Phase I KOMET-007 trial long-term results: Ziftomenib + IC for ND NPM1m/KMT2Ar AML

Long-term results from the ongoing phase Ia/Ib KOMET-007 (NCT05735184) trial, evaluating ziftomenib in combination with intensive chemotherapy in adults with newly diagnosed (ND) or relapsed/refractory (R/R) NPM1-mutated (NPM1m) or KMT2A-rearranged (KMT2Ar) acute myeloid leukemia (AML), were presented by Amer Zeidan at the European Hematology Association (EHA) 2026 Congress, June 11–14, 2026, Stockholm, SE. Data are reported for patients with ND AML treated with the recommended phase II dose (RP2D) of ziftomenib 600 mg once daily (QD) across both phases (NPM1m, n = 49; KMT2Ar, n = 50). The primary endpoints were adverse events (AEs), dose-limiting toxicities (DLTs; phase Ia), and complete remission (CR) rate.

Key data: Any-grade treatment-emergent AEs (TEAEs) occurred in all patients, and Grade ≥3 TEAEs occurred in 96%. Grade ≥3 ziftomenib-related TEAEs occurred in 53% of patients; the most common were thrombocytopenia (21%), anemia (15%), febrile neutropenia (13%), neutropenia (13%), and pruritus (10%). The CR rate was 88% overall (NPM1m, 94%; KMT2Ar, 82%), while the composite CR (CRc) rate was 93% (NPM1m, 96%; KMT2Ar, 90%) and the overall response rate (ORR) was 95% (NPM1m, 98%; KMT2Ar, 92%). Measurable residual disease (MRD) negativity was observed in 85% of CR responders (NPM1m, 85%; KMT2Ar, 86%) and 84% of CRc responders (NPM1m, 85%; KMT2Ar, 82%). At a median follow-up of 17.6 months in the NPM1m arm and 11.0 months in the KMT2Ar arm, median overall survival (mOS) was not reported (NR) in both groups; 12-month OS rates were 94% and 71%, respectively. Grade 3 differentiation syndrome (DS) and corrected QT interval (QTc) prolongation occurred in 4% and 3% of patients, respectively; all resolved and no Grade 4 events were reported.

Key learning: Ziftomenib 600 mg QD in combination with intensive chemotherapy demonstrated a manageable safety profile alongside deep and durable responses in adults with ND NPM1m or KMT2Ar AML, supporting ongoing evaluation of ziftomenib-based intensive chemotherapy in the phase III KOMET-017 trial (NCT07007312).