September 23, 2025--PRINCETON, N.J.--(BUSINESS WIRE)-- Bristol Myers Squibb (NYSE: BMY) today announced that the Phase 3 EXCALIBER-RRMM study evaluating iberdomide, an investigational cereblon E3 ligase modulator (CELMoD™), combined with standard therapies (daratumumab + dexamethasone) in patients with relapsed or refractory multiple myeloma (RRMM) demonstrated a statistically significant improvement in minimal residual disease (MRD) negativity rates, compared with the control arm, in a planned interim analysis of the MRD endpoint. In accordance with the trial design and based on the recommendation from the Data Monitoring Committee, the trial will continue without changes to evaluate the other dual-primary endpoint of progression-free survival (PFS), and the key secondary endpoint of overall survival and safety. The safety profile of iberdomide in combination with daratumumab and dexamethasone in this study is generally consistent with previous studies.
“This result builds on our significant experience in both targeted protein degradation and developing new treatment options for patients living with multiple myeloma,” said Anne Kerber, Senior Vice President, Head of Development, Hematology, Oncology and Cell Therapy. “Iberdomide represents the first of a novel class of medicines, called CELMoDs, which has the potential to create a new foundation for multiple myeloma treatment that may be combined with other therapies.”
The company plans to discuss these results with health authorities.
About EXCALIBER-RRMM
EXCALIBER-RRMM (NCT04975997) is a Phase 3, multicenter, two-stage, randomized, open-label study evaluating the efficacy and safety of iberdomide in combination with daratumumab and dexamethasone (IberDd) versus daratumumab, bortezomib, and dexamethasone (DVd) in patients with relapsed or refractory multiple myeloma (RRMM). The study is 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), duration of response (DoR), time to progression (TTP), time to next treatment (TTNT), and health-related quality of life (HR-QoL). Stage 1 of the study identified 1.0 mg iberdomide as the optimal dose based on safety, pharmacokinetics, and efficacy data. In Stage 2, approximately 664 patients were randomized to receive either IberDd or DVd.
About Minimal Residual Disease (MRD)
Minimal residual disease (MRD) refers to the small number of cancer cells that may remain in a patient’s body after treatment and are undetectable using conventional diagnostic methods. In multiple myeloma, MRD assessment has emerged as a highly sensitive and clinically meaningful tool for evaluating treatment response. MRD negativity does not necessarily mean all cancer cells are gone, but it may predict improved clinical outcomes, including longer remission and survival.
Modern MRD detection methods, such as next-generation sequencing (NGS) and next-generation flow cytometry (NGF), can identify one malignant cell among 100,000 (threshold for MRD) to 1,000,000 normal cells, offering unprecedented precision in measuring disease burden. MRD is increasingly being used in clinical trials as a surrogate endpoint for progression-free survival (PFS) and is gaining recognition from regulatory authorities for its role in accelerating therapeutic development.
About Targeted Protein Degradation and Novel CELMoD™ Agents
Targeted protein degradation (TPD) is a differentiated research platform at Bristol Myers Squibb built on more than two decades of scientific expertise, providing new avenues to degrade therapeutically relevant proteins that were previously considered "undruggable." We are the only company that has successfully developed and commercialized protein degrader agents – immunomodulatory drugs (IMiD®) which helped establish the current standard of care in the treatment of multiple myeloma. We are building on this foundation with several investigational protein degraders in clinical trials, leveraging three different modalities including CELMoD™ agents, ligand-directed degraders (LDDs), and degrader antibody conjugates (DACs). This three-pronged approach allows us to match the right therapeutic modality to a molecular mechanism of action to modulate targets most effectively and ultimately provides more opportunities for potential breakthroughs that may offer meaningful new options for patients across a broad range of diseases, in and beyond hematology and oncology. Learn more about the science behind TPD at Bristol Myers Squibb here.
About Bristol Myers Squibb
Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases.