Bristol Myers Squibb (BMS) reported positive late‑breaking Phase 3 data showing that its CELMoD (cereblon E3 ligase modulator) mezigdomide, combined with carfilzomib and dexamethasone (MeziKd), significantly reduced the risk of disease progression or death versus carfilzomib and dexamethasone alone (Kd) in relapsed or refractory multiple myeloma (RRMM). In the Phase 3 SUCCESSOR‑2 trial (NCT05552976), MeziKd achieved a median progression‑free survival (PFS) of 18 months compared with 8.3 months for Kd, corresponding to a 52% reduction in the risk of progression or death (HR 0.48; p<0.0001). These first Phase 3 results for mezigdomide are being presented in a late‑breaking oral session (#LBA7506) at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting.
Paul Richardson, MD, director of clinical research and clinical program leader at the Jerome Lipper Multiple Myeloma Center at Dana‑Farber Cancer Institute and RJ Corman Professor of Medicine at Harvard Medical School, said the MeziKd combination delivered a “promising” median PFS of 18 months across multiple RRMM settings, with a consistent safety profile and the convenience of oral administration. He noted that maintaining durable disease control becomes more challenging with each line of therapy as resistance increases, and that achieving an extended PFS of a year and a half is particularly meaningful for patients who need options after both early and later relapse.
Beyond the primary endpoint, MeziKd showed significantly improved PFS rates in patients treated in the second‑ and third‑line settings and in those with higher‑risk disease. The regimen also produced higher overall response rates (80.2% vs 53.4% with Kd) and higher rates of complete response or better (26.7% vs 8.9%). Median overall survival had not yet been reached at the time of analysis. The safety profile of the combination was consistent with known data for mezigdomide and the regimen: grade 3–4 treatment‑emergent adverse events occurred in 83.7% of patients on MeziKd versus 56.5% on Kd, including neutropenia in 61.1% vs 9.1% and infections in 34.0% vs 15.6%, 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 at Bristol Myers Squibb. He said the SUCCESSOR‑2 data further validate the company’s targeted protein degradation platform and reinforce cereblon as a key therapeutic target in multiple myeloma. Massacesi described mezigdomide as a very potent, oral CELMoD and stated that BMS is committed to advancing it as a potential new standard of care for relapsed or refractory multiple myeloma across multiple treatment settings.
Bristol Myers Squibb plans to share the SUCCESSOR‑2 results with health authorities.
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