Bristol Myers Squibb (BMS) has presented results from the prespecified analysis of the pivotal phase 3 EXCALIBER-RRMM trial evaluating Zenbexus (iberdomide) in combination with daratumumab and dexamethasone (ZDd) versus daratumumab, bortezomib and dexamethasone (DVd) in patients with Relapsed or Refractory Multiple Myeloma (RRMM).

At a median follow-up of 15.7 months among 420 evaluable patients, ZDd demonstrated a statistically significant improvement in the rate of Minimal Residual Disease (MRD)-negative Complete Response (CR). The MRD-negative CR rate was 41.1 percent with ZDd compared with 20.7 percent with DVd, with a difference of 20.4 percentage points.

MRD-negative CR rate and Progression-Free Survival (PFS) are the dual primary endpoints of the trial. The data were presented in a late-breaking oral presentation at the 23rd Annual Meeting of the International Myeloma Society (IMS 2026) in Glasgow, Scotland, from September 23–26, 2026, and were simultaneously published in The Lancet Oncology.

The treatment benefit with ZDd was consistent across prespecified subgroups, including patients previously exposed to lenalidomide and those whose disease was refractory to lenalidomide, including in the last prior line of treatment.

The Overall Response Rate (ORR) was 88.9 percent with ZDd compared with 76.1 percent with DVd. The rate of complete response or better was 45.9 percent with ZDd versus 24.9 percent with DVd.

The safety profile of ZDd was consistent with the known profile of the combination. Grade 3/4 neutropenia occurred in 84.3 percent of patients receiving ZDd compared with 11.3 percent receiving DVd, primarily during the first two treatment cycles. Neutropenia was managed mainly with G-CSF support and temporary dose interruptions. Zenbexus dose reduction due to neutropenia occurred in 13.2 percent of patients, while discontinuation due to neutropenia occurred in 1.0 percent.

Grade 3/4 infections occurred in 39.2 percent of patients in the ZDd group and 21.6 percent in the DVd group. Fatal infections occurred in 2.0 percent and 1.5 percent of patients, respectively. Peripheral sensory neuropathy was reported less frequently with ZDd, occurring in 12.3 percent of patients compared with 42.6 percent with DVd. Grade 3/4 peripheral sensory neuropathy occurred in 2.9 percent and 5.4 percent of patients, respectively.

Based on the EXCALIBER-RRMM results, the US Food and Drug Administration granted accelerated approval on August 13 to Zenbexus in combination with daratumumab and hyaluronidase-fihj and dexamethasone for adults with multiple myeloma who have received at least one prior line of therapy including a proteasome inhibitor and an immunomodulatory agent.

The confirmatory analysis of the PFS endpoint in a cohort of 800 patients is ongoing.

EXCALIBER-RRMM is a phase 3, multicentre, two-stage, randomised, open-label study evaluating the efficacy and safety of ZDd versus DVd in patients with RRMM. The trial included a dose-optimisation stage and assessed MRD-negative CR rate and PFS as dual primary endpoints, along with overall survival, ORR, safety and sustained MRD negativity.

Eligible participants were adults who had received one to two prior lines of anti-myeloma therapy and had progressive disease. A total of 939 patients were randomized. The primary efficacy population for MRD-negative CR comprised the first 420 patients randomised to Zenbexus 1 mg plus daratumumab and dexamethasone or DVd. Treatment in both groups continued until disease progression or unacceptable toxicity.

Zenbexus in combination with daratumumab and hyaluronidase-fihj and dexamethasone is indicated for adults with multiple myeloma who have received at least one prior line of therapy including a proteasome inhibitor and an immunomodulatory agent. The indication was approved under accelerated approval based on MRD-negative CR at any time, with continued approval potentially dependent on verification and description of clinical benefit in confirmatory trials.