C4 Therapeutics Reports Cemsidomide Biomarker Data at IMS; 75 µg Elranatamab Combo Dose Cleared as Safe
核心洞察
C4 Therapeutics presented Phase 1 biomarker data at the 23rd IMS Annual Meeting showing cemsidomide plus dexamethasone drove coordinated T-cell activation and NK cell reprogramming in 62 heavily pretreated RRMM patients.
A safety data review committee declared the 75 µg cemsidomide dose combined with elranatamab safe after a six-patient safety cohort, allowing dose expansion at 75 µg and escalation to 100 µg.
Biomarker data from the first two Phase 1b patients showed cemsidomide expanded and activated CD8+ effector memory T cells while preventing rises in PD-1, TIM-3 and LAG3 exhaustion markers.
C4 Therapeutics presented new biomarker data from its Phase 1 trial of cemsidomide plus dexamethasone and preliminary Phase 1b data combining cemsidomide with elranatamab (ELREXFIO) in relapsed/refractory multiple myeloma (搜索) (RRMM) at the 23rd IMS Annual Meeting. The company reported that the first cemsidomide dose level in the Phase 1b combination trial, 75 µg, was declared safe by a safety data review committee, clearing the trial to advance into dose expansion and escalation cohorts.
In the Phase 1 trial, 62 heavily pretreated RRMM patients treated across once-daily dose levels showed coordinated activation of T cells, including CD8+ T cells, and functional reprogramming of natural killer (NK) cells. Enhanced immune cell function was observed at the highest dose levels studied, 75 µg and 100 µg, which also achieved compelling overall response rates in the trial.
Phase 1b Combination Data
The Phase 1b poster included biomarker data from the first two patients treated with cemsidomide plus elranatamab. According to the company, cemsidomide drove expansion and activation of CD8+ effector memory T cells, measured by elevated HLA-DR, and prevented T-cell exhaustion, measured by PD-1, TIM-3 and LAG3 expression. The analysis was based on available biomarker data as of June 22, 2026, from the first two patients to complete Cycle 1.
"Immune-based therapies have transformed the treatment landscape for multiple myeloma (搜索), however T-cell exhaustion is associated with both primary resistance and relapse in these patients. Maintaining T-cell fitness is an important component of achieving deep and durable responses," said Len Reyno, M.D., chief medical officer of C4 Therapeutics. "The totality of data presented today demonstrate that cemsidomide activates immune cell function, consistent with the hypothesis that cemsidomide will enhance the clinical benefit of immune-based therapies when used in combination."
Reyno added that clearing the 75 µg dose level in the Phase 1b trial is a step toward identifying an effective and safe dose of cemsidomide with a BCMA (搜索)-directed T-cell engager such as elranatamab.
Trial Design and Next Steps
The Phase 1b trial is designed to evaluate the safety, tolerability and preliminary efficacy of cemsidomide and dexamethasone in combination with elranatamab, an FDA-approved B-cell maturation antigen CD3 (搜索) targeted bispecific antibody. The study will evaluate different cemsidomide dose levels, beginning with 75 µg, with the opportunity to simultaneously explore 50 µg and 100 µg, in patients who have received one to four prior lines of therapy, which must have included at least one IKZF1/3 (搜索) degrader. Patients who received prior treatment with a BCMA (搜索)-directed T-cell engager or BCMA-directed CAR-T therapy are excluded. The trial is registered as NCT07280013.
Following completion of the first safety cohort of six patients, the safety data review committee declared the 75 µg cemsidomide dose level in combination with elranatamab safe. The trial is now advancing into a dose escalation safety cohort at 100 µg and an expansion cohort at 75 µg. Data from all cohorts evaluated in the Phase 1b trial are expected in mid-2027.
Separately, the Phase 2 MOMENTUM trial evaluating the 100 µg recommended Phase 2 dose is expected to complete enrollment in the first quarter of 2027, with initial overall response rate data anticipated in the second half of 2027.
Mechanism and Disease Context
Cemsidomide is an investigational oral cereblon (搜索)-modulating protein degrader of IKZF1/3 (搜索), transcription factors described by the company as foundational to multiple myeloma (搜索) biology. Data from the fully enrolled Phase 1 trial show a differentiated safety and tolerability profile and potentially class-leading anti-myeloma activity supporting the potential for durable outcomes, according to C4 Therapeutics. The company states that by activating immune T cells, cemsidomide combined with a BCMAxCD3 bispecific such as elranatamab may amplify the anti-myeloma immune response and lead to deeper and more durable responses.
Multiple myeloma (搜索) is a blood cancer affecting plasma cells in the bone marrow and is the second most common blood cancer, with approximately 36,000 people in the United States diagnosed each year. The disease is characterized by cycles of remission and relapse, requiring multiple lines of therapy. More than 175,000 patients in the United States are estimated to be living with or in remission from myeloma, and despite treatment advances approximately 40% of patients do not survive beyond five years.