On May 29, 2026 Bristol Myers Squibb (NYSE: BMY) reported positive late-breaking results from the Phase 3 SUCCESSOR-2 trial (NCT05552976) of CELMoD (cereblon E3 ligase modulation) mezigdomide in combination with carfilzomib and dexamethasone (MeziKd) versus carfilzomib and dexamethasone alone (Kd) in patients with relapsed or refractory multiple myeloma (RRMM). Results showed MeziKd demonstrated a clinically meaningful and statistically significant improvement in progression-free survival (PFS) (95% CI: 18 months vs. 8.3 months [HR:0.48; p<0.0001]), representing a 52% reduction in the risk of disease progression or death compared with Kd.
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These data, representing the first Phase 3 results for mezigdomide, are being presented in a late-breaking oral presentation (#LBA7506) at the 2026 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.
"The combination of MeziKd demonstrated a promising median progression-free survival rate of 18 months in multiple settings of relapsed, refractory multiple myeloma, along with a consistent safety profile and the convenience of oral administration and ability to implement across diverse care settings," said Paul Richardson, MD, Director of Clinical Research and Clinical Program Leader at the Jerome Lipper Multiple Myeloma Center, the Dana-Farber Cancer Institute and RJ Corman Professor of Medicine, Harvard Medical School. "Maintaining durable disease control becomes an increasing challenge with each line of therapy for patients with relapsed or refractory disease and increasing resistance to therapy, so achieving extended progression-free survival of a year and a half is especially meaningful. These promising results at ASCO (Free ASCO Whitepaper) underscore MeziKd’s potential, particularly for those patients who need additional options after both early and later relapse."
Results also showed significantly improved PFS rates with MeziKd across patients in second- and third-line as well as those with higher-risk disease. Higher overall response rate (80.2% vs 53.4%) and complete response or better (26.7% vs 8.9%) were also seen with MeziKd. Median overall survival was not yet reached. The safety profile of MeziKd was consistent with the known profile of mezigdomide and the combination regimen. Grade 3-4 treatment-emergent adverse events were seen in 83.7% vs 56.5% of patients, with neutropenia in 61.1% vs 9.1%, and infections in 34.0% vs 15.6% of patients treated with MeziKd and Kd, respectively.
"Multiple myeloma is a persistent disease and there remains an urgent unmet need for patients as early as first relapse," said Cristian Massacesi, MD, executive vice president, chief medical officer and head of development, Bristol Myers Squibb. "Importantly, these compelling data further validate our targeted protein degradation platform, and cereblon as a critical therapeutic target in multiple myeloma. Mezigdomide is a very potent, oral CELMoD and we’re committed to bringing it forward as a potential new standard of care for relapsed/refractory multiple myeloma across multiple settings."
Results from SUCCESSOR-2 will be shared with health authorities. Bristol Myers Squibb thanks the patients and investigators involved in this clinical trial.
About SUCCESSOR-2
There is a growing number of patients exposed and/or refractory to lenalidomide and anti-CD38 antibodies from first relapse. The SUCCESSOR-2 trial addressed this growing need. SUCCESSOR-2 (NCT05552976) is an inferential, seamless Phase 2/3, multicenter, randomized, open-label study evaluating the efficacy and safety of mezigdomide in combination with carfilzomib and dexamethasone (MeziKd) versus carfilzomib and dexamethasone (Kd) in patients with relapsed or refractory multiple myeloma (RRMM).
The primary endpoint of the Phase 3 portion is progression-free survival. Key secondary endpoints include overall survival, overall response rate, duration of response, time to progression, time to next treatment, minimal residual disease negativity, and health-related quality of life.
The mezigdomide dose selected for stage 2 of the study was 1.0 mg. In total, 479 patients (288 MeziKd at 1.0 mg of mezigdomide; 191 Kd) were included in the analysis. Median age was 68 with 25.1% of patients ≥75 years old; median number of prior therapies was 2; 92.1% of patients were triple-class-exposed, with 85.8% refractory to an anti-CD38 monoclonal antibody and 75.8% to lenalidomide; 37.2% were exposed to pomalidomide and 7.3% to anti-BCMA treatment. At data cutoff, median follow-up was 10.6 months with 52.4% (MeziKd) and 31.4% (Kd) of patients still on treatment.
About Mezigdomide
Mezigdomide is an oral CELMoD agent from BMS’ targeted protein degradation platform specifically optimized for maximal and rapid degradation of Ikaros and Aiolos target proteins, leading to higher multiple myeloma cell killing and immune stimulation. Early pre-clinical data suggest mezigdomide enhances T cell function and prevents and reinvigorates an exhausted immune system. Two ongoing phase 3 trials (SUCCESSOR-1 and SUCCESSOR-2) are evaluating mezigdomide oral combinations vs. standard of care regimens in relapsed or refractory multiple myeloma.
About Targeted Protein Degradation and CELMoD
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, 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.
(Press release, Bristol-Myers Squibb, MAY 29, 2026, View Source;Standard-of-Care-in-Relapsed-or-Refractory-Multiple-Myeloma/default.aspx [SID1234666193])