Forimtamig (GPRC5D×CD3 2:1 bispecific) posts 72% ORR at optimized SC dosing—but toxicity caps escalation in RRMM

Forimtamig is a subcutaneous GPRC5D×CD3 T-cell–engaging bispecific antibody using a novel 2:1 format, evaluated in a Phase 1 dose-escalation/backfill study in relapsed/refractory multiple myeloma (RRMM; NCT04557150). In 171 enrolled patients (median age 64; high-risk cytogenetics 32.2%; triple-class refractory 60.2%), MTD was not identified and escalation stopped at a 7.2mg target dose due to accumulating toxicity; dose-limiting toxicities occurred in 11.7%, CRS was common (75.4%), and grade 5 AEs occurred in 6.4% (treatment-related in 2 patients). Across all cohorts ORR was 59.6%; at optimized target doses (0.75mg/1.5mg), ORR was 71.7% with a condensed step-up schedule (n=46) vs 47.1% with weekly step-up (n=34)—numerically in the same ballpark as the approved GPRC5D×CD3 bispecific talquetamab at its RP2Ds (ORR ~69–74% in MonumenTAL-1), while CRS rates look similarly high for the GPRC5D class (talquetamab CRS ~73–80%).