Ziftomenib-Chemotherapy Combo Shows 94% Survival in NPM1-Mutant AML
Updated KOMET-007 trial data show ziftomenib plus chemotherapy achieves 94% twelve-month overall survival in newly diagnosed NPM1-mutant AML. The oral menin inhibitor, approved by the FDA in November 2025 for relapsed/refractory disease, is being evaluated in a Japanese Phase II trial and a global Phase 3 study.
Updated data from the KOMET-007 trial show that ziftomenib plus standard chemotherapy yields a 94% twelve-month overall survival rate in newly diagnosed NPM1-mutant acute myeloid leukemia, with a 96% composite complete remission rate. The oral menin inhibitor, which received FDA approval in November 2025 for relapsed or refractory disease, is now being tested in a Phase 3 trial for frontline treatment.
The single-arm KOMET-007 trial enrolled 49 patients with NPM1-mutant AML who received ziftomenib at 600 mg once daily added to standard 7+3 induction chemotherapy. Among these patients, the composite complete remission (CRc) rate was 96%, and median overall survival remains unreached at 17.6 months of follow-up. Historical benchmarks for 7+3 chemotherapy show complete remission rates around 75% in younger fit patients, with lower survival at twelve months in older populations.
Measurable residual disease negativity was high: local MRD negativity among responders reached 85%, and central next-generation sequencing-based MRD negativity at a 0.01% threshold was 56%, with all MRD-negative patients achieving clearance by Cycle 2. Safety data showed no Grade 4 differentiation syndrome; Grade 3 differentiation syndrome occurred in 4% of patients and resolved in all cases. Ziftomenib did not delay neutrophil or platelet recovery, and the 60-day mortality rate was 2%.
Ziftomenib, marketed as Komzifti, received FDA approval in November 2025 as monotherapy for adults with relapsed or refractory NPM1-mutant AML who have no satisfactory alternative treatment options. The approval includes a boxed warning for differentiation syndrome. Frontline combination use of ziftomenib with chemotherapy remains investigational pending results from the Phase 3 KOMET-017 trial, which will evaluate MRD negativity as a key endpoint.
Kyowa Kirin and Kura Oncology have initiated a Japanese Phase II registrational trial of ziftomenib in adult patients with relapsed or refractory NPM1-mutated AML. The single-arm, open-label, multi-center study has a primary endpoint of composite complete remission rate, and Kyowa Kirin intends to seek regulatory approval in Japan following trial completion.
Ziftomenib is an oral menin inhibitor that blocks the protein-protein interaction between menin and KMT2A fusion proteins, disrupting downstream transcriptional programs that promote leukemogenesis. In the earlier KOMET-001 phase 1/2 trial, 600 mg daily ziftomenib produced a complete remission in 22% of relapsed or refractory NPM1-mutant AML patients. Ziftomenib is also in development for front-line AML with NPM1 mutations, KMT2A rearrangements, and FLT3 mutations.