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Narazaciclib + dexamethasone is an investigational combination therapy being evaluated for the treatment of relapsed and/or refractory multiple myeloma. Narazaciclib (ON 123300) is a first-in-class, multi-targeted oral kinase inhibitor that targets cyclin-dependent kinases 4 and 6 (CDK4/6) and AMPK-related protein kinase 5 (ARK5/NUAK1), as well as CSF1R, c-Kit, and FLT3. By inhibiting these pathways, narazaciclib suppresses DNA synthesis by preventing the G1-S phase transition and induces mitochondria-mediated apoptosis in cancer cells. Dexamethasone is a potent synthetic glucocorticoid that provides anti-inflammatory and immunosuppressive effects, commonly used in combination with targeted agents to enhance therapeutic efficacy in plasma cell dyscrasias. This specific combination is being investigated in a Phase I/II clinical trial led by Adriana Rossi at Weill Cornell Medicine.
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