Multinational phase 1-2 trial of ziftomenib for relapsed or refractory acute myeloid leukemia: phase 1 results of KOMET-001

Ziftomenib (KO-539) is an oral selective menin inhibitor with preclinical activity in menin-dependent acute myeloid leukemia (AML) models. The multinational phase 1-2 trial KOMET-001 evaluates ziftomenib for relapsed or refractory (R/R) AML. Phase 1 results of the trial have now been published. Overall 68 of 83 patients had serious adverse events, with two treatment-related deaths (one differentiation syndrome and one cardiac arrest). At the recommended phase 2 dose of 600 mg once daily, 25% of patiens with KMT2A rearrangement of NPM1 mutation had complete remission or complete remission with partial hematologic recovery. The authors conclude that ziftomenib showed promising clinical activity with manageable toxicity in heavily pretreated patients with R/R AML. Phase 2 is ungoing.