ZENBEXUS (iberdomide) in combination with daratumumab and hyaluronidase-fihj and dexamethasone (ZDd) - (EXCALIBER-RRMM)

September 24, 2026: Bristol Myers Squibb (NYSE: BMY) reported first presentation at IMS 2026 of a prespecified analysis from the pivotal Phase 3 EXCALIBER-RRMM trial (NCT04975997) of ZENBEXUS (iberdomide) plus daratumumab and dexamethasone (ZDd) in relapsed/refractory multiple myeloma.

At median follow-up of 15.7 months in 420 evaluable patients, ZDd significantly improved the dual primary endpoint of MRD-negative complete response rate versus daratumumab, bortezomib and dexamethasone (DVd): 41.1% vs 20.7% (95% CI 11.5%-28.6%; p<0.0001; OR 2.75, 95% CI 1.77-4.30). ORR was 88.9% vs 76.1%, and complete response or better was 45.9% vs 24.9%. Benefit was consistent across prespecified subgroups, including prior lenalidomide-exposed and lenalidomide-refractory patients.

Safety was consistent with the regimen: grade 3/4 neutropenia 84.3% vs 11.3%, grade 3/4 infections 39.2% vs 21.6%, fatal infections 2.0% vs 1.5%, while peripheral sensory neuropathy was lower with ZDd (12.3% vs 42.6%; grade 3/4 2.9% vs 5.4%).

The results were simultaneously published in The Lancet Oncology. The company said the regimen received FDA accelerated approval on August 13 for adults with multiple myeloma after at least one prior line including a proteasome inhibitor and an immunomodulatory agent; confirmatory PFS analysis in an n=800 cohort is ongoing.