Bristol Myers Squibb reports positive interim Phase 3 SUCCESSOR-2 results showing mezigdomide plus carfilzomib and dexamethasone significantly improved progression-free survival in relapsed or refractory multiple myeloma.
Written By: Samiksha Jadhav BPharm
Reviewed By: Pharmacally Editorial Team
Bristol Myers Squibb has reported positive interim results from the Phase 3 SUCCESSOR-2 trial (NCT05552976), showing that the investigational oral CELMoD agent mezigdomide combined with carfilzomib and dexamethasone significantly improved progression-free survival (PFS) in patients with relapsed or refractory multiple myeloma (RRMM).
The triplet regimen, known as MeziKd, demonstrated a statistically significant and clinically meaningful improvement in PFS compared with the standard doublet regimen of carfilzomib and dexamethasone (Kd). According to the interim analysis, the safety profile of the combination was consistent with the known safety characteristics of mezigdomide and the existing regimen. Patients enrolled in the study will continue to be followed to further assess overall survival and long-term safety outcomes.
Cristian Massacesi, Executive Vice President, Chief Medical Officer and Head of Development at Bristol Myers Squibb, said the results highlight the company’s continued focus on advancing therapies for patients living with multiple myeloma. He noted that the findings reinforce the potential of the company’s CELMoD program and its broader targeted protein degradation platform to deliver effective oral treatment options for patients with difficult-to-treat blood cancers.
Bristol Myers Squibb’s work in multiple myeloma is supported by its targeted protein degradation (TPD) platform, an approach designed to eliminate disease-driving proteins that were previously considered difficult to target using conventional drugs.
Over the past two decades, the company has helped pioneer protein degrader therapies known as immunomodulatory drugs (IMiDs), which have become a cornerstone of treatment for multiple myeloma.
Building on this foundation, the company is advancing a next generation of protein degraders, including CELMoD agents such as mezigdomide, as well as other modalities like ligand-directed degraders (LDDs) and degrader antibody conjugates (DACs). These approaches aim to selectively degrade harmful proteins and expand treatment possibilities across hematologic malignancies and other diseases.
Clinical investigators involved in the study emphasized the need for additional treatment options in relapsed disease. Paul Richardson, MD, Director of Clinical Research and Clinical Program Leader at the Jerome Lipper Multiple Myeloma Center at Dana-Farber Cancer Institute, noted that although treatment advances have improved outcomes, many patients eventually relapse or become resistant to existing therapies. He added that the MeziKd regimen may address an important unmet need for patients previously treated with anti-CD38 therapies and lenalidomide.
Meletios-A. (Thanos) Dimopoulos, MD, Professor and Chairman of the Department of Clinical Therapeutics at Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, said the interim findings suggest that adding mezigdomide to carfilzomib and dexamethasone could provide meaningful clinical benefit earlier in relapse. He also highlighted that CELMoD agents are specifically designed to enhance myeloma cell killing and immune activation compared with earlier IMiD therapies.
SUCCESSOR-2 is a seamless Phase 2/3, multicentre, randomized, open-label trial evaluating the efficacy and safety of mezigdomide in combination with carfilzomib and dexamethasone versus the standard doublet regimen in patients with relapsed or refractory multiple myeloma. The primary endpoint for 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.
Bristol Myers Squibb plans to present detailed results from the study at a future medical meeting and share the findings with health authorities.
References
Bristol Myers Squibb Announces Positive Phase 3 Results from the SUCCESSOR-2 Study of Oral Mezigdomide in Relapsed or Refractory Multiple Myeloma, 09 March 2026, Bristol Myers Squibb – Bristol Myers Squibb Announces Positive Phase 3 Results from the SUCCESSOR-2 Study of Oral Mezigdomide in Relapsed or Refractory Multiple Myeloma
A Study to Evaluate Mezigdomide in Combination with Carfilzomib and Dexamethasone (MeziKD) Versus Carfilzomib and Dexamethasone (Kd) in Participants with Relapsed or Refractory Multiple Myeloma (SUCCESSOR-2) (SUCCESSOR-2), ClinicalTrials.gov ID NCT05552976, https://clinicaltrials.gov/study/NCT05552976
About the Writer
Samiksha Vikram Jadhav is a B.Pharm graduate with a strong academic foundation in pharmaceutical sciences, pharmacology, and drug development. She has a keen interest in healthcare advancements, clinical research, medical writing, and emerging therapies. Her work focuses on presenting developments in the pharmaceutical and healthcare sectors through clear and accurate scientific communication.