Phase 2 ramantamig BCMA×GPRC5D×CD3 trispecific mAb with IL-6R blockade (tocilizumab)

Janssen Research & Development (Johnson & Johnson) is running this Phase 2 randomized, double-blind, placebo-controlled trial to test whether a single prophylactic dose of tocilizumab—an IL-6 receptor–blocking monoclonal antibody (marketed by Genentech/Roche as Actemra, also sold by Chugai in some markets)—can prevent or lessen cytokine release syndrome (CRS) when patients start ramantamig (JNJ-79635322). Ramantamig is an IgG1 trispecific T-cell–redirecting antibody targeting BCMA and GPRC5D on myeloma cells and CD3 on T cells, designed to drive cytotoxic T-cell killing but with CRS risk typical of T-cell engagers. Adults with relapsed/refractory multiple myeloma and measurable disease after prior therapy are eligible, and the primary readout focuses on being alive and free of ASTCT grade 2+ CRS through day 28. The key commercial/scientific angle is “supportive-care as an enabler”: if IL-6R prophylaxis reduces clinically meaningful CRS without blunting activity, it could broaden outpatient feasibility and accelerate adoption of next-generation trispecifics. Today’s care for later-line myeloma is sequential combinations (anti-CD38 antibodies, IMiDs, proteasome inhibitors), plus BCMA-directed options (CAR-T or bispecifics) when available, with CRS typically managed reactively rather than prevented.