As reported in the Journal of Clinical Oncology by Wang et al, a phase I/II trial (KOMET-001) has shown activity of the oral menin inhibitor ziftomenib in patients with relapsed or refractory NPM1-mutant acute myeloid leukemia (AML).
Study Details
In the phase II portion of the trial, 92 patients enrolled from sites in seven countries (United States and Canada = 49%, Europe = 51%) between January 2023 and May 2024 received ziftomenib at 600 mg once daily. Patients had received a median of two prior therapies (range = 1–7 therapies), including venetoclax in 54 (59%). Median patient age was 69 years (range = 33–84 years). The primary endpoint was the rate of complete remission with full hematologic recovery (CR)/CR with partial hematologic recovery (CRh), with the aim of exceeding a CR/CRh rate of 10%.
Key Findings
The primary endpoint was met, with CR/CRh being achieved in 20 patients (22%, 95% confidence interval [CI] = 14%–32%, P = .0058). Among 18 evaluable patients, 11 (61%) achieved measurable residual disease negativity. Partial response or better was achieved in 30 patients (33%, 95% CI = 23%–43%), with a median response duration of 4.6 months (95% CI = 2.8–7.4 months).
Subgroup analyses showed comparable CR/CRh rates regardless of previous therapy, including venetoclax, or type of co-mutations.
Median overall survival was 6.6 months (95% CI = 3.6–8.6 months) among all patients and 18.4 months (95% CI = 8.6 months to not estimable) among responders.
Grade ≥ 3 adverse events were reported in 93% of patients, commonly febrile neutropenia (26%), anemia (20%), and thrombocytopenia (20%). Differentiation syndrome occurred in 25% of patients (grade 3 in 15%). Discontinuation of treatment as a result of ziftomenib-related adverse events occurred in three patients (3%). No treatment-related deaths were reported.
The investigators concluded: “Ziftomenib demonstrated significant clinical benefit and deep responses in patients with heavily pretreated, relapsed/refractory [NPM1-mutated] AML. Ziftomenib was well tolerated with a safety profile consistent with previous studies, including manageable differentiation syndrome, lack of clinically significant QTc prolongation, and low rates of myelosuppression.”
Eunice S. Wang, MD, of Roswell Park Comprehensive Cancer Center, Buffalo, New York, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: The study was supported by Kura Oncology. For full disclosures of all study authors, visit ascopubs.org.
