Ziftomenib in combination with intensive chemotherapy in newly diagnosed NPM1m or KMT2Ar AML: Updated KOMET-007 results

Mutations in NPM1 and KMT2A genes drive leukemogenesis in ~35–40% of patients with AML.¹ Ziftomenib is a potent, selective, oral menin inhibitor under investigation in clinical trials as a monotherapy and in combination regimens for patients with NPM1-mutated (NPM1m) or KMT2A-rearranged (KMT2Ar) AML.¹

During the European Hematology Association (EHA) 2025 Congress, Harry Erba presented updated results from the ongoing phase Ia/b KOMET-007 trial (NCT05735184) of ziftomenib at the RP2D of 600 mg QD in combination with intensive induction chemotherapy (7+3), in patients with newly diagnosed NPM1m (n = 49) or KMT2Ar (n = 33) AML (N = 82).¹ The primary endpoints were AEs, DLTs in phase Ia, and CR.¹

Key learnings

Robust clinical responses were demonstrated in both newly diagnosed NPM1m (n = 44; cCR, 93%) and KMT2Ar (n = 27; cCR, 89%) response-evaluable patients, with cCR MRD negativity observed in 68% and 83% of patients, respectively.

At median follow ups of 25 and 16 weeks, respectively, 96% of patients with NPM1m AML and 88% of patients with KMT2Ar AML remained alive and continued on study.

Grade ≥3 TRAEs of interest were observed in 35% of all patients; the most common were febrile neutropenia (15%), decreased platelet count (15%), anemia (11%), and decreased neutrophil count (11%). Differentiation syndrome, reported in one patient with KMT2Ar AML, was successfully brought under control.

These tolerability and clinical activity data support the continued investigation of ziftomenib as a combination therapy in patients with newly diagnosed NPM1m and KMT2Ar AML in the upcoming phase III KOMET-017 trial.