C4 Therapeutics reports early biomarker findings for cemsidomide in multiple myeloma, including T-cell activity and Phase 1b data with elranatamab.
Written By: Aasritha Thippavajjala, PharmD
Reviewed By: Pharmacally Editorial Team
C4 Therapeutics presented new biomarker findings from two ongoing clinical trials of cemsidomide in relapsed/refractory multiple myeloma (RRMM) at the 23rd International Myeloma Society (IMS) Annual Meeting on September 25, 2026. The Phase 1 study is evaluating cemsidomide with dexamethasone across multiple once-daily dose cohorts, while the Phase 1b study is evaluating cemsidomide in combination with elranatamab (ELREXFIO), a BCMA × CD3 bispecific T-cell engager.
Phase 1 Shows T-Cell and NK-Cell Activity
The Phase 1 study (NCT04756726) enrolled 62 heavily pretreated patients with RRMM across multiple cemsidomide dose cohorts. Biomarker findings showed coordinated activation of T cells, including CD8+ T cells, along with functional reprogramming of natural killer (NK) cells.
The immune effects were most pronounced at the two highest doses tested, 75 µg and 100 µg. These findings provide early evidence of immune-cell changes associated with cemsidomide treatment but do not establish clinical efficacy.
Early Findings from the Elranatamab Combination
The separate Phase 1b trial (NCT07280013) is evaluating cemsidomide with elranatamab in patients with one to four prior lines of therapy. Participants had previously received at least one IKZF1/3 degrader and had no prior BCMA-directed T-cell engager or CAR-T therapy.
Biomarker data from the first two patients to complete Cycle 1, collected as of June 22, showed expansion and activation of CD8+ effector-memory T cells, measured by increased HLA-DR expression. The analysis also showed reduced PD-1, TIM-3 and LAG3, markers associated with T-cell exhaustion.
The findings are consistent with the proposed mechanism of cemsidomide, but the analysis involved only two patients. The limited sample size prevents conclusions about clinical efficacy, response durability or the broader effects of the combination.
75 µg Dose Cleared for Further Evaluation
Six patients completed the first safety cohort of the Phase 1b study at the 75 µg cemsidomide dose. Following review of the available safety data, the safety data review committee cleared the 75µg dose level for continued evaluation.
The study is now advancing to a dose-escalation cohort at 100 µg, while a parallel expansion cohort continues at 75 µg. The company expects data from all cohorts by mid-2027.
C4 Therapeutics Chief Medical Officer Len Reyno said the findings support the company’s premise that cemsidomide could potentially be used with immune-based therapies. He described the 75µg clearance as a step toward identifying a dose for combination with a T-cell engager.
Cemsidomide Targets IKZF1 and IKZF3
Cemsidomide is an oral cereblon-modulating agent designed to induce degradation of the transcription factors IKZF1 and IKZF3, which are involved in the biology and survival of multiple myeloma cells. The approach belongs to the broader cereblon-modulator class that includes lenalidomide and pomalidomide.
C4 Therapeutics is developing cemsidomide using its TORPEDO targeted protein degradation platform to selectively target IKZF1 and IKZF3.
Future Clinical Development
The current findings remain interim and provide an early assessment of biomarker changes and safety during combination treatment. Whether the observed immune changes translate into clinically meaningful and durable responses will require additional patient data and longer follow-up.
Cemsidomide has not received regulatory approval for any indication. C4 Therapeutics expects the next broader dataset from the Phase 1b study by mid-2027.
Reference
C4 Therapeutics Presents New Biomarker Data from the Cemsidomide Phase 1 Trial with Dexamethasone and Phase 1b Trial with Elranatamab (ELREXFIO®) in Relapsed/Refractory Multiple Myeloma at the 23rd International Myeloma Society (IMS) Annual Meeting, C4 Therapeutics, 25 September 2026
Study to Assess the Safety and Tolerability of CFT7455 in Relapsed/Refractory Non-Hodgkin’s Lymphoma or Multiple Myeloma, ClinicalTrials.gov ID NCT04756726
A Study to Learn About the Effects of Cemsidomide in Combination With Elranatamab in Relapsed/Refractory Multiple Myeloma Subjects, ClinicalTrials.gov ID NCT07280013
About the Writer
Aasritha Thippavajjala (Linkedin) is a pharm D student and aspiring medical writer with medical writing, clinical training experience and a strong interest in clinical research and patient safety She has hands-on exposure to clinical pharmacy activities including medication profile assessment, clinical case review, identification of potential drug-related problems, ADR awareness, patient counselling, and clinical documentation. She has also gained experience in medical literature review, evidence synthesis, and scientific communication through her published review article on digital twin-based patient simulation and her poster presentation at the 74th Indian Pharmaceutical Congress. Certified in ICH Good Clinical Practice (E6(R3)) and Scientific Writing in Health Research, she is passionate about applying her clinical knowledge and research skills to medical writing ,clinical research and contributing to accurate, evidence-based healthcare.