Abstract: Background: This first-in-human phase 1 study evaluated the B-cell maturation antigen (BCMA)×CD3 bispecific antibody WVT078 alone and in combination with the ?-secretase inhibitor WHG626 in patients with relapsed/refractory multiple myeloma (r/r MM).
Method: 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.
Result: 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.
Conclusion: 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.
