Phase 1 study of talquetamab, a humanized GPRC5D x CD3 bispecific antibody, in Japanese patients with relapsed/refractory MM.

The bispecific antibody talquetamab demonstrated substantial responses in heavily pretreated relapsed or refractory multiple myeloma (RRMM) in the global phase 1/2 MonumenTAL-1 study. This study, evaluated the safety and efficacy of talquetamab in Japanese patients with RRMM pretreated with a proteasome inhibitor, immunomodulatory drug, and anti-CD38 monoclonal antibody. The primary endpoints were frequency and type of treatment-emergent adverse events (TEAEs) and serious AEs including dose-limiting toxicity (DLT). The secondary endpoints were overall response (ORR; partial response or better), duration of, and time to response. At data cutoff, 15 patients had received subcutaneous talquetamab at three doses (Cohort 1: 135 µg/kg weekly [QW, n = 4]; Cohort 2: 400 µg/kg [QW, n = 5]; Cohort 3: 800 µg/kg [Q2W, n = 6]). No DLTs, deaths, or AE-related dose reductions/treatment discontinuation were observed. Common TEAEs were neutropenia (60.0%), lymphopenia (53.3%), and CRS (46.7%). TEAEs of clinical interest (all Grade ≤ 2) were dysgeusia, skin toxicity, nail disorder, and dry mouth. With an overall median follow-up of 9.0 months, the ORR was 60.0% (95% confidence interval 32.3%, 83.7%). Talquetamab showed substantial responses in Japanese patients with RRMM, consistent with the global MonumenTAL-1 study, supporting its potential as a new standard of care for Japanese RRMM patients.