MK-4002 (BCMA×CD3 trispecific T-cell engager) drives 63% ORR at 12 mg in heavily pretreated RRMM

MK-4002 (formerly HPN217) is an intravenous trispecific T-cell engager that binds BCMA on myeloma cells, CD3 on T cells, and serum albumin to extend its circulating half-life; it was evaluated in a first-in-human, open-label Phase 1 dose-escalation/expansion study in relapsed/refractory multiple myeloma after ≥3 prior therapies (median 6 prior lines; n=97; NCT04184050) across France/Spain/USA. Safety was dominated by cytopenias (grade 3+ AEs in 79%), with grade 3+ anemia 34%, decreased neutrophil count 23%, and neutropenia 19%; cytokine release syndrome occurred in 30% (mostly grade 1–2; grade 3 in 2 patients, both at 24 mg) and there was 1 treatment-related death (traumatic subdural hematoma). Among response-evaluable patients, ORR was 41% at 2.15–6 mg (n=27), 63% at 12 mg (n=19), and 48% at 24 mg (n=33), with ≥VGPR in 9/27, 10/19, and 12/33, respectively; the preliminary RP2D was set at 12 mg—numerically in the ballpark of BCMA bispecific benchmarks like teclistamab (ORR ~63%) and elranatamab (ORR ~61%) and higher than historical belantamab mafodotin monotherapy in similar late-line populations (ORR ~31–32%), though cross-trial comparisons are inherently noisy.