Updated KOMET-007 Data Support Frontline Ziftomenib Combinations in Molecularly Defined AML

Updated phase 1 findings from the KOMET-007 trial suggest that adding the menin inhibitor ziftomenib to standard 7+3 induction chemotherapy may produce high response rates in newly diagnosed acute myeloid leukemia (AML) with NPM1 mutations (NPM1-m) or KMT2A rearrangements (KMT2A-r).¹

The dataset, which includes 99 patients, will be presented at the European Hematology Association (EHA) 2026 Congress.¹ According to Kura Oncology and Kyowa Kirin, the oral combination of ziftomenib with cytarabine and daunorubicin demonstrated high composite complete response (CRc) and measurable residual disease (MRD)-negativity rates across both genetically defined AML subgroups.¹

“With nearly 100 patients treated as well as extended follow-up, ziftomenib in combination with 7+3 continues to demonstrate consistently high response rates, deep MRD negativity, and encouraging durability across genetically defined AML subsets,” said Mollie Leoni, MD, chief medical officer of Kura Oncology, in the company release.¹

High Remission Rates Reported Across AML Subtypes

As of the January 16, 2026, data cutoff, investigators reported CRc rates of 96% (47 of 49 patients) in NPM1-mutated AML and 90% (45 of 50 patients) in KMT2A-rearranged AML.¹ Among responding patients, MRD negativity rates reached 83% and 82%, respectively.¹

Median follow-up was longer in the NPM1-mutated cohort at 14.9 months, compared with 9.3 months in the KMT2A-rearranged group.¹ Median duration of CRc had not yet been reached in the NPM1-mutated cohort, while it was reported as 11.2 months in patients with KMT2A rearrangements.¹

The companies stated that no new safety signals were observed during longer-term follow-up and that safety findings appeared consistent across molecular subtypes.¹ However, detailed adverse-event data were not included in the announcement.

Menin Inhibition Expands in AML

The findings add to growing interest in menin inhibition as a targeted therapeutic strategy in AML driven by NPM1 mutations and KMT2A rearrangements.² Menin-dependent transcriptional programs are believed to sustain leukemogenesis in these molecular subsets, making the pathway an attractive therapeutic target.²^,³

NPM1 mutations represent one of the most common genomic alterations in AML, while KMT2A rearrangements are typically associated with more aggressive disease biology and poorer outcomes.² Current frontline treatment for fit adults often includes intensive induction chemotherapy with the 7+3 regimen, although outcomes vary significantly depending on molecular subtype and patient characteristics.

Ziftomenib is already approved in the United States as Komzifti for adults with relapsed or refractory AML harboring susceptible NPM1 mutations and lacking satisfactory alternative treatment options.¹ The frontline combination strategy remains investigational.

Safety and Durability Questions Remain

Despite encouraging efficacy findings, experts caution that the data remain preliminary. The current report is based on a conference presentation and company release rather than a peer-reviewed publication.¹ Important details regarding patient selection, transplant rates, event-free survival, overall survival, and hematologic recovery have not yet been fully disclosed.

Safety interpretation is particularly important because intensive induction chemotherapy already carries risks of prolonged cytopenias, infections, and organ toxicity. Menin inhibitors as a class have also been associated with differentiation syndrome and QTc prolongation.⁴

According to the FDA prescribing information for Komzifti, differentiation syndrome occurred in 26% of patients treated in the relapsed or refractory AML setting and was fatal in 2 patients.⁴ Whether combining ziftomenib with frontline induction chemotherapy alters those risks remains unclear.

The ongoing phase 3 KOMET-017 study is now evaluating ziftomenib in combination with intensive and nonintensive chemotherapy regimens for newly diagnosed NPM1-mutated or KMT2A-rearranged AML.¹ If the high remission and MRD-negativity rates observed in KOMET-007 translate into durable survival benefits in randomized testing, ziftomenib-based combinations could further strengthen the role of molecularly targeted frontline AML therapy.

References

1. Kura Oncology, Kyowa Kirin. (2026, May 12). Kura Oncology and Kyowa Kirin to present updated frontline ziftomenib / 7+3 combination data at EHA 2026 Congress. GlobeNewswire. https://www.globenewswire.com/news-release/2026/05/12/3293020/35186/en/kura-oncology-and-kyowa-kirin-to-present-updated-frontline-ziftomenib-7-3-combination-data-at-eha-2026-congress.html
2. Fiskus, W., Boettcher, S., Daver, N., Mill, C. P., Sasaki, K., Birdwell, C. E., Davis, J. A., Takahashi, K., Kadia, T. M., DiNardo, C. D., Jin, Q., Qi, Y., Su, X., McGeehan, G. M., Khoury, J. D., Ebert, B. L., & Bhalla, K. N. (2022 Jan 11). Effective Menin inhibitor-based combinations against AML with MLL rearrangement or NPM1 mutation (NPM1c). Blood cancer journal. https://doi.org/10.1038/s41408-021-00603-3
3. Erb, M. A., Scott, T. G., Li, B. E., et al. (2017). Transcription control by the ENL YEATS domain in acute leukaemia. Nature. https://www.nature.com/articles/nature21688
4. US Food and Drug Administration. (2025). KOMZIFTI (ziftomenib) prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/219678s000lbl.pdf