Bristol Myers Squibb announced Thursday that its Phase 3 EXCALIBER-RRMM study of ZENBEXUS (iberdomide) in combination with daratumumab and dexamethasone met its progression-free survival endpoint in relapsed or refractory multiple myeloma. The trial randomized 800 patients as early as first relapse to the Zenbexus combo (ZDd) or daratumumab, bortezomib and dexamethasone (DVd).
The headline numbers are strong. Median progression-free survival was 42 months on ZDd versus 20 months on DVd, a hazard ratio of 0.49 with a p-value below 0.000001, translating to a 51 percent reduction in the risk of disease progression or death. Median follow-up was 23 months. Safety was consistent with previously reported findings from the study, and the trial is open-label.
The context matters more than the headline. EXCALIBER-RRMM carried dual primary endpoints: the minimal residual disease-negative complete response result reported earlier, which supported the FDA’s accelerated approval of Zenbexus for relapsed or refractory myeloma, and now the PFS confirmation. Accelerated approvals require clinical-benefit confirmation, so a clean PFS win de-risks the drug’s continued approval and backs the earlier surrogate-endpoint evidence with hard survival data.
Commercially, the result strengthens Bristol Myers’s hand in the earlier-relapse segment of myeloma, where treatment choice is contested among Johnson and Johnson’s Darzalex-based regimens, AbbVie’s Epkinly franchise expansion, and now Zenbexus. The company did not report overall survival trends or detailed subgroup data in the topline; those will come at a future medical meeting. For investors watching whether accelerated approvals survive confirmatory readouts, this one did.