Bristol Myers Squibb announced positive topline results from the Phase 3 EXCALIBER-RRMM trial, showing that iberdomide (ZENBEXUS) in combination with daratumumab and dexamethasone significantly improved progression-free survival in patients with relapsed or refractory multiple myeloma, as early as first relapse.
Median progression-free survival reached 42 months with the iberdomide combination, compared with 20 months with daratumumab, bortezomib and dexamethasone. The findings represent a 51% reduction in the risk of disease progression or death, with a hazard ratio of 0.49 and a p-value below 0.000001.
The analysis included 800 patients, with a median follow-up of 23 months. According to the company, the safety profile of the iberdomide combination remained consistent with previously reported findings.
Progression-Free Survival Results Build on Earlier MRD Findings
The latest analysis demonstrated a statistically significant improvement in progression-free survival, one of the trial’s two primary endpoints.
These results build on the previously reported improvement in minimal residual disease (MRD)-negative complete response compared with daratumumab, bortezomib and dexamethasone, the other primary endpoint. Those earlier findings supported the U.S. Food and Drug Administration’s accelerated approval of iberdomide in combination with daratumumab and hyaluronidase-fihj and dexamethasone for previously treated multiple myeloma.
Detailed MRD results were presented at the 23rd Annual Meeting of the International Myeloma Society and simultaneously published in The Lancet Oncology.
Cristian Massacesi, MD, chief medical officer and head of development at Bristol Myers Squibb, said:
“The results from EXCALIBER-RRMM reinforce the clinical value of ZENBEXUS in combination with daratumumab and dexamethasone as a treatment approach for relapsed or refractory multiple myeloma, demonstrating the strong benefit observed for minimal residual disease negativity translated to a meaningful improvement in progression-free survival for patients.”
Massacesi also highlighted the findings as further evidence supporting iberdomide as an effective oral treatment option that can be administered across diverse care settings, including community practices where many patients receive care. He said the company looks forward to sharing the full study results.
Inside the Phase 3 EXCALIBER-RRMM Trial
EXCALIBER-RRMM (NCT04975997) is a multicenter, two-stage, randomized, open-label Phase 3 study evaluating the efficacy and safety of iberdomide in combination with daratumumab and hyaluronidase-fihj and dexamethasone against daratumumab, bortezomib and dexamethasone.
Eligible participants were adults with progressive multiple myeloma who had received one or two prior lines of anti-myeloma therapy.
The progression-free survival confirmatory analysis population included 800 patients, with 400 randomized to each treatment group. Treatment continued until disease progression or unacceptable toxicity.
The study included a dose optimization stage and was designed to assess MRD negativity and progression-free survival as its two primary endpoints. Secondary endpoints included overall survival, overall response rate, safety and sustained MRD negativity.
Current Indication and Safety Profile
Iberdomide, 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 containing a proteasome inhibitor and an immunomodulatory agent.
The indication received accelerated approval based on MRD-negative complete response at any time. The release states that continued approval may depend on verification and description of clinical benefit in confirmatory trials.
While the safety profile in the latest analysis remained consistent with earlier findings, the release outlines significant treatment risks. Iberdomide carries boxed warnings for embryo-fetal toxicity and serious venous and arterial thromboembolism. It is contraindicated during pregnancy and is available through a restricted distribution program because of the risk of fetal harm.
Additional warnings include severe neutropenia, serious infections and second primary malignancies. The release recommends thromboprophylaxis and monitoring for blood count changes, infections and thromboembolic events.
Full Results to Be Presented at ASH
Bristol Myers Squibb plans to present the new data at the 68th Annual Meeting of the American Society of Hematology in New Orleans.
The topline findings add progression-free survival evidence to the previously reported MRD-negative complete response benefit. Full results will provide further detail on the iberdomide combination’s performance in patients with relapsed or refractory multiple myeloma.