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**milademetan + quizartinib** is an investigational combination therapy currently in phase 1 clinical studies for the treatment of acute myeloid leukemia (AML) characterized by FLT3-internal tandem duplication (FLT3-ITD) mutations. **Milademetan** is an oral selective inhibitor of murine double minute 2 (MDM2), while **quizartinib** is an oral, potent, and selective type II inhibitor of FMS-like tyrosine kinase 3 (FLT3). The combination aims to co-target both **FLT3** and **MDM2** pathways, thus leveraging milademetan-driven activation of **p53**-dependent apoptosis and quizartinib-mediated suppression of oncogenic FLT3 signaling. Preclinical models and early-phase clinical data have shown that this combination induces synergistic apoptosis in FLT3-ITD/TP53 wild-type AML, overcomes resistance to FLT3 inhibition, reduces tumor burden, and improves survival compared to either agent alone. The main clinical indications under evaluation are relapsed/refractory FLT3-ITD AML and newly diagnosed FLT3-ITD AML in patients unfit for intensive chemotherapy[1][3][4][5].
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