Multicenter phase 1-2 trial of REGN5459 for relapsed or refractory multiple myeloma

Multiple myeloma remains incurable, and new treatment options are needed, especially in heavily pretreated relapsed or refractory patients. REGN5459 is a BCMAxCD3 bispecific antibody with low affinity to CD3 on T cells, triggering T-cell activation and plasma cell depletion with low cytokine release preclinically. A multicenter first-in-human phase 1-2 trial evaluated REGN5459 monotherapy for RRMM. REGN5459 had acceptable safety/tolerability, with no grade 3 or higher cytokine release syndrome, and grade 2 ICANS in one patient (2%). The ORR was 100% among patients receiving the RP2D. Median DOR was not reached, with 12-month DOR 66.7% with RP2D. The authors conclude that efficacy in this heavily pretreated cohort was encouraging.