Kura Oncology and Kyowa Kirin have dosed the first patient in a new cohort of the Phase 1b KOMET-007 trial (NCT05735184) evaluating ziftomenib, an oral menin inhibitor, added to 7+3 induction and quizartinib in newly diagnosed FLT3-ITD/NPM1 co-mutated AML. The cohort will assess safety, tolerability, and activity with complete remission and composite complete remission as key endpoints.
The move shifts ziftomenib squarely into a genomically defined frontline setting where FLT3 inhibition is already part of standard intensive therapy. By layering menin inhibition onto 7+3 plus quizartinib, the sponsors are testing whether dual targeting of NPM1-driven leukemogenesis and FLT3 signaling can improve depth and durability of response in a population with high relapse risk. Ziftomenib holds FDA Breakthrough Therapy Designation in relapsed/refractory NPM1-mutated AML, and KOMET-007 now runs in parallel with Kura’s registrational KOMET-017 program combining ziftomenib with both intensive and non-intensive backbones across multiple frontline segments.
Strategically, this is an expansion play aimed at turning a salvage-stage asset into a foundational component of frontline AML regimens. The selection of quizartinib, rather than midostaurin, signals a bet on greater FLT3-ITD selectivity and a path to differentiate against entrenched midostaurin-based induction. It also aligns with an industry pivot toward triplet strategies that marry targeted agents to chemotherapy in molecularly defined subsets. The risk is operational and regulatory complexity: triplets magnify toxicity management, drug–drug interactions, and study logistics, and raise the bar on evidence when regulators weigh additive benefit over established backbones.
For sites, the cohort heightens the premium on rapid molecular workup. Screening hinges on confirming both FLT3-ITD and NPM1 mutations before or during induction, which compresses timelines and demands real-time PCR/NGS capacity, coordinated pharmacy workflows, and careful antifungal prophylaxis planning given CYP3A interactions across the regimen. Monitoring will need to capture overlapping myelosuppression, differentiation syndrome associated with menin inhibitors, and QTc risks from quizartinib, with clear mitigation algorithms and DSMB oversight. CROs should expect intensive safety signal management and adjudication of differentiation-like events versus infectious complications typical of induction.
For sponsors and regulators, the central question is endpoints. Early cohorts can credibly focus on CR/CRc and MRD dynamics to de-risk the triplet. But any path to a label in the frontline intensive setting will likely require randomized evidence on event-free survival or overall survival against a quizartinib-containing standard. The registrational KOMET-017 effort suggests Kura is architecting multiple shots on goal across intensive and non-intensive care, but convergence on a coherent Phase 3 strategy that isolates ziftomenib’s contribution will be essential.
Watch for early safety and MRD readouts that indicate whether the triplet is tolerable without compromising delivery of 7+3 and consolidation. Dosing schemas that navigate azole co-administration and QTc management will be telling for real-world feasibility. Competitive pressure will intensify as other menin inhibitors and FLT3 combinations advance in both intensive and venetoclax-based backbones. If ziftomenib can demonstrate an additive benefit without operational friction that overwhelms induction workflows, it could reshape protocols for a meaningful slice of newly diagnosed AML; if not, the field may consolidate around simpler doublets with clearer execution economics.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
