Journal Article

DKFZ-2026-00690

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Final clinical data of a phase 1 dose-escalation study of WVT078, a BCMA×CD3 bispecific antibody, alone and in combination with γ-secretase inhibitor WHG626 in patients with relapsed and/or refractory multiple myeloma.

Schjesvold, F. ; Spencer, A. ; Cohen, Y. C. ; Ocio, E. M. ; Lopez-Pardo, J. ; Cafro, A. M. ; Callander, N. S. ; Kaufman, J. L. ; Mohan, M. ; Wermke, M.DKFZ* ; Doki, N. ; Kan, R. ; Milanez-Almeida, P. ; Stein, A. ; Trabucco, G. ; Ye, S. ; Kulec, K. ; Sechaud, R. ; Banerjee, S. ; Zhong, H. ; Lai, C. ; Rauch, P. J. ; Raab, M. S.

2026
Wiley-Liss New York, NY

Abstract: This first-in-human phase 1 study evaluated the B-cell maturation antigen (BCMA)×CD3 bispecific antibody WVT078 alone and in combination with the γ-secretase inhibitor WHG626 in patients with relapsed/refractory multiple myeloma (r/r MM).The primary objectives were to assess safety, tolerability, and to determine the recommended doses (RDs) and regimens for expansion for WVT078 and WHG626. Secondary objectives included the assessment of preliminary antitumor activity and characterization of pharmacokinetics and immunogenicity.Overall, 56 patients were treated in the dose-escalation part of the study, seven of whom experienced dose-limiting toxicities. Across all dose levels, cytokine release syndrome was the most common treatment-related adverse event. WVT078 monotherapy showed an overall response rate (ORR) of 27.3% and a complete response rate (CRR) of 12.1%. WVT078 combined with WHG626 demonstrated an ORR of 47.8% and a CRR of 21.7%. RDs were not declared, and dose expansion was not initiated.WVT078 administered with and without WHG626 showed a manageable safety profile. Preliminary activity was observed in patients with r/r MM. The addition of WHG626 numerically improved response over WVT078 monotherapy. Findings from this study support further evaluation of WHG626 as a combination partner of BCMA-targeting agents for r/r MM treatment.

Keyword(s): Humans (MeSH) ; Antibodies, Bispecific: administration & dosage (MeSH) ; Antibodies, Bispecific: adverse effects (MeSH) ; Antibodies, Bispecific: pharmacokinetics (MeSH) ; Antibodies, Bispecific: therapeutic use (MeSH) ; Female (MeSH) ; Male (MeSH) ; Middle Aged (MeSH) ; Amyloid Precursor Protein Secretases: antagonists & inhibitors (MeSH) ; Multiple Myeloma: drug therapy (MeSH) ; Multiple Myeloma: pathology (MeSH) ; Multiple Myeloma: immunology (MeSH) ; Aged (MeSH) ; B-Cell Maturation Antigen: immunology (MeSH) ; Adult (MeSH) ; Antineoplastic Combined Chemotherapy Protocols: therapeutic use (MeSH) ; Antineoplastic Combined Chemotherapy Protocols: adverse effects (MeSH) ; Antineoplastic Combined Chemotherapy Protocols: administration & dosage (MeSH) ; Antineoplastic Combined Chemotherapy Protocols: pharmacokinetics (MeSH) ; Antigens, CD19: immunology (MeSH) ; Aged, 80 and over (MeSH) ; Maximum Tolerated Dose (MeSH) ; Neoplasm Recurrence, Local: drug therapy (MeSH) ; Dose-Response Relationship, Drug (MeSH) ; BCMA×CD3 bispecific antibody ; WHG626 ; WVT078 ; combination therapy ; dose‐escalation study ; relapsed and/or refractory multiple myeloma ; γ‐secretase inhibitor ; Antibodies, Bispecific ; Amyloid Precursor Protein Secretases ; B-Cell Maturation Antigen ; Antigens, CD19

Note: #NCTZFB9#

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Contributing Institute(s):

1. Koordinierungsstelle NCT Dresden (DD04)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2026

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; DEAL Wiley ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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