Ziftomenib plus 7+3 achieved 94% one‑year survival in NPM1‑mutant AML with deep MRD clearance, durable remissions, and strong safety in KOMET‑007.
Written By: Chikkula Pavan Kumar, PharmD
Reviewed By: Pharmacally Editorial Team
Updated Phase 1/2 KOMET-007 (NCT05735184) data presented at the European Hematology Association (EHA) 2026 Congress showed that ziftomenib plus intensive chemotherapy (7+3) delivered a 12-month overall survival (OS) rate of 94% in newly diagnosed NPM1-mutant (NPM1-m) acute myeloid leukemia (AML) and 71% in KMT2A-rearranged (KMT2A-r) AML. Median OS was not reached in either cohort after a median follow-up of 17.6 months in NPM1-m AML and 11.0 months in KMT2A-r AML.
High Remission and Molecular Clearance
The analysis included 49 patients with NPM1-m AML and 50 patients with KMT2A-r AML treated with ziftomenib 600 mg once daily plus 7+3 chemotherapy.
Clinical activity was robust across both genetic subtypes. In NPM1-m AML, the composite complete remission (CRc) rate reached 96%, with an overall response rate (ORR) of 98%. In KMT2A-r AML, CRc and ORR were 90% and 92%, respectively.
Local measurable residual disease (MRD) negativity was achieved in 85% of NPM1-m patients and 82% of KMT2A-r patients who achieved CRc. Central next-generation sequencing assessment confirmed MRD negativity in 79% of NPM1-m responders at the <0.1% threshold and 56% at the more stringent <0.01% threshold. All centrally confirmed MRD-negative responses occurred by Cycle 2.
Durable Responses
Responses remained durable with extended follow-up. Median duration of complete response was not reached in the NPM1-m cohort and was 12 months in patients with KMT2A-r AML.
At the data cutoff, 90% (44/49) of NPM1-m patients and 62% (31/50) of KMT2A-r patients remained alive and continued on study treatment.
Safety Profile
The combination maintained a manageable safety profile with no new safety signals observed. Investigators reported minimal additive myelosuppression and no delays in neutrophil or platelet recovery.
Four patients experienced Grade 3 differentiation syndrome, with all cases resolving following protocol-specified management. No Grade 4 differentiation syndrome or QTc prolongation events were reported. Three patients experienced Grade 3 QTc prolongation, all of which resolved and did not require discontinuation of ziftomenib treatment.
The 60-day mortality rate among NPM1-m patients was 2%.
Mechanistic and Regulatory Context
Ziftomenib is a selective menin inhibitor that targets aberrant gene expression programs driving leukemogenesis in NPM1-mutant and KMT2A-rearranged AML. The therapy is approved in the United States as monotherapy for adults with relapsed or refractory NPM1-mutant AML who have no satisfactory alternative treatment options. Its use in combination with 7+3 chemotherapy remains investigational.
Clinical Implications
Amer Zeidan, M.B.B.S., M.H.S., lead investigator of the registrational KOMET-017 program, highlighted the high remission rates, deep MRD clearance, and encouraging durability observed across both molecularly defined AML populations.
He noted that the depth of response may ultimately allow some patients to avoid allogeneic hematopoietic cell transplantation, a procedure associated with substantial morbidity and mortality.
Toward Confirmatory Evaluation
Kura Oncology and Kyowa Kirin said the findings strengthen confidence in the ongoing Phase 3 KOMET-017 (NCT07007312) registrational program evaluating ziftomenib in combination with intensive chemotherapy in frontline AML. The companies plan to publish the data in a peer-reviewed journal during the second half of 2026.
Reference
About the Writer
Chikkula Pavan Kumar (LinkedIn), PharmD is a Doctor of Pharmacy with a keen interest in clinical pharmacy, pharmacovigilance, and evidence-based practice. In his words, he is passionate about patient safety and translating complex medical information into clear, research-driven communication.