C4 Therapeutics presents cemsidomide Phase 1 data at ASH

C4 Therapeutics (CCCC) presented clinical data from the ongoing Phase 1 trial of cemsidomide, an orally bioavailable small molecule degrader of IKZF1/3, at the ASH Annual Meeting. Presentations included a poster highlighting results for cemsidomide in combination with dexamethasone in multiple myeloma, and an oral presentation delivering initial results for cemsidomide as a monotherapy for non-Hodgkin’s lymphoma. These presentations reinforce the potential of cemsidomide to become a backbone therapy of choice in both multiple myeloma and non-Hodgkin’s lymphoma where IKZF1/3 degradation is warranted. C4T designed cemsidomide to be a more potent and selective degrader of IKZF1/3 with unique pharmacokinetic properties, with the goal to improve the therapeutic index to treat multiple myeloma and non-Hodgkin’s lymphoma-both alone and in combination with other therapeutic agents in these therapeutic areas. At the ASH Annual Meeting, C4T presented safety and anti-myeloma data demonstrating cemsidomide has the potential to become a best-in-class IKZF1/3 degrader used as a backbone therapy of choice for patients with multiple myeloma where IKZF1/3 degradation is warranted. These data support the future development of cemsidomide across treatment lines in combination with other anti-myeloma agents. As of the data cutoff date of October 11, 2024, a total of 47 patients received cemsidomide in combination with dexamethasone across four dose levels. Patients were heavily pretreated, receiving a median of six prior therapies. All patients were triple-class exposed, defined as exposure to one or more immunomodulatory agents, one or more proteasome inhibitors, and one anti-CD38 antibody. Thirty-three patients received prior BCMA directed therapy. Thirty-one patients received prior CAR-T or T-cell engager therapy. Cemsidomide in combination with dexamethasone was well tolerated. As of the data cutoff date, 47 patients were evaluable for safety. No patients experienced a treatment emergent adverse event that led to dose reduction. The maximum tolerated dose has not yet been identified. Enrollment is currently ongoing at the 100 microgram QD dose level. Cemsidomide in combination with dexamethasone demonstrated anti-myeloma activity across a broad range of doses, highlighting a wide therapeutic range. As of the data cutoff, 42 patients were evaluable for anti-myeloma activity. Across all dose levels, cemsidomide in combination with dexamethasone achieved a 26 percent ORR and a 40 percent clinical benefit rate. At the highest dose level explored to date, cemsidomide achieved a 36 percent ORR and a 45 percent CBR. At the two highest dose levels evaluated to date, 62 percent of patients remained on therapy as of the data cutoff date. C4T has identified 75 microgram QD as a target dose for various dexamethasone combination regimens; as dose escalation continues, higher doses may also be considered. For immune-based combination strategies, C4T believes doses lower than 75 microgram QD will be optimal based on anti-myeloma activity and immune activation observed in the previously disclosed monotherapy data set.