C4 Therapeutics Shows Immune Activation in Multiple Myeloma Trials with Cemsidomide

C4 Therapeutics Inc. presented preliminary biomarker findings from its Phase 1 clinical trials of cemsidomide, an investigational oral cereblon-modulating agent targeting IKZF1/3 transcription factors in relapsed/refractory multiple myeloma. The data, presented at the 23rd IMS Annual Meeting, underscored immune system engagement at specific dose levels, with early signs of T-cell activation and natural killer cell reprogramming in patients receiving cemsidomide combined with dexamethasone. In the Phase 1 trial (NCT05032470), 62 patients with advanced multiple myeloma showed enhanced immune cell function at 75 µg and 100 µg doses of cemsidomide, according to Len Reyno, C4’s chief medical officer. The company also advanced Phase 1b trial data, where cemsidomide combined with elranatamab—a CD3-targeted bispecific antibody approved by the FDA for multiple myeloma—demonstrated expansion and activation of CD8+ effector memory T cells while preventing exhaustion markers (PD-1, TIM-3, LAG3). Preliminary biomarker data from the first two patients met safety criteria, and the 75 µg dose level was deemed safe after evaluating six patients in the initial cohort. The trial is now progressing to a 100 µg dose escalation cohort and an expansion cohort at 75 µg. Full biomarker data from all cohorts are expected in mid-2027. Multiple myeloma remains a significant unmet need, with an estimated 36,000 new diagnoses annually in the U.S. and over 175,000 patients currently living with or in remission from the disease. Reyno emphasized that maintaining T-cell fitness is critical for achieving durable responses, a principle the trials aim to validate further.