C4 Therapeutics’ Cemsidomide Shows 53% ORR at 100 µg in Heavily Pretreated Myeloma
CCCC•At 100 µg RP2D, cemsidomide plus dexamethasone produced a 53% overall response rate in heavily pretreated relapsed/refractory multiple myeloma patients, including MRD-negative complete responses. Treatment was tolerable, with 7% dose reductions, no discontinuations, and a median response duration of 7.9 months.
1. Trial Design and Patient Population
The Phase 1 trial enrolled 73 heavily pretreated relapsed/refractory multiple myeloma patients with a median of seven prior lines of therapy; 75% had received prior BCMA-targeted treatment and 75% had undergone CAR-T or T-cell engager therapy. Cemsidomide was administered orally in combination with dexamethasone at escalating dose levels up to 100 µg, established as the recommended Phase 2 dose and maximum tolerated dose.
2. Efficacy Results
At the 100 µg RP2D, the combination achieved a 53% overall response rate, including complete responses and minimal residual disease–negative outcomes. The 75 µg dose produced a 40% response rate, while the overall response rate across all dose levels was 36%, indicating depth and consistency of anti-myeloma activity.
3. Safety and Tolerability
Cemsidomide plus dexamethasone demonstrated a manageable safety profile, with 58% of patients experiencing grade 3/4 neutropenia and only 7% requiring dose reductions. No treatment discontinuations were attributed to cemsidomide, and seven patients remained on therapy at the data cutoff of February 27, 2026.
4. Next Steps and Outlook
C4 Therapeutics plans to advance cemsidomide into Phase 2 studies, exploring combination regimens across earlier lines of therapy and with approved agents. The strategy aims to leverage its differentiated safety and efficacy profile to establish cemsidomide as a foundational therapy for relapsed/refractory multiple myeloma.
