ziftomenib + midazolam

Ziftomenib + midazolam is a combination of two drugs administered to assess drug-drug interactions in clinical research settings, specifically in patients with relapsed or refractory acute myeloid leukemia (AML) harboring relevant genetic mutations. Ziftomenib is an investigational, orally administered small molecule inhibitor targeting the menin-MLL (KMT2A) protein-protein interaction, blocking transcriptional programs driven by NPM1 mutations and KMT2A rearrangements, and ultimately suppressing leukemic proliferation through downregulation of oncogenic pathways such as MEIS1, PBX3, FLT3, and BCL2. Midazolam is a benzodiazepine commonly used as a sensitive probe substrate for cytochrome P450 3A (CYP3A) enzyme activity in vivo, serving as a standard tool for pharmacokinetic studies of drug interactions. The combination is not an approved therapy but is utilized in clinical pharmacology sub-studies to measure whether ziftomenib alters the metabolism of CYP3A substrates, as part of the broader regulatory assessment of ziftomenib in AML[3].