ziftomenib + gilteritinib

**Ziftomenib + gilteritinib** is an investigational combination therapy under Phase 1 clinical evaluation for the treatment of relapsed or refractory acute myeloid leukemia (AML) harboring NPM1 mutations or KMT2A rearrangements, including those with concurrent FLT3 mutations. **Ziftomenib** is an orally available, selective **menin inhibitor** that disrupts the menin–KMT2A/MLL protein interaction, thereby inhibiting leukemogenic gene expression driven by KMT2A or NPM1 mutations. **Gilteritinib** is an oral, small molecule inhibitor of **FLT3** and **AXL** tyrosine kinases, targeting FLT3-mutant leukemia. Preclinical data indicate these agents have synergistic anti-leukemic effects when combined. The combination is designed for AML patients with poor prognosis due to genetic alterations such as FLT3, NPM1, and KMT2A mutations and is being tested in the ongoing KOMET-008 trial.