Expert Outlines KOMET-001 Trial Design Assessing Ziftomenib in AML

An expert from Duke Health reviews the design of the phase 1/2 trial of the KOMET-001 study in heavily pretreated patients with relapsed/refractory acute myeloid leukemia.

Ziftomenib was assessed in a heavily pretreated population of patients with relapsed/refractory acute myeloid leukemia, with doses ranging from 50 mg to 1000 mg, according to Harry Erba, MD.

In an interview with CancerNetwork®, Erba, a professor of medicine, member, and clinical investigator of the Division of Hematologic Malignancies at Duke Health, reviewed the design of the phase 1/2 KOMET-001 trial (NCT04067336).

The study set out to assess ziftomenib’s safety, tolerability, pharmacokinetics, and anti-leukemic activity in a population of 30 patients with AML. Patients had a median age of 65.5 years (range, 22-85). Moreover, 33% of patients had a KMT2Ar mutation and 13% had an NPM1 mutation.

The recommended phase 2 dose was determined to be 600 mg.


The KOMET-001 study was a phase 1/2, first-in-human study of the menin inhibitor ziftomenib or KO-539. It was for patients with relapsed/refractory acute myeloid leukemia.

There were 2 components to the study. First, there was a phase 1a dose escalation [portion, where we evaluated doses from 50 mg up to 1000 mg of daily ziftomenib looking at safety, tolerability, pharmacokinetics, and any evidence of early anti-tumor activity. However, this was not just in patients with the targets, NPM1 mutation or KMT2A rearrangement, but in all comers.

There was then a phase 1b or dose validation portion where we had 2 cohorts—200 mg and 600 mg a day—[and were] trying to identify the optimal recommended phase 2 dose based on those 2 doses in a genetically enriched cohort with KMT2A rearrangements and NPM1 mutation.

Then we are entering into a phase 2 portion at the recommended phase 2 dose of 600 mg once daily.


Erba HP, Fathi AT, Issa GC, et al. Update on a phase 1/2 first-in-human study of the menin-KMT2A (MLL) inhibitor ziftomenib (KO-539) in patients with relapsed or refractory acute myeloid leukemia. Blood. 2022; 140(suppl 1):153-156. doi:10.1182/blood-2022-167412

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