Phase 1b monzosertib CDC7 kinase inhibitor tests azole–drug interaction dosing in AML/MDS

MD Anderson Cancer Center is running this Phase 1b, open-label, investigator-initiated study to define the recommended Phase 2 dose of monzosertib, a small-molecule CDC7 (cell-division cycle 7) kinase inhibitor that aims to block DNA replication initiation and slow malignant proliferation. The key design feature is three exposure-safety cohorts: monzosertib alone (no azoles) versus monzosertib given with posaconazole or isavuconazole—azole antifungals (CYP3A inhibitors) commonly used for prophylaxis/treatment in AML/MDS that can significantly change oral drug levels. Eligible patients include adults with relapsed/refractory AML, MDS/AML, high-risk MDS, or CMML with >5% marrow blasts, reflecting a population where outcomes remain poor and treatment is often sequential therapy such as venetoclax-based combinations, hypomethylating agents, re-induction chemotherapy in select patients, targeted agents when mutations match (e.g., FLT3/IDH), and transplant when feasible. The commercial/scientific angle is practical: if CDC7 inhibition shows tolerability and activity, nailing the azole co-administration strategy could make the regimen workable in real-world AML care where antifungal prophylaxis is routine.