Phase 1 trial of WVT078 with/without WHG626 shows preliminary activity in relapsed/refractory multiple myeloma

This phase 1 dose-escalation clinical trial evaluated the safety, tolerability, and preliminary antitumor activity of the BCMA×CD3 bispecific antibody WVT078, both as monotherapy and in combination with the γ-secretase inhibitor WHG626, in 56 patients with relapsed and/or refractory multiple myeloma. The primary objectives were to determine safety and recommended doses for expansion. The study setting and median follow-up duration were not reported.

Preliminary efficacy data showed an overall response rate (ORR) of 27.3% and a complete response (CR) rate of 12.1% for WVT078 monotherapy. For the combination of WVT078 and WHG626, the ORR was 47.8% and the CR rate was 21.7%. The addition of WHG626 was associated with a numerically higher response rate, but no statistical comparisons or effect sizes were reported. The study has not yet declared recommended doses for expansion, and dose expansion cohorts have not been initiated.

Regarding safety, cytokine release syndrome was the most common treatment-related adverse event across all dose levels. Seven patients experienced dose-limiting toxicities. Data on serious adverse events, discontinuation rates, and specific tolerability profiles were not reported. Key limitations include the early-phase, non-randomized design, small sample size, and lack of long-term follow-up data. The funding source and author conflicts of interest were not disclosed.

For clinical practice, these findings represent preliminary, non-comparative activity signals from a dose-finding study. The observed numerical improvement with the combination requires rigorous evaluation in controlled trials before any conclusions about efficacy or superiority can be drawn. Clinicians should interpret these early results with caution.