The investigational agent ziftomenib, a menin-MLL inhibitor, demonstrated activity in patients with relapsed or refractory NPM1-mutant acute myeloid leukemia (AML), regardless of prior venetoclax treatment, according to findings from the phase II KOMET-001 trial. Findings from the study were presented at the 2025 ASCO Annual Meeting (Abstract 6506). The agent was also reported to be well tolerated, with 3% treatment-related discontinuations noted.
“The results of this phase II trial establish the potential for ziftomenib to induce responses and prolong life in responding patients with relapsed or refractory acute myeloid leukemia characterized by NPM1 mutations, a disease [that] currently carries a poor prognosis with no approved targeted treatment options,” stated lead study author Eunice Wang, MD, Chief of Leukemia and Professor of Oncology in the Department of Medicine at Roswell Park Comprehensive Cancer Center, Buffalo, New York.
About the Study
Approximately 30% of patients with AML have NPM1 mutations, with relapse or resistance to standard therapy usually occurring within a year for these patients.
Menin inhibitors block the interaction of menin and KMT2A proteins that allow certain leukemia cells to survive and spread.
The phase I/II KOMET-001 trial is the first-in-human study of ziftomenib in patients with relapsed or refractory AML. Prior results from phase I of the study were published in The Lancet Oncology; they showed clinical activity and manageable toxicity for the agent in patients with heavily pretreated disease.
Key Study Findings
Phase II of the study enrolled 112 patients with relapsed or refractory NPM1-mutated AML from North America and Europe. All patients received 600 mg of ziftomenib monotherapy orally once a day.
At a median of 4.2 months of follow-up, complete remissions with full or partial hematologic recovery were reported in 25% of patients, and composite complete remission was observed in 29%. Two-thirds of patients who had complete remission with full or partial hematologic recovery achieved measurable residual disease negativity.
The median duration of complete remission with full or partial hematologic recovery was 3.7 months (95% confidence interval [CI] = 1.9–7.7 months) and 5.1 months (95% CI = 2.8–8.1 months) for composite complete remission.
A total of 40% of patients had a grade 3 or higher treatment-related adverse event, including differentiation syndrome (13%, all grade 3), anemia (≤ 5%), febrile neutropenia (≤ 5%), thrombocytopenia (≤ 5%), and QTc prolongation (2%, grade 3).
Disclosure: For full disclosures of the study authors, visit coi.asco.org.
