Mezigdomide (molecular glue) plus Dexamethasone in RRMMDespite recent progress, multiple myeloma remains incurable.
An experimental pill developed by Bristol Myers Squibb has shown promising efficacy in a clinical trial for advanced multiple myeloma patients who have exhausted most other options. The drug, mezigdomide, is in a class of medicines called “molecular glues”.
Mezigdomide is a novel cereblon E3 ubiquitin ligase modulator with potent antiproliferative and tumoricidal activity in preclinical models of multiple myeloma, including those resistant to lenalidomide and pomalidomide.
In a phase 1–2 study released today, oral mezigdomid was administered in combination with dexamethasone to patients with relapsed and refractory myeloma. The primary objectives of phase 1 (dose-escalation cohort) were to assess safety and pharmacokinetics and to identify the dose and schedule for phase 2. In phase 2 (dose-expansion cohort), objectives included the assessment of the overall response (partial response or better), safety, and efficacy of mezigdomide plus dexamethasone at the dose and schedule determined in phase 1. Conclusions: The all-oral combination of mezigdomide plus dexamethasone showed promising efficacy in patients with heavily pretreated multiple myeloma, with treatment-related adverse events consisting mainly of myelotoxic effects. (Funded by Celgene, a Bristol-Myers Squibb Company)
https://www.nejm.org/doi/full/10.1056/NEJMoa2303194