WATERTOWN, Mass. — September 25, 2026
C4 Therapeutics presented new biomarker data from clinical trials of cemsidomide in patients with relapsed/refractory multiple myeloma (RRMM) at the 23rd International Myeloma Society (IMS) Annual Meeting. The data included results from the Phase 1 trial of cemsidomide in combination with dexamethasone and preliminary biomarker findings from the first two patients in the ongoing Phase 1b trial combining cemsidomide with elranatamab (ELREXFIO®). The company reported evidence of T-cell activation and immune-cell modulation, supporting further evaluation of cemsidomide as a potential combination partner for immune-based therapies. The first 75 µg dose level in the Phase 1b combination trial was declared safe following review of the initial six-patient safety cohort.
Phase 1 Data Show Immune Activation With Cemsidomide
The Phase 1 trial evaluated cemsidomide with dexamethasone in 62 heavily pre-treated RRMM patients across once-daily dose levels. C4 Therapeutics reported coordinated activation of T cells, including CD8+ T cells, together with functional reprogramming of natural killer (NK) cells. Enhanced immune-cell activity was observed at the 75 µg and 100 µg dose levels, which the company said also produced encouraging overall response rates in the Phase 1 study. Cemsidomide is an investigational oral cereblon-modulating protein degrader targeting IKZF1 and IKZF3, transcription factors involved in multiple myeloma biology. The biomarker findings are intended to provide mechanistic evidence for its immunomodulatory activity, while clinical efficacy conclusions remain dependent on the full clinical dataset and ongoing development.
Early Phase 1b Biomarkers Support Combination With Elranatamab
Preliminary biomarker data from the first two patients in the Phase 1b trial showed expansion and activation of CD8+ effector memory T cells, measured through increased HLA-DR expression. The analysis also indicated reduced markers associated with T-cell exhaustion, including PD-1, TIM-3 and LAG3, according to the company. These findings provide early translational support for evaluating cemsidomide alongside immune-based therapies, although the dataset remains limited to the first two patients. The Phase 1b study is evaluating cemsidomide and dexamethasone in combination with elranatamab, a BCMA-directed CD3 T-cell-engaging bispecific antibody, in patients who have received one to four prior lines of therapy and at least one IKZF1/3 degrader.
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Cemsidomide Combination Study Advances to Additional Cohorts
Following review of the first six-patient safety cohort, the Phase 1b trial has advanced to both dose escalation and dose expansion. The 75 µg cemsidomide dose level was declared safe, allowing the study to proceed with a 100 µg dose-escalation safety cohort and a 75 µg expansion cohort. The trial also provides an opportunity to explore additional dose levels, including 50 µg and 100 µg, as development progresses. Patients previously treated with a BCMA-directed T-cell engager or BCMA-directed CAR-T therapy are excluded from the study. C4 Therapeutics expects data from all evaluated Phase 1b cohorts in mid-2027. The company is evaluating whether cemsidomide’s immunomodulatory properties can complement BCMA-directed immune therapy and potentially support deeper or more durable responses, but these potential benefits remain investigational.
Source :C4 Therapeutics, press release
