Phase I KOMET-007 trial: Ziftomenib with Ven + Aza in R/R NPM1m AML

Results from the phase Ia/b KOMET-007 trial (NCT05735184), investigating ziftomenib combined with venetoclax (Ven) + azacitidine (Aza) in adults with relapsed/refractory (R/R) NPM1-mutated (NPM1m) acute myeloid leukemia (AML; N = 67), were recently published in Blood by Wang et al. The primary endpoints were dose-limiting toxicities (DLTs; phase Ia), adverse events (AEs), and complete remission (CR) rate.

Key data: No DLTs were observed in phase Ia (n = 27). In all response-evaluable patients (n = 64) the composite CR (CRc) rate was 45%, with central measurable residual disease (MRD) negativity achieved in 61% of responding patients. In response-evaluable patients treated with the recommended dose of ziftomenib 600 mg once daily (QD; n = 48), the CRc rate was 46%; among patients achieving CRc (n = 18), 67% achieved central MRD negativity. In patients treated with ziftomenib 600 mg QD, median overall survival (OS) was not reached at a median follow-up of 9.9 months; 1-year OS rate was 62%. The most common (≥20%) Grade ≥3 treatment-emergent adverse events (TEAEs) among all patients were leukopenia (34%), thrombocytopenia (28%), and febrile neutropenia and neutropenia (25% each). Six patients experienced corrected QT interval (QTc) prolongation (one ziftomenib-related, Grade 1). Grade 3 differentiation syndrome occurred in two patients; all events resolved.

Key learning: Ziftomenib combined with Ven + Aza demonstrated durable clinical activity with a manageable safety profile in adults with R/R NPM1m AML, supporting further evaluation of this triplet regimen.