mezigdomide (CC-92480)

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.

P1/2, N=260, Recruiting, Bristol-Myers Squibb | N=160 --> 260

P1, N=18, Recruiting, Memorial Sloan Kettering Cancer Center | Not yet recruiting --> Recruiting

Building on the success of immunomodulatory agents, CRBN E3 ligase modulators (CELMoDs), iberdomide (CC-220) and mezigdomide (CC-92480), have been designed as promising and more selective agents. Combining CELMoDs with cellular therapies significantly improves the response rate in MM patients. In this paper, based on the literature presented at the Annual Meeting of the American Society of Hematology (ASH), the American Society of Clinical Oncology (ASCO), the International Myeloma Society (IMS), and the European Hematology Association (EHA) in the 2020-2025 timeframe, we explore the rationale and emerging evidence of combining CELMoDs with immunotherapies, and their use as a bridge to transplant or as post-ASCT maintenance therapy in MM.

P1, N=18, Not yet recruiting, Memorial Sloan Kettering Cancer Center

P1, N=25, Not yet recruiting, Massachusetts General Hospital

P1, N=26, Completed, Celgene | Recruiting --> Completed | Trial completion date: Mar 2025 --> Nov 2024 | Trial primary completion date: Mar 2025 --> Nov 2024

P=N/A, N=0, Available, Bristol-Myers Squibb

P1/2, N=62, Not yet recruiting, Celgene