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Bristol Myers Squibb's mezigdomide shows positive phase 3 results in relapsed multiple myeloma

Bristol Myers Squibb announced positive interim results from the SUCCESSOR-2 study, a Phase 3 trial evaluating oral mezigdomide in combination with...

Edited by Robert McTiernan··3 min read

Bristol Myers Squibb Reports Positive Mezigdomide Phase 3 Data in Relapsed Multiple Myeloma

Bristol Myers Squibb announced positive interim results from the SUCCESSOR-2 study, a Phase 3 trial evaluating oral mezigdomide in combination with carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma. The readout marks the first positive Phase 3 study for mezigdomide and the second for the company's CELMoD program, a platform of next-generation cereblon-modulating protein degraders that Bristol Myers Squibb has positioned as central to its hematology pipeline.

Trial specifics

SUCCESSOR-2 (NCT05552976) is a seamless Phase 2/3, multicenter, randomized, open-label trial comparing mezigdomide plus carfilzomib and dexamethasone (MeziKd) against carfilzomib and dexamethasone alone (Kd) in patients with relapsed or refractory multiple myeloma previously exposed to anti-CD38 therapy and lenalidomide. The primary endpoint of the Phase 3 portion was progression-free survival. According to the company, MeziKd demonstrated a statistically significant and clinically meaningful improvement in PFS over Kd. Exact hazard ratios, median PFS values, and p-values were not disclosed in the topline release. Safety findings were consistent with the known profile of mezigdomide and the combination regimen, with no new signals reported. Key secondary endpoints — including overall survival, overall response rate, duration of response, MRD negativity, and health-related quality of life — will be reported at a future medical meeting. Patients continue to be followed for survival and safety.

Bristol Myers Squibb stated that data will be shared with health authorities, though no specific NDA filing timeline was disclosed. Cristian Massacesi, the company's chief medical officer, said the results "reinforce the value of our CELMoD program and our targeted protein degradation platform" and "strengthen our confidence in bringing forward effective, accessible oral treatment options." Mezigdomide has not yet received regulatory approval in any jurisdiction.

Research context

Mezigdomide is a CELMoD agent that binds cereblon, a substrate receptor of the CRL4 E3 ubiquitin ligase complex, and redirects it to ubiquitinate and degrade the transcription factors Ikaros (IKZF1) and Aiolos (IKZF3). These proteins are essential for myeloma cell survival and immune evasion. The mechanism builds on the established IMiD class — lenalidomide and pomalidomide — which Bristol Myers Squibb previously commercialized and which form part of the current standard of care. Mezigdomide was designed for enhanced potency at cereblon relative to earlier IMiDs.

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Multiple myeloma remains incurable, and most patients eventually relapse or become refractory to available regimens. Treatment in the relapsed setting has expanded with bispecific antibodies, CAR-T therapies, and antibody-drug conjugates, but oral options with durable disease control remain limited, particularly for patients who have progressed on anti-CD38 agents and lenalidomide.

The competitive landscape for relapsed or refractory multiple myeloma is dense and spans several modalities. Key competitors include:

  • Bristol Myers Squibb's own iberdomide (CC-220), another CELMoD agent in Phase 3 development in combination with dexamethasone and daratumumab for RRMM.
  • Janssen's talquetamab, a GPRC5D×CD3 bispecific T-cell engager in Phase 3 trials for RRMM.
  • Pfizer's elranatamab, a BCMA×CD3 bispecific antibody in Phase 3 development.
  • Janssen/Legend Biotech's ciltacabtagene autoleucel, a BCMA-directed CAR-T cell therapy approved and in further Phase 3 expansion studies.
  • GSK's belantamab mafodotin, a BCMA-targeted antibody-drug conjugate in ongoing combination studies.

Mezigdomide's oral formulation and its combinability with existing backbone regimens such as carfilzomib-dexamethasone could differentiate it from injectable bispecifics and cell therapies, though full data disclosure will be needed to assess its place in the treatment sequence.

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