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**Milademetan + azacitidine** is an investigational combination therapy of two agents for hematologic malignancies. **Milademetan** is a small-molecule, oral inhibitor of Mouse Double Minute 2 homolog (MDM2), which blocks the MDM2-p53 interaction, thereby reactivating p53 signaling and promoting apoptosis in cancer cells with wild-type TP53. **Azacitidine** is a hypomethylating agent and DNA methyltransferase inhibitor that induces DNA hypomethylation and cell death, commonly used in myelodysplastic syndromes and acute myeloid leukemia. The combination has been studied primarily for relapsed or refractory acute myeloid leukemia (AML) and high-risk myelodysplastic syndromes (MDS), based on both mechanistic rationale and preclinical synergy. Clinical studies have focused on evaluating safety, dosing schedules, maximum tolerated dose, and initial efficacy signals.
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