C4 Therapeutics is taking cemsidomide to Phase II in multiple myeloma after the success of an early-stage study.
During a Phase I trial (NCT04756726), the zinc finger protein-1 and 3 (IKZF1/3) degrader triggered high overall response rates (ORR) in a heavily pretreated patient population when combined with glucocorticoid agonist, dexamethasone.
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At the maximum oral dose of 100µg, cemsidomide exhibited an ORR of 50%, while one patient achieved a minimal residual disease (MRD)-negative complete response (CR) after treatment with the targeted combination.
Though the drug prompted the most pronounced effects at a 100µg dose, 34% of patients across all dose levels received a partial response (PR) or better, which lasted for a median of 9.3 months.
Meanwhile, the drug has proven safe and tolerable – with low rates of both febrile neutropenia (5% of patients) and thrombocytopenia (11%) across all dose levels. Both neutropenia and thrombocytopenia are key severe and potentially life-threatening adverse events (AEs) commonly associated with targeted oncology drug classes such as IKZF1/3 degraders.
Up to the cutoff, there have been no treatment-associated deaths in any of the trial arms.
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By GlobalDataAccording to C4’s CMO Len Reyno, these clinical results highlight cemsidomide’s potential to become “the IKZF1/3 degrader of choice among approved medicines in this class,” due to its favourable safety and efficacy profile compared with competitors like Imnovid (pomalidomide) and lenalidomide.
Such drugs are commonly used in combination regimens across a wide range of therapeutic lines in multiple myeloma.
Cemsidomide’s future direction
In a bid to obtain accelerated approval from the US Food and Drug Administration (FDA) for cemsidomide, C4 will initiate a single-arm Phase II trial exploring the drug’s potential alongside dexamethasone in fourth-line, anti-B cell maturation antigen (BCMA) therapy refractory patients. This trial will begin in Q1 of 2026, with initial ORR data expected to be mature by H2 2027.
However, C4 has also set its sights on cemsidomide approval in the second line, with the US-based biotech planning to initiate a Phase Ib trial looking into the drug’s efficacy when used with dexamethasone and a BCMA bispecific T-cell engager (BiTE). This study will begin in Q2 of 2026, with data expected by mid-2027.
The progression of cemsidomide to pivotal trials will be welcome news for C4, which had to lay off 30% of its labour force after pulling the plug on its bromodomain-containing protein 9 (BRD9) degrader, CFT8634, after its lacklustre performance in a Phase I/II study.
However, cemsidomide will have to come up against blockbuster IKZF1-3 degrader Imnovid, which is deeply ingrained into the multiple myeloma treatment paradigm. It is commonly used in combination with other targeted agents such as Darzalex (daratumumab) and Sarclisa (isatuximab-irfc) and made $3.5bn for owner Bristol Myers Squibb (BMS) in 2024, according to GlobalData’s Intelligence Centre.
GlobalData is the parent company of Clinical Trials Arena.
Cemsidomide will also face fierce competition from lenalidomide in the second line, which is commonly combined with Darzalex and dexamethasone. At its peak, the drug made $12.8bn for BMS before a patent cliff saw the drug face significant generic competition.
