Bristol Myers Squibb reports 51% lower progression or death risk with Zenbexus regimen
EXCALIBER-RRMM met its second primary endpoint, with median progression-free survival estimated at 42 months versus 20 months.
Adrian Kessler
A 51 per cent reduction in progression or death risk for a Zenbexus combination marked its second positive primary endpoint as Bristol Myers Squibb NYSEBMY reported on Oct. 8 that its Phase 3 myeloma trial met the progression-free survival endpoint. Estimated median progression-free survival was 42 months on the Zenbexus regimen against 20 months on the active control.
The open-label EXCALIBER-RRMM study randomized 800 adults after one or two prior lines of treatment, with 400 in each arm. Zenbexus, also called iberdomide, was combined with daratumumab and dexamethasone; the control replaced Zenbexus with bortezomib while keeping the other two medicines. The trial record identifies progression-free survival and minimal residual disease-negative complete response as its two primary measures.
Bristol Myers is a Princeton-based drugmaker that develops and sells medicines for cancer, blood disorders and other serious diseases worldwide.
Bristol Myers shares fell in New York on Oct. 9. They stood at US$59.12 as of 4:00:03 p.m. EDT, according to the NYSEBMY quote. The company plans to present full results at the American Society of Hematology's Dec. 12 to 15 meeting in New Orleans.
Progression-Free Survival Tests Clinical Benefit
At a median follow-up of 23 months, Bristol Myers reported a progression-free survival hazard ratio of 0.49 and a p value below 0.000001. The hazard ratio corresponds to a 51 per cent reduction in progression or death risk for the Zenbexus combination against the trial's active control. The company described the combination's safety as consistent with earlier findings, though its Oct. 8 topline announcement did not give adverse event rates by treatment arm or overall survival figures.
The result follows the trial's earlier success on minimal residual disease-negative complete response, a measure of how much cancer remains after treatment. That first measure supported the FDA's accelerated approval of Zenbexus in combination with daratumumab and dexamethasone; the August 2026 label limits use to adults whose prior treatment included a proteasome inhibitor and an immunomodulatory agent.
"Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s)," the FDA says in its August 2026 prescribing information.
The FDA's August review recommended accelerated approval based on the earlier response data. Bristol Myers calls the new progression-free survival analysis confirmatory evidence, while the drug's current FDA label still describes accelerated approval.
Read more: Roche Holding AG gains FDA approval for Tecentriq in stage III dMMR colon cancer
The Control Arm Used the Same Antibody
Daratumumab appeared in both trial arms, so Zenbexus was tested against a regimen using bortezomib on the same antibody and steroid backbone. The October result measures that specific switch. It does not establish how Zenbexus compares with every other treatment used after a myeloma relapse.
The two primary endpoints answer different questions: the earlier response measure assessed remaining cancer, while progression-free survival tracked how long patients lived without worsening disease. The reported medians are estimates from the trial population, and the 23-month median follow-up is shorter than the 42-month estimated median for the Zenbexus arm.
Read more: argenx reports Phase 2 FB102 celiac trial met primary endpoint
The FDA label also carries boxed warnings about embryo-fetal toxicity and serious blood clots, and warns of neutropenia and infections. The Dec. 12 to 15 ASH presentation will show how the progression-free survival benefit sits alongside the trial's detailed safety findings.
