Talquetamab (GPRC5D×CD3) + teclistamab (BCMA×CD3) lands on Q2W RP2R with 61.1% ORR and 44.4% ≥CR in extramedullary MM

Talquetamab (Tal), a first-in-class GPRC5D-targeting T-cell–redirecting bispecific antibody, was combined with teclistamab (Tec), a first-in-class BCMA-targeting T-cell–redirecting bispecific, in the RedirecTT-1 Phase 1b/2 dose escalation/expansion study (NCT04586426) in triple-class–exposed RRMM including extramedullary disease (EMD). At the March 18, 2025 cutoff, 38 EMD patients were treated in Phase 1 across multiple schedules; the selected RP2R (Tal 0.8mg/kg + Tec 3.0mg/kg Q2W; n=18) delivered ORR 61.1% with ≥CR 44.4% (vs non-trial “physician’s choice” outcomes in triple-class–exposed EMD where ORR is ~24% and median PFS ~2.7 months). Safety at RP2R was described as manageable and consistent with each monotherapy, and exposure–response modeling in EMD linked higher early-cycle exposure (CavgC1/CtroughC1) to higher ≥CR rates; responders in Phase 2 could later de-escalate to Q4W dosing after early cycles if achieving ≥VGPR.