Phase 2 Linvoseltamab BCMA×CD3 bispecific T‑cell engager vs Isa‑KRd + ASCT in high‑risk NDMM.

MMRC Horizon Two (NCT07053436) is an open-label, randomized, adaptive platform Phase 2 trial in transplant-eligible, high-risk newly diagnosed multiple myeloma with measurable, symptomatic disease. The shared control arm is Isa‑KRd plus autologous stem cell transplant (ASCT): isatuximab (Sanofi; CD38-directed cytolytic monoclonal antibody) combined with carfilzomib (proteasome inhibitor), lenalidomide (IMiD), and dexamethasone, followed by ASCT. An experimental arm adds linvoseltamab (Regeneron; BCMA×CD3 bispecific antibody that redirects T cells to BCMA-expressing plasma cells) into an induction/consolidation/maintenance framework alongside backbone triplet therapy. The key scientific/commercial angle is moving a BCMA T‑cell engager—validated in relapsed myeloma—into first-line, high-risk disease within a learn-as-you-go platform that can add/retire arms over time. Today’s care for high-risk, transplant-eligible NDMM is induction with a proteasome inhibitor + IMiD + steroid (often with an anti‑CD38 antibody at many centers), then ASCT, consolidation, and maintenance; this trial tests whether earlier BCMA-directed T‑cell engagement can deepen early responses and improve durability beyond intensified quadruplet/transplant approaches.