Ziftomenib Receives FDA Approval for Acute Myeloid Leukemia With NPM1 Mutations

The FDA approved ziftomenib (Komzifti, Kura Oncology, Inc) for treatment of patients with adults with relapsed or refractory acute myeloid leukemia (AML) with a susceptible nucleophosmin 1 (NPM1) mutation who have no alternative treatment options. The data supporting the approval are from the KO-MEN-001 trial (NCT04067336).¹

Approximately 22,010 people will be diagnosed with AML in 2025, with an anticipated 11,090 deaths. AML represents 1% of all cancers and 1 out 3 leukemias in adults. Although AML can occur in children, which is uncommon, patients are typically diagnosed around 69 years of age. It is a fast-growing, progressive cancer that requires prompt treatment.²

NPM1 mutations are among the most frequent genetic alterations, occurring in up to 30% of newly diagnosed AML cases. Although these mutations are generally linked to a favorable prognosis in the frontline setting, their positive impact diminishes significantly in patients who become refractory or experience relapse, as response rates and overall survival decline with each successive line of therapy.³

Menin inhibitors are an emerging approach for patients, demonstrating promising capabilities in targeting NPM1 mutations and lysine KMT2A rearrangements, which are foundational leukemogenic drivers for clonal evolution of the disease. Ziftomenib, a potent and highly selective oral menin inhibitor, disrupts the menin-KMT2A complex and inhibits the oncogenic effects of mutant NPM1, promoting terminal differentiation of leukemia blasts.³

In the open-label, single-arm, multicenter KO-MEN-001 trial, ziftomenib led to meaningful remission benefits in patients with relapsed or refractory AML with an NPM1 mutation. The trial included 112 adults with NPM1 mutations, including type A, B, and D mutations and other NPM1 mutations likely to result in cytoplasmic localization of the NPM1 protein.⁴

The primary outcomes measured included complete remission (CR) plus CR with partial hematological recovery (CRh), the duration of CR+CRh, and the rate of conversion from transfusion dependence to transfusion independence.⁴

At the median follow-up of 4.2 months (range, 0.1-41.2 months), patients treated with ziftomenib achieved a CR+CRh rate of 21.4% (95% CI: 14.2, 30.2) with a duration of 5 months (95% CI: 1.9, 8.1). The trial investigators reported a CR rate of 17.0% (95% CI: 10.5, 25.2) and a CRh rate of 4.5% (95% CI: 1.5, 10.1).⁴

Of the patients who required red blood cell (RBC; n = 66) and/or platelet transfusions at baseline, 21.2% achieved independence from both RBC and platelet transfusions for at least one 56-day period following baseline. Meanwhile, among the 46 patients who began the study without a need for transfusions, 26.1% remained free from RBC and platelet transfusions during any 56-day period after baseline.⁴

The findings from the KO-MEN-001 trial highlight its potential to induce meaningful remissions and reduce transfusion dependence in a heavily pretreated population. As menin inhibition continues to emerge as a promising therapeutic strategy, ziftomenib represents an important step toward more precise, mutation-specific therapies in AML.

The recommended dose for ziftomenib is 600 mg taken orally once daily until disease progression or unacceptable toxicity.

REFERENCES

1. First in human study of ziftomenib in relapsed or refractory acute myeloid leukemia. Clinicaltrials.gov. Updated November 10, 2025. Accessed November 13, 2025. https://clinicaltrials.gov/study/NCT04067336#study-plan

2. Acute myeloid leukemia (AML) in adults. American Cancer Society. Updated March 4, 2205. Accessed November 13, 2025. https://www.cancer.org/cancer/types/acute-myeloid-leukemia/about/what-is-aml.html

3. Wang E, Montesinos P, Foran J, et al. Ziftomenib in relapsed or refractory NPM1-mutated AML. J Clin Oncol. September 25, 2025. Doi: 10.1200/JCO-25-01694

4. FDA approves ziftomenib for relapsed or refractory acute myeloid leukemia with a NPM1 mutation. FDA. November 13, 2025. Accessed November 13, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-ziftomenib-relapsed-or-refractory-acute-myeloid-leukemia-npm1-mutation?utm_medium=email&utm_source=govdelivery