No new efficacy data were disclosed. The registrational Phase 3 program will test ziftomenib in two frontline settings with dual-primary endpoints: in the intensive 7+3 backbone, minimal residual disease (MRD)-negative complete response and event-free survival; in the non-intensive venetoclax/azacitidine backbone, complete response and overall survival. The design is intended to support potential accelerated approval on response-based endpoints with time-to-event endpoints as confirmatory.
Kura Oncology and Kyowa Kirin have dosed the first patient in KOMET-017 (NCT07007312), a protocol comprising two independent, global, randomized, double-blind, placebo-controlled Phase 3 trials in newly diagnosed NPM1-mutated or KMT2A-rearranged AML. One trial layers ziftomenib onto standard induction cytarabine/daunorubicin; the other adds the menin inhibitor to venetoclax plus azacitidine. The sponsors plan to activate up to 200 sites worldwide and position the program for both accelerated and traditional approval in the United States.
Strategically, running parallel, backbone-specific trials signals an intent to establish menin inhibition as a genotype-directed pillar across the full frontline intensity spectrum rather than pursuing a narrower salvage niche. The dual-primary construct is also a regulatory hedge: response-based endpoints can open an accelerated pathway, while EFS and OS anchor durability. The inclusion of MRD-negative CR up front is notable and reflects the FDA’s growing, but still selective, willingness to consider MRD as a surrogate in hematologic malignancies. It also pushes the program into operationally complex territory where assay standardization, sampling windows, and central read logistics can make or break timelines. Competitive pressure is real: multiple menin inhibitors are advancing with combination strategies in similar genotypes, making speed, safety differentiation, and clean execution decisive.
For sites, the trials will require rapid molecular triage of newly diagnosed patients, with reliable local testing for NPM1 mutations and KMT2A rearrangements and, likely, central confirmation without delaying induction. That favors centers with 24/7 molecular pathology and established AML intake pathways. The intensive arm’s blinded add-on to 7+3 raises practical issues around drug supply at admission, emergent cytoreduction policies, and protocol allowances for bridging therapy. The venetoclax/azacitidine arm compounds familiar myelosuppression and infection risks; layering a menin inhibitor will demand tight supportive care protocols, careful management of azole prophylaxis and potential drug–drug interactions, and vigilance for differentiation-like events. CROs and data vendors should expect heavy MRD operational burden—assay harmonization, chain-of-custody, and adjudication of MRD negativity—alongside event-driven analyses that require clean endpoint definitions across geographies. Regulators will gain a real-world stress test of MRD-negative CR as a basis for accelerated approval in frontline AML, and payers will watch for consistency of benefit across NPM1-mutant and KMT2A-rearranged subgroups.
The near-term watch items are enrollment velocity against a crowded AML study landscape, site activation in regions with heterogeneous MRD capabilities, and early safety signals when ziftomenib is combined with venetoclax or intensive chemotherapy. Any interim that looks focused on response or MRD conversion will set expectations for the viability of the accelerated path. The bigger unknown is whether MRD-negative CR translates into a robust EFS/OS delta in genetically diverse, frontline populations—a threshold regulators and guideline bodies will scrutinize. If the program can navigate MRD operational complexity, deliver a clean safety profile without exacerbating cytopenias, and sustain a time-to-event advantage, it could reset how genotype-directed therapy is integrated into both intensive and non-intensive AML induction. If not, the field may revert to later-line use or narrower biomarker segmentation, and the window for first-mover advantage in menin inhibition will narrow.
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.
