Mezigdomide NDA Accepted After Phase 3 Trial Doubled Progression-Free Survival

Bristol Myers Squibb has secured U.S. Food and Drug Administration acceptance of its New Drug Application (NDA) for mezigdomide in combination with carfilzomib and dexamethasone (MeziKd) for adults with relapsed or refractory multiple myeloma (RRMM). The agency has assigned a Prescription Drug User Fee Act target action date of May 13, 2027.

The application is supported by results from the pivotal Phase 3 SUCCESSOR-2 trial (NCT05552976), which demonstrated that MeziKd significantly improved progression-free survival compared with carfilzomib and dexamethasone (Kd) alone in patients whose disease had relapsed after prior therapies, including lenalidomide and anti-CD38 monoclonal antibodies.

Mezigdomide targets cereblon to enhance anti-myeloma activity

Mezigdomide is an investigational oral cereblon E3 ligase modulator (CELMoD), a next-generation targeted protein degradation therapy. By promoting rapid degradation of the transcription factors Ikaros and Aiolos, the drug directly suppresses multiple myeloma cells while enhancing T-cell function and immune activity. Preclinical studies also suggest it may help restore exhausted immune responses.

Relapsed or refractory multiple myeloma remains difficult to treat as many patients become resistant to established therapies, particularly lenalidomide and anti-CD38 antibodies, creating a need for effective new treatment options at first relapse and beyond.

SUCCESSOR-2 showed significant progression-free survival benefit

SUCCESSOR-2 was a global, randomized, open-label, seamless Phase 3 study comparing MeziKd with standard Kd therapy in patients with RRMM. The trial enrolled 479 patients, including 288 treated with MeziKd containing 1.0 mg mezigdomide and 191 receiving Kd.

The primary endpoint was progression-free survival (PFS). Key secondary endpoints included overall survival, overall response rate, duration of response, minimal residual disease negativity, time to next treatment, and health-related quality of life.

The study met its primary endpoint, with median PFS of 18.0 months for MeziKd versus 8.3 months for Kd (hazard ratio 0.48; p<0.0001), representing a 52% reduction in the risk of disease progression or death.

The benefit was observed in a heavily pretreated population. More than 92% of participants had prior exposure to three major drug classes, while 85.8% were refractory to anti-CD38 therapy and 75.8% were refractory to lenalidomide. At the data cutoff, median follow-up was 10.6 months.

The safety profile of MeziKd was consistent with previous studies of mezigdomide and aligned with the established safety profiles of the individual agents in the regimen. No new safety signals were reported.

The SUCCESSOR-2 findings were presented as a late-breaking oral presentation at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting and simultaneously published in The Lancet.

Expanding Bristol Myers Squibb’s CELMoD pipeline

Commenting on the milestone, Cristian Massacesi, MD, executive vice president, chief medical officer and head of development at Bristol Myers Squibb, said the FDA acceptance reflects continued progress in the company’s targeted protein degradation portfolio. He noted that the company now has two investigational agents under FDA review for relapsed or refractory multiple myeloma and continues to expand its CELMoD platform across hematologic malignancies and solid tumors.

Beyond the current filing, mezigdomide is also being evaluated in the ongoing Phase 3 SUCCESSOR-1 trial against another standard-of-care regimen in relapsed or refractory multiple myeloma.

If approved, mezigdomide could provide a new oral CELMoD-based treatment option for patients with relapsed or refractory multiple myeloma whose disease has progressed after current frontline therapies, further expanding the therapeutic landscape for this incurable blood cancer.

Reference

Bristol Myers Squibb – U.S. Food and Drug Administration Accepts Bristol Myers Squibb’s New Drug Application for Mezigdomide in Patients with Relapsed or Refractory Multiple Myeloma