By: Kerri Fitzgerald
Results from the phase 1/2 CA057-003 study showed early efficacy and safety with the addition of mezigdomide to novel combinations for relapsed or refractory multiple myeloma (MM).
The study was presented by Paul G. Richardson, MD, of the Dana-Farber Cancer Institute, as part of the SOHO 2025 Annual Meeting.
The multicenter, open-label trial is assessing all-oral, novel triplet combinations using a mezigdomide plus dexamethasone backbone plus tazemetostat, BMS-986158, or trametinib in this patient population.
Mezigdomide was assessed at three dose levels: 0.3, 0.6, and 1.0 mg; dexamethasone is dosed at 40 mg, tazemetostat at 800 mg twice daily, BMS-986158 at 2 or 3 mg, and trametinib at 1.5 or 2 mg.
As of October 4, 2024, patients received mezigdomide plus dexamethasone plus tazemetostat (n=16), BMS-986158 (n=20), or trametinib (n=20). The median patient age is 53 years, and patients had received a median of five prior therapies. Most (82.1%) were triple-class-refractory.
At data cutoff, 30% to 60% of patients remained on treatment across the combination cohorts, with median follow-up ranging from 4.2 to 5.7 months.
The most common grade 3/4 treatment-emergent adverse event was neutropenia, occurring in 62.5% to 85.0% of patients across treatment cohorts. Eight patients experienced dose-limiting toxicities.
The overall response rate was:
- 50% with mezigdomide plus dexamethasone and tazemetostat
- 35% mezigdomide plus dexamethasone and BMS-986158
- 75% with mezigdomide plus dexamethasone and trametinib
Deeper responses occurred with the mezigdomide 1.0 mg dose in both the in the tazemetostat (50%) and BMS-986158 (20%) cohorts. The mezigdomide 1.0 dose had the “greatest effect,” according to the authors, with 84.6% experiencing ongoing responses at that dose level.
There were no reported drug-drug interactions. Mezigdomide induced Ikaros/Aiolos degradation and B-cell reduction in all combinations and dose levels.
This abstract was accepted and previously presented at the 2024 ASH Annual Meeting.
Reference
Costa LJ, Schjesvold F, Popat R, et al. Mezigdomide (MEZI) in novel combinations for relapsed or refractory multiple myeloma (RRMM): updated results from the CA057-003 trial. Abstract #MM-552. Presented at the Society of Hematologic Oncology 2025 Annual Meeting; September 3-6, 2025; Houston, Texas.
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