding arms defined by different antibody sequences. The term “trispecific antibody” is to be understood as an antibody having three different antigenbinding arms defined by different antibody sequences. This can be understood as different target binding but includes as well binding to different epitopes in one target.

[0070] The term “humanized antibody” refers to an antibody in which at least one CDR is derived from non-human species and at least one framework is derived from human immunoglobulin sequences. Humanized antibody can include substitutions in the frameworks so that the frameworks can not be exact copies of expressed human immunoglobulin or human immunoglobulin germline gene sequences.224897-1598-5221.1

[0071] A “reference sample” is a sample that may be compared against another sample, such as a test sample, to allow for characterization of the compared sample. The reference sample will have some characterized property that serves as the basis for comparison with the test sample. For instance, a reference sample may be used as a benchmark for GPRC5D or BCMA levels that are indicative of a subject having cancer. The reference sample does not necessarily have to be analyzed in parallel with the test sample, thus in some instances the reference sample may be a numerical value or range previously determined to characterize a given condition, such as GPRC5D or BCMA levels that are indicative of cancer in a subject. The term also includes samples used for comparative purposes that are known to be associated with a physiologic state or disease condition, such as GPRC5D- or BCMA-expressing cancer, but that have an unknown amount of GPRC5D or BCMA.

[0072] “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 can also metastasize to distant parts of the body through the lymphatic system or bloodstream. A “cancer” or “cancer tissue” can include a tumor.

[0073] “Combination” means that two or more therapeutics are administered to a subject concurrently as single agents or sequentially as single agents in any order.

[0074] “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 weight- based 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 different234897-1598-5221.1“Flat Dose B” may be administered if the patent is less than the pre-defined threshold weight.

[0075] “Pharmaceutical composition” refers to composition that comprises an active ingredient and a pharmaceutically acceptable carrier.

[0076] “Pharmaceutically acceptable carrier” or “excipient” refers to an ingredient in a pharmaceutical composition, other than the active ingredient, which is nontoxic to a subject.

[0077] “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.

[0078] “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.

[0079] “Newly diagnosed” or “newly diagnosed multiple myeloma” refers to a clinical status in which a patient has been diagnosed with multiple myeloma for the first time and has not yet received any systemic therapy for the disease, or has received only limited initial treatment (such as corticosteroids or a single cycle of chemotherapy) not intended as full induction therapy. This term encompasses patients at the time of diagnosis prior to initiation of a standard treatment regimen and may include those who are transplant- eligible or transplant-ineligible.

[0080] The term “progression,” as used in the context of progression of GPRC5D and / or BCMA -expressing cancer, includes the change of a cancer from a less severe to a more severe state. This may include an increase in the number or severity of tumors, the degree of metastasis, the speed with which the cancer is growing or spreading, and the like. For example, “the progression of colon cancer” includes the progression of such a cancer from a less severe to a more severe state, such as the progression from stage I to stage II, from stage II to stage III, etc.

[0081] The term “regression,” as used in the context of regression of GPRC5D and / or BCMA -expressing cancer, includes the change of a cancer from a more severe to a less severe state. This could include a decrease in the number or severity of tumors, the degree 244897-1598-5221.1of metastasis, the speed with which the cancer is growing or spreading, and the like. For example, “the regression of colon cancer” includes the regression of such a cancer from a more severe to a less severe state, such as the progression from stage III to stage II, from stage II to stage I, etc.

[0082] The term “stable” as used in the context of stable GPRC5D and / or BCMA- expressing cancer, is intended to describe a disease condition that is not, or has not, changed significantly enough over a clinically relevant period of time to be considered a progressing cancer or a regressing cancer.

[0083] The term “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. To prevent or lessen certain toxicities, such as cytokine release syndrome (CRS), a “priming” dose strategy may include one or more lower step-up dose(s) followed by higher treatment doses.

[0084] The term “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, biweekly, monthly). A treatment dose may be preceded by one or more step-up doses.

[0085] As used herein, the term “outpatient” is a patient who attends a hospital or clinic for treatment without staying at the hospital or clinic overnight, and the patient is administered the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof described herein by a health care professional.

[0086] The term "high-risk cytogenetic abnormalities" described herein refers to genetic alterations in multiple myeloma cells that are associated with poor prognosis, increased disease aggressiveness, or resistance to standard therapies, including but not limited to deletions, translocations, or amplifications such as del(17p), t(4; 14), t(14; 16), or lq21 gain / lq21 amplification, as identified through methods such as fluorescence in situ hybridization (FISH), next-generation sequencing (NGS), or equivalent cytogenetic analysis techniques.254897-1598-5221.1

[0087] The embodiments described herein are not limited to particular methods, reagents, compounds, compositions or biological systems, which can, of course, vary.BCMA x GPRC5D x CD3 trispecific antibodies

[0088] Any suitable BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof known to those skilled in the art in view of the present disclosure can be used in the disclosed methods.

[0089] The methods provided herein comprise administering trispecific antibodies that bind to BCMA, GPRC5D, and CD3 (“BCMA x GPRC5D x CD3 trispecific antibodies”), or trispecific binding fragments thereof. Such antibodies or antibody fragments may allow for more specific targeting to particular subsets of cells as compared to antibodies targeting only one or two of these targets.

[0090] In some embodiments, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof comprises any one of the BCMA binding domains described in WO2022 / 175255, the entire content of which is incorporated herein by reference. In some embodiments, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof comprises any one of the GPRC5D binding domains described in WO2022 / 175255. In some embodiments, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof comprises any one of the CD3 binding domains described in WO2022 / 175255. In some embodiments, the BCMA x GPRC5D x CD3 trispecific antibody comprises any one of the BCMA x GPRC5D x CD3 trispecific antibodies described in WO2022 / 175255.

[0091] The BCMA x GPRC5D x CD3 trispecific antibodies or binding fragments thereof can be provided by making a molecule which comprises a first antigen-binding arm binding to CD3, a second antigen-binding arm binding to GPRC5D and a third antigenbinding arm binding to the BCMA.

[0092] Accordingly, the methods comprise administering trispecific molecules comprising three different antigen-binding arms which bind BCMA, GPRC5D, and CD3, respectively.264897-1598-5221.1

[0093] In some embodiments, the BCMA x GPRC5D x CD3 -trispecific antibody or trispecific binding fragment thereof comprises(a) a first antigen-binding arm comprising a first heavy chain variable domain (VH1) and a first light chain variable domain (VL1);(b) a second antigen-binding arm comprising a second heavy chain variable domain (VH2) and a second light chain variable domain (VL2); and(c) a third antigen-binding arm comprising a third heavy chain variable domain (VH3) and a third light chain variable domain (VL3), wherein the first antigen-binding arm binds to an epitope on CD3, the second antigen-binding arm binds to an epitope on GPRC5D, and the third antigen-binding arm binds to an epitope on BCMA.

[0094] In some embodiments, the first antigen-binding arm that binds CD3 comprises a HCDR 1, a HCDR2 and a HCDR3 of the VH1 of SEQ ID NO: 8. In some embodiments, the first antigen-binding arm that binds CD3 comprises a LCDR1, a LCDR2 and a LCDR3 of the VL1 of SEQ ID NO: 7. In some embodiments, the first antigen-binding arm that binds CD3 comprises a HCDR1 comprising the amino acid sequence of GDSVFNNNAAWS (SEQ ID NO: 4), a HCDR2 comprising the amino acid sequence of RTYYRSKWLYD (SEQ ID NO: 5), and a HCDR3 comprising the amino acid sequence of GYSSSFDY (SEQ ID NO: 6). In some embodiments, the first antigen-binding arm that binds CD3 comprises a LCDR1 comprising the amino acid sequence of TGTSSNIGTYKFVS (SEQ ID NO: 1), a LCDR2 comprising the amino acid sequence of EVSKRPS (SEQ ID NO: 2), and a LCDR3 comprising the amino acid sequence of VSYAGSGTLL (SEQ ID NO: 3). In some embodiments, the first antigen-binding arm that binds CD3 comprises the VH1 of SEQ ID NO: 8. In some embodiments, the first antigenbinding arm that binds CD3 comprises the VL1 of SEQ ID NO: 7.

[0095] In some embodiments, the second antigen-binding arm that binds GPRC5D comprises a HCDR1, a HCDR2 and a HCDR3 of the VH2 of SEQ ID NO: 16. In some embodiments, the second antigen-binding arm that binds GPRC5D comprises a LCDR1, a LCDR2 and a LCDR3 of the VL2 of SEQ ID NO: 15. In some embodiments, the second antigen-binding arm that binds GPRC5D comprises a HCDR1 comprising the amino acid 274897-1598-5221.1sequence of GFSLTNIRMSVS (SEQ ID NO: 12), HCDR2 comprising the amino acid sequence of HIFSNDEKS (SEQ ID NO: 13), and a HCDR3 comprising the amino acid sequence of MRLPYGMDV (SEQ ID NO: 14). In some embodiments, the second antigenbinding arm that binds GPRC5D comprises a LCDR1 comprising the amino acid sequence of RSSQSLVHSDGNTYLS (SEQ ID NO: 9), a LCDR2 comprising the ammo acid sequence of KISNRFF (SEQ ID NO: 10), and a LCDR3 comprising the amino acid sequence of MQATQFPHT (SEQ ID NO: 11). In some embodiments, the second antigenbinding arm that binds GPRC5D comprises the VH1 of SEQ ID NO: 16. In some embodiments, the second antigen-binding arm that binds GPRC5D comprises the VL1 of SEQ ID NO: 15.

[0096] In some embodiments, the third antigen-binding arm that binds BCMA comprises a HCDR1, a HCDR2 and a HCDR3 of the VH3 of SEQ ID NO: 24. In some embodiments, the third antigen-binding arm that binds BCMA comprises a LCDR1, a LCDR2 and a LCDR3 of the VL3 of SEQ ID NO: 23. In some embodiments, the third antigen-binding arm that binds BCMA comprises a HCDR1 comprising the amino acid sequence of GFTFSSYAMS (SEQ ID NO: 20), a HCDR2 comprising the amino acid sequence of AISGSGGSTY (SEQ ID NO: 21), and a HCDR3 comprising the amino acid sequence of DEGYSSGHYYGMDV (SEQ ID NO: 22); and a LCDR1 comprising the ammo acid sequence of RASQSISSSFLT (SEQ ID NO: 17). In some embodiments, the third antigenbinding arm that binds BCMA comprises a LCDR2 comprising the amino acid sequence of GASSRAT (SEQ ID NO: 18), and a LCDR3 comprising the amino acid sequence of QHYGSSPMYT (SEQ ID NO: 19). In some embodiments, the third antigen-binding arm that binds BCMA comprises the VH1 of SEQ ID NO: 24. In some embodiments, the third antigen-binding arm that binds BCMA comprises the VL1 of SEQ ID NO: 23.

[0097] In some embodiments, the VH1 and VL1 of the antigen-binding arm that binds to CD3 epitope are present in a diabody, a Fab, Fab’, a F(ab’)2, a Fv, a scFv, a Fd, a disulfide stabilized Fv fragment (dsFv), or a disulfide stabilized diabody (ds diabody).4897-1598-5221.1

[0098] In some embodiments, the VH2 and VL2 of the antigen-binding arm that binds to GPRC5D epitope are present in a diabody, a Fab, Fab’, a F(ab’)2, a Fv, a scFv, a Fd, a disulfide stabilized Fv fragment (dsFv), or a disulfide stabilized diabody (ds diabody).

[0099] In some embodiments, the VH3 and VL3 of the antigen-binding arm that binds to BCMA epitope are present in a diabody, a Fab, Fab’, a F(ab’)2, a Fv, a scFv, a Fd, a disulfide stabilized Fv fragment (dsFv), or a disulfide stabilized diabody (ds diabody).

[0100] In one embodiment, the CD3-binding arm comprises an antigen-binding fragment (Fab), the BCMA-binding arm comprises a single-chain variable fragment (scFv), and the GPRC5D-binding arm comprises a single-chain variable fragment (scFv).

[0101] In some embodiments, the CD3-binding arm of the trispecific antibody comprises the HC1 and the LC. The HC1 may comprise constant heavy chain regions (CHI, CH2, and CH3) and the VH1. The LC may comprise the VL1. The VH1 and VL1 combine to form the CD3 antigen binding domain.

[0102] In some embodiments, the BCMA-binding arm of the trispecific antibody comprises the HC2. The HC2 may comprise constant heavy chain regions (CH2 and CH3), and a single-chain variable fragment (scFv) attached at the N-terminus of the CH2 region, wherein the scFv comprises the BCMA antigen binding domain.

[0103] In some embodiments, the trispecific antibody further comprises GPRC5D antigenbinding arm attached to the C-terminus of the CH3 region of the CD3 -binding arm to form a CD3 / GPRC5D binding arm. In some embodiments, the BCMA antigen-binding arm comprises a second single-chain variable fragment (scFv). In some embodiments, the CD3 / GPRC5D arm may have the structure: Fab containing the CD3 binding domain, CH2 and CH3 regions, scFv containing the GPRC5D binding domain.

[0104] In some embodiments, the trispecific antibodies include antibodies having a full length antibody structure. "Full length antibody" as used herein refers to an antibody having two full length antibody heavy chains and two full length antibody light chains. A full length antibody heavy chain (HC) includes heavy chain variable and constant domains VH, CHI, CH2, and CH3. A full length antibody light chain (LC) includes light chain variable and constant domains VL and CL. The full length antibody may be lacking the C- 294897-1598-5221.1terminal lysine (K) in either one or both heavy chains. The term "Fab-arm" or "half molecule" refers to one heavy chain-light chain pair that binds an antigen.BCMA-binding arm

[0105] The BCMA x GPRC5D x CD3 trispecific antibody described herein comprises an antigen-binding arm specific for BCMA. In some embodiments, the BCMA-binding arm binds human BCMA. In some embodiments, the BCMA-binding arm binds to residues 17- 26 (LLHACIPCQL (SEQ ID NO: 162)) of BCMA BCMW37 chain.

[0106] Characteristics of some BCMA-specific antibodies or antigen-binding fragments may be found in e.g., WO2022 / 175255, the content of which is herein incorporated by reference in its entirety.

[0107] In one embodiment, the BCMA-binding arm comprises heavy chain CDR1, CDR2, and CDR3 and light chain CDR1, CDR2, and CDR3 of clone BCMB519. In one embodiment, the BCMA-binding arm comprises heavy chain variable domain and light chain variable domain of clone BCMB519.

[0108] In some embodiments, the BCMA-binding arm comprises a heavy chain CDR1 comprising SEQ ID NO: 20, a heavy chain CDR2 comprising SEQ ID NO: 21, and a heavy chain CDR3 comprising SEQ ID NO: 22. In some embodiments, the BCMA- binding arm comprises a heavy chain CDR1 comprising SEQ ID NO: 20, a heavy chain CDR2 comprising SEQ ID NO: 21, a heavy chain CDR3 comprising SEQ ID NO: 22, a light chain CDR1 comprising SEQ ID NO: 17, a light chain CDR2 comprising SEQ ID NO: 18, and a light chain CDR3 comprising SEQ ID NO: 19. The BCMA-binding arm may comprise human framework sequences. In some embodiments, the BCMA-binding arm comprises a heavy chain variable domain substantially the same as, or identical to, SEQ ID NO: 24. In some embodiments, the BCMA-binding arm comprises a heavy chain variable domain substantially the same as, or identical to, SEQ ID NO: 24 and a light chain variable domain substantially the same as, or identical to, SEQ ID NO: 23.

[0109] In some embodiments, the BCMA-binding arm comprises humanized antigenbinding fragments. Humanized antigen-binding fragments may be derived from chimeric 304897-1598-5221.1immunoglobulins, immunoglobulin chains or fragments thereof (such as Fv, Fab, Fab’, F(ab’)2 or other antigen-binding subsequences of antibodies) that contain minimal sequence derived from non-human immunoglobulin. For the most part, humanized antibodies or antigen-binding fragments are human immunoglobulins (recipient antibody) or antigen-binding fragments in which residues from a complementary- determining region (CDR) of the recipient are replaced by residues from a CDR of a non-human species (donor antibody) such as mouse, rat or rabbit having the desired specificity, affinity, and capacity. In general, the humanized antibody antigen-binding fragments will comprise substantially all of at least one, and typically two, variable domains, in which all or substantially all of the CDR regions correspond to those of a non-human immunoglobulin and all or substantially all of the framework regions are those of a human immunoglobulin sequence. The humanized antibody antigen-binding fragments may include at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin.GPRC5D-binding arm

[0110] The BCMA x GPRC5D x CD3 -trispecific antibody or trispecific binding fragment thereof described herein comprises an antigen-binding arm specific for GPRC5D.

[0111] In some embodiments, the GPRC5D-binding arm binds human GPRC5D. In some embodiments, the GPRC5D-binding arm binds to one or more residues of a polypeptide having the amino acid sequence of SEQ ID NO: 116.

[0112] Characteristics of some GPRC5D-specific antibodies or antigen-binding fragments may be found in e.g., United States Published Application US2020 / 0231686, the content of which is herein incorporated by reference in its entirety.

[0113] In one embodiment, the GPRC5D-binding arm comprises heavy chain CDR1, CDR2, and CDR3 and light chain CDR1, CDR2, and CDR3 of clone GC5B680. In one embodiment, the GPRC5D-binding arm comprises heavy chain variable domain and light chain variable domain of clone GC5B680.314897-1598-5221.1

[0114] In some embodiments, the GPRC5D-binding arm comprises a heavy chain CDR1 comprising SEQ ID NO: 12, a heavy chain CDR2 comprising SEQ ID NO: 13, and a heavy chain CDR3 comprising SEQ ID NO: 14. In some embodiments, the GPRC5D- binding arm comprises a heavy chain CDR1 comprising SEQ ID NO: 12, a heavy chain CDR2 comprising SEQ ID NO: 13, a heavy chain CDR3 comprising SEQ ID NO: 14, a light chain CDR1 comprising SEQ ID NO: 9, a light chain CDR2 comprising SEQ ID NO: 10, and a light chain CDR3 comprising SEQ ID NO: 11. The GPRC5D-binding arm may comprise human framework sequences. In some embodiments, the GPRC5D-binding arm comprises a heavy chain variable domain substantially the same as, or identical to, SEQ ID NO: 16. In some embodiments, the GPRC5D-binding arm comprises a heavy chain variable domain substantially the same as, or identical to, SEQ ID NO: 16 and a light chain variable domain substantially the same as, or identical to, SEQ ID NO: 15.CD3 -binding arm

[0115] The BCMA x GPRC5D x CD3 -trispecific antibody or trispecific binding fragment thereof described herein comprises an antigen-binding arm that binds CD3. In some embodiments, the CD3-binding arm binds human CD3. In some embodiments, the CD3- specific arm of the BCMA x GPRC5D x CD3 trispecific antibody is derived from a CD3- specific antibody that binds and activates human primary T cells and / or cynomolgus monkey primary T cells. In some embodiments, the trispecific antibodies or trispecific antigen-binding fragments described herein bind to CD3s. In some embodiments, the CD3-binding arm binds to an epitope at the N-terminus of CD3s. In some embodiments, the CD3-binding arm binds to residues 22-35 (QDGNEEMGGITQTP (SEQ ID NO: 161)) of the CD3s chain.

[0116] Human CD3s is described under UniProt P07766 (CD3E HUMAN). An anti CD3s antibody described in the state of the art is SP34 (Yang SJ, The Journal of Immunology (1986) 137; 1097-1100). SP34 reacts with both primate and human CD3. SP34 is available from Pharmingen. A further anti CD3 antibody described in the state of the art is UCHT-1 (see W02000041474). A further anti-CD3 antibody described in the 324897-1598-5221.1state of the art is BC-3 (Fred Hutchinson Cancer Research Institute; used in Phase I / II trials of GvHD, Anasetti et al., Transplantation 54: 844 (1992)). SP34 differs from UCHT-1 and BC-3 in that SP-34 recognizes an epitope present on solely the £ chain ofCD3 (see Salmeron et al., (1991) J. Immunol. 147: 3047) whereas UCHT-1 and BC-3 recognize an epitope contributed by both the £ and y chains. The sequence of an antibody with the same sequence as of antibody SP34 is mentioned inW02008119565, W02008119566, W02008119567, W02010037836, W02010037837 and W02010037838. A sequence which is 96% identical to VH of antibody SP34 is mentioned in US8236308 (W02007042261).

[0117] Characteristics of some CD3 -specific antibodies or antigen-binding fragments may be found in e.g., WO2019 / 224717, United States Patents No. 11,603,405, United States Published Application US2023 / 322924, the content of each of which is herein incorporated by reference in its entirety.

[0118] In some embodiments, the CD3-binding arm (or “CD3-specific arm”) of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is derived from the monoclonal antibody CD3B376. In some embodiments, the CD3-binding arm comprises heavy chain CDR1 , CDR2, and CDR3 and light chain CDR1 , CDR2, and CDR3 of clone CD3B376.

[0119] In some embodiments, the CD3-binding arm comprises a heavy chain CDR1 comprising SEQ ID NO: 4, a heavy chain CDR2 comprising SEQ ID NO: 5, and a heavy chain CDR3 comprising SEQ ID NO: 6. In some embodiments, the CD3-binding arm comprises a heavy chain CDR1 comprising SEQ ID NO: 4, a heavy chain CDR2 comprising SEQ ID NO: 5, a heavy chain CDR3 comprising SEQ ID NO: 6, a light chain CDR1 comprising SEQ ID NO: 1, a light chain CDR2 comprising SEQ ID NO: 2, and a light chain CDR3 comprising SEQ ID NO: 3. The CD3-binding arm may comprise human framework sequences. In some embodiments, the CD3 -binding arm comprises a heavy chain variable domain substantially the same as, or identical to, SEQ ID NO: 8. In some embodiments, the CD3 -binding arm comprises a heavy chain variable domain substantially334897-1598-5221.1the same as, or identical to, SEQ ID NO: 8 and a light chain variable domain substantially the same as, or identical to, SEQ ID NO: 7.

[0120] In some embodiments, the CD3-binding arm is IgG, or a derivative thereof. In some embodiments, the CD3 -specific antibody or antigen-binding fragment from which the CD3-specific arm of the trispecific antibody is derived is IgGl, or a derivative thereof. In some embodiments, for example, the Fc region of the CD3 -specific IgGl antibody from which the CD3-binding arm is derived comprises L234A, L235A, and D265S substitutions in its Fc region.

[0121] "Homodimerization" as used herein refers to an interaction of two heavy chains having identical CH3 amino acid sequences. "Homodimer" as used herein refers to an antibody having two heavy chains with identical CH3 amino acid sequences.

[0122] "Heterodimerization" as used herein refers to an interaction of two heavy chains having non-identical CH3 amino acid sequences. "Heterodimer" as used herein refers to an antibody having two heavy chains with non-identical CH3 amino acid sequences.

[0123] The "knob-in-hole" strategy (see, e.g., PCT Inti. Publ. No. WO 2006 / 028936) may be used to generate full length trispecific 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 binding a first antigen and an amino acid with a large side chain (knob) is introduced into a heavy chain of an antibody 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.

[0124] In some embodiments of the trispecific antibody or trispecific binding fragment described herein, one of the Fc domains comprise mutations T366S, L368A and Y407V 344897-1598-5221.1and the other Fc domain comprises mutation T366W. In some embodiments, the Fc domain of the first heavy chain portion (HC1) of the first antigen binding arm (e.g., CD3 binding arm) comprises mutations T366S, L368A and Y407V, and the Fc domain of the second heavy chain portion (HC2) of the third antigen-binding arm (e.g., the BCMA binding arm) comprises mutation T366W.

[0125] In some embodiments, the trispecific antibodies or antigen-binding fragments are IgG, or derivatives thereof.

[0126] In some embodiments wherein the antibody is of IgGl isotype, the antibody comprises an IgGl Fc region (SEQ ID NO: 158).SEQ ID NO: 158ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAV LQS SGLYSLS S V VT VPS S SLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPC PAPELLGGPSVFLFPPI<PI<DTLMISRTPEVTCVVVDVSHEDPEVI<FNWYVDGVEV HNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKA KGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTT PPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0127] In some embodiments wherein the antibody is of IgGl isotype, the antibody comprises L234A, L235A, and D265S substitutions (underlined) in its Fc region (SEQ ID NO: 159).SEQ ID NO: 159ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAV LQS SGLYSLS S V VT VPS S SLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPC PAPEAAGGPSVFLFPPI<PI<DTLMISRTPEVTCVVVSVSHEDPEVI<FNWYVDGVEV HNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKA KGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTT PPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0128] In some embodiments wherein the antibody has an IgGl isotype, the antibody contains L234A, L235A, D265S and / or K409R substitution(s) in its Fc region. The antibodies described herein may include these modifications.354897-1598-5221.1

[0129] In some embodiments, the Fc domains of a trispecific antibody described herein each comprise one or more mutations selected from L234A, L235A, and D265S. In some embodiments, the Fc domains of HC1 and HC2 each comprise mutations L234A, L235A, and D265S.

[0130] In some embodiments, the Fc domain of one of the heavy chain portions of a trispecific antibody described herein further comprise one or more mutations which reduce Fc binding to protein A. In some embodiments, the Fc domain of the HC1 comprises mutations H435R and / or Y436F, preferably H435R and Y436F.

[0131] In some embodiments of a trispecific antibody described herein, the HC1 comprises, from the N- to C-terminus, the VH1 of the first antigen-binding arm, a CHI domain, the Fc domain, a linker, and the second antigen-binding arm.

[0132] In various embodiments, the scFvs used in trispecific antibodies or trispecific binding fragments described herein comprise, from the N- to C-terminus, a VH, a linker and a VL (VH-L-VL) or the VL, the linker and the VH (VL-L-VH). In some embodiments, the scFv comprises, from the N- to C-terminus, the VL, the linker and the VH (VL-L-VH).

[0133] In some embodiments, the linker comprises the amino acid sequence of SEQ ID NO: 25.

[0134] In some embodiments, the linker comprises the amino acid sequence of SEQ ID NO: 163.

[0135] In one embodiment, a CD3 / GPRC5D coupled HC1 of a BCMA x GPRC5D x CD3 trispecific antibody comprises an amino acid sequence substantially the same as, or identical to, SEQ ID NO: 29.

[0136] In one embodiment, the LC of a BCMA x GPRC5D x CD3 trispecific antibody comprises an amino acid sequence substantially the same as, or identical to, SEQ ID NO: 30.

[0137] In one embodiment, the BCMA binding arm (HC2) comprises an amino acid sequence substantially the same as, or identical to, SEQ ID NO: 31.

[0138] In one embodiment, provided herein is an isolated trispecific antibody, or a trispecific binding fragment thereof, comprising:364897-1598-5221.1a) a CD3 binding arm comprising a heavy chain (HC1) and a light chain (LC), wherein the HC1 further comprises the GPRC5D binding arm; and b) a BCMA binding arm, wherein HC1 comprises an amino acid sequence substantially the same as, or identical to, SEQ ID NO: 29, LC comprises an amino acid sequence substantially the same as, or identical to, SEQ ID NO: 30, and the BCMA binding arm comprises an amino acid sequence substantially the same as, or identical to, SEQ ID NO: 31.

[0139] In one embodiment, provided herein is an isolated trispecific antibody, or a trispecific binding fragment thereof, comprising: a) a CD3 binding arm comprising a heavy chain (HC1) and a light chain (LC), wherein the HC1 further comprises the GPRC5D binding arm; and b) a BCMA binding arm, wherein HC1 comprises the amino acid sequence of SEQ ID NO: 29, LC comprises the amino acid sequence of SEQ ID NO: 30, and the BCMA binding arm comprises the amino acid sequence of SEQ ID NO: 31.

[0140] In one embodiment, the BCMA x GPRC5D x CD3 trispecific antibody is BGCB491.Pomalidomide

[0141] Pomalidomide, sold under the brand names Pomalyst® and Imnovid® is an anticancer medication used for the treatment of multiple myeloma and AIDS-related Kaposi sarcoma.

[0142] Pomalidomide was approved for medical use in the United States in February 2013 and in the European Union in August 2013.Dexamethasone

[0143] Dexamethasone is a synthetic adrenocortical steroid with potent glucocorticoid activity and minimal mineralocorticoid activity. It exerts broad anti-inflammatory and374897-1598-5221.1immunosuppressive effects by binding to cytosolic glucocorticoid receptors and modulating the transcription of corticosteroid-responsive genes involved in immune cell proliferation, cytokine production, and inflammatory mediator release.

[0144] Clinically, dexamethasone is used to treat a wide range of inflammatory, allergic, and autoimmune disorders, including rheumatoid arthritis, systemic lupus erythematosus, asthma, and bronchospasm. It also exerts cytotoxic and apoptotic effects on certain hematologic malignancies, thereby serving as a chemotherapeutic agent in various oncologic regimens.

[0145] In the context of hematologic cancers such as multiple myeloma, dexamethasone is routinely administered as a component of multi-drug regimens to potentiate the anti-tumor effects of immunomodulatory agents (e.g., lenalidomide or pomalidomide), proteasome inhibitors (e.g., bortezomib or carfilzomib), and monoclonal or multispecific antibodies (e.g., BCMA- or GPRC5D-targeted antibodies). The glucocorticoid reduces tumor- associated inflammation, mitigates cytokine-mediated adverse events, and induces apoptosis in plasma cells, thereby contributing directly to anti-myeloma activity and improving tolerability of combination therapies.

[0146] Accordingly, dexamethasone may be administered alone or in combination with one or more chemotherapeutic, immunomodulatory, or antibody-based agents described herein, including but not limited to trispecific antibodies targeting BCMA x GPRC5D x CD3. When used in combination therapy, dexamethasone may be administered prior to, concurrently with, or subsequent to administration of the antibody or antibody fragment, at dosages effective to enhance therapeutic efficacy and reduce immune-related toxicity.Treatment of multiple myeloma

[0147] The trispecific antibodies discussed above, for example the BCMA x GPRC5D x CD3 trispecific antibodies discussed above, are for use in treating multiple myeloma (MM).

[0148] Similarly, pomalidomide discussed above is for use in treating multiple myeloma (MM).384897-1598-5221.1

[0149] Disclosed herein is a method of treating multiple myeloma in a subject in need thereof, comprising administering a therapeutically effective amount of aBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof and pomalidomide, to the subject to treat the multiple myeloma, wherein theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered at a treatment dose of at least about 20 mg.

[0150] In one aspect, the disclosed herein is a method of treating multiple myeloma in a subject in need thereof, comprising administering a therapeutically effective amount of a BCMA x GPRC5D x CD3 trispecific antibody or a trispecific binding fragment thereof and pomalidomide, to the subject to treat the multiple myeloma, wherein theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered at a treatment dose of at least about 20mg.

[0151] In another aspect, disclosed herein is a method of treating multiple myeloma in a subject in need thereof, comprising administering a therapeutically effective of aBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof and pomalidomide, to the subject to treat the multiple myeloma, wherein theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered at a treatment dose of about 20 mg and wherein the treatment dose is administered once every four weeks.

[0152] In another aspect, disclosed herein is a method of treating multiple myeloma in a subject in need thereof, comprising administering a therapeutically effective amount of a BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof and pomalidomide, to the subject to treat the multiple myeloma, wherein theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered at a treatment dose of about 50 mg and wherein the treatment dose is administered once every four weeks.

[0153] In another aspect, disclosed herein is a method of treating multiple myeloma in a subject in need thereof, comprising administering a therapeutically effective of aBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof and 394897-1598-5221.1pomalidomide, to the subject to treat the multiple myeloma, wherein theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered at a treatment dose of about 100 mg and wherein the treatment dose is administered once every four weeks.

[0154] In another aspect, disclosed herein is a method of treating multiple myeloma in a subject in need thereof, comprising administering a therapeutically effective amount of a BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof and pomalidomide, to the subject to treat the multiple myeloma, wherein theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered at a treatment dose of about 200 mg and wherein the treatment dose is administered once every four weeks.

[0155] In another aspect, disclosed herein is a method of treating multiple myeloma in a subject in need thereof, comprising administering a therapeutically effective amount of a BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof and pomalidomide, to the subject to treat the multiple myeloma, wherein theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered at a treatment dose of about 300 mg and wherein the treatment dose is administered once every four weeks.Administration

[0156] In particular, the inventors have developed new regimens for administering a BCMA x GPRC5D x CD3 trispecific antibodies or trispecific fragments thereof and pomalidomide to treat multiple myeloma in a subject.Dosing

[0157] According to the disclosed methods, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered to a subject at a treatment dose of at least about 20 mg.404897-1598-5221.1

[0158] In some embodiments, the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is at least about 20 mg, at least about 50 mg, at least about 100 mg, at least about 200 mg or at least about 300 mg.

[0159] In some embodiments, the treatment dose is at least about 20 mg. In a certain embodiment, the treatment dose is at least about 50 mg. In a certain embodiment, the treatment dose is at least about 100 mg. In a certain embodiment, the treatment dose is at least about 200 mg. In a certain embodiment, the treatment dose is at least about 300 mg.

[0160] In some embodiments, the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is about 20 mg to about 300 mg, about 20 mg to about 200 mg, about 20 mg to about 100 mg, about 20 mg to about 50 mg, about 50 mg to about 300 mg, about 50 mg to about 100 mg, about 100 mg to about 300 mg,

[0161] The treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof may be a flat dose, as defined herein. Flat dosing may provide advantages compared to dosing according to body weight, such as reduced preparation time, and simpler administration and manufacturing. In some embodiments, the treatment dose is a flat dose.

[0162] For example, in some embodiments, the treatment dose is a flat dose of at least about 20 mg, at least about 50 mg, at least about 100 mg, at least about 200 mg, or at least about 300 mg.

[0163] In some embodiments, the treatment dose is a flat dose within the range of about 20 mg to about 300 mg, about 20 mg to about 200 mg, about 20 mg to about 100 mg, about 20 mg to about 50 mg, about 50 mg to about 300 mg, about 50 mg to about 100 mg, about 100 mg to about 300 mg.

[0164] In certain embodiments, the treatment dose is a flat dose of about 204 mg, about 50 mg, about 100 mg, about 200 mg, about 300 mg. In one embodiment, the treatment dose is a flat dose of about 20 mg. In one embodiment, the treatment dose is a flat dose of about 50 mg. In one embodiment, the treatment dose is a flat dose of about 100 mg. In one414897-1598-5221.1embodiment, the treatment dose is a flat dose of about 200 mg. In one embodiment, the treatment dose is a flat dose of about 300 mg.

[0165] The treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof may be a weight-based dose. Therefore, in some embodiments, the treatment dose is a weight-based dose. 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).

[0166] The treatment dose of pomalidomide may be a flat dose, as defined herein. . In some embodiments pomalidomide is administered at a daily dose of 2 mg. In some embodiments pomalidomide is administered at a daily dose of 4 mg. Flat dosing may provide advantages compared to dosing according to body weight, such as reduced preparation time, and simpler administration and manufacturing. In some embodiments, the treatment dose is a flat dose.Administration route

[0167] In some embodiments, the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered intravenously, intramuscularly, intraperitoneally, and / or subcutaneously to the subject. In some embodiments, the treatment dose is administered intravenously or subcutaneously to the subject. In some embodiments, the treatment dose is administered intravenously to the subject. In certain embodiments, the treatment dose is administered subcutaneously to the subject.

[0168] The administration may be performed by continuous infusion over a period of from 2 to 24 hr, such as from 2 to 12 hr. In one embodiment, the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof may be administered by slow continuous infusion over a long period, such as more than 24 hours, in order to reduce toxic side effects. In some embodiments, the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered intravenously as a bolus or by continuous infusion over a period of time. In a 424897-1598-5221.1certain embodiment, the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is injected subcutaneously, to exert local as well as systemic therapeutic effects.

[0169] In some embodiments, pomalidomide is administered orally.Administration frequency

[0170] In some embodiments, the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered once every four weeks.

[0171] In some embodiments the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered on Day 1 of at least one treatment cycle of every four weeks or about 28 days.

[0172] The administration of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof once every 4 weeks can therefore also be understood to start a treatment cycle, which can also here be referred to as a“BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle”.

[0173] In some embodiments the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered on Day 1 of each BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle.

[0174] In some embodiments the duration of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle is about 28 days. In some embodiments the duration of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle is 28 days.

[0175] In some embodiments the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment dose is administered at least for 1, 2, 3, 4, 5,434897-1598-5221.16, 7, 8, 9, 10 or more about 28 day BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles.

[0176] In some embodiments, the pomalidomide dose is administered during at least one BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle.

[0177] In some embodiments, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment is administered at least for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more about 28 day cycles BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles. For the purpose of sequencing of the treatment events the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles which can also be referred to as Cycle 1, Cycle 2, Cycle 3, Cycle 4 to signal their temporal occurence. etc.

[0178] In some embodiments, there is no pomalidomide administered during a BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle. As shown in FIG. 11, during Cycle 1, only the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered.

[0179] In some embodiments during the first BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle, or here also called Cycle 1, no pomalidomide is administered.

[0180] In some embodiments, pomalidomide is administered during the second BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle, or here also called Cycle 2.

[0181] In some embodiments the pomalidomide dose is administered during at least one BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle, beginning on Day 1 of Cycle 2.

[0182] In some embodiments, the pomalidomide is administered at a daily dose of about 2mg.

[0183] In some embodiments, the pomalidomide dose is administered during at least one BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof 444897-1598-5221.1treatment cycle, wherein the administration begins on Day 1 of Cycle 2 . In certain such embodiments, dexamethasone is administered in conjunction with pomalidomide. In certain such embodiments, dexamethasone is administered in conjunction with pomalidomide on designated days of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles. In certain such embodiments, dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2. In certain such embodiments, dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 in Cycles 2 to 4. In certain such embodiments, dexamethasone is administered at a dose of about 20 mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the administration begins at Day 1 of Cycle 2. In certain such embodiments, dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the dexamethasone is administered at a dose of about 20 mg on Days 1, 8, 15, and 22 in Cycles 2 to 4. In certain such embodiments the dexamethasone is administered orally. In certain such embodiments the dexamethasone is administered intravenously.

[0184] In some embodiments, the pomalidomide dose is administered for at least 21 days within the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle, wherein the administration begins on Day 1 of the cycle.

[0185] In some embodiments, the pomalidomide dose is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of Cycle 3 at a dose of about 4 mgdaily for at least 21 days. . In certain such embodiments, dexamethasone is administered in conjunction with pomalidomide. In certain such 454897-1598-5221.1embodiments, dexamethasone is administered in conjunction with pomalidomide on designated days of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles. In certain such embodiments, dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2. In certain such embodiments, dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 in Cycles 2 to 4. In certain such embodiments, dexamethasone is administered at a dose of about 20 mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the administration begins at Day 1 of Cycle 2. In certain such embodiments, dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the dexamethasone is administered at a dose of about 20 mg on Days 1, 8, 15, and 22 in Cycles 2 to 4. In certain such embodiments the dexamethasone is administered orally. In certain such embodiments the dexamethasone is administered intravenously.

[0186] In some embodiments, the pomalidomide dose is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of any Cycle >2 at a dose of about 4 mg daily for at least 21 days. . In certain such embodiments, dexamethasone is administered in conjunction with pomalidomide. In certain such embodiments, dexamethasone is administered in conjunction with pomalidomide on designated days of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles. In certain such embodiments, dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof 464897-1598-5221.1treatment cycles, wherein the administration begins at Day 1 of Cycle 2. In certain such embodiments, dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 in Cycles 2 to 4. In certain such embodiments, dexamethasone is administered at a dose of about 20 mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the administration begins at Day 1 of Cycle 2. In certain such embodiments, dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the dexamethasone is administered at a dose of about 20 mg on Days 1, 8, 15, and 22 in Cycles 2 to 4. In certain such embodiments the dexamethasone is administered orally. In certain such embodiments the dexamethasone is administered intravenously.

[0187] In some embodiments, the pomalidomide dose is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of any Cycle >2 at a dose of about 2 mg daily, for at least 21 days. . In certain such embodiments, dexamethasone is administered in conjunction with pomalidomide. In certain such embodiments, dexamethasone is administered in conjunction with pomalidomide on designated days of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles. In certain such embodiments, dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2. In certain such embodiments, dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 in Cycles 2 to 4. In certain such embodiments, dexamethasone is administered at a dose of about 20 474897-1598-5221.1mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the administration begins at Day 1 of Cycle 2. In certain such embodiments, dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the dexamethasone is administered at a dose of about 20 mg on Days 1, 8, 15, and 22 in Cycles 2 to 4. In certain such embodiments the dexamethasone is administered orally. In certain such embodiments the dexamethasone is administered intravenously.Step-up dosing

[0188] In some embodiments, at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered prior to the administration of the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof. In some embodiments, one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered.

[0189] Step-up doses are lower than the treatment dose. To prevent or lessen certain toxicities, such as cytokine release syndrome (CRS), a “priming” dose strategy may include one or more lower step-up dose(s) followed by higher treatment doses.

[0190] In some embodiments, the step-up dose(s) of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered intravenously, intramuscularly, intraperitoneally, and / or subcutaneously to the subject. In some embodiments, the step-up dose(s) is administered intravenously or subcutaneously to the subject. In some embodiments, the step-up dose(s) is administered intravenously to the subject. In a certain embodiment, the step-up dose(s) is administered subcutaneously to the subject. In some embodiments, the step-up dose(s) is administered using a different administration route than the treatment dose. In a certain embodiment, the step-up dose(s) is administered using the same administration route as the treatment dose.484897-1598-5221.1

[0191] In a certain embodiment, at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose of theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof. In some embodiments, the first step-up dose is about 2.5 mg to about 5 mg.

[0192] In certain embodiments, the first step-up dose is about 2.5 mg,

[0193] In another embodiment, the first step-up dose is about 5 mg.

[0194] In some embodiments, the first step-up dose is administered about 2-8 days prior to the administration of the treatment dose .In some embodiments, the first step-up dose is administered about one week prior to the administration of the treatment dose. In some embodiments, the first step-up dose is administered about 6-8 days prior to the administration of the treatment dose. In some embodiments, the first step-up dose is administered about 1-5 days prior to the administration of the treatment dose. In some embodiments, the first step-up dose is administered about 2-4 days prior to the administration of the treatment dose.

[0195] . In some embodiments, the first step-up dose is subcutaneously administered about 2-8 days prior to the subcutaneous administration of the treatment dose.In some embodiments, the first step-up dose is subcutaneously administered about one week prior to the subcutaneous administration of the treatment dose. In some embodiments, the first step-up dose is subcutaneously administered about 6-8 days prior to the subcutaneous administration of the treatment dose. In some embodiments, the first step-up dose is subcutaneously administered about 1-5 days (e.g. about 2-4 days) prior to the subcutaneous administration of the treatment dose. In a certain embodiment, the first step-up dose is subcutaneously administered about one week prior to the subcutaneous administration of the treatment dose, and wherein the first step-up dose is about 5 mg. In a certain embodiment, the first step-up dose is subcutaneously administered about 6-8 days prior to the subcutaneous administration of the treatment dose, and wherein the first step-up dose is about 5 mg. In a certain embodiment, the first step-up dose is subcutaneously administered about 2-4 days prior to the subcutaneous administration of the treatment dose, and wherein 494897-1598-5221.1the first step-up dose is about 2.5 mg. In a certain embodiment, the first step-up dose is subcutaneously administered about 2-4 days prior to the subcutaneous administration of the treatment dose, and wherein the first step-up dose is about 5 mg.

[0196] In some embodiments, the first step-up dose is a flat dose. For example, in some embodiments, the first step-up dose is a flat dose of about 2.5 mg to about 50 mg. In certain such embodiments, , the first step-up dose is a flat dose of about 2.5 mg to about 5 mg.

[0197] In some embodiments, the first step-up dose is a flat dose of no greater no greater than about 5 mg, or no greater than about 2.5 mg.

[0198] In certain embodiments, the first step-up dose is a flat dose of about 2.5 mg, or about 5 mg. In one embodiment, the first step-up dose is a flat dose of about 2.5 mg. In another embodiment, the first step-up dose is a flat dose of about 5 mg.

[0199] In some embodiments, the first step-up dose is no greater than one tenth of the treatment dose. In some embodiments, the first step-up dose is no greater than one twentieth of the treatment dose. In some embodiments, the first step-up dose is no greater than one twenty-fifth of the treatment dose. In some embodiments, the first step-up dose is no greater than one fortieth of the treatment dose. In some embodiments, the second step- up dose is no greater than one half of the treatment dose. In some embodiments, the second step-up dose is no greater than one third of the treatment dose. In some embodiments, the second step-up dose is no greater than one fifth of the treatment dose. In some embodiments, the second step-up dose is no greater than one seventh of the treatment dose. In some embodiments, the first step-up dose is no greater than one tenth of the treatment dose and the second step-up dose is no greater than one half of the treatment dose. In some embodiments, the first step-up dose is no greater than one twentieth of the treatment dose and the second step-up dose is no greater than one third of the treatment dose. In some embodiments, the first step-up dose is no greater than one twenty-fifth of the treatment dose and the second step-up dose is no greater than one fifth of the treatment dose. In some embodiments, the first step-up dose is no greater than one fortieth of the treatment dose and the second step-up dose is no greater than one seventh of the treatment dose.504897-1598-5221.1

[0200] In some embodiments, no step-up doses are administered prior to the administration of the treatment dose.Dosing regimens

[0201] As explained herein, the administration of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof once every 4 weeks can also be understood to start a treatment cycle, which can also here be referred to as a“BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle” of 4 weeks or about 28 days.

[0202] The BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment dose can be administered at least for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more about 28 day BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles.

[0203] In some embodiments the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment is administered at least for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more about 28 day cycles BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles. For the purpose of sequencing of the treatment events the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles which can also be referred to as Cycle 1, Cycle 2, Cycle 3, Cycle 4 to signal their temporal occurrence, etc.

[0204] In some embodiments, there is no pomalidomide administered during a BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle. As shown in FIG. 11, during Cycle 1, only the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered.

[0205] In some embodiments during the first BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle, or here also called Cycle 1, no pomalidomide is administered.514897-1598-5221.1

[0206] In some embodiments, pomalidomide is administered during the second BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle, or here also called Cycle 2.

[0207] In certain embodiments, the dosing and combination schedules described herein correspond to specific treatment regimens as summarized in Table 1.Table 1524897-1598-5221.120mg treatment dose [BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof]

[0209] In some embodiments, the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is about 20 mg and wherein the treatment dose is subcutaneously administered once every four weeks.

[0210] In some embodiments, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 20 mg, and wherein at least one step-up dose of theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose.

[0211] In certain such embodiments, the first step-up dose is about 5 mg and is administered about 2-4 days prior to the administration of the treatment dose.

[0212] In a certain embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 20 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose. In certain such embodiments, the first step-up dose is about 2.5 mg and is administered about 2-4 days prior to the administration of the treatment dose. In a certain embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 20 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered 534897-1598-5221.1prior to the subcutaneous administration of the treatment dose. In certain such embodiments, the first step-up dose is about 5 mg and is administered about one 2 to 8 days prior to the administration of the treatment dose. In certain such embodiments, the first step-up dose is about 5 mg and is administered about one week prior to the administration of the treatment dose. In one embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 20 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose. In certain such embodiments, the first step-up dose is about 5 mg and is administered about 6-8 days prior to the administration of the treatment dose. Often such dosing regimens comprise further step-up doses prior to administration of the treatment dose.

[0213] In one embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 20 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose, wherein the step-up dose is about 5 mg and is administered about 2-8 days prior to the administration of the treatment dose, wherein the pomalidomide dose is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of Cycle 3 at a dose of about 4 mg daily for at least 21 days. In certain such embodiments, dexamethasone is administered in conjunction with pomalidomide. In certain such embodiments, dexamethasone is administered in conjunction with pomalidomide on designated days of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles. In certain such embodiments, dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 of each544897-1598-5221.1of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2. In certain such embodiments, dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 in Cycles 2 to 4. In certain such embodiments, dexamethasone is administered at a dose of about 20 mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the administration begins at Day 1 of Cycle 2. In certain such embodiments, dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the dexamethasone is administered at a dose of about 20 mg on Days 1, 8, 15, and 22 in Cycles 2 to 4. In certain such embodiments the dexamethasone is administered orally. In certain such embodiments the dexamethasone is administered intravenously. In certain such embodiments the BCMA x GPRC5D x CD3 trispecific antibody is BGCB491. In certain such embodiments the duration of theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle is 28 days.

[0214] In one embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 20 mg, and wherein at least one step-up dose of theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose, wherein the step-up dose is about 5 mg and is administered about 2-8 days prior to the administration of the treatment dose, wherein the pomalidomide dose is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of any Cycle >2 at a dose of about 4 mg daily for at least 21 days In certain such embodiments, dexamethasone is administered in conjunction with pomalidomide. In 554897-1598-5221.1certain such embodiments, dexamethasone is administered in conjunction with pomalidomide on designated days of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles. In certain such embodiments, dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2. In certain such embodiments, dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 in Cycles 2 to 4. In certain such embodiments, dexamethasone is administered at a dose of about 20 mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the administration begins at Day 1 of Cycle 2. In certain such embodiments, dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the dexamethasone is administered at a dose of about 20 mg on Days 1, 8, 15, and 22 in Cycles 2 to 4. In certain such embodiments the dexamethasone is administered orally. In certain such embodiments the dexamethasone is administered intravenously. In certain such embodiments the BCMA x GPRC5D x CD3 trispecific antibody is BGCB491. In certain embodiments, the BCMA x GPRC5D x CD3 trispecific antibody is subcutaneously administered once every four weeks at a treatment dose of about 20 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody is subcutaneously administered prior to the subcutaneous administration of the treatment dose, wherein the step-up dose is about 5 mg and is administered about 2 to 8 days prior to the administration of the treatment dose, wherein the pomalidomide dose is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of any Cycle >2 at a dose of about 4 mg daily for at least 21 days, wherein the dexamethasone is administered during three564897-1598-5221.1BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2, wherein the dexamethasone is administered in Cycles 2 to 4, wherein the BCMA x GPRC5D x CD3 trispecific antibody is BGCB491. In certain such embodiments the duration of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle is 28 days.

[0215] In one embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 20 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose, wherein the step-up dose is about 5 mg and is administered about 2-8 days prior to the administration of the treatment dose, wherein the pomalidomide dose is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of any Cycle >2 at a dose of about 2 mg daily, for at least 21 days. In certain such embodiments, dexamethasone is administered in conjunction with pomalidomide. In certain such embodiments, dexamethasone is administered in conjunction with pomalidomide on designated days of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles. In certain such embodiments, dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2. In certain such embodiments, dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the574897-1598-5221.1dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 in Cycles 2 to 4. In certain such embodiments, dexamethasone is administered at a dose of about 20 mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the administration begins at Day 1 of Cycle 2. In certain such embodiments, dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the dexamethasone is administered at a dose of about 20 mg on Days 1, 8, 15, and 22 in Cycles 2 to 4. In certain such embodiments the dexamethasone is administered orally. In certain such embodiments the dexamethasone is administered intravenously. In certain such embodiments the BCMA x GPRC5D x CD3 trispecific antibody is BGCB491. In certain such embodiments the duration of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle is 28 days. In certain embodiments, the BCMA x GPRC5D x CD3 trispecific antibody is subcutaneously administered once every four weeks at a treatment dose of about 20 mg, and wherein at least one step-up dose of theBCMA x GPRC5D x CD3 trispecific antibody is subcutaneously administered prior to the subcutaneous administration of the treatment dose, wherein the step-up dose is about 5 mg and is administered about 2 to 8 days prior to the administration of the treatment dose, wherein the pomalidomide dose is administered during at least twoBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of any Cycle >2 at a dose of about 2 mg daily for at least 21 days, wherein the dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein dexamethasone is administered is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2, wherein the dexamethasone is administered in Cycles 2 to 4, wherein the BCMA x GPRC5D x CD3 584897-1598-5221.1trispecific antibody is BGCB491. In certain such embodiments the duration of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle is 28 days.

[0216] In one embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 20 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose, wherein the step-up dose is about 5 mg and is administered about one week prior to the administration of the treatment dose, wherein the pomalidomide dose is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of Cycle 3 at a dose of about 4 mg daily for at least 21 days. In certain such embodiments, dexamethasone is administered in conjunction with pomalidomide. In certain such embodiments, dexamethasone is administered in conjunction with pomalidomide on designated days of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles. In certain such embodiments, dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2. In certain such embodiments, dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 in Cycles 2 to 4. In certain such embodiments, dexamethasone is administered at a dose of about 20 mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the administration begins at Day 1 of Cycle 2. In certain such embodiments, dexamethasone is administered during 594897-1598-5221.1three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the dexamethasone is administered at a dose of about 20 mg on Days 1, 8, 15, and 22 in Cycles 2 to 4. In certain such embodiments the dexamethasone is administered orally. In certain such embodiments the dexamethasone is administered intravenously. In certain such embodiments the BCMA x GPRC5D x CD3 trispecific antibody is BGCB491. In certain such embodiments the duration of theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle is 28 days.

[0217] In one embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 20 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose, wherein the step-up dose is about 5 mg and is administered about one week prior to the administration of the treatment dose, wherein the pomalidomide dose is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of any Cycle >2 at a dose of about 4 mg daily for at least 21 days In certain such embodiments, dexamethasone is administered in conjunction with pomalidomide. In certain such embodiments, dexamethasone is administered in conjunction with pomalidomide on designated days of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles. In certain such embodiments, dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2. In certain such embodiments, dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the604897-1598-5221.1dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 in Cycles 2 to 4. In certain such embodiments, dexamethasone is administered at a dose of about 20 mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the administration begins at Day 1 of Cycle 2. In certain such embodiments, dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the dexamethasone is administered at a dose of about 20 mg on Days 1, 8, 15, and 22 in Cycles 2 to 4. In certain such embodiments the dexamethasone is administered orally. In certain such embodiments the dexamethasone is administered intravenously.. In certain such embodiments the BCMA x GPRC5D x CD3 trispecific antibody is BGCB491. In certain such embodiments the duration of theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle is 28 days.

[0218] In one embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 20 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose, wherein the the step-up dose is about 5 mg and is administered about one week prior to the administration of the treatment dose, wherein the pomalidomide dose is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of any Cycle >2 at a dose of about 2 mg daily, for at least 21 days. In certain such embodiments, dexamethasone is administered in conjunction with pomalidomide. In certain such embodiments, dexamethasone is administered in conjunction with pomalidomide on designated days of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles. In certain such embodiments, dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 of each614897-1598-5221.1of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2. In certain such embodiments, dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 in Cycles 2 to 4. In certain such embodiments, dexamethasone is administered at a dose of about 20 mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the administration begins at Day 1 of Cycle 2. In certain such embodiments, dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the dexamethasone is administered at a dose of about 20 mg on Days 1, 8, 15, and 22 in Cycles 2 to 4. In certain such embodiments the dexamethasone is administered orally. In certain such embodiments the dexamethasone is administered intravenously. In certain such embodiments the BCMA x GPRC5D x CD3 trispecific antibody is BGCB491. In certain such embodiments the duration of theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle is 28 days.50 mg treatment dose [BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof]In a certain embodiment, the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is about 50 mg and wherein the treatment dose is subcutaneously administered once every four weeks. In a certain embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 50 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose. In certain such embodiments, the first step-up dose is about 5 mg and is administered about 2-4 days prior to the administration624897-1598-5221.1of the treatment dose. In a certain embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 50 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose. In certain such embodiments, the first step-up dose is about 2.5 mg and is administered about 2-4 days prior to the administration of the treatment dose. In a certain embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 50 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose. In certain such embodiments, the first step-up dose is about 5 mg and is administered about one week prior to the administration of the treatment dose. In one embodiment, theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 50 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose. In certain such embodiments, the first step-up dose is about 5 mg and is administered about 6-8 days prior to the administration of the treatment dose. Often such dosing regimens comprise further step-up doses prior to administration of the treatment dose.

[0219] In one embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 50 mg, and wherein at least one step-up dose of theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose, wherein the step-up dose is about 5 mg and is administered about 2-8 days prior to the administration of the treatment dose, wherein the pomalidomide dose is administered 634897-1598-5221.1during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of Cycle 3 at a dose of about 4 mg daily for at least 21 days. In certain such embodiments, dexamethasone is administered in conjunction with pomalidomide. In certain such embodiments, dexamethasone is administered in conjunction with pomalidomide on designated days of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles. In certain such embodiments, dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2. In certain such embodiments, dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the

[0220] dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 in Cycles 2 to 4. In certain such embodiments, dexamethasone is administered at a dose of about 20 mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the administration begins at Day 1 of Cycle 2. In certain such embodiments, dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the dexamethasone is administered at a dose of about 20 mg on Days 1, 8, 15, and 22 in Cycles 2 to 4. In certain such embodiments the dexamethasone is administered orally. In certain such embodiments the dexamethasone is administered intravenously. In certain such embodiments the BCMA x GPRC5D x CD3 trispecific antibody is BGCB491. In certain such embodiments the duration of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle is 28 days.

[0221] In one embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 50 mg, and wherein at least one step-up dose of the 644897-1598-5221.1BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose, wherein the step-up dose is about 5 mg and is administered about 2-8 days prior to the administration of the treatment dose, wherein the pomalidomide dose is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of any Cycle >2 at a dose of about 4 mg daily for at least 21 days. . In certain such embodiments, dexamethasone is administered in conjunction with pomalidomide. In certain such embodiments, dexamethasone is administered in conjunction with pomalidomide on designated days of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles. In certain such embodiments, dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2. In certain such embodiments, dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 in Cycles 2 to 4. In certain such embodiments, dexamethasone is administered at a dose of about 20 mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the administration begins at Day 1 of Cycle 2. In certain such embodiments, dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the dexamethasone is administered at a dose of about 20 mg on Days 1, 8, 15, and 22 in Cycles 2 to 4. In certain such embodiments the dexamethasone is administered orally. In certain such embodiments the dexamethasone is administered intravenously. In certain such embodiments the BCMA x GPRC5D x CD3 trispecific antibody is BGCB491. In certain such embodiments the duration of theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof 654897-1598-5221.1treatment cycle is 28 days. In certain embodiments, the BCMA x GPRC5D x CD3 trispecific antibody is subcutaneously administered once every four weeks at a treatment dose of about 50 mg, and wherein at least one step-up dose of theBCMA x GPRC5D x CD3 trispecific antibody is subcutaneously administered prior to the subcutaneous administration of the treatment dose, wherein the step-up dose is about 5 mg and is administered about 2 to 8 days prior to the administration of the treatment dose, wherein the pomalidomide dose is administered during at least twoBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of any Cycle >2 at a dose of about 4 mg daily for at least 21 days, wherein the dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2, wherein the dexamethasone is administered in Cycles 2 to 4, wherein the BCMA x GPRC5D x CD3 trispecific antibody is BGCB491. In certain such embodiments the duration of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle is 28 days.

[0222] In one embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 50 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose, wherein the the step-up dose is about 5 mg and is administered about 2-8 days prior to the administration of the treatment dose, wherein the pomalidomide dose is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at 664897-1598-5221.1a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of any Cycle >2 at a dose of about 2 mg daily, for at least 21 days. In certain such embodiments, dexamethasone is administered in conjunction with pomalidomide. In certain such embodiments, dexamethasone is administered in conjunction with pomalidomide on designated days of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles. In certain such embodiments, dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2. In certain such embodiments, dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 in Cycles 2 to 4. In certain such embodiments, dexamethasone is administered at a dose of about 20 mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the administration begins at Day 1 of Cycle 2. In certain such embodiments, dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the dexamethasone is administered at a dose of about 20 mg on Days 1, 8, 15, and 22 in Cycles 2 to 4. In certain such embodiments the dexamethasone is administered orally. In certain such embodiments the dexamethasone is administered intravenously. In certain such embodiments the BCMA x GPRC5D x CD3 trispecific antibody is BGCB491. In certain such embodiments the duration of theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle is 28 days. In certain embodiments, the BCMA x GPRC5D x CD3 trispecific antibody is subcutaneously administered once every four weeks at a treatment dose of about 50 mg, and wherein at least one step-up dose of theBCMA x GPRC5D x CD3 trispecific antibody is subcutaneously administered prior to the subcutaneous administration of the treatment dose, wherein the step-up dose is about 5 mg and is administered about 2 to 8 days prior to the administration of the treatment dose, 674897-1598-5221.1wherein the pomalidomide dose is administered during at least twoBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of any Cycle >2 at a dose of about 2 mg daily for at least 21 days, wherein the dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein dexamethasone is administered is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 of each of the the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2, wherein the dexamethasone is administered in Cycles 2 to 4, wherein the BCMA x GPRC5D x CD3 trispecific antibody is BGCB491. In certain such embodiments the duration of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle is 28 days.

[0223] In one embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 50 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose, wherein the the step-up dose is about 5 mg and is administered about one week prior to the administration of the treatment dose, wherein the pomalidomide dose is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of Cycle 3 at a dose of about 4 mg daily for at least 21 days. In certain such embodiments, dexamethasone is administered in conjunction with pomalidomide. In certain such embodiments, dexamethasone is administered in conjunction with pomalidomide on designated days of the BCMA x GPRC5D x CD3 trispecific antibody or 684897-1598-5221.1trispecific binding fragment thereof treatment cycles. In certain such embodiments, dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2. In certain such embodiments, dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 in Cycles 2 to 4. In certain such embodiments, dexamethasone is administered at a dose of about 20 mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the administration begins at Day 1 of Cycle 2. In certain such embodiments, dexamethasone is administered at a dose of about 20 mg on Days 1, 8, 15, and 22 in Cycles 2 to 4. In certain such embodiments the dexamethasone is administered orally. In certain such embodiments the dexamethasone is administered intravenously. In certain such embodiments the BCMA x GPRC5D x CD3 trispecific antibody is BGCB491. In certain such embodiments the duration of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle is 28 days.

[0224] In one embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 50 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose, wherein the the step-up dose is about 5 mg and is administered about one week prior to the administration of the treatment dose, wherein the pomalidomide dose is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of any Cycle >2 at a dose of about 4 mg daily for at least 21 days. In certain such 694897-1598-5221.1embodiments, dexamethasone is administered in conjunction with pomalidomide. In certain such embodiments, dexamethasone is administered in conjunction with pomalidomide on designated days of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles. In certain such embodiments, dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2. In certain such embodiments, dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 in Cycles 2 to 4. In certain such embodiments, dexamethasone is administered at a dose of about 20 mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the administration begins at Day 1 of Cycle 2. In certain such embodiments, dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the dexamethasone is administered at a dose of about 20 mg on Days 1, 8, 15, and 22 in Cycles 2 to 4. In certain such embodiments the dexamethasone is administered orally. In certain such embodiments the dexamethasone is administered intravenously. In certain such embodiments the BCMA x GPRC5D x CD3 trispecific antibody is BGCB491. In certain such embodiments the duration of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle is 28 days.

[0225] In one embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 50 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose, wherein the the step-up dose is about 5 mg and is administered about one week prior 704897-1598-5221.1to the administration of the treatment dose, wherein the pomalidomide dose is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of any Cycle >2 at a dose of about 2 mg daily, for at least 21 days. In certain such embodiments, dexamethasone is administered in conjunction with pomalidomide. In certain such embodiments, dexamethasone is administered in conjunction with pomalidomide on designated days of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles. In certain such embodiments, dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2. In certain such embodiments, dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 in Cycles 2 to 4. In certain such embodiments, dexamethasone is administered at a dose of about 20 mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the administration begins at Day 1 of Cycle 2. In certain such embodiments, dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the dexamethasone is administered at a dose of about 20 mg on Days 1, 8, 15, and 22 in Cycles 2 to 4. In certain such embodiments the dexamethasone is administered orally. In certain such embodiments the dexamethasone is administered intravenously. In certain such embodiments the BCMA x GPRC5D x CD3 trispecific antibody is BGCB491. In certain such embodiments the duration of theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle is 28 days.4897-1598-5221.1100 mg treatment dose [BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof]

[0226] In one embodiment, the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is about 100 mg and wherein the treatment dose is subcutaneously administered once every four weeks. In a certain embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 100 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose. In certain such embodiments, the first step-up dose is about 5 mg and is administered about 2-4 days prior to the administration of the treatment dose. In a certain embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 100 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose. In certain such embodiments, the first step-up dose is about 2.5 mg and is administered about 2-4 days prior to the administration of the treatment dose. In a certain embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 100 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose. In certain such embodiments, the first step-up dose is about 5 mg and is administered about one week prior to the administration of the treatment dose. In a certain embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 100 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the724897-1598-5221.1subcutaneous administration of the treatment dose. In certain such embodiments, the first step-up dose is about 5 mg and is administered about 6-8 days prior to the administration of the treatment dose. Often such dosing regimens comprise further step-up doses prior to administration of the treatment dose.

[0227] In one embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 100 mg, and wherein at least one step-up dose of theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose, wherein the the step-up dose is about 5 mg and is administered about 2-8 days prior to the administration of the treatment dose, wherein the pomalidomide dose is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of Cycle 3 at a dose of about 4 mg daily for at least 21 days.In one embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 100 mg, and wherein at least one step-up dose of theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose, wherein the the step-up dose is about 5 mg and is administered about 2-8 days prior to the administration of the treatment dose, wherein the pomalidomide dose is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of any Cycle >2 at a dose of about 4 mg daily for at least 21 days. In certain such embodiments, dexamethasone is administered in conjunction with pomalidomide. In certain such embodiments, dexamethasone is administered in conjunction with pomalidomide on designated days of the BCMA x GPRC5D x CD3 trispecific antibody or 734897-1598-5221.1trispecific binding fragment thereof treatment cycles. In certain such embodiments, dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 of each of the the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2. In certain such embodiments, dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 in Cycles 2 to 4. In certain such embodiments, dexamethasone is administered at a dose of about 20 mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the administration begins at Day 1 of Cycle 2. In certain such embodiments, dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the dexamethasone is administered at a dose of about 20 mg on Days 1, 8, 15, and 22 in Cycles 2 to 4. In certain such embodiments the dexamethasone is administered orally. In certain such embodiments the dexamethasone is administered intravenously. In certain such embodiments the BCMA x GPRC5D x CD3 trispecific antibody is BGCB491. In certain such embodiments the duration of theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle is 28 days. In certain embodiments, the BCMA x GPRC5D x CD3 trispecific antibody is subcutaneously administered once every four weeks at a treatment dose of about 100 mg, and wherein at least one step-up dose of theBCMA x GPRC5D x CD3 trispecific antibody is subcutaneously administered prior to the subcutaneous administration of the treatment dose, wherein the step-up dose is about 5 mg and is administered about 2 to 8 days prior to the administration of the treatment dose, wherein the pomalidomide dose is administered during at least twoBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of any Cycle >2 at a dose of about 4 mg daily for at least 21 days, wherein the dexamethasone is 744897-1598-5221.1administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein dexamethasone is administered is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 of each of tthe BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2, wherein the dexamethasone is administered in Cycles 2 to 4, wherein the BCMA x GPRC5D x CD3 trispecific antibody is BGCB491. In certain such embodiments the duration of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle is 28 days.

[0228] In one embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 100 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose, wherein the the step-up dose is about 5 mg and is administered about 2-8 days prior to the administration of the treatment dose, wherein the pomalidomide dose is administered during at least 2 BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the pomalidomide dose is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of any Cycle >2 at a dose of about 2 mg daily, for at least 21 days. . In certain such embodiments, dexamethasone is administered in conjunction with pomalidomide. In certain such embodiments, dexamethasone is administered in conjunction with pomalidomide on designated days of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles. In certain such embodiments, dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof754897-1598-5221.1treatment cycles, wherein the administration begins at Day 1 of Cycle 2. In certain such embodiments, dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 in Cycles 2 to 4. In certain such embodiments, dexamethasone is administered at a dose of about 20 mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the administration begins at Day 1 of Cycle 2. In certain such embodiments, dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the dexamethasone is administered at a dose of about 20 mg on Days 1, 8, 15, and 22 in Cycles 2 to 4. In certain such embodiments the dexamethasone is administered orally. In certain such embodiments the dexamethasone is administered intravenously. In certain such embodiments the BCMA x GPRC5D x CD3 trispecific antibody is BGCB491. In certain such embodiments the duration of theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle is 28 days. In certain embodiments, the BCMA x GPRC5D x CD3 trispecific antibody is subcutaneously administered once every four weeks at a treatment dose of about 100 mg, and wherein at least one step-up dose of theBCMA x GPRC5D x CD3 trispecific antibody is subcutaneously administered prior to the subcutaneous administration of the treatment dose, wherein the step-up dose is about 5 mg and is administered about 2 to 8 days prior to the administration of the treatment dose, wherein the pomalidomide dose is administered during at least twoBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of any Cycle >2 at a dose of about 2 mg daily for at least 21 days, wherein the dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 764897-1598-5221.1trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2, wherein the dexamethasone is administered in Cycles 2 to 4, wherein the BCMA x GPRC5D x CD3 trispecific antibody is BGCB491. In certain such embodiments the duration of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle is 28 days.

[0229] In one embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 100 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose, wherein the the step-up dose is about 5 mg and is administered about one week prior to the administration of the treatment dose, wherein the pomalidomide dose is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of Cycle 3 at a dose of about 4 mg daily for at least 21 days. . In certain such embodiments, dexamethasone is administered in conjunction with pomalidomide. In certain such embodiments, dexamethasone is administered in conjunction with pomalidomide on designated days of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles. In certain such embodiments, dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2. In certain such embodiments, dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 in Cycles 2 to 4. In certain such embodiments, dexamethasone is administered at a dose of about 20 mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the administration begins 774897-1598-5221.1at Day 1 of Cycle 2. In certain such embodiments, dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the dexamethasone is administered at a dose of about 20 mg on Days 1, 8, 15, and 22 in Cycles 2 to 4. In certain such embodiments the dexamethasone is administered orally. In certain such embodiments the dexamethasone is administered intravenously. In certain such embodiments the BCMA x GPRC5D x CD3 trispecific antibody is BGCB491. In certain such embodiments the duration of theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle is 28 days .In one embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 100 mg, and wherein at least one step-up dose of theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose, wherein the the step-up dose is about 5 mg and is administered about one week prior to the administration of the treatment dose, wherein the pomalidomide dose is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of any Cycle >2 at a dose of about 4 mg daily for at least 21 days . In certain such embodiments, dexamethasone is administered in conjunction with pomalidomide. In certain such embodiments, dexamethasone is administered in conjunction with pomalidomide on designated days of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles. In certain such embodiments, dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2. In certain such embodiments, dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the 784897-1598-5221.1dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 in Cycles 2 to 4. In certain such embodiments, dexamethasone is administered at a dose of about 20 mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the administration begins at Day 1 of Cycle 2. In certain such embodiments, dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the dexamethasone is administered at a dose of about 20 mg on Days 1, 8, 15, and 22 in Cycles 2 to 4. In certain such embodiments the dexamethasone is administered orally. In certain such embodiments the dexamethasone is administered intravenously. In certain such embodiments the BCMA x GPRC5D x CD3 trispecific antibody is BGCB491. In certain such embodiments the duration of theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle is 28 days.

[0230] In one embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 100 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose, wherein the the step-up dose is about 5 mg and is administered about one week prior to the administration of the treatment dose, wherein the pomalidomide dose is administered during at least 2 BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the pomalidomide dose is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of any Cycle >2 at a dose of about 2 mg daily, for at least 21 days. . In certain such embodiments, dexamethasone is administered in conjunction with pomalidomide. In certain such embodiments, dexamethasone is administered in conjunction with pomalidomide on designated days of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding 794897-1598-5221.1fragment thereof treatment cycles. In certain such embodiments, dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2. In certain such embodiments, dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 in Cycles 2 to 4. In certain such embodiments, dexamethasone is administered at a dose of about 20 mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the administration begins at Day 1 of Cycle 2. In certain such embodiments, dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the dexamethasone is administered at a dose of about 20 mg on Days 1, 8, 15, and 22 in Cycles 2 to 4. In certain such embodiments the dexamethasone is administered orally. In certain such embodiments the dexamethasone is administered intravenously. In certain such embodiments the BCMA x GPRC5D x CD3 trispecific antibody is BGCB491. In certain such embodiments the duration of theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle is 28 days.200 mg treatment dose [BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof]

[0231] In one embodiment, the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is about 200 mg and wherein the treatment dose is subcutaneously administered once every four weeks. In a certain embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 200 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the804897-1598-5221.1subcutaneous administration of the treatment dose. In certain such embodiments, the first step-up dose is about 5 mg and is administered about 2-4 days prior to the administration of the treatment dose. In a certain embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 200 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose. In certain such embodiments, the first step-up dose is about 2.5 mg and is administered about 2-4 days prior to the administration of the treatment dose. In a certain embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 200 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose. In certain such embodiments, the first step-up dose is about 5 mg and is administered about one week prior to the administration of the treatment dose. In a certain embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 200 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose. In certain such embodiments, the first step-up dose is about 5 mg and is administered about 6-8 days prior to the administration of the treatment dose. Often such dosing regimens comprise further step-up doses prior to administration of the treatment dose.In one embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 200 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment 814897-1598-5221.1dose, wherein the the step-up dose is about 5 mg and is administered about 2-8 days prior to the administration of the treatment dose, wherein the pomalidomide dose is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of Cycle 3 at a dose of about 4 mg daily for at least 21 days. .In certain such embodiments, dexamethasone is administered in conjunction with pomalidomide. In certain such embodiments, dexamethasone is administered in conjunction with pomalidomide on designated days of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles. In certain such embodiments, dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2. In certain such embodiments, dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 in Cycles 2 to 4. In certain such embodiments, dexamethasone is administered at a dose of about 20 mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the administration begins at Day 1 of Cycle 2. In certain such embodiments, dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the dexamethasone is administered at a dose of about 20 mg on Days 1, 8, 15, and 22 in Cycles 2 to 4. In certain such embodiments the dexamethasone is administered orally. In certain such embodiments the dexamethasone is administered intravenously. In certain such embodiments the BCMA x GPRC5D x CD3 trispecific antibody is BGCB491. In certain such embodiments the duration of theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle is 28 days.824897-1598-5221.1In one embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 200 mg, and wherein at least one step-up dose of theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose, wherein the step-up dose is about 5 mg and is administered about 2-8 days prior to the administration of the treatment dose, wherein the pomalidomide dose is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of any Cycle >2 at a dose of about 4 mg daily for at least 21 days. . In certain such embodiments, dexamethasone is administered in conjunction with pomalidomide. In certain such embodiments, dexamethasone is administered in conjunction with pomalidomide on designated days of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles. In certain such embodiments, dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2. In certain such embodiments, dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 in Cycles 2 to 4. In certain such embodiments, dexamethasone is administered at a dose of about 20 mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the administration begins at Day 1 of Cycle 2. In certain such embodiments, dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the dexamethasone is administered at a dose of about 20 mg on Days 1, 8, 15, and 22 in Cycles 2 to 4. In certain such embodiments the dexamethasone is administered orally. In certain such embodiments the dexamethasone is administered834897-1598-5221.1intravenously. In certain such embodiments the BCMA x GPRC5D x CD3 trispecific antibody is BGCB491. In certain such embodiments the duration of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle is 28 days. In certain embodiments, the BCMA x GPRC5D x CD3 trispecific antibody is subcutaneously administered once every four weeks at a treatment dose of about 200 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody is subcutaneously administered prior to the subcutaneous administration of the treatment dose, wherein the step-up dose is about 5 mg and is administered about 2 to 8 days prior to the administration of the treatment dose, wherein the pomalidomide dose is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of any Cycle >2 at a dose of about 4 mg daily for at least 21 days, wherein the dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein dexamethasone is administered is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2, wherein the dexamethasone is administered in Cycles 2 to 4, wherein the BCMA x GPRC5D x CD3 trispecific antibody is BGCB491. In certain such embodiments the duration of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle is 28 days.

[0232] In one embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 200 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose, wherein the the step-up dose is about 5 mg and is administered about 2-8 days prior 844897-1598-5221.1to the administration of the treatment dose, wherein the pomalidomide dose is administered during at least 2 BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the pomalidomide dose is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of any Cycle >2 at a dose of about 2 mg daily, for at least 21 days. In certain such embodiments, dexamethasone is administered in conjunction with pomalidomide. In certain such embodiments, dexamethasone is administered in conjunction with pomalidomide on designated days of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles. In certain such embodiments, dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2. In certain such embodiments, dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 in Cycles 2 to 4. In certain such embodiments, dexamethasone is administered at a dose of about 20 mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the administration begins at Day 1 of Cycle 2. In certain such embodiments, dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the dexamethasone is administered at a dose of about 20 mg on Days 1, 8, 15, and 22 in Cycles 2 to 4. In certain such embodiments the dexamethasone is administered orally. In certain such embodiments the dexamethasone is administered intravenously. In certain such embodiments the BCMA x GPRC5D x CD3 trispecific antibody is BGCB491. In certain such embodiments the duration of theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle is 28 days. In certain embodiments, the BCMA x GPRC5D x CD3 854897-1598-5221.1trispecific antibody is subcutaneously administered once every four weeks at a treatment dose of about 200 mg, and wherein at least one step-up dose of theBCMA x GPRC5D x CD3 trispecific antibody is subcutaneously administered prior to the subcutaneous administration of the treatment dose, wherein the step-up dose is about 5 mg and is administered about 2 to 8 days prior to the administration of the treatment dose, wherein the pomalidomide dose is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of any Cycle >2 at a dose of about 2 mg daily for at least 21 days, wherein the dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein dexamethasone is administered is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2, wherein the dexamethasone is administered in Cycles 2 to 4, wherein the BCMA x GPRC5D x CD3 trispecific antibody is BGCB491. In certain such embodiments the duration of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle is 28 days.

[0233] In one embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 200 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose, wherein the the step-up dose is about 5 mg and is administered about one week prior to the administration of the treatment dose, wherein the pomalidomide dose is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at 864897-1598-5221.1Day 1 of Cycle 3 at a dose of about 4 mg daily for at least 21 days. . In certain such embodiments, dexamethasone is administered in conjunction with pomalidomide. In certain such embodiments, dexamethasone is administered in conjunction with pomalidomide on designated days of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles. In certain such embodiments, dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2. In certain such embodiments, dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 in Cycles 2 to 4. In certain such embodiments, dexamethasone is administered at a dose of about 20 mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the administration begins at Day 1 of Cycle 2. In certain such embodiments, dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the dexamethasone is administered at a dose of about 20 mg on Days 1, 8, 15, and 22 in Cycles 2 to 4. In certain such embodiments the dexamethasone is administered orally. In certain such embodiments the dexamethasone is administered intravenously. In certain such embodiments the BCMA x GPRC5D x CD3 trispecific antibody is BGCB491. In certain such embodiments the duration of theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle is 28 days.

[0234] In one embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 200 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose, wherein the the step-up dose is about 5 mg and is administered about one week prior874897-1598-5221.1to the administration of the treatment dose, wherein the pomalidomide dose is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of any Cycle >2 at a dose of about 4 mg daily for at least 21 days. . In certain such embodiments, dexamethasone is administered in conjunction with pomalidomide. In certain such embodiments, dexamethasone is administered in conjunction with pomalidomide on designated days of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles. In certain such embodiments, dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2. In certain such embodiments, dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 in Cycles 2 to 4. In certain such embodiments, dexamethasone is administered at a dose of about 20 mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the administration begins at Day 1 of Cycle 2. In certain such embodiments, dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the dexamethasone is administered at a dose of about 20 mg on Days 1, 8, 15, and 22 in Cycles 2 to 4. In certain such embodiments the dexamethasone is administered orally. In certain such embodiments the dexamethasone is administered intravenously. In certain such embodiments the BCMA x GPRC5D x CD3 trispecific antibody is BGCB491. In certain such embodiments the duration of theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle is 28 days.

[0235] In one embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks884897-1598-5221.1at a treatment dose of about 200 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose, wherein the the step-up dose is about 5 mg and is administered about one week prior to the administration of the treatment dose, wherein the pomalidomide dose is administered during at least 2 BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the pomalidomide dose is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of any Cycle >2 at a dose of about 2 mg daily, for at least 21 days. . In certain such embodiments, dexamethasone is administered in conjunction with pomalidomide. In certain such embodiments, dexamethasone is administered in conjunction with pomalidomide on designated days of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles. In certain such embodiments, dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2. In certain such embodiments, dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 in Cycles 2 to 4. In certain such embodiments, dexamethasone is administered at a dose of about 20 mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the administration begins at Day 1 of Cycle 2. In certain such embodiments, dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the dexamethasone is administered at a dose of about 20 mg on Days 1, 8, 15, and 22 in Cycles 2 to 4. In certain such embodiments the dexamethasone is administered orally. In certain such embodiments the dexamethasone is administered894897-1598-5221.1intravenously. In certain such embodiments the BCMA x GPRC5D x CD3 trispecific antibody is BGCB491. In certain such embodiments the duration of theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle is 28 days.

[0236] 300 mg treatment dose [BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof]

[0237] In one embodiment, the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is about 300 mg and wherein the treatment dose is subcutaneously administered once every four weeks. In a certain embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 300 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose. In certain such embodiments, the first step-up dose is about 5 mg and is administered about 2-4 days prior to the administration of the treatment dose. In a certain embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 300 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose. In certain such embodiments, the first step-up dose is about 5 mg and is administered about one week prior to the administration of the treatment dose. In a certain embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 300 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose. In certain such embodiments, the first step-up dose is about 5 mg and is administered about 6-8 days prior to the administration 904897-1598-5221.1of the treatment dose. Often such dosing regimens comprise further step-up doses prior to administration of the treatment dose.

[0238] In one embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 300 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose, wherein the the step-up dose is about 5 mg and is administered about 2-8 days prior to the administration of the treatment dose, wherein the pomalidomide dose is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of Cycle 3 at a dose of about 4 mg daily for at least 21 days.

[0239] In one embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 300 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose, wherein the the step-up dose is about 5 mg and is administered about 2-8 days prior to the administration of the treatment dose, wherein the pomalidomide dose is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of any Cycle >2 at a dose of about 4 mg daily for at least 21 days. . In certain such embodiments, dexamethasone is administered in conjunction with pomalidomide. In certain such embodiments, dexamethasone is administered in conjunction with pomalidomide on designated days of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles. In certain such embodiments, dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 of each 914897-1598-5221.1of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2. In certain such embodiments, dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 in Cycles 2 to 4. In certain such embodiments, dexamethasone is administered at a dose of about 20 mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the administration begins at Day 1 of Cycle 2. In certain such embodiments, dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the dexamethasone is administered at a dose of about 20 mg on Days 1, 8, 15, and 22 in Cycles 2 to 4. In certain such embodiments the dexamethasone is administered orally. In certain such embodiments the dexamethasone is administered intravenously. In certain such embodiments the BCMA x GPRC5D x CD3 trispecific antibody is BGCB491. In certain such embodiments the duration of theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle is 28 days. In certain embodiments, the BCMA x GPRC5D x CD3 trispecific antibody is subcutaneously administered once every four weeks at a treatment dose of about 300 mg, and wherein at least one step-up dose of theBCMA x GPRC5D x CD3 trispecific antibody is subcutaneously administered prior to the subcutaneous administration of the treatment dose, wherein the step-up dose is about 5 mg and is administered about 2 to 8 days prior to the administration of the treatment dose, wherein the pomalidomide dose is administered during at least twoBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of any Cycle >2 at a dose of about 4 mg daily for at least 21 days, wherein the dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein dexamethasone is administered is 924897-1598-5221.1administered at a dose of about 40 mg on Days 1, 8, 15, and 22 of each of theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2, wherein the dexamethasone is administered in Cycles 2 to 4, wherein the BCMA x GPRC5D x CD3 trispecific antibody is BGCB491. In certain such embodiments the duration of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle is 28 days.

[0240] In one embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 300 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose, wherein the the step-up dose is about 5 mg and is administered about 2-8 days prior to the administration of the treatment dose, wherein the pomalidomide dose is administered during at least 2 BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the pomalidomide dose is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of any Cycle >2 at a dose of about 2 mg daily, for at least 21 days. . In certain such embodiments, dexamethasone is administered in conjunction with pomalidomide. In certain such embodiments, dexamethasone is administered in conjunction with pomalidomide on designated days of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles. In certain such embodiments, dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2. In certain such embodiments, dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the934897-1598-5221.1dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 in Cycles 2 to 4. In certain such embodiments, dexamethasone is administered at a dose of about 20 mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the administration begins at Day 1 of Cycle 2. In certain such embodiments, dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the dexamethasone is administered at a dose of about 20 mg on Days 1, 8, 15, and 22 in Cycles 2 to 4. In certain such embodiments the dexamethasone is administered orally. In certain such embodiments the dexamethasone is administered intravenously. In certain such embodiments the BCMA x GPRC5D x CD3 trispecific antibody is BGCB491. In certain such embodiments the duration of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle is 28 days . In certain embodiments, the BCMA x GPRC5D x CD3 trispecific antibody is subcutaneously administered once every four weeks at a treatment dose of about 300 mg, and wherein at least one step-up dose of theBCMA x GPRC5D x CD3 trispecific antibody is subcutaneously administered prior to the subcutaneous administration of the treatment dose, wherein the step-up dose is about 5 mg and is administered about 2 to 8 days prior to the administration of the treatment dose, wherein the pomalidomide dose is administered during at least twoBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of any Cycle >2 at a dose of about 2 mg daily for at least 21 days, wherein the dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein dexamethasone is administered is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2, wherein the dexamethasone is administered in Cycles 2 to 4, wherein the BCMA x GPRC5D x CD3 944897-1598-5221.1trispecific antibody is BGCB491. In certain such embodiments the duration of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle is 28 days.

[0241] In one embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 300 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose, wherein the the step-up dose is about 5 mg and is administered about one week prior to the administration of the treatment dose, wherein the pomalidomide dose is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of Cycle 3 at a dose of about 4 mg daily for at least 21 days. . In certain such embodiments, dexamethasone is administered in conjunction with pomalidomide. In certain such embodiments, dexamethasone is administered in conjunction with pomalidomide on designated days of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles. In certain such embodiments, dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2. In certain such embodiments, dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 in Cycles 2 to 4. In certain such embodiments, dexamethasone is administered at a dose of about 20 mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the administration begins at Day 1 of Cycle 2. In certain such embodiments, dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof 954897-1598-5221.1treatment cycles wherein the dexamethasone is administered at a dose of about 20 mg on Days 1, 8, 15, and 22 in Cycles 2 to 4. In certain such embodiments the dexamethasone is administered orally. In certain such embodiments the dexamethasone is administered intravenously. In certain such embodiments the BCMA x GPRC5D x CD3 trispecific antibody is BGCB491. In certain such embodiments the duration of theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle is 28 days.

[0242] In one embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 300 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose, wherein the step-up dose is about 5 mg and is administered about one week prior to the administration of the treatment dose, wherein the pomalidomide dose is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of any Cycle >2 at a dose of about 4 mg daily for at least 21 days. . In certain such embodiments, dexamethasone is administered in conjunction with pomalidomide. In certain such embodiments, dexamethasone is administered in conjunction with pomalidomide on designated days of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles. In certain such embodiments, dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2. In certain such embodiments, dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 in Cycles 2 to 4. In certain such embodiments, dexamethasone is administered at a dose of about 20 964897-1598-5221.1mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the administration begins at Day 1 of Cycle 2. In certain such embodiments, dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the dexamethasone is administered at a dose of about 20 mg on Days 1, 8, 15, and 22 in Cycles 2 to 4. In certain such embodiments the dexamethasone is administered orally. In certain such embodiments the dexamethasone is administered intravenously. In certain such embodiments the BCMA x GPRC5D x CD3 trispecific antibody is BGCB491. In certain such embodiments the duration of theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle is 28 days.

[0243] In one embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 300 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose, wherein the the step-up dose is about 5 mg and is administered about one week prior to the administration of the treatment dose, wherein the pomalidomide dose is administered during at least 2 BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the pomalidomide dose is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of any Cycle >2 at a dose of about 2 mg daily, for at least 21 days. . In certain such embodiments, dexamethasone is administered in conjunction with pomalidomide. In certain such embodiments, dexamethasone is administered in conjunction with pomalidomide on designated days of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles. In certain such embodiments, dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 of each of the974897-1598-5221.1BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2. In certain such embodiments, dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 in Cycles 2 to 4. In certain such embodiments, dexamethasone is administered at a dose of about 20 mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the administration begins at Day 1 of Cycle 2. In certain such embodiments, dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the dexamethasone is administered at a dose of about 20 mg on Days 1, 8, 15, and 22 in Cycles 2 to 4. In certain such embodiments the dexamethasone is administered orally. In certain such embodiments the dexamethasone is administered intravenously. In certain such embodiments the BCMA x GPRC5D x CD3 trispecific antibody is BGCB491. In certain such embodiments the duration of theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle is 28 days.

[0244] Dosage regimens in the above methods of treatment are adjusted to provide the optimum desired response (e.g., a therapeutic response). For example, the dose may be proportionally reduced or increased as indicated by the exigencies of the therapeutic situation. Parenteral compositions may be formulated in dosage unit form for ease of administration and uniformity of dosage.

[0245] The efficient dosages and the dosage regimens for the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof and for pomalidomide, respectively, may be determined by one skilled in the art.

[0246] A physician, pharmacist or veterinarian having ordinary skill in the art may readily determine and prescribe the effective amount of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof and for pomalidomide, respectively, required. For example, the physician or veterinarian could start doses of the984897-1598-5221.1BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof and for pomalidomide, respectively, employed in the pharmaceutical composition at levels lower than that required in order to achieve the desired therapeutic effect and gradually increase the dosage until the desired effect is achieved. In general, a suitable daily dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof and for pomalidomide, respectively, will be that amount of the compound which is the lowest dose effective to produce a therapeutic effect.

[0247] The dosage may be determined or adjusted by measuring the amount of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof, as disclosed herein, and for pomalidomide, respectively, in the blood upon administration by for instance taking out a biological sample and using anti-idiotypic antibodies which target the GPRC5D and / or BCMA antigen binding arms of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof and for pomalidomide, respectively.

[0248] The doses depend on the desired effect, the duration of the treatment and the route of administration used. In general, the doctor will determine the appropriate dosage depending on the age, weight and any other factors specific to the subject to be treated.

[0249] The dosing regimens may be repeated one or more times as necessary, for example, after six months or twelve months.

[0250] In one embodiment, the trispecific antibody or trispecific binding fragment thereof and pomalidomide may be administered by maintenance therapy, such as, e.g for a period of six months or more.

[0251] The administration of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof once every 4 weeks can therefore also be understood to start a treatment cycle, which can also here be referred to as a“BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle”.

[0252] In some embodiments the duration of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle is about 28 days.994897-1598-5221.1

[0253] In some embodiments the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment is administered at least for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more about 28-day cycles, which can also be referred to as Cycle 1, Cycle 2, Cycle 3, Cycle 4, etc.

[0254] In some embodiments the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment is administered at least for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 , 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or more about 28 day cycles, which can also be referred to as Cycle 1, Cycle 2, Cycle 3, Cycle 4, Cycle 5, Cycle 6, Cycle 7, Cycle 8, Cycle 9, Cycle 10, Cycle 11, Cycle 12, Cycle 13, Cycle 14, Cycle 15, Cycle 16, Cycle 17, Cycle 18, Cycle 19, Cycle 20, Cycle 21, Cycle 22, Cycle 23, Cycle 24 etc, wherein pomalidomide is administered as defined herein.

[0255] In some embodiments the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment is administered at least for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 , 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or more about 28 day cycles, which can also be referred to as Cycle 1, Cycle 2, Cycle 3, Cycle 4, Cycle 5, Cycle 6, Cycle 7, Cycle 8, Cycle 9, Cycle 10, Cycle 11, Cycle 12, Cycle 13, Cycle 14, Cycle 15, Cycle 16, Cycle 17, Cycle 18, Cycle 19, Cycle 20, Cycle 21, Cycle 22, Cycle 23, Cycle 24 etc, wherein pomalidomide and dexamethasone are administered as defined herein.Treatment of multiple myeloma (MM)

[0256] In some embodiments, the multiple myeloma is newly diagnosed multiple myeloma. In some embodiments, the multiple myeloma is relapsed, refractory, or malignant, or any combination thereof.

[0257] Various qualitative and / or quantitative methods can be used to determine relapse or refractory nature of the disease. Symptoms that can be associated are for example a decline or plateau of the well-being of the patient or re-establishment or worsening of various symptoms associated with solid tumors, and / or the spread of cancerous cells in the body from one location to other organs, tissues or cells.1004897-1598-5221.1

[0258] The BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof, and pomalidomide may also be administered prophylactically in order to reduce the risk of developing multiple myeloma, delay the onset of the occurrence of an event in multiple myeloma progression, and / or reduce the risk of recurrence when a multiple myeloma is in remission.

[0259] In some embodiments, the multiple myeloma is a high-risk multiple myeloma. Subjects with high-risk multiple myeloma are known to relapse early and have poor prognosis and outcome. Subjects can be classified as having high-risk multiple myeloma if they have one or more of the following cytogenetic abnormalities: t(4;14)(pl6;q32), t(14;16)(q32;q23), dell7p, IqAmp, t(4; 14)(pl6;q32) and t(14;16)(q32;q23), t(4; 14)(pl 6;q32) and dell7p, t(14; 16)(q32;q23) and dell7p, or t(4;14)(pl6;q32), t(14; 16)(q32;q23) and dell7p. In some embodiments, the subject having the high-risk multiple myeloma has one or more chromosomal abnormalities comprising: t(4;14)(pl6;q32), t(14;16)(q32;q23), dell7p, IqAmp, t(4; 14)(pl6;q32) and t(14;16)(q32;q23), t(4; 14)(pl 6;q32) and dell7p, t(14; 16)(q32;q23) and dell7p; or t(4;14)(pl6;q32), t(14; 16)(q32;q23) and dell7p, or any combination thereof.

[0260] In some embodiments, the high-risk multiple myeloma is a newly diagnosed multiple myeloma. Newly diagnosed multiple myeloma subjects can be classified as having high-risk multiple myeloma if they exhibit one or more of the following cytogenetic abnormalities: del(17p), t(4;14), t(14;16), and lq21 gain / lq21 amplification, or any combination thereof. In some embodiments, the newly diagnosed multiple myeloma subjects exhibit a del(17p), t(4; 14), t(14; 16) high-risk cytogenetic abnormality. In some embodiments, the newly diagnosed multiple myeloma subjects exhibit a lq21 gain / lq21 amplification high-risk cytogenetic abnormality.

[0261] The cytogenetic abnormalities can be detected for example by fluorescent in situ hybridization (FISH). In chromosomal translocations, an oncogene is translocated to the IgH region on chromosome 14q32, resulting in dysregulation of these genes. t(4; 14)(pl 6;q32) involves translocation of fibroblast growth factor receptor 3 (FGFR3) and multiple myeloma SET domain containing protein (MMSET) (also called WHSC1 / NSD2), 1014897-1598-5221.1and t(14;16)(q32;q23) involves translocation of the MAF transcription factor C-MAF. Deletion of 17p (dell7p) involves loss of the p53 gene locus.

[0262] Chromosomal rearrangements can be identified using well known methods, for example fluorescent in situ hybridization, karyotyping, pulsed field gel electrophoresis, or sequencing.

[0263] Particular trispecific antibodies that may be used to treat MM include BGCB491.

[0264] As disclosed herein, pomalidomide may be used to treat MM.

[0265] In some embodiments the multiple myeloma is newly diagnosed multiple myeloma.

[0266] In some embodiments wherein the multiple myeloma is relapsed or refractory multiple myeloma (RRMM).

[0267] In some embodiments the relapsed or refractory multiple myeloma is relapsed multiple myeloma. In some embodiments the relapsed or refractory multiple myeloma is refractory multiple myeloma.

[0268] In some embodiments, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof and pomalidomide are utilized for the treatment of relapsed or refractory multiple myeloma. In some embodiments, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof and pomalidomide are utilized for the treatment of relapsed multiple myeloma. In some embodiments, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof and pomalidomide are utilized for the treatment of refractory multiple myeloma.

[0269] In some embodiments, the subject is relapsed or refractory to treatment with a prior anti-cancer treatment. In some embodiments, the prior anti-cancer treatment comprises administering at least one of a proteasome inhibitor and immunomodulatory drug, such as bortezomib, carfilzomib, lenalidomide, or pomalidomide. In some embodiments, the subject is relapsed or refractory to treatment with an anti-CD38 antibody, selinexor, lenalinomide, bortezomib, pomalidomide, carfilzomib, elotozumab, ixazomib, melphalan, thalidomide, melphalan flufenamide, venetoclax or any combination thereof. In some embodiments, the anti-CD38 antibody is daratumumab or isatuximab. In some embodiments, the anti-CD38 antibody is daratumumab. In some embodiments, the subject 1024897-1598-5221.1is refractory to treatment with a proteasome inhibitor (PI). In certain such embodiments, the PI is bortezomib, carfilzomib, or ixazomib. In some embodiments, the subject is refractory to treatment with an immunomodulatory agent (IMiD). In certain such embodiments, the IMiD is thalidomide, lenalidomide, or pomalidomide. In some embodiments, the subject is refractory to treatment with CAR-T. In some embodiments, the subject is refractory to treatment with a proteasome inhibitor (PI), an immunomodulatory agent, and an anti-CD38 antibody. In some embodiments, the subject is refractory to treatment with two proteasome inhibitors (PI), two immunomodulatory agents, and an anti-CD38 antibody. In some embodiments, the subject is refractory to treatment with a BCMA directed therapy. In some embodiments, the subject is refractory to treatment with a GPRC5D directed therapy. In some embodiments, the subject is refractory to treatment with the last line of prior therapy.

[0270] In some embodiments, the subject receiving the BCMA x GPRC5D x CD3 trispecific antibody or binding fragment thereof and pomalidomide has received a prior treatment. In some embodiments, the prior treatment is a BCMA or GPRC directed therapy. In some embodiments, the prior BCMA or GPRC directed therapy is CAR-T therapy. In certain such embodiments, the CAR-T therapy is Carvykti® (ciltacabtagene autoleucel). In some embodiments, the prior BCMA or GPRC directed therapy is a bispecific antibody. In some embodiments, the prior treatment is a BCMA directed therapy. In some embodiments, the prior BCMA directed therapy is CAR-T therapy. In certain such embodiments, the CAR-T therapy is Carvykti® (ciltacabtagene autoleucel). In some embodiments, the prior BCMA directed therapy is a bispecific antibody. In some embodiments, the prior treatment is a GPRC directed therapy, such as a GPRC5D directed therapy. In some embodiments, the prior GPRC directed therapy is CAR-T therapy. In some embodiments, the prior GPRC directed therapy is a bispecific antibody. In other embodiments, the patient is naive to prior BCMA or GPRC directed therapy. In some embodiments, the prior treatment comprises a proteasome inhibitor, an immunomodulatory drug, a CD38 antibody, a CAR-T therapy, or any combination thereof. For example, the subject may have received one or more therapeutics, such as proteasome inhibitors (Pls) 1034897-1598-5221.1(e.g., Marizomib (salinosporamide A), Carfilzomib, Ixazomib), immunomodulatory drugs (IMiDs), CAR-T therapies, and / or anti-CD38 antibodies, for treating multiple myeloma. In certain such embodiments, the PI is bortezomib, carfilzomib or ixazomib. In certain such embodiments, the IMiD is lenalidomide, pomalidomide or thalidomide.In certain such embodiments, the anti-CD38 antibody is daratumumab or isatuximab. In certain such embodiments. In certain such embodiments, the CAR-T therapy is a BCMA CAR-T therapy. In certain such embodiments, the BCMA CAR-T therapy is Carvykti® (ciltacabtagene autoleucel). In some embodiments, the subject receiving the BCMA x GPRC5D x CD3 trispecific antibody or binding fragment thereof has received two prior Pls, two prior IMiDs, and a prior anti-CD38 antibody. In some embodiments, the prior treatment is selinexor. In some embodiments, the prior treatment is venetoclax. In some embodiments, the prior treatment is an antibody-drug conjugate. In some embodiments, the subject has received under three lines of prior therapy. In some embodiments, the subject has received over three lines of prior therapy. In some embodiments, the subject has received 1-3 lines of prior therapy. In some embodiments, the subject suffers from relapsed or refractory multiple myeloma and has received prior treatment with a proteasome inhibitor, an immunomodulatory drug (IMiD), and an anti-CD38-based therapy.

[0271] In some embodiments the subject is relapsed or refractory to treatment with a prior anti-cancer treatment.

[0272] In some embodiments the subject has received >1 lines of prior treatment. In some embodiments the subject has received 1-3 lines of prior treatment.

[0273] In some embodiments, the subject suffers from relapsed or refractory multiple myeloma and has received 1-3 lines of prior therapy. In certain such embodiments, the subject has received a prior PI. In certain such embodiments, the subject has received prior lenalidomide. In certain such embodiments, the subject has received a prior PI and prior lenalidomide.

[0274] In some embodiments the subject is relapsed or refractory to treatment with a prior anti-cancer treatment. In certain such embodiments the prior treatment comprises a proteasome inhibitor, and / or an immunomodulatory drug, such as bortezomib, carfilzomib, 1044897-1598-5221.1lenalidomide, or pomalidomide, or any combination thereof. In certain such embodiments the subject has received >1 lines of prior treatment. In certain such embodiments the subject has received >1 lines of prior treatment. In certain such embodiments the subject has received >2 lines of prior treatment. In certain such embodiments the subject has received 1-3 lines of prior treatment. In certain such embodiments the subject is relapsed or refractory to the lines of prior treatment. In certain such embodiments the subject is refractory to the lines of prior treatment. In certain such embodiments the prior treatment comprises a proteasome inhibitor. In certain such embodiments the prior treatment comprises lenalidomide. In certain such embodiments the prior treatment comprises a proteasome inhibitor and lenalidomide. In certain such embodiments the prior treatment comprises lenalidomide, and wherein the subject is lenalidomide refractory. In certain such embodiments the prior treatment comprises a proteasome inhibitor and lenalidomide, and wherein the subject is lenalidomide refractory.

[0275] In some embodiments the subject has received >1 line of prior treatment. In certain such embodiments the subject is relapsed or refractory to the lines of prior treatment. In certain such embodiments the subject is refractory to the lines of prior treatment. In certain such embodiments the prior treatment comprises a proteasome inhibitor and lenalidomide, and wherein the subject is lenalidomide refractory. In certain such embodiments the subject has received >1 line of prior treatment wherein the prior treatment comprises lenalidomide. In certain such embodiments the subject has received >1 line of prior treatment wherein the prior treatment comprises a proteasome inhibitor and lenalidomide. In certain such embodiments the subject has received >1 line of prior treatment wherein the prior treatment comprises lenalidomide, and wherein the subject is lenalidomide refractory. In certain such embodiments the subject has received >1 line of prior treatment wherein the prior treatment comprises a proteasome inhibitor and lenalidomide, and wherein the subject is lenalidomide refractory.

[0276] In some embodiments the subject has received >2 lines of prior treatment. In certain such embodiments the subject is relapsed or refractory to the lines of prior treatment. In certain such embodiments the subject is refractory to the lines of prior treatment. In certain 1054897-1598-5221.1such embodiments the subject has received >2 lines of prior treatment wherein the prior treatment comprises lenalidomide. In certain such embodiments the subject has received >2 lines of prior treatment wherein the prior treatment comprises a proteasome inhibitor and lenalidomide. In certain such embodiments the subject has received >2 lines of prior treatment wherein the prior treatment comprises lenalidomide, and wherein the subject is lenalidomide refractory. In certain such embodiments the subject has received >2 lines of prior treatment wherein the prior treatment comprises a proteasome inhibitor and lenalidomide, and wherein the subject is lenalidomide refractory.

[0277] It has been found that treatment with a BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof and pomalidomide, and according to specific dosing regimens, may result in safe and effective outcomes for subjects in need of treatment for multiple myeloma (MM).

[0278] Thus, in some embodiments, the subject does not exhibit a dose-limiting toxicity (DLT) or Grade 5 treatment emergent adverse event (TEAE) following administration of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof.

[0279] In some embodiments, the method achieves a partial response (PR), very good partial response (VGPR), complete response (CR) or stringent complete response (sCR) in the subject. In certain such embodiments, the method achieves a partial response (PR), very good partial response (VGPR), complete response (CR) or stringent complete response (sCR) in the subject, according to IMWG criteria.

[0280] In some embodiments, the method achieves a very good partial response (VGPR), complete response (CR) or stringent complete response (sCR) in the subject. In certain such embodiments, the method achieves a very good partial response (VGPR), complete response (CR) or stringent complete response (sCR) in the subject, according to IMWG criteria.

[0281] In some embodiments, the method achieves a complete response (CR) or stringent complete response (sCR) in the subject. In certain such embodiments, the method achieves1064897-1598-5221.1a complete response (CR) or stringent complete response (sCR) in the subject, according to IMWG criteria.

[0282] In some embodiments, the method achieves a stringent complete response (sCR) in the subject. In certain such embodiments, the method achieves a stringent complete response (sCR) in the subject, according to IMWG criteria.

[0283] In some embodiments, the method achieves an overall response rate of about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or about 100% of treated subjects. In one embodiment, the method achieves an overall response rate of about 50% of treated subjects. The overall response rate may be deciphered by calculating the proportion of patients who achieve a partial response, a very good partial response, a complete response, or a stringent complete response.Compositions

[0284] The BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof can be formulated as a pharmaceutical composition. In some embodiments, the pharmaceutical compositions comprise: a) an effective amount of a trispecific antibody or trispecific binding fragmentas disclosed herein , and b) a pharmaceutically acceptable carrier, which may be inert or physiologically active. In some embodiments, the pharmaceutical compositions comprise: a) an effective amount of a trispecific antibody or trispecific binding fragmentas disclosed herein, and b) a pharmaceutically acceptable carrier, which may be inert or physiologically active.

[0285] As used herein, the term "pharmaceutically acceptable carriers" includes any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, and the like that are physiologically compatible.

[0286] In some embodiments, the pharmaceutical composition further comprises one or more excipients. In some embodiments, the one or more excipients include, but are not limited to a buffering agent, a sugar, a surfactant, a chelator, or any combination thereof.

[0287] Examples of suitable carriers, diluents and / or excipients include one or more of water, saline, phosphate buffered saline, dextrose, glycerol, ethanol, and the like, as well as 1074897-1598-5221.1any combination thereof. In many cases, it will be preferable to include isotonic agents, such as sugars, polyalcohols, or sodium chloride in the composition. In particular, relevant examples of suitable carrier include: (1) Dulbecco's phosphate buffered saline, pH.about.7.4, containing or not containing about 1 mg / mL to 25 mg / mL human serum albumin, (2) 0.9% saline (0.9% w / v sodium chloride (NaCl)), and (3) 5% (w / v) dextrose; and may also contain an antioxidant such as tryptamine and a stabilizing agent such as Tween 20®.

[0288] The disclosed compositions may be in a variety of forms. These include for example liquid, semi-solid, and solid dosage forms, but the most suitable form depends on the intended mode of administration and therapeutic application. Typical suitable compositions are in the form of injectable or infusible solutions.

[0289] Sterile compositions for parenteral administration can be prepared by incorporating the disclosed antibody, antibody fragment or antibody conjugate in the required amount in the appropriate solvent, followed by sterilization by microfiltration. As solvent or vehicle, there may be used water, saline, phosphate buffered saline, dextrose, glycerol, ethanol, and the like, as well as combination thereof. In many cases, it will be preferable to include isotonic agents, such as sugars, polyalcohol’s, or sodium chloride in the composition. These compositions may also contain adjuvants, in particular wetting, isotonizing, emulsifying, dispersing and stabilizing agents. Sterile compositions for parenteral administration may also be prepared in the form of sterile solid compositions which may be dissolved at the time of use in sterile water or any other injectable sterile medium.

[0290] Pomalidomide can be formulated as a pharmaceutical composition and is available in the form of commercial formulations (sold under the brand names Pomalyst® and Imnovid®).

[0291] BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof and pomalidomide, are used for the treatment of multiple myeloma (MM). In some embodiments, the multiple myeloma is newly diagnosed multiple myeloma. In some embodiments, the multiple myeloma is a relapsed or refractory form of multiple myeloma.1084897-1598-5221.1In some embodiments, the multiple myeloma is a relapsed form of multiple myeloma. In some embodiments, the multiple myeloma is a refractory form of multiple myeloma.

[0292] Accordingly, the disclosed pharmaceutical compositions are useful in the treatment or prevention of multiple myeloma (MM).

[0293] In some embodiments, the multiple myeloma is a relapsed or refractory form of multiple myeloma.

[0294] A therapeutically effective amount of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof and pomalidomide, is administered to a subject in need thereof. In some embodiments, the subject is a mammal, preferably a human.EMBODIMENTS

[0295] The disclosure provided herein also provides the following non-limiting embodiments.1. A method of treating multiple myeloma in a subject in need thereof, comprising administering a therapeutically effective amount of a BCMA x GPRC5D x CD3 trispecific antibody or a trispecific binding fragment thereof and pomalidomide, to the subject to treat the multiple myeloma, wherein the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered at a treatment dose of at least about 20 mg.2. The method of embodiment 1, wherein the BCMA x GPRC5D x CD3 trispecific antibody or a trispecific binding fragment thereof treatment dose and the pomalidomide dose, respectively, is a flat dose.3. The method of embodiment 1 or embodiment 2, wherein theBCMA x GPRC5D x CD3 trispecific antibody or a trispecific binding fragment thereof treatment dose is about 50 mg, about 100 mg, about 200 mg, or about 300 mg.1094897-1598-5221.14. The method of any one of embodiments 1 to 3, wherein theBCMA x GPRC5D x CD3 trispecific antibody or a trispecific binding fragment thereof treatment dose is about 50 mg.5. The method of any one of embodiments 1-3, wherein theBCMA x GPRC5D x CD3 trispecific antibody or a trispecific binding fragment thereof treatment dose is about 100 mg.6. The method of any one of embodiments 1-3, wherein theBCMA x GPRC5D x CD3 trispecific antibody or a trispecific binding fragment thereof treatment dose is about 200 mg.7. The method of any one of embodiments 1-3, wherein theBCMA x GPRC5D x CD3 trispecific antibody or a trispecific binding fragment thereof treatment dose is about 300 mg.8. The method of any one of embodiments 1-7, wherein the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered once every four weeks.9. The method of embodiment 8, wherein the treatment dose of theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered on Day 1 of at least one treatment cycle of every four weeks or about 28 days.10. The method of embodiment 9, wherein the duration of theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle is about 28 days.11. The method of embodiment 10, wherein the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment dose is administered at least for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more about 28-day BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles.1 . The method of embodiments 10 or 11, wherein the pomalidomide dose is administered during at least one BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle.1104897-1598-5221.113. The method of embodiment 12, wherein the pomalidomide dose is administered during at least one BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle, wherein the administration begins on Day 1 of Cycle 2.14. The method of embodiment 13, wherein the pomalidomide dose is administered for at least 21 days within the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle, wherein the administration begins on Day 1 of the cycle.15. The method of embodiment 14, wherein the pomalidomide is administered at a daily dose of about 2mg, optionally 4mg.16. The method of any one of embodiment 13 to 15, wherein the pomalidomide dose is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of Cycle 3 at a dose of about 4 mg daily for at least 21 days.17. The method of any one of embodiments 13 to 15, wherein the pomalidomide dose is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of any Cycle >2 at a dose of about 4 mg daily for at least 21 days.18. The method of any one of embodiments 13 to 15, wherein the pomalidomide dose is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of any Cycle >2 at a dose of about 2 mg daily, for at least 21 days.I l l4897-1598-5221.119. The method of any one of embodiments 12-18, wherein the pomalidomide dose is administered orally.20. The method of any one of embodiments 1-19, wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof.21. The method of embodiment 20, wherein the first step-up dose is about 5 mg.22. The method of embodiments 20 or 21, wherein the first step-up dose is subcutaneously administered about one week, optionally 2-8 days, prior to the subcutaneous administration of the treatment dose.23. The method of embodiments 20 or 21, wherein the first step-up dose is subcutaneously administered about 6-8 days prior to the subcutaneous administration of the treatment dose.24. The method of embodiments 20 or 21, wherein the first step-up dose is subcutaneously administered about 2-4 days prior to the subcutaneous administration of the treatment dose.25. The method of embodiments 20 or 21, wherein the first step-up dose is subcutaneously administered about 2 to 8 days prior to the subcutaneous administration of the treatment dose, and wherein the first step-up dose is about 5 mg.26. The method of any one of embodiments 20 to 22, wherein the first step-up dose is subcutaneously administered about one week prior to the subcutaneous administration of the treatment dose, and wherein the first step-up dose is about 5 mg.27. The method of any one of embodiments 20, 21 or 23, wherein the first step-up dose is subcutaneously administered about 6-8 days prior to the subcutaneous administration of the treatment dose, and wherein the first step-up dose is about 5 mg.1124897-1598-5221.128. The method of embodiments 20 or 24, wherein the first step-up dose is subcutaneously administered about 2-4 days prior to the subcutaneous administration of the treatment dose, and wherein the first step-up dose is about 2.5 mg.29. The method of any one of embodiments 20, 21 or 24, wherein the first step-up dose is subcutaneously administered about 2-4 days prior to the subcutaneous administration of the treatment dose, and wherein the first step-up dose is about 5 mg.30. A method of treating multiple myeloma in a subject in need thereof, comprising administering a therapeutically effective amount of BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof and pomalidomide, to the subject to treat the multiple myeloma, wherein the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered at a treatment dose of about 50 mg and wherein the treatment dose is administered once every four weeks.31. The method of embodiment 30, wherein the treatment dose of theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered on Day 1 of at least one treatment cycle of every four weeks or about 28 days.32. The method of embodiment 31, wherein the duration of theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle is about 28 days.33. The method of embodiment 32, wherein the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment dose is administered at least for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more about 28-day BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles.34. The method of embodiments 32 or 33, wherein the Pomalidomide dose is administered during at least one BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle.1134897-1598-5221.135. The method of embodiment 34, wherein the pomalidomide dose is administered during at least one BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle, wherein the administration begins on Day 1 of Cycle 2.36. The method of embodiment 35, wherein the pomalidomide dose is administered for at least 21 days within the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle, wherein the administration begins on Day 1 of the cycle.37. The method of embodiment 36, wherein pomalidomide is administered at a daily dose of about 2mg, optionally 4mg.38. The method of any one of embodiments 35 to 37, wherein the pomalidomide dose is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of Cycle 3 at a dose of about 4 mg daily for at least 21 days.39. The method of any one of embodiments 35 to 37, wherein the pomalidomide dose is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of any Cycle >2 at a dose of about 4 mg daily, for at least 21 days.40. The method of any one of embodiments 35 to 37, wherein the pomalidomide dose is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of any Cycle >2 at a dose of about 2 mg daily, for at least 21 days.1144897-1598-5221.141. The method of any one of embodiments 34-40, wherein the pomalidomide dose is administered orally.42. The method of any one of embodiments 30 to 41, wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof.43. The method of embodiment 42, wherein the first step-up dose is about 2.5 mg and is administered about 2-4 days prior to administration of the treatment dose.44. The method of embodiment 42, wherein the first step-up dose is about 5 mg and is administered about 2-4 days prior to administration of the treatment dose.45. The method of embodiment 42, wherein the first step-up dose is about 5 mg and is administered about 2 to 8 days prior to administration of the treatment dose.46. The method of embodiment 42, wherein the first step-up dose is about 5 mg and is administered about one week prior to administration of the treatment dose.47. The method of embodiment 42, wherein the first step-up dose is about 5 mg and is administered about 6-8 days prior to administration of the treatment dose.48. A method of treating multiple myeloma in a subject in need thereof, comprising administering a therapeutically effective amount of BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof and pomalidomide, to the subject to treat the multiple myeloma, wherein the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered at a treatment dose of about 100 mg and wherein the treatment dose is administered once every four weeks.49. The method of embodiment 48, wherein the treatment dose of theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered on Day 1 of at least one treatment cycle of every four weeks or about 28 days.1154897-1598-5221.150. The method of embodiment 49, wherein the duration of theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle is about 28 days.51. The method of embodiment 50, wherein the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment dose is administered at least for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more about 28 day BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles.52. The method of embodiments 50 or 51, wherein the pomalidomide dose is administered during at least one BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle.53. The method of embodiment 52, wherein the pomalidomide dose is administered during at least one BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle, wherein the administration begins on Day 1 of Cycle 254. The method of embodiment 53, wherein the Pomalidomide dose is administered for at least 21 days within the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle, wherein the administration begins on Day 1 of the cycle.55. The method of embodiment 54, wherein the pomalidomide is administered at a daily dose of about 2 mg, optionally 4mg.56. The method of any one of embodiments 53 to 55, wherein the pomalidomide dose is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of Cycle 3 at a dose of about 4 mg daily for at least 21 days.57. The method of any one of embodiments 53 to 55, wherein the pomalidomide dose is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration1164897-1598-5221.1begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of any Cycle >2 at a dose of about 4 mg daily, for at least 21 days.58. The method of any one of embodiments 53 to 55, wherein the pomalidomide dose is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of any Cycle >2 at a dose of about 2 mg daily, for at least 21 days.59. The method of any one of embodiments 52-58, wherein the pomalidomide dose is administered orally.60. The method of any one of embodiments 48-59, wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof.61. The method of embodiment 60, wherein the first step-up dose is about 5 mg and is administered about 2-4 days prior to administration of the treatment dose.62. The method of embodiment 60, wherein the first step-up dose is about 2.5 mg and is administered about 2-4 days prior to administration of the treatment dose.63. The method of embodiment 60, wherein the first step-up dose is about 5 mg and is administered about 2 to 8 days prior to administration of the treatment dose.64. The method of embodiment 60, wherein the first step-up dose is about 5 mg and is administered about one week prior to administration of the treatment dose.65. The method of embodiment 60, wherein the first step-up dose is about 5 mg and is administered about 6-8 days prior to administration of the treatment dose.66. A method of treating multiple myeloma in a subject in need thereof, comprising administering a therapeutically effective amount of BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof and pomalidomide, to1174897-1598-5221.1the subject to treat the multiple myeloma, wherein the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered at a treatment dose of about 200 mg and wherein the treatment dose is administered once every four weeks.67. The method of embodiment 66, wherein the treatment dose of theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered on Day 1 of at least one treatment cycle of every four weeks or about 28 days.68. The method of embodiment 67, wherein the duration of theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle is about 28 days.69. The method of embodiment 68, wherein the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment dose is administered at least for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more about 28 day BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles.70. The method of embodiments 68 or 69, wherein the pomalidomide dose is administered during at least one BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle.71. The method of embodiment 70, wherein the pomalidomide dose is administered during at least one BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle, wherein the administration begins on Day 1 of Cycle 272. The method of embodiment 71, wherein the Pomalidomide dose is administered for at least 21 days within the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle, wherein the administration begins on Day 1 of the cycle.73. The method of embodiment 72, wherein the pomalidomide is administered at a daily dose of about 2 mg, optionally 4mg.1184897-1598-5221.174. The method of any one of embodiments 71 to 73, wherein the pomalidomide dose is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of Cycle 3 at a dose of about 4 mg daily for at least 21 days.75. The method of any one of embodiments 71 to 73, wherein the pomalidomide dose is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of any Cycle >2 at a dose of about 4 mg daily, for at least 21 days.76. The method of any one of embodiments 71 to 73, wherein the pomalidomide dose is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of any Cycle >2 at a dose of about 2 mg daily, for at least 21 days.77. The method of any one of embodiments 70-76, wherein the pomalidomide dose is administered orally.78. The method of any one of embodiments 66-77, wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof.79. The method of embodiment 78, wherein the first step-up dose is about 5 mg and is administered about 2-4 days prior to administration of the treatment dose.80. The method of embodiment 78, wherein the first step-up dose is about 2.5 mg and is administered about 2-4 days prior to administration of the treatment dose.1194897-1598-5221.181. The method of embodiment 78, wherein the first step-up dose is about 5 mg and is administered about 2 to 8 days prior to administration of the treatment dose.82. The method of embodiment 78, wherein the first step-up dose is about 5 mg and is administered about one week prior to administration of the treatment dose.83. The method of embodiment 78, wherein the first step-up dose is about 5 mg and is administered about 6-8 days prior to administration of the treatment dose.84. A method of treating multiple myeloma in a subject in need thereof, comprising administering a therapeutically effective amount of BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof and pomalidomide, to the subject to treat the multiple myeloma, wherein the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered at a treatment dose of about 300 mg and wherein the treatment dose is administered once every four weeks.85. The method of embodiment 84, wherein the treatment dose of theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered on Day 1 of at least one treatment cycle of every four weeks or about 28 days.86. The method of embodiment 85, wherein the duration of theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle is about 28 days.87. The method of embodiment 86 wherein the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment dose is administered at least for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more about 28-day BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles.88. The method of embodiments 86 or 87, wherein the pomalidomide dose is administered during at least one BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle.89. The method of embodiment 88, wherein the pomalidomide dose is administered during at least one BCMA x GPRC5D x CD3 trispecific antibody or trispecific1204897-1598-5221.1binding fragment thereof treatment cycle, wherein the administration begins on Day 1 of Cycle 2.90. The method of embodiment 89, wherein the pomalidomide dose is administered for at least 21 days within the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle, wherein the administration begins on Day 1 of the cycle.91 . The method of embodiment 90, wherein the pomalidomide is administered at a daily dose of about 2 mg, optionally 4mg.92. The method of any one of embodiments 89 to 91, wherein the pomalidomide dose is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of Cycle 3 at a dose of about 4 mg daily for at least 21 days.93. The method of any one of embodiments 89 to 91, wherein the pomalidomide dose is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of any Cycle >2 at a dose of about 4 mg daily, for at least 21 days.94. The method of any one of embodiments 89 to 91, wherein the pomalidomide dose is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of any Cycle >2 at a dose of about 2 mg daily, for at least 21 days.95. The method of any one of embodiments 88-94, wherein the pomalidomide dose is administered orally.1214897-1598-5221.196. The method of any one of embodiments 84-95, wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof.97. The method of embodiment 96, wherein the first step-up dose is about 5 mg and is administered about 2-4 days prior to administration of the treatment dose.98. The method of embodiment 96, wherein the first step-up dose is about 2.5 mg and is administered about 2-4 days prior to administration of the treatment dose.99. The method of embodiment 96, wherein the first step-up dose is about 5 mg and is administered about 2 to 8 days prior to administration of the treatment dose.100. The method of embodiment 96, wherein the first step-up dose is about 5 mg and is administered about one week prior to administration of the treatment dose.101. The method of embodiment 96, wherein the first step-up dose is about 5 mg and is administered about 6-8 days prior to administration of the treatment dose.102. The method of any of embodiments 12-101, wherein dexamethasone is administered in conjunction with pomalidomide.103. The method of embodiment 102, wherein the dexamethasone is administered in conjunction with pomalidomide on designated days of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles.104. The method of any of embodiments 102 or 103 wherein the dexamethasone is administered on Days 1 , 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the administration begins at Day 1 of Cycle 2.105. The method of embodiment 104, wherein the dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein dexamethasone is administered on Days 1, 8, 15, and 22 in Cycles 2 to 4.1224897-1598-5221.1106. The method of any of embodiments 102-105, wherein the dexamethasone is administered at a dose of about 20mg.107. The method of any of embodiments 102-105, wherein the dexamethasone is administered at a dose of about 40mg.108. The method of any of embodiments 102-107, wherein dexamethasone is administered orally.109. The method of any of embodiments 102-107, wherein dexamethasone is administered intravenously.110. The method of any one of embodiments 1-109, wherein theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof comprises:(a) a first antigen-binding arm comprising a first heavy chain variable domain (VH1) and a first light chain variable domain (VL1);(b) a second antigen-binding arm comprising a second heavy chain variable domain (VH2) and a second light chain variable domain (VL2);(c) a third antigen-binding arm comprising a third heavy chain variable domain (VH3) and a third light chain variable domain (VL3), wherein the first antigen-binding arm binds to an epitope on cluster of differentiation 3 (CD3), the second antigen-binding arm binds to an epitope on G-protein coupled receptor family C group 5 member D (GPRC5D), and the third antigen-binding arm binds to an epitope on B cell maturation antigen (BCMA).111. The method of embodiment 110, wherein the VH1 and VL1 of first antigenbinding arm are present in a Fab, the VH2 and VL2 of the second antigen-binding arm are present in a scFv, and the VH3 and VL3 of the third antigen-binding arm are present in a scFv.112. The method of embodiment 110 or embodiment 111, wherein the first antigen-binding arm that binds CD3 comprises a HCDR1 comprising the amino acid sequence of GDSVFNNNAAWS (SEQ ID NO: 4), a HCDR2 comprising the ammo acid sequence of RTYYRSKWLYD (SEQ ID NO: 5), and a HCDR31234897-1598-5221.1comprising the amino acid sequence of GYSSSFDY (SEQ ID NO: 6); and a LCDR1 comprising the amino acid sequence of TGTSSNIGTYKFVS (SEQ ID NO: 1), a LCDR2 comprising the amino acid sequence of EVSKRPS (SEQ ID NO: 2), and a LCDR3 comprising the amino acid sequence of VSYAGSGTLL (SEQ ID NO: 3).113. The method of any one of embodiments 110-112, wherein the first antigenbinding arm that binds CD3 comprises the VH1 of SEQ ID NO: 8 and the VL1 of SEQ ID NO: 7.114. The method of any one of embodiments 110-113, wherein the second antigen-binding arm that binds GPRC5D comprises a HCDR1 comprising the amino acid sequence of GFSLTNIRMSVS (SEQ ID NO: 12), HCDR2 comprising the amino acid sequence of HIFSNDEKS (SEQ ID NO: 13), and a HCDR3 comprising the amino acid sequence of MRLPYGMDV (SEQ ID NO: 14); and a LCDR1 comprising the amino acid sequence of RSSQSLVHSDGNTYLS (SEQ ID NO: 9), a LCDR2 comprising the amino acid sequence of KISNRFF (SEQ ID NO: 10), and a LCDR3 comprising the amino acid sequence of MQATQFPHT (SEQ ID NO: 11).115. The method of any one of embodiments 110-114, wherein the second antigen-binding arm that binds GPRC5D comprises the VH2 of SEQ ID NO: 16 and the VL2 of SEQ ID NO: 15.116. The method of any one of embodiments 110-115, wherein the third antigenbinding arm that binds BCMA comprises a HCDR1 comprising the amino acid sequence of GFTFSSYAMS (SEQ ID NO: 20), a HCDR2 comprising the amino acid sequence of AISGSGGSTY (SEQ ID NO: 21), and a HCDR3 comprising the ammo acid sequence of DEGYSSGHYYGMDV (SEQ ID NO: 22); and a LCDR1 comprising the amino acid sequence of RASQSISSSFLT (SEQ ID NO: 17), a LCDR2 comprising the amino acid sequence of GASSRAT (SEQ ID NO: 18), and a LCDR3 comprising the amino acid sequence of QHYGSSPMYT (SEQ ID NO: 19).1244897-1598-5221.1117. The method of any one of embodiments 110-116, wherein the third antigenbinding arm that binds BCMA comprises the VH3 of SEQ ID NO: 24 and the VL3 of SEQ ID NO: 23.118. The method of any one of embodiments 110-117, wherein the first antigenbinding arm that binds CD3 comprises the HCDR1, the HCDR2, the HCDR3, the LCDR1, the LCDR2 and the LCDR3 of SEQ ID NOs: 4, 5, 6, 1, 2, 3, respectively; the second antigen-binding arm that binds GPRC5D comprises the HCDR1, the HCDR2, the HCDR3, the LCDR1, the LCDR2 and the LCDR3 of SEQ ID NOs: 12, 13, 14, 9, 10 and 11, respectively; and the third antigen-binding arm that binds BCMA comprises the HCDR1, the HCDR2, the HCDR3, the LCDR1, the LCDR2 and the LCDR3 of SEQ ID NOs: 20, 21, 22, 17, 18 and 19, respectively.119. The method of any one of embodiments 110-118, wherein the first antigenbinding arm that binds CD3 comprises the VH1 of SEQ ID NO: 8 and the VL1 of SEQ ID NO: 7; the second antigen-binding arm that binds GPRC5D comprises the VH2 of SEQ ID NO: 16 and the VL2 of SEQ ID NO: 15; and the third antigenbinding arm that binds BCMA comprises the VH3 of SEQ ID NO: 24 and the VL3 of SEQ ID NO: 23.120. The method of any one of embodiments 110-119, wherein theBCMA x GPRC5D x CD3 trispecific antibody comprises a first antigen-binding arm that binds to an epitope on cluster of differentiation 3 (CD3), a second antigen-binding arm that binds to an epitope on G-protein coupled receptor family C group 5 member D (GPRC5D), and a third antigen-binding arm that binds to an epitope on B cell maturation antigen (BCMA), wherein the first antigen-binding arm comprises a heavy chain (HC1) polypeptide and a light chain (LC) polypeptide, wherein the heavy chain (HC1) polypeptide further comprises the second antigen-binding arm, wherein the trispecific antibody, or the trispecific binding fragment thereof, further comprises a single polypeptide comprising the third antigen-binding arm.1254897-1598-5221.1121. The method of embodiment 120, wherein the HC1 of the first antigenbinding arm comprises the amino acid sequence of SEQ ID NO: 29.122. The method of embodiments 120 or 121, wherein the LC of the first antigen-binding arm comprises the amino acid sequence of SEQ ID NO: 30.123. The method of any one of embodiments 120-122, wherein the single polypeptide comprising the third antigen-binding arm comprises an amino acid sequence of SEQ ID NO: 31.124. The method of any one of embodiments 120-123, wherein the first antigenbinding arm comprises an HC1 comprising the amino acid sequence of SEQ ID NO: 29, and a LC comprising the amino acid sequence of SEQ ID NO: 30, and the single polypeptide comprising the third antigen-binding arm comprises the amino acid sequence of SEQ ID NO: 31.125. The method of any one of embodiments 120-124, wherein theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is an (human) IgGl isotype.126. The method of any one of embodiments 120-125, wherein the BCMA x GPRC5D x CD3 trispecific antibody is BGCB491.127. The method of any one of embodiments 1-126, wherein the multiple myeloma is newly diagnosed multiple myeloma.128. The method of embodiment 127, wherein the subject exhibits high-risk cytogenetic abnormalities selected from the group consisting of del(17p), t(4; 14), t(14; 16), and lq21 gain / lq21 amplification.129. The method of embodiment 128, wherein the high-risk cytogenetic abnormalities are identified using fluorescence in situ hybridization (FISH) or next-generation sequencing (NGS).130. The method of any one of embodiments 1-126, wherein the multiple myeloma is relapsed or refractory multiple myeloma (RRMM).131. The method of embodiment 130, wherein the relapsed or refractory multiple myeloma is relapsed multiple myeloma.1264897-1598-5221.1132. The method of embodiment 130, wherein the relapsed or refractory multiple myeloma is refractory multiple myeloma.133. The method of any one of embodiments 1-126 and 130-132, wherein the subject is relapsed or refractory to treatment with a prior anti-cancer treatment.134. The method of embodiment 133, wherein the prior anti-cancer treatment comprises administering at least one of a proteasome inhibitor and immunomodulatory drug, such as bortezomib, carfilzomib, lenalidomide, or pomalidomide.135. The method of any one of embodiments 1-126 and 130-134, wherein the subject has received a prior treatment.136. The method of embodiment 135, wherein the prior treatment comprises a proteasome inhibitor, and / or an immunomodulatory drug, , such as bortezomib, carfilzomib, lenalidomide, or pomalidomide, or any combination thereof.137. The method of any one of embodiments 1-126 and 130-136, wherein the subject has received >1 lines of prior treatment.138. The method of any one of embodiments 1-126 and 130-137, wherein the subject has received >1 lines of prior treatment.139. The method of any one of embodiments 1-126 and 130-138, wherein the subject has received >2 lines of prior treatment.140. The method of any one of embodiments 1-126 and 130-136, wherein the subject has received 1-3 lines of prior treatment141. The method of embodiments 1-126 and 130-140, wherein the subject is relapsed or refractory to the lines of prior treatment.142. The method of embodiment 141, wherein the subject is refractory to the lines of prior treatment.143. The method of any one of embodiments 130 to 142, wherein the prior treatment comprises a proteasome inhibitor.144. The method of any one of embodiments 130 to 142, wherein the prior treatment comprises lenalidomide.1274897-1598-5221.1145. The method of any one of embodiments 130 to 144, wherein the prior treatment comprises a proteasome inhibitor and lenalidomide.146. The method of any one of embodiments 130 to 142 or 144 wherein the prior treatment comprises lenalidomide, and wherein the subject is lenalidomide refractory.147. The method of any of embodiments 130 to 146, wherein the prior treatment comprises a proteasome inhibitor and lenalidomide, and wherein the subject is lenalidomide refractory.148. The method of any one of embodiments 1-147, wherein the subject is a human subject.149. A method of treating multiple myeloma in a subject in need thereof, comprising administering a therapeutically effective amount of aBCMA x GPRC5D x CD3 trispecific antibody and pomalidomide, to the subject to treat the multiple myeloma, wherein:(a) the BCMA x GPRC5D x CD3 trispecific antibody is BGCB491, and wherein the BGCB491 is administered once every four weeks;(b. wherein at least one step-up dose of BGCB491 is subcutaneously administered prior to the subcutaneous administration of the treatment dose, wherein the step-up dose is about 5 mg and is administered about 2 to 8 days prior to the administration of the treatment dose,(c) wherein pomalidomide is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of any Cycle >2 at a dose of about 2 mg daily for at least 21 days,(d) wherein dexamethasone is administered in conjunction with pomalidomide , wherein the dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 of1284897-1598-5221.1each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2, wherein the dexamethasone is administered in Cycles 2 to 4,(e) wherein BGCB491 is administered on Day 1 of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles and(f) wherein the subject has received >1 lines of treatment.150. The method of embodiment 149, wherein the BBGCB491 treatment dose is about 50 mg, about 100 mg, about 200 mg, or about 300 mg.EXAMPLES

[0296] The following examples are provided to supplement the prior disclosure and to provide a better understanding of the subject matter described herein. These examples should not be considered to limit the described subject matter. It is understood that the examples and embodiments described herein are for illustrative purposes only and that various modifications or changes in light thereof will be apparent to persons skilled in the art and are to be included within, and can be made without departing from, the true scope of the invention.EXAMPLE 1 : MOLECULE DESIGN, SEQUENCE, AND STRUCTURE OF BGCB491 TRISPECIFIC ANTIBODY

[0297] BGCB491 is an immunoglobulin (Ig) G1 trispecific antibody that can bind simultaneously or independently to the epsilon subunit of the cluster of differentiation 3 receptor complex (CD3e) (Uniprot ID: P07766) on T lymphocytes (T cells), and to1294897-1598-5221.1GPRC5D (G- protein coupled receptor family C group 5 member D, Uniprot ID: Q9NZD1) and BCMA (B cell maturation antigen, TNFRSF17, Uniprot ID: Q02223) on tumor cells. The antibody features mutations of L234A, L235A, and D265S in the constant region (Fc) to abolish interaction with Fc receptors and heterodimerization is enhanced using the knobs-into-holes platform mutations The anti-CD3e “hole” chain also featured “RF” mutations (H435R, Y436F) to disrupt protein A binding of monomeric and homodimerized hole chains. The molecule comprises an anti-CD3e Fab region on the “hole, RF” chain and an anti-GPRC5D scFv v-region fused onto the C-terminus. The “knob” chain features the anti-BCMA scFv. The trispecific antibody was developed to evaluate the therapeutic potential of dual tumor targeting GPRC5D and BCMA and CD3 for T cell redirection. An illustration of BGCB491 is depicted in FIG. 10.

[0298] The trispecific BGCB491 antibody was generated by co-expression of the anti-CD3 heavy chain (HC) A fused to the C-terminal anti-GPRC5D scFv and anti-CD3 light chain (LC) with the anti-BCMA scFv fused to “knob” containing heavy chain B. The anti-CD3 variable region (VR000017350) was discovered by immunizing transgenic humanized rats [OmniRat (OMT™)] with recombinant CD3s protein. The anti-GPRC5d variable region (VR000038761) featured in BGCB491 is derived from the mAb GC5B680, discovered by immunizing transgenic humanized mice [Ablexis] with DNA encoding GPRC5d. The parent v-region (VR000029832) contained an “NSS” motif in the HC framework 3 region which presented a risk for N-linked glycosylation and which represented a mutation from the IGHV2-26*01 germline. The site was mutated back to the germline sequence “STS” to eliminate the risk for N-linked glycosylation, and this change resulted in the final variable region VR000038761. The anti-BCMA variable region (VR000003260) featured in BGCB491 is derived from the mAb BCMB519, discovered by immunizing transgenic humanized mice [Ablexis] with recombinant BCMA protein. No further modifications were made to this v-region. Both the anti-GPRC5D and anti-BCMA v-regions were formatted as single-chain fragment variable (scFv) in the final molecule.

[0299] The amino acid sequence for the BGCB491 heavy chains and light chain, as deduced from the cDNA sequence (SEQ ID Nos: 165, 166, and 167) of BGCB491 and 1304897-1598-5221.1confirmed by peptide mapping and mass spectrometry is shown below (Table 1). The complementarity-determining regions (CDRs) are defined according to ABM numbering. The Gin residue at position 1 of BGCB491 heavy chain 1, Gin residue at position 1 of BGCB491 light chain, and Glu residue at position 1 of BGCB491 heavy chain 2 constitute the N-termini of the mature chains. Both heavy chains comprising BGCB491 IgGl AAS have the following point mutations: L234A, L235A, and D265S. Heavy chain 1 from BGCB491 features the “hole” mutations: T366S, L368A, Y407V and the RF mutations: H435R, Y436F, while heavy chain 2 features the “knob” mutation: T366W. The knobs- into-holes mutations promote heterodimerization of the Fc3. The “RF” mutations disrupt binding to protein A. The mutations for FcyR receptor silencing (AAS) and the knobs- into-holes mutations are underlined in the sequences below.Table 1. Amino Acid Sequence of BGCB4911314897-1598-5221.1EXAMPLE 2: IN VITRO COMBINATION STUDIES FOR BGCB491 WITH POMALIDOMIDE FOR MULTIPLE MYELOMA

[0300] As described in Example 1, BGCB491 (GPRC5DxBCMAxCD3) is a fully human immunoglobulin (Ig)Gl - L234A, L235A, and D265S (AAS) trispecific antibody that binds to BCMA (LH scFv), GPRC5D (LH scFv), and the epsilon subunit of the CD3 (Fab) T cell receptor complex. The BCMA arm of BGCB491 has a high affinity towards the antigen with a dissociation constant (Kd) value of 0.21nM and the CD3 -engaging arm has a low affinity with a Kd value of 25nM. The GPRC5D arm of BGCB491 has an undetermined binding affinity due to lack of soluble antigen. BGCB491 draws BCMA-1324897-1598-5221.1and GPRC5D- expressing malignant multiple myeloma (MM) cells in close proximity to T cells expressing CD3, leading to T-cell activation and the release of cytotoxic factors such as perforin and granzymes, resulting in subsequent lysis of tumor cells.

[0301] Pomalidomide is an immunomodulatory drug (IMiD) that augments natural killer and T-cell mediated immunity and broadly impacts various molecular and cellular elements within the tumor microenvironment, affecting the concentration of several cytokines that support tumor cell growth (Trudel, Suzanne et al. Belantamab mafodotin, pomalidomide and dexamethasone in refractory multiple myeloma: a phase 1 / 2 trial. Nature medicine vol. 30,2 (2024): 543-551.; Chanan-Khan, A A et al. Pomalidomide: the new immunomodulatory agent for the treatment of multiple myeloma. Blood cancer journal vol. 3,9 el43. 6 Sep. 2013.). Pomalidomide interacts with the E3 ligase cereblon inducing degradation of Ikaros transcription factors as well as modulating various immune compartments through multiple mechanisms [Zhu, Yuan Xiao et al. Molecular mechanism of action of immune-modulatory drugs thalidomide, lenalidomide and pomalidomide in multiple myeloma. Leukemia & lymphoma vol. 54,4 (2013).; Gandhi AK, Kang J, Havens CG, Conklin T, Ning Y, Wu L, Ito T, Ando H, Waldman MF, Thakurta A, Klippel A, Handa H, Daniel TO, Schafer PH, Chopra R. Immunomodulatory agents lenalidomide and pomalidomide co-stimulate T cells by inducing degradation of T cell repressors Ikaros and Aiolos via modulation of the E3 ubiquitin ligase complex CRL4(CRBN.). Br J Haematol. 2014 Mar;164(6):811-21.). It enhances CD4+ and CD8+ T cell co-stimulation, suppresses Tregs, augments NK and NKT cell activation leading to enhanced Antibody-dependent cellular cytotoxicity (ADCC), and induces cell cycle arrest and apoptosis directly in MM cells (Zhu, Yuan Xiao et al. Molecular mechanism of action of immune-modulatory drugs thalidomide, lenalidomide and pomalidomide in multiple myeloma. Leukemia & lymphoma vol. 54,4 (2013).; Quach, H., Ritchie, D., Stewart, A. et al. Mechanism of action of immunomodulatory drugs (IMiDS) in multiple myeloma. Leukemia 24, 22-32 (2010).). Pomalidomide as monotherapy and in combination with other standard of care regimens has been approved for the treatment of patients with MM (U.S. Food and Drug Administration, Center for Drug Evaluation and Research. Pomalyst capsules1334897-1598-5221.12040260rigls000 approval letter, February 3, 2013. Retrieved August 21, 2024, from https: / / www.accessdata.fda.gov / drugsatfda_docs / nda / 2013 / 204026Origls000Approv.pdf)

[0302] This Example describes the cytotoxic effect of pomalidomide in combination with BGCB491 to a Multiple Myeloma cell line (H929). Data generated as part of this Example show that:• Concurrent treatment of H929 tumor cells with pomalidomide and BGCB491 decreases EC50 for tumor cytotoxicity relative to BGCB491 monotherapy treatment• Pomalidomide might increase BGCB491 -mediated T cell activation when treated concurrently with BGCB491 in a donor-dependent mannerPeripheral Blood Mononuclear Cell (PBMC)-mediated Immune Killing Assays.Cell lines and primary cells

[0303] H929 cell lines and Pan T cell lines collected from healthy donor leukopaks were cultured at 37°C, 5% CO2 in complete culture medium (RPMI 1640 with GlutaMAX, 10% HIFBS). All cell lines tested negative for mycoplasma.Table 2. List of ReagentsReagent Catalog number SourceDrug:Pomalidomide P0018-25mg Millipore SigmaCell culture:Heat-inactivated fetal bovine serum 16140-071 GibcoRPMI + GlutaMAX 72400-047 GibcoFlow cytometry:96 well U bottom tissue plates 353077 CorningPBS (no Ca2+ / Mg2+) 10010-023 GibcoStain Buffer (containing BSA) 554657 BD BiosciencesBrilliant Stain Buffer Plus 566385 BD BiosciencesHuman Trustain FcX 422302 Biolegend1344897-1598-5221.1UltraComp Beads Plus Compensation Beads 01-3333-42 ThermoFisherCellTrace™ CFSE Cell Proliferation Kit C34554 ThermoFisherFixable Near-IR Dead Cell Stain Kit L34976 ThermoFisher5mL Eppendorf Tubes 0030119487 EppendorfBUV395Mouse Anti -Human CD3 Antibody 563546 BD BiosciencesBUV737 Mouse Anti -Human TIM3 Antibody 568680 BD BiosciencesBV421 Mouse Anti -Human CD25 Antibody 356114 BiolegendBV650 Mouse Anti -Human CD 137 Antibody 309828 BiolegendBV786 Mouse Anti-Human CD8a Antibody 301046 BiolegendPerCP / Cy5.5 Mouse Anti-Human CD4 Antibody 300530 BiolegendPE Mouse Anti -Human CD69 Antibody 310906 BiolegendPE-Dazzle 594 Mouse Anti-Human CD279 329940 BiolegendAntibodyAlexa 647 Mouse Anti-Human LAG3 Antibody 369304 BiolegendAlexa Fluor 700 Mouse Anti-Human HLA-DR 307626 BiolegendAntibody*BSA, bovine serum albumin; DPBS, Dulbecco’s phosphate-buffered saline; FBS, fetal bovine serum; Fc, fragment crystallizable; RPMI, Roswell Park Memorial Institute; IR infrared; CFSE Carboxyfluorescein succinimidyl ester; BUV Brilliant Ultraviolet; BV Brilliant Violet; PerCP / Cy5.5 Peridinin-chlorophyll-protein complex / Cyanine5.5; PE Phycoerythrin; CD cluster of differentiationTrispecific-mediated T-cell Killing AssaysPreparation of effector and target cells for co-treatment experiments

[0304] T-cell killing assays were performed to determine the cytotoxic effect of the combination of pomalidomide with BGCB491. Briefly, on day 0, Pan T cells were thawed in complete media (RPMI GlutaMAX + 10% v / v HI FBS). Frozen vials were wiped with 70% isopropanol and thawed in a 37°C water bath by gently swirling the vial. After a small amount of ice remained, vials were wiped again with 70% isopropanol and transferred into biosafety cabinet. 10 mL of complete media were transferred to a 15 mL tube and the components of the vials were transferred to the 15mL tube. Cells were centrifuged at 400 x g for 5 minutes at room temperature. After centrifugation, the supernatant was discarded, and the cell pellet was resuspended with 10 mL of complete media and an aliquot was used1354897-1598-5221.1to count cells and assess viability by trypan blue exclusion using the Vi-CELL XR Cell Viability Analyzer (Beckman Coulter). 30 million Pan T cells were transferred to a new 15mL tube and centrifuged at 400 x g for 5 minutes at room temperature. The cells were washed once in lOmL sterile PBS before being stained with a CellTrace Dye. Briefly, a 5 mM stock of the CellTrace CFSE dye was prepared by adding 18pL of sterile DMSO to the vial containing 50pg CFSE and allowing to sit at room temperature in the dark for 30 minutes and then diluted to 1 : 10,000 in PBS. One ml of the diluted CFSE per 10 million effector cells was added to the cells and incubated for 8 minutes at room temperature in the dark. At the end of incubation, staining was quenched by adding 5X RPMI GlutaMAX + 20% v / v HI FBS media. The CellTrace dye - loaded cells were washed three times with RPMI GlutaMAX + 20% v / v HI FBS media then resuspended in lOmL complete media and recounted using the Vi-CELL XR Cell Viability Analyzer (Beckman Coulter). Pan T cells were plated first at a concentration of 20,000 cells per 80pL of complete media in each well of 96well U-bottom plates.

[0305] Tumor cells H929 were collected from a 37°C, 5% CO2 incubator. Cells were counted and viability was determined using Trypan blue exclusion with the Vi-CELL XR Cell Viability Analyzer. Cell suspensions were removed from culture flasks and centrifuged at 400 x g for 5 minutes at room temperature. Target cells were then added at a density of 60,000 cells per 80pl of complete media in each well of 96-well U-bottom plates (1:3 effector (E): target (T) ratio).Trispecific antibody (BGCB491) preparation

[0306] BGCB491 was prepared at a 1 OX concentration in complete media to yield IX when 20pL were added for a total volume of 200pL in each well of a 96-well U-bottom plate. The volume in each well at this step will be 180pL prior to the addition of pomalidomide. Serial dilutions of BGCB491 trispecific antibody (1:3) with a final concentration of: 10, 3, 1, 0.3, 0.1, 0.03, 0.01, 0.003, 0.001, and 0.0003 nM were prepared in a multi-channel reservoir.1364897-1598-5221.1Pomalidomide preparation

[0307] Pomalidomide was prepared at lOx concentration in 2-step dilution (first in DMSO and then in complete media) to yield IX when 20 pl was added to a total volume of 200 pl in each well of 96 well, U-bottom plate. Pomalidomide stock concentration was prepared by dissolving 25mg in 9.1 pL sterile DMSO for a final concentration of lOmM. First, serial dilutions of pomalidomide (1 :3) were done in DMSO to ensure equal concentration of DMSO in each well (lOOOpM, 300 pM, 100 pM, 30 pM, 10 pM, 3 pM and 1 pM). Second, 10X concentrations of 10 pM, 3 pM, 1 pM, 0.3 pM, 0.1 pM, 0.03 pM and 0.01 pM were prepared in complete media using a multi-channel reservoir. Final concentrations of pomalidomide used were 1 pM, 0.3 pM, 0.1 pM, 0.03 pM, 0.01 pM, 0.003 pM and 0.001 pM with a final DMSO concentration of 0.1% per well.Flow Cytometry

[0308] After 72-hour incubation, the cells were spun down and supernatant was saved at - 80°C for cytokine assessment by MSD. The cells were washed in 200pL 1 x PBS and spun down at 400 x g for 5 minutes at room temperature. The supernatant was removed and 50pL of 1:2,000 Live / Dead Viability stain in IxPBS was added and incubated for 30 minutes with shaking at room temperature in the dark. Live / Dead Fixable Near-IR Dead Cell Stain Kit was prepared following manufacturer’s instructions by adding 50ul of sterile DMSO per vial and allowing to sit at room temperature in the dark for 30 minutes and then diluted to 1:2000 in PBS. Following the 30-minute incubation, cells were washed with 200pL BD Stain Buffer (containing BSA) and spun down at 400 x g for 5 minutes. Supernatant was discarded and the cells were then resuspended in 50pL of 1 : 20 Hum...

Claims

CLAIMS1. A method of treating multiple myeloma in a subject in need thereof, comprising administering a therapeutically effective amount of a BCMA x GPRC5D x CD3 trispecific antibody or a trispecific binding fragment thereof and pomalidomide, to the subject to treat the multiple myeloma, wherein the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered at a treatment dose of at least about 20 mg.

2. The method of claim 1, wherein the BCMA x GPRC5D x CD3 trispecific antibody or a trispecific binding fragment thereof treatment dose and the pomalidomide dose, respectively, is a flat dose.

3. The method of claim 1 or claim 2, wherein the BCMA x GPRC5D x CD3 trispecific antibody or a trispecific binding fragment thereof treatment dose is about 50 mg, about 100 mg, about 200 mg, or about 300 mg.

4. The method of any one of claims 1-3, wherein the BCMA x GPRC5D x CD3 trispecific antibody or a trispecific binding fragment thereof treatment dose is about 50 mg.

5. The method of any one of claims 1-3, wherein the BCMA x GPRC5D x CD3 trispecific antibody or a trispecific binding fragment thereof treatment dose is about 100 mg.

6. The method of any one of claims 1-3, wherein the BCMA x GPRC5D x CD3 trispecific antibody or a trispecific binding fragment thereof treatment dose is about 200 mg.

7. The method of any one of claims 1-3, wherein the BCMA x GPRC5D x CD3 trispecific antibody or a trispecific binding fragment thereof treatment dose is about 300 mg.

8. The method of any one of claims 1-7, wherein the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered once every four weeks.1694897-1598-5221.

19. The method of claim 8, wherein the treatment dose of theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered on Day 1 of at least one treatment cycle of every four weeks or about 28 days.

10. The method of claim 9, wherein the duration of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle is about 28 days.

11. The method of claim 10, wherein the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment dose is administered at least for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more about 28-day BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles.

12. The method of claims 10 or 11, wherein the pomalidomide dose is administered during at least one BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle.

13. The method of claim 12, wherein the pomalidomide dose is administered during at least one BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle, wherein the administration begins on Day 1 of Cycle 2.

14. The method of claim 13, wherein the pomalidomide dose is administered for at least 21 days within the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle, wherein the administration begins on Day 1 of the cycle.

15. The method of claim 14, wherein the pomalidomide is administered at a daily dose of about 2mg, optionally 4mg.

16. The method of any one of claim 13 to 15, wherein the pomalidomide dose is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and1704897-1598-5221.1wherein the administration begins at Day 1 of Cycle 3 at a dose of about 4 mg daily for at least 21 days.

17. The method of any one of claims 13 to 15, wherein the pomalidomide dose is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of any Cycle >2 at a dose of about 4 mg daily for at least 21 days.

18. The method of any one of claims 13 to 15, wherein the pomalidomide dose is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of any Cycle >2 at a dose of about 2 mg daily, for at least 21 days.

19. The method of any one of claims 12-18, wherein the pomalidomide dose is administered orally.

20. The method of any one of claims 1-19, wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof.

21. The method of claim 20, wherein the first step-up dose is about 5 mg.

22. The method of claims 20 or 21, wherein the first step-up dose is subcutaneously administered about one week, optionally 2-8 days, prior to the subcutaneous administration of the treatment dose.

23. The method of claims 20 or 21, wherein the first step-up dose is subcutaneously administered about 6-8 days prior to the subcutaneous administration of the treatment dose.1714897-1598-5221.

124. The method of claims 20 or 21, wherein the first step-up dose is subcutaneously administered about 2-4 days prior to the subcutaneous administration of the treatment dose.

25. The method of claims 20 or 21, wherein the first step-up dose is subcutaneously administered about 2 to 8 days prior to the subcutaneous administration of the treatment dose, and wherein the first step-up dose is about 5 mg.

26. The method of any one of claims 20 to 22, wherein the first step-up dose is subcutaneously administered about one week prior to the subcutaneous administration of the treatment dose, and wherein the first step-up dose is about 5 mg.

27. The method of claims 20, 21 or 23, wherein the first step-up dose is subcutaneously administered about 6-8 days prior to the subcutaneous administration of the treatment dose, and wherein the first step-up dose is about 5 mg.

28. The method of claims 20 or 24, wherein the first step-up dose is subcutaneously administered about 2-4 days prior to the subcutaneous administration of the treatment dose, and wherein the first step-up dose is about 2.5 mg.

29. The method of claims 20, 21 or 24, wherein the first step-up dose is subcutaneously administered about 2-4 days prior to the subcutaneous administration of the treatment dose, and wherein the first step-up dose is about 5 mg.

30. A method of treating multiple myeloma in a subject in need thereof, comprising administering a therapeutically effective amount of a BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof and pomalidomide, to the subject to treat the multiple myeloma, wherein the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered at a treatment dose of about 50 mg and wherein the treatment dose is administered once every four weeks.1724897-1598-5221.

131. The method of claim 30, wherein the treatment dose of theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered on Day 1 of at least one treatment cycle of every four weeks or about 28 days.

32. The method of claim 31, wherein the duration of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle is about 28 days.

33. The method of claim 32, wherein the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment dose is administered at least for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more about 28-day BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles.

34. The method of claims 32 or 33, wherein the Pomalidomide dose is administered during at least one BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle.

35. The method of claim 34, wherein the pomalidomide dose is administered during at least one BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle, wherein the administration begins on Day 1 of Cycle 2.

36. The method of claim 35, wherein the pomalidomide dose is administered for at least 21 days within the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle, wherein the administration begins on Day 1 of the cycle.

37. The method of claim 36, wherein pomalidomide is administered at a daily dose of about 2mg, optionally 4mg.

38. The method of any one of claim 35 to 37, wherein the pomalidomide dose is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and1734897-1598-5221.1wherein the administration begins at Day 1 of Cycle 3 at a dose of about 4 mg daily for at least 21 days.

39. The method of any one of claim 35 to 37, wherein the pomalidomide dose is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of any Cycle >2 at a dose of about 4 mg daily, for at least 21 days.

40. The method of any one of claim 35 to 37, wherein the pomalidomide dose is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of any Cycle >2 at a dose of about 2 mg daily, for at least 21 days.

41. The method of any one of claims 34-40, wherein the pomalidomide dose is administered orally.

42. The method of any one of claims 30 to 41, wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof.

43. The method of claim 42, wherein the first step-up dose is about 2.5 mg and is administered about 2-4 days prior to administration of the treatment dose.

44. The method of claim 42, wherein the first step-up dose is about 5 mg and is administered about 2-4 days prior to administration of the treatment dose.

45. The method of claim 42, wherein the first step-up dose is about 5 mg and is administered about 2 to 8 days prior to administration of the treatment dose.

46. The method of claim 42, wherein the first step-up dose is about 5 mg and is administered about one week prior to administration of the treatment dose.1744897-1598-5221.

147. The method of claim 42, wherein the first step-up dose is about 5 mg and is administered about 6-8 days prior to administration of the treatment dose.

48. A method of treating multiple myeloma in a subject in need thereof, comprising administering a therapeutically effective amount of a BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof and pomalidomide, to the subject to treat the multiple myeloma, wherein the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered at a treatment dose of about 100 mg and wherein the treatment dose is administered once every four weeks.

49. The method of claim 48, wherein the treatment dose of theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered on Day 1 of at least one treatment cycle of every four weeks or about 28 days.

50. The method of claim 49, wherein the duration of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle is about 28 days.

51. The method of claim 50, wherein the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment dose is administered at least for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more about 28 day BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles.

52. The method of claims 50 or 51, wherein the pomalidomide dose is administered during at least one BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle.

53. The method of claim 52, wherein the pomalidomide dose is administered during at least one BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle, wherein the administration begins on Day 1 of Cycle 254. The method of claim 53, wherein the Pomalidomide dose is administered for at least 21 days within the BCMA x GPRC5D x CD3 trispecific antibody or1754897-1598-5221.1trispecific binding fragment thereof treatment cycle, wherein the administration begins on Day 1 of the cycle.

55. The method of claim 54, wherein the pomalidomide is administered at a daily dose of about 2 mg, optionally 4mg.

56. The method of any one of claims 53 to 55, wherein the pomalidomide dose is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of Cycle 3 at a dose of about 4 mg daily for at least 21 days.

57. The method of any one of claims 53 to 55, wherein the pomalidomide dose is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of any Cycle >2 at a dose of about 4 mg daily, for at least 21 days.

58. The method of any one of claims 53 to 55, wherein the pomalidomide dose is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of any Cycle >2 at a dose of about 2 mg daily, for at least 21 days.

59. The method of any one of claims 52-58, wherein the pomalidomide dose is administered orally.

60. The method of any one of claims 48-59, wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof.1764897-1598-5221.

161. The method of claim 60, wherein the first step-up dose is about 5 mg and is administered about 2-4 days prior to administration of the treatment dose.

62. The method of claim 60, wherein the first step-up dose is about 2.5 mg and is administered about 2-4 days prior to administration of the treatment dose.

63. The method of claim 60, wherein the first step-up dose is about 5 mg and is administered about 2 to 8 days prior to administration of the treatment dose.

64. The method of claim 60, wherein the first step-up dose is about 5 mg and is administered about one week prior to administration of the treatment dose.

65. The method of claim 60, wherein the first step-up dose is about 5 mg and is administered about 6-8 days prior to administration of the treatment dose.

66. A method of treating multiple myeloma in a subject in need thereof, comprising administering a therapeutically effective amount of a BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof and pomalidomide, to the subject to treat the multiple myeloma, wherein the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered at a treatment dose of about 200 mg and wherein the treatment dose is administered once every four weeks.

67. The method of claim 66, wherein the treatment dose of theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered on Day 1 of at least one treatment cycle of every four weeks or about 28 days.

68. The method of claim 67, wherein the duration of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle is about 28 days.

69. The method of claim 68, wherein the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment dose is administered at least for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more about 28 day BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles.1774897-1598-5221.

170. The method of claims 68 or 69, wherein the pomalidomide dose is administered during at least one BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle.

71. The method of claim 70, wherein the pomalidomide dose is administered during at least one BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle, wherein the administration begins on Day 1 of Cycle 272. The method of claim 71, wherein the Pomalidomide dose is administered for at least 21 days within the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle, wherein the administration begins on Day 1 of the cycle.

73. The method of claim 72, wherein the pomalidomide is administered at a daily dose of about 2 mg, optionally 4mg.

74. The method of any one of claims 71 to 73, wherein the pomalidomide dose is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of Cycle 3 at a dose of about 4 mg daily for at least 21 days.

75. The method of any one of claims 71 to 73, wherein the pomalidomide dose is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of any Cycle >2 at a dose of about 4 mg daily, for at least 21 days.

76. The method of any one of claims 71 to 73, wherein the pomalidomide dose is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and1784897-1598-5221.1wherein the administration begins at Day 1 of any Cycle >2 at a dose of about 2 mg daily, for at least 21 days.

77. The method of any one of claims 70-76, wherein the pomalidomide dose is administered orally.

78. The method of any one of claims 66-77, wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof.

79. The method of claim 78, wherein the first step-up dose is about 5 mg and is administered about 2-4 days prior to administration of the treatment dose.

80. The method of claim 78, wherein the first step-up dose is about 2.5 mg and is administered about 2-4 days prior to administration of the treatment dose.

81. The method of claim 78, wherein the first step-up dose is about 5 mg and is administered about 2 to 8 days prior to administration of the treatment dose.

82. The method of claim 78, wherein the first step-up dose is about 5 mg and is administered about one week prior to administration of the treatment dose.

83. The method of claim 78, wherein the first step-up dose is about 5 mg and is administered about 6-8 days prior to administration of the treatment dose.

84. A method of treating multiple myeloma in a subject in need thereof, comprising administering a therapeutically effective amount of a BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof and pomalidomide, to the subject to treat the multiple myeloma, wherein the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered at a treatment dose of about 300 mg and wherein the treatment dose is administered once every four weeks.

85. The method of claim 84, wherein the treatment dose of theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment1794897-1598-5221.1thereof is administered on Day 1 of at least one treatment cycle of every four weeks or about 28 days.

86. The method of claim 85, wherein the duration of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle is about 28 days.

87. The method of claim 86 wherein the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment dose is administered at least for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more about 28-day BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles.

88. The method of claims 86 or 87, wherein the pomalidomide dose is administered during at least one BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle.

89. The method of claim 88, wherein the pomalidomide dose is administered during at least one BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle, wherein the administration begins on Day 1 of Cycle 2.

90. The method of claim 89, wherein the pomalidomide dose is administered for at least 21 days within the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycle, wherein the administration begins on Day 1 of the cycle.

91. The method of claim 90, wherein the pomalidomide is administered at a daily dose of about 2 mg, optionally 4mg.

92. The method of any one of claims 89 to 91, wherein the pomalidomide dose is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of Cycle 3 at a dose of about 4 mg daily for at least 21 days.1804897-1598-5221.

193. The method of any one of claims 89 to 91, wherein the pomalidomide dose is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of any Cycle >2 at a dose of about 4 mg daily, for at least 21 days.

94. The method of any one of claims 89 to 91, wherein the pomalidomide dose is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of any Cycle >2 at a dose of about 2 mg daily, for at least 21 days.

95. The method of any one of claims 88-94, wherein the pomalidomide dose is administered orally.

96. The method of any one of claims 84-95, wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof.

97. The method of claim 96, wherein the first step-up dose is about 5 mg and is administered about 2-4 days prior to administration of the treatment dose.

98. The method of claim 96, wherein the first step-up dose is about 2.5 mg and is administered about 2-4 days prior to administration of the treatment dose.

99. The method of claim 96, wherein the first step-up dose is about 5 mg and is administered about 2 to 8 days prior to administration of the treatment dose.

100. The method of claim 96, wherein the first step-up dose is about 5 mg and is administered about one week prior to administration of the treatment dose.

101. The method of claim 96, wherein the first step-up dose is about 5 mg and is administered about 6-8 days prior to administration of the treatment dose.1814897-1598-5221.1102. The method of any of claims 12-101, wherein dexamethasone is administered in conjunction with pomalidomide.

103. The method of claim 102, wherein the dexamethasone is administered in conjunction with pomalidomide on designated days of theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles.

104. The method of any of claims 102 or 103 wherein the dexamethasone is administered on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein the administration begins at Day 1 of Cycle 2.

105. The method of claim 104, wherein the dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein dexamethasone is administered on Days 1, 8, 15, and 22 in Cycles 2 to 4.

106. The method of any of claims 102-105, wherein the dexamethasone is administered at a dose of about 20mg.

107. The method of any of claims 102-105, wherein the dexamethasone is administered at a dose of about 40mg.

108. The method of any of claims 102-107, wherein dexamethasone is administered orally.

109. The method of any of claims 102-107, wherein dexamethasone is administered intravenously.

110. The method of any one of claims 1-109, wherein theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof comprises:(a) a first antigen-binding arm comprising a first heavy chain variable domain (VH1) and a first light chain variable domain (VL1);(b) a second antigen-binding arm comprising a second heavy chain variable domain (VH2) and a second light chain variable domain (VL2);1824897-1598-5221.1(c) a third antigen-binding arm comprising a third heavy chain variable domain (VH3) and a third light chain variable domain (VL3), wherein the first antigen-binding arm binds to an epitope on cluster of differentiation 3 (CD3), the second antigen-binding arm binds to an epitope on G-protein coupled receptor family C group 5 member D (GPRC5D), and the third antigen-binding arm binds to an epitope on B cell maturation antigen (BCMA).

111. The method of claim 110, wherein the VH1 and VL1 of first antigenbinding arm are present in a Fab, the VH2 and VL2 of the second antigen-binding arm are present in a scFv, and the VH3 and VL3 of the third antigen-binding arm are present in a scFv.

112. The method of claim 110 or claim 111, wherein the first antigen-binding arm that binds CD3 comprises a HCDR1 comprising the amino acid sequence of GDSVFNNNAAWS (SEQ ID NO: 4), a HCDR2 comprising the ammo acid sequence of RTYYRSKWLYD (SEQ ID NO: 5), and a HCDR3 comprising the amino acid sequence of GYSSSFDY (SEQ ID NO: 6); and a LCDR1 comprising the ammo acid sequence of TGTSSNIGTYKFVS (SEQ ID NO: 1), a LCDR2 comprising the amino acid sequence of EVSKRPS (SEQ ID NO: 2), and a LCDR3 comprising the amino acid sequence of VSYAGSGTLL (SEQ ID NO: 3).

113. The method of any one of claims 110-112, wherein the first antigen-binding arm that binds CD3 comprises the VH1 of SEQ ID NO: 8 and the VL1 of SEQ ID NO: 7.

114. The method of any one of claims 110-113, wherein the second antigenbinding arm that binds GPRC5D comprises a HCDR1 comprising the amino acid sequence of GFSLTNIRMSVS (SEQ ID NO: 12), HCDR2 comprising the amino acid sequence of HIFSNDEKS (SEQ ID NO: 13), and a HCDR3 comprising the amino acid sequence of MRLPYGMDV (SEQ ID NO: 14); and a LCDR1 comprising the amino acid sequence of RSSQSLVHSDGNTYLS (SEQ ID NO: 9), a LCDR2 comprising the amino acid sequence of KISNRFF (SEQ ID NO: 10),1834897-1598-5221.1and a LCDR3 comprising the amino acid sequence of MQATQFPHT (SEQ ID NO: 11).

115. The method of any one of claims 110-114, wherein the second antigenbinding arm that binds GPRC5D comprises the VH2 of SEQ ID NO: 16 and the VL2 of SEQ ID NO: 15.

116. The method of any one of claims 110-115, wherein the third antigenbinding arm that binds BCMA comprises a HCDR1 comprising the amino acid sequence of GFTFSSYAMS (SEQ ID NO: 20), a HCDR2 comprising the amino acid sequence of AISGSGGSTY (SEQ ID NO: 21), and a HCDR3 comprising the ammo acid sequence of DEGYSSGHYYGMDV (SEQ ID NO: 22); and a LCDR1 comprising the amino acid sequence of RASQSISSSFLT (SEQ ID NO: 17), a LCDR2 comprising the amino acid sequence of GASSRAT (SEQ ID NO: 18), and a LCDR3 comprising the amino acid sequence of QHYGSSPMYT (SEQ ID NO: 19).

117. The method of any one of claims 110-116, wherein the third antigenbinding arm that binds BCMA comprises the VH3 of SEQ ID NO: 24 and the VL3 of SEQ ID NO: 23.

118. The method of any one of claims 110-117, wherein the first antigen-binding arm that binds CD3 comprises the HCDR1, the HCDR2, the HCDR3, the LCDR1, the LCDR2 and the LCDR3 of SEQ ID NOs: 4, 5, 6, 1, 2, 3, respectively; the second antigen-binding arm that binds GPRC5D comprises the HCDR1, the HCDR2, the HCDR3, the LCDR1, the LCDR2 and the LCDR3 of SEQ ID NOs: 12, 13, 14, 9, 10 and 11, respectively; and the third antigen-binding arm that binds BCMA comprises the HCDR1, the HCDR2, the HCDR3, the LCDR1, the LCDR2 and the LCDR3 of SEQ ID NOs: 20, 21, 22, 17, 18 and 19, respectively.

119. The method of any one of claims 110-118, wherein the first antigen-binding arm that binds CD3 comprises the VH1 of SEQ ID NO: 8 and the VL1 of SEQ ID NO: 7; the second antigen-binding arm that binds GPRC5D comprises the VH2 of SEQ ID NO: 16 and the VL2 of SEQ ID NO: 15; and the third antigen-binding1844897-1598-5221.1arm that binds BCMA comprises the VH3 of SEQ ID NO: 24 and the VL3 of SEQ ID NO: 23.

120. The method of any one of claims 110-119, wherein theBCMA x GPRC5D x CD3 trispecific antibody comprises a first antigen-binding arm that binds to an epitope on cluster of differentiation 3 (CD3), a second antigen-binding arm that binds to an epitope on G-protein coupled receptor family C group 5 member D (GPRC5D), and a third antigen-binding arm that binds to an epitope on B cell maturation antigen (BCMA), wherein the first antigen-binding arm comprises a heavy chain (HC1) polypeptide and a light chain (LC) polypeptide, wherein the heavy chain (HC1) polypeptide further comprises the second antigen-binding arm, wherein the trispecific antibody, or the trispecific binding fragment thereof, further comprises a single polypeptide comprising the third antigen-binding arm.

121. The method of claim 120, wherein the HC1 of the first antigen-binding arm comprises the amino acid sequence of SEQ ID NO: 29.

122. The method of claims 120 or 121, wherein the LC of the first antigenbinding arm comprises the amino acid sequence of SEQ ID NO: 30.

123. The method of any one of claims 120-122, wherein the single polypeptide comprising the third antigen-binding arm comprises an amino acid sequence of SEQ ID NO: 31.

124. The method of any one of claims 120-123, wherein the first antigen-binding arm comprises an HC1 comprising the amino acid sequence of SEQ ID NO: 29, and a LC comprising the amino acid sequence of SEQ ID NO: 30, and the single polypeptide comprising the third antigen-binding arm comprises the amino acid sequence of SEQ ID NO: 31.

125. The method of any one of claims 120-124, wherein theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is an (human) IgGl isotype.1854897-1598-5221.1126. The method of any one of claims 1-125, wherein the multiple myeloma is newly diagnosed multiple myeloma.

127. The method of claim 126, wherein the subject exhibits high-risk cytogenetic abnormalities selected from the group consisting of del(17p), t(4; 14), t(14; 16), and lq21 gain / lq21 amplification.

128. The method of claim 127, wherein the high-risk cytogenetic abnormalities are identified using fluorescence in situ hybridization (FISH) or next-generation sequencing (NGS).

129. The method of any one of claims 1-125, wherein the multiple myeloma is relapsed or refractory multiple myeloma (RRMM).

130. The method of claim 129, wherein the relapsed or refractory multiple myeloma is relapsed multiple myeloma.

131. The method of claim 129, wherein the relapsed or refractory multiple myeloma is refractory multiple myeloma.

132. The method of any one of claims 1-126 and 129-131, wherein the subject is relapsed or refractory to treatment with a prior anti-cancer treatment.

133. The method of claim 132, wherein the prior anti-cancer treatment comprises administering at least one of a proteasome inhibitor and immunomodulatory drug, such as bortezomib, carfilzomib, lenalidomide, or pomalidomide.

134. The method of any one of claims 1-125 and 129-133, wherein the subject has received a prior treatment.

135. The method of claim 134, wherein the prior treatment comprises a proteasome inhibitor, and / or an immunomodulatory drug, such as bortezomib, carfilzomib, lenalidomide, or pomalidomide, or any combination thereof.

136. The method of any one of claims 1-125 and 129-135, wherein the subject has received >1 lines of prior treatment.

137. The method of any one of claims 1-125 and 129-136, wherein the subject has received >1 lines of prior treatment.1864897-1598-5221.1138. The method of any one of claims 1-125 and 129-137, wherein the subject has received >2 lines of prior treatment.

139. The method of any one of claims 1-125 and 129-135, wherein the subject has received 1 -3 lines of prior treatment140. The method of claims 1-125 and 129-139, wherein the subject is relapsed or refractory to the lines of prior treatment.

141. The method of claim 140, wherein the subject is refractory to the lines of prior treatment.

142. The method of any one of claims 129 to 141, wherein the prior treatment comprises a proteasome inhibitor.

143. The method of any one of claims 129 to 141, wherein the prior treatment comprises lenalidomide.

144. The method of any one of claims 129 to 143, wherein the prior treatment comprises a proteasome inhibitor and lenalidomide.

145. The method of any one of claims 129 to 141 or 143 wherein the prior treatment comprises lenalidomide, and wherein the subject is lenalidomide refractory.

146. The method of any of claims 129 to 145, wherein the prior treatment comprises a proteasome inhibitor and lenalidomide, and wherein the subject is lenalidomide refractory.

147. The method of any one of claims 1-146, wherein the subject is a human subject.

148. A method of treating multiple myeloma in a subject in need thereof, comprising administering a therapeutically effective amount of aBCMA x GPRC5D x CD3 trispecific antibody and pomalidomide, to the subject to treat the multiple myeloma, wherein:(a) the BCMA x GPRC5D x CD3 trispecific antibody is BGCB491, and wherein the BGCB491 is administered once every four weeks;1874897-1598-5221.1(b. wherein at least one step-up dose of BGCB491 is subcutaneously administered prior to the subcutaneous administration of the treatment dose, wherein the step-up dose is about 5 mg and is administered about 2 to 8 days prior to the administration of the treatment dose,(c) wherein pomalidomide is administered during at least two BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2 at a dose of about 2 mg daily for at least 21 days and wherein the administration begins at Day 1 of any Cycle >2 at a dose of about 2 mg daily for at least 21 days,(d) wherein dexamethasone is administered in conjunction with pomalidomide , wherein the dexamethasone is administered during three BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles wherein dexamethasone is administered at a dose of about 40 mg on Days 1, 8, 15, and 22 of each of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, wherein the administration begins at Day 1 of Cycle 2, wherein the dexamethasone is administered in Cycles 2 to 4,(e) wherein BGCB491is administered on Day 1 of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof treatment cycles, and(f) the subject has received >1 lines of treatment.

149. The method of claim 149, wherein the BBGCB491 treatment dose is about 50 mg, about 100 mg, about 200 mg, or about 300 mg.1884897-1598-5221.1

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