C4 Therapeutics reported a 53% response rate with cemsidomide at the recommended Phase 2 dose in relapsed/refractory multiple myeloma, with MRD-negative remissions, durable responses, and manageable safety at EHA 2026.
Written By: Nalam Karthik, PharmD
Reviewed By: Pharmacally Editorial Team
C4 Therapeutics presented updated results from its fully enrolled Phase 1 trial (NCT04756726) of cemsidomide at the European Hematology Association (EHA) 2026 Congress, reporting a 53% overall response rate (ORR) at the recommended Phase 2 dose (RP2D) in patients with relapsed/refractory multiple myeloma (RRMM).
The findings highlight durable activity, deepening remissions, and a manageable safety profile, reinforcing cemsidomide’s potential as a next-generation IKZF1/3 degrader in myeloma.
Clinical and Scientific Context
Cemsidomide is an investigational oral molecular glue degrader that selectively targets IKZF1 and IKZF3, transcription factors central to myeloma biology. Their degradation reduces IRF4 signaling, induces myeloma cell death, and enhances T-cell activation, providing both direct anti-tumor and immune-mediated effects.
IKZF1/3 degradation remains a validated therapeutic mechanism underpinning several approved regimens, positioning cemsidomide as a candidate for broad integration across treatment settings.
Phase 1 Data Show Deepening Responses and Durable Activity
The analysis included 73 patients with a median of seven prior lines of therapy, reflecting a highly refractory population. Seventy-five percent had received prior BCMA-directed therapy, and an equal proportion had been treated with CAR-T cell therapy or T-cell engagers.
At the RP2D of 100 µg, cemsidomide plus dexamethasone achieved a 53% ORR, compared with 40% at 75 µg and 36% across all evaluated dose levels. Responses deepened with follow-up. At the 100 µg dose level, one patient improved from a partial response to a stringent complete response, while another improved from a partial response to a very good partial response. Two patients who achieved complete or stringent complete responses also became minimal residual disease (MRD) negative.
Clinical activity remained consistent across difficult-to-treat subgroups. At the RP2D, ORR reached 53% among patients previously exposed to CAR-T therapy or T-cell engagers and 47% among those who had received prior BCMA-directed therapy. Patients who had undergone more than five prior treatment lines also achieved a 47% ORR.
Responses were durable across dose levels, with a median duration of response of 7.9 months. Seven patients remained on treatment at the time of data cutoff.
Safety findings were consistent with previous reports. Grade 3/4 neutropenia occurred in 58% of patients but remained manageable. No treatment discontinuations were attributed to cemsidomide, and only five patients (7%) required dose reductions because of adverse events.
Clinical Implication
Dr. Sagar Lonial highlighted the continued importance of IKZF1/3 degradation in multiple myeloma treatment, noting that the approach directly targets disease biology while enhancing immune function. Company leadership emphasized the continued deepening of responses over time, including MRD-negative complete remissions, as support for advancing cemsidomide across multiple treatment settings and combination regimens.
Pipeline Expansion and Next Milestones
The updated findings support continued development of cemsidomide through the ongoing Phase 2 MOMENTUM study (NCT07284758), which is enrolling approximately 100 patients with relapsed/refractory multiple myeloma who have received multiple prior therapies.
The company is also evaluating cemsidomide in a Phase 1b combination study with Pfizer’s BCMA-directed bispecific antibody ELREXFIO (elranatamab), based on evidence that cemsidomide enhances T-cell activation and may strengthen anti-myeloma immune responses.
Upcoming data from the MOMENTUM study and combination trials will help determine whether cemsidomide can further expand the role of IKZF1/3 degradation in relapsed/refractory multiple myeloma and support its use across broader treatment settings.
References
About the Writer
Nalam Karthik (LinkedIn) is a healthcare writer and PharmD graduate with interests in pharmacovigilance, drug safety, clinical data analysis, and quality assurance. He is passionate about translating clinical and pharmaceutical knowledge into accessible healthcare content while staying engaged with advancements in drug development and patient safety initiatives.