ZENBEXUS triplet shows superior PFS in relapsed and refractory multiple myeloma – BMS
Bristol Myers Squibb announced positive topline results from the Phase 3 EXCALIBER-RRMM study, evaluating ZENBEXUS (iberdomide) in combination with daratumumab and dexamethasone (ZDd) in 800 patients with multiple myeloma (MM), as early as first relapse.
Results showed ZDd demonstrated a statistically significant improvement in the dual-primary endpoint of progression-free survival (PFS), with median PFS of 42 months for ZDd vs. 20 months for daratumumab, bortezomib and dexamethasone (DVd) [HR:0.49, p<0.000001], representing a 51% reduction in the risk of disease progression or death. Median follow-up was 23 months. The safety profile of ZENBEXUS in combination with standard therapies remained consistent with previously reported safety findings from the study.
These results build on the previously reported improvement in minimal residual disease (MRD)-negative complete response vs. DVd, the other dual-primary endpoint, which supported the FDA approval of ZENBEXUS for RRMM. Detailed MRD results were presented at the International Myeloma Society 23rd annual meeting and simultaneously published in Lancet Oncology.
“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,” said Cristian Massacesi, MD, chief medical officer and head of development at Bristol Myers Squibb. “These findings further underscore the value of ZENBEXUS as an effective oral treatment option that can be easily used in diverse care settings, including community settings, where many patients receive their care. We look forward to sharing full results from the study.”
This data will be presented at the 68th Annual Meeting of the American Society of Hematology in New Orleans, L.A.
About EXCALIBER-RRMM
EXCALIBER-RRMM (NCT04975997) is a Phase 3, multicenter, two-stage, randomized, open-label study evaluating the efficacy and safety of ZENBEXUS (iberdomide) in combination with daratumumab and hyaluronidase-fihj and dexamethasone (ZDd) versus daratumumab, bortezomib, and dexamethasone (DVd) in patients with relapsed or refractory multiple myeloma (RRMM). The study included a dose optimization stage and was designed to assess dual-primary endpoints of minimal residual disease (MRD) negativity and progression-free survival (PFS), with additional secondary endpoints including overall survival (OS), overall response rate (ORR), safety and sustained MRD negativity. Eligible participants included adults with 1 to 2 prior lines of anti-myeloma therapy and progressive disease. The PFS confirmatory analysis population included all 800 patients randomized to ZDd (n=400) or DVd (n=400). Treatment in both arms was administered until disease progression or unacceptable toxicity.
Citation: Iberdomide plus daratumumab and dexamethasone versus daratumumab, bortezomib, and dexamethasone in patients with relapsed or refractory multiple myeloma (EXCALIBER-RRMM): an open-label, randomised, controlled, phase 3 trial. Authors: Sagar Lonial, Meletios A Dimopoulos, Maria Gavriatopoulou et al. Lancet Oncol. 2026 Sep 25:S1470-2045(26)00450-X. doi: 10.1016/S1470-2045(26)00450-X. Epub ahead of print. PMID: 42790445.
