Andrew Moreno

Blood Cancers Today

A phase I clinical trial has been performed of ziftomenib, an oral selective menin inhibitor, for treatment of acute myeloid leukemia. Its findings were published in The Lancet Oncology.
“Ziftomenib showed promising clinical activity with manageable toxicity in heavily pretreated patients with relapsed or refractory acute myeloid leukaemia,” wrote lead author Eunice S Wang, MD, of Roswell Park Comprehensive Cancer Center in Buffalo, New York.
The published results were from the phase Ia and Ib components of the international, multi-center, open-label KOMET-001 trial. These phase I data were gathered to determine the recommended dose in this setting for the phase II trial which is currently in progress.
In phase Ia, 83 adults received 50-1000 mg oral ziftomenib once daily in 28-day cycles. This cohort was 53% female and had a median follow-up of 22.3 months.
The most common grade 3 or worse severity treatment-emergent adverse events encountered by this cohort were anemia which occurred in 24% of the patients, febrile neutropenia in 22%, pneumonia in 19%, differentiation syndrome in 15%, thrombocytopenia in 13%, and sepsis in 12%. Serious adverse events were experienced by 68 patients and there were two treatment-related mortalities, one due to cardiac arrest and the other from differentiation syndrome.
In phase Ib, patients from the cohort who had NPM1 mutations or KMT2A rearrangements were randomly assigned 1-to-1 to two cohorts to receive either 200 mg or 600 mg ziftomenib.
None of the patients assigned to receive 200 mg ziftomenib reported response. Among the 36 patients who received 600 mg ziftomenib—the recommended phase II dose—nine achieved complete remission or complete remission with partial hematologic recovery. Among the 20 patients with NPM1 mutation who received 600 mg dosing, seven achieved complete remission.
The KOMET-001 trial is funded by Kura Oncology.
Reference
Wang ES, Issa GC, Erba HP, et al. Ziftomenib in relapsed or refractory acute myeloid leukaemia (KOMET-001): a multicentre, open-label, multi-cohort, phase 1 trial [published correction appears in Lancet Oncol. 2024 Nov;25(11):e542. doi: 10.1016/S1470-2045(24)00584-9]. Lancet Oncol. 2024;25(10):1310-1324. doi:10.1016/S1470-2045(24)00386-3

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