KOMET-007 phase Ia/b updated results: Ziftomenib + Ven/Aza in R/R NPM1-m or KMT2A-r AML

During the 67th American Society of Hematology (ASH) Annual Meeting and Exposition, December 6–9, 2025, Orlando, US, Amir Fathi reported updated results from the phase Ia/b KOMET-007 trial (NCT05735184) evaluating ziftomenib 600 mg once daily in combination with venetoclax (Ven) and azacitidine (Aza) in 83 patients with relapsed/refractory (R/R) NPM1-mutated (NPM1-m) [n = 51] or KMT2A-rearranged (KMT2A-r) [n = 32] acute myeloid leukemia (AML). The primary endpoints were complete remission (CR) and adverse events (AEs). Secondary endpoints included composite CR (CRc) and overall response rate (ORR).

Key data: The ORR was 65% and the CRc rate was 48% in the NPM1-m cohort; the ORR was 41% and the CRc rate was 28% in the KMT2A-r cohort. The median duration of CRc was 39.9 weeks for NPM1-m and 12.4 weeks for KMT2A-r. Ziftomenib + Ven/Aza was well tolerated, with 58% of patients experiencing any-grade ziftomenib-related treatment-emergent adverse events (TEAEs) and no ziftomenib-related corrected QT interval (QTc) prolongation reported.

Key learning: Ziftomenib + Ven/Aza demonstrated encouraging clinical activity in heavily pretreated patients with R/R NPM1-m or KMT2A-r AML, including those with prior Ven exposure, supporting further investigation of this menin inhibitor-based combination approach.