KOMET-007: Ziftomenib + Ven/Aza for ND NPM1-mutant AML

During the 67th American Society of Hematology (ASH) Annual Meeting and Exposition, December 6–9, 2025, Orlando, US, Gail Roboz presented results from the ongoing phase Ib KOMET-007 trial (NCT05735184) evaluating the safety and efficacy of ziftomenib 600 mg once daily (QD) combined with venetoclax + azacitidine (Ven/Aza) for the treatment of patients with newly diagnosed NPM1-mutant (NPM1-m) acute myeloid leukemia (AML). The primary endpoints were complete response (CR) and adverse events (AEs). Key secondary endpoints were composite complete remission (CRc), duration of response (DoR), overall response rate (ORR), and measurable residual disease (MRD).

Key data: Of 40 patients enrolled in the study, 37 were NPM1-m. The CRc rate was 86%, with a median time to first CRc of 3.4 weeks (range, 2.4–9.6). The ORR was 89%, with a CR observed in 73% of patients. After a median follow-up of 26.1 weeks (range, 1.6–54.1), median duration of CR and overall survival (OS) were not reached. The addition of ziftomenib to Ven/Aza combination therapy was well tolerated, showing safety outcomes similar to those reported for Ven/Aza alone. Grade ≥3 treatment-emergent adverse events (TEAEs) were reported in 85% of patients, and ziftomenib-related Grade ≥3 TEAEs in 40% of patients. 

Key learning: Ziftomenib 600 mg QD combined with Ven/Aza demonstrated promising clinical activity and was well tolerated in patients with newly diagnosed NPM1-m AML, supporting advancement to the randomized phase III KOMET-017 trial (NCT07007312).