Bristol Myers Squibb (NYSE: BMY) reported Phase III data from the SUCCESSOR-2 trial showing that mezigdomide combined with carfilzomib and dexamethasone cut the risk of disease progression or death by 52% compared with carfilzomib and dexamethasone alone in relapsed or refractory multiple myeloma — the first positive Phase III readout for the CELMoD class and a result that will accelerate BMS's push to file for regulatory approval.
SUCCESSOR-2 is a seamless Phase II/III, multicenter, randomized, open-label study comparing mezigdomide plus carfilzomib and dexamethasone (MeziKd) against carfilzomib and dexamethasone (Kd) in patients with relapsed or refractory multiple myeloma. The Phase III primary endpoint analysis enrolled 479 patients — 288 on MeziKd and 191 on Kd — with a median age of 68 and a heavily pretreated profile: 92.1% were triple-class-exposed, 85.8% were refractory to an anti-CD38 antibody, and 75.8% were refractory to lenalidomide. Median follow-up at the data cutoff was 10.6 months.
MeziKd produced a median progression-free survival of 18 months versus 8.3 months for Kd (HR: 0.48; p < 0.0001). The overall response rate was 80.2% with MeziKd compared with 53.4% for Kd, and complete response or better was achieved in 26.7% versus 8.9% of patients, respectively. Median overall survival had not been reached in either arm. The safety profile carried the expected burden of the combination: Grade 3–4 treatment-emergent adverse events occurred in 83.7% of MeziKd patients versus 56.5% on Kd, driven largely by neutropenia (61.1% vs. 9.1%) and infections (34.0% vs. 15.6%). BMS described the profile as consistent with mezigdomide's known safety data.
Mezigdomide is an oral agent designed to degrade the transcription factors Ikaros and Aiolos with greater potency than earlier immunomodulatory drugs such as BMS's own Revlimid (lenalidomide) or Pomalyst (pomalidomide), targeting a patient population where both are increasingly exhausted as treatment options. The SUCCESSOR-2 population — predominantly anti-CD38 refractory and lenalidomide refractory — represents the growing cohort of patients who have run through the current standard backbone early. The 18-month median PFS in that context is a clinically notable number, though cross-trial comparisons are limited by differences in patient selection, prior therapy exposure, and trial design across the relapsed or refractory multiple myeloma landscape. BMS said it will share the SUCCESSOR-2 results with health authorities; a regulatory submission timeline was not disclosed. A second Phase III study, SUCCESSOR-1, evaluating mezigdomide in a separate combination regimen, remains ongoing.
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