mezigdomide (CC-92480)

P1, N=27, Recruiting, Abdullah Khan | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026

Triplet regimens that include an immunomodulatory agent, proteasome inhibitor, and dexamethasone are widely used in newly diagnosed and relapsed/refractory (R/R) multiple myeloma (MM)...Additionally, we have compared these results with similar combinations with the immunomodulatory agent pomalidomide (POM). Our studies indicate that the MEZI/BTZ/DEX triplet is superior to all single agents and POM/BTZ/DEX in terms of potency of antiproliferative and proapoptotic activities, substrate degradation depth and kinetics in the presence of BTZ, and in vivo efficacy. We show that the combination of MEZI with BTZ increases cell death through disruption of multiple phases of the cell cycle and this thereby enhances the direct cytotoxic effects of the combination treatment.

P1, N=24, Not yet recruiting, Massachusetts General Hospital

P1/2, N=52, Recruiting, Memorial Sloan Kettering Cancer Center

P2, N=70, Not yet recruiting, Assistance Publique - Hôpitaux de Paris

P2, N=28, Recruiting, Roswell Park Cancer Institute | Suspended --> Recruiting

P1, N=125, Recruiting, K36 Therapeutics, Inc. | Trial completion date: Jun 2026 --> Jun 2028 | Trial primary completion date: Dec 2025 --> Dec 2027

P3, N=810, Recruiting, Celgene | Trial primary completion date: Nov 2025 --> Jan 2027

P2, N=28, Suspended, Roswell Park Cancer Institute | Recruiting --> Suspended

Standard-of-care regimens for newly diagnosed MM and early relapsed/refractory disease (RRMM) include quadruplets and triplets comprising CD38 monoclonal antibodies, proteasome inhibitors, and/or immunomodulatory drugs, plus dexamethasone. We searched the published literature using PubMed, plus congress abstracts from the past 5 years and current records on ClinicalTrials.gov, using the terms 'mezigdomide' or 'CC-92480' and 'myeloma.' Mezigdomide, which is not currently approved for the treatment of MM, has higher cereblon binding affinity and greater potency for substrate protein degradation than the immunomodulatory drugs, and this is translating into notable clinical efficacy in early-phase trials, including in poor-prognosis settings such as triple-class-refractory disease. It has shown synergistic effects in preclinical studies with standard-of-care therapies and is being evaluated clinically in various combinations, including with/following T-cell engaging therapies for RRMM.

P1/2, N=62, Recruiting, Celgene | Not yet recruiting --> Recruiting

A PBPK-informed Phase I clinical DDI study was conducted that evaluated MEZI as an object of CYP3A induction (rifampin) and inhibition (itraconazole) and as a precipitant of transporter-mediated interactions (digoxin and rosuvastatin). This iterative "learn-confirm" approach underscores the utility of PBPK modeling in optimizing clinical trial design, ensuring participant safety, and anticipating DDI risks. The findings support MEZI's clinical development with informed dosing strategies, particularly for coadministration with CYP3A modulators.