C4 Therapeutics has dosed the first patient in a Phase 1b study assessing cemsidomide plus dexamethasone in combination with elranatamab for relapsed or refractory multiple myeloma. The open-label, multicenter trial will enroll up to 54 patients to determine an optimal cemsidomide dose alongside elranatamab, starting at 75 µg with exploration of 50 µg and 100 µg. Safety and tolerability are primary, with secondary measures including overall response, MRD-negative complete response, and duration of response by IMWG criteria. Under a previously disclosed collaboration-supply agreement, Pfizer is providing elranatamab at no cost, while C4T sponsors and runs the study. Readout across cohorts is targeted for mid-2027.
The move signals C4T’s intent to position cemsidomide beyond late-line monotherapy and into combination backbones that are rapidly redefining myeloma care. IKZF1/3 degraders remain embedded across treatment lines; pairing a next-generation oral degrader with a BCMAxCD3 bispecific aims to leverage both direct tumor cytotoxicity and immune potentiation. The company is effectively building a two-pronged path: MOMENTUM, a single-arm Phase 2 in fourth line and beyond anchored on cemsidomide plus dexamethasone at a 100 µg recommended dose, and this elranatamab combination to test whether immunomodulatory synergy can drive deeper and more durable responses applicable to earlier lines.
The design choices reflect both opportunity and constraint. Eligible patients must have received one to four prior regimens, including at least one IKZF1/3 degrader, which aligns with real-world exposure to IMiDs and emerging CELMoDs. However, exclusion of patients previously treated with BCMA-directed T-cell engagers or CAR-T narrows the addressable pool as BCMA options migrate earlier in the algorithm. That may aid signal detection by avoiding confounding resistance biology but could slow accrual at high-volume centers already cycling patients through BCMA-directed modalities. Operationally, sites will need to manage elranatamab’s step-up dosing and monitor for CRS and neurotoxicity, with added vigilance for overlapping cytopenias and infections when layered with cemsidomide. Incorporation of MRD-negative CR as a secondary endpoint raises logistics demands for standardized MRD assessment and independent review coordination.
Strategically, the combination tests whether a differentiated IKZF1/3 degrader can reclaim relevance as bispecifics and cell therapies become dominant pillars. The bar is not only activity; sponsors and regulators increasingly expect combinations to preserve or improve tolerability and real-world manageability, particularly around infection risk that has complicated bispecific adoption. Any need to reduce cemsidomide dose below the 100 µg monotherapy RP2D to accommodate combination safety will be closely watched, as will signals of improved durability that could justify the added complexity and cost versus established triplets and quadruplets. The broader context is competitive, with multiple next-generation degraders and CELMoDs probing similar synergies with T-cell engagers and anti-CD38 antibodies.
In the near term, pace of enrollment and early safety patterns will be the key indicators, especially given the trial’s BCMA-naïve requirement. Sponsors, CROs, and sites should monitor whether infection-mitigation strategies and outpatient workflows for bispecifics remain feasible when combined with continuous oral immunomodulation. For C4T, the mid-2027 data milestone will need to delineate a clear path to a randomized program against contemporary standards as bispecifics move earlier. Additional combination plans, slated for disclosure in mid-2026, will indicate how broadly the company intends to position cemsidomide across BCMA and non-BCMA backbones, including GPRC5D-directed agents. The risk is that treatment sequencing continues to shift faster than the development cadence, compressing the eligible population and raising the evidentiary bar for adoption.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
