FDA Grants Ziftomenib Breakthrough Therapy Designation in NPM1-Mutant AML


This breakthrough therapy designation of ziftomenib marks the first of its kinds in NPM1-mutant acute myeloid leukemia.

  • The FDA has granted a breakthrough therapy designation to ziftomenib for the treatment of patients with relapsed/refractory NPM1-mutant acute myeloid leukemia (AML).
  • This is the first investigational treatment to be granted this designation in NPM1-mutant AML.
  • The designation is supported by the phase 1/2 KOMET-001 study (NCT04067336).

Acute myeloid leukemia cells: © LASZLO - stock.adobe.com

Acute myeloid leukemia cells: © LASZLO - stock.adobe.com

Ziftomenib, a Menin-MLL inhibitor, has been granted a breakthrough therapy designation by the FDA in relapsed/refractory NPM1-mutant AML, according to Kura Oncology.1

“We are highly encouraged by FDA’s decision to grant breakthrough therapy designation to ziftomenib, recognizing its potential as an innovative medicine for patients with relapsed/refractory NPM1-mutant AML,” said Troy Wilson, PhD, JD, president, chief executive officer of Kura Oncology, in a press release.

NPM1-mutant AML represents approximately 30% of new AML cases annually, and this designation reflects that NPM1-mutant AML is a disease of significant unmet need for which there is no approved targeted therapy as well as the fact that ziftomenib offers potential to demonstrate substantial improvement over available therapies. We remain committed to bringing ziftomenib to the market as quickly as possible and look forward to working more closely with FDA to bring our ziftomenib program to patients in urgent need of effective treatments,” Wilson added in the press release.

The breakthrough therapy designation is designed to expedite the development of review of drugs. Agents granted this designation can be eligible for rolling review and priority review. The FDA also granted ziftoemenib an orphan drug designation for the treatment of AML.

The designation is supported by KOMET-001, a phase 1/2 clinical trial evaluating ziftomenib in the intent-to-treat population. Ziftomenib monotherapy at 600 mg demonstrated a 25% complete remission rate, according to preliminary data.

The study has an estimated enrollment of 199 patients across 17 states in the US and 7 additional countries.2 The primary end points are maximum tolerated dose, incidence of adverse events, minimal biologically effective dose, and evidence of antileukemia activity. Secondary end points include pharmacokinetics, complete responses with and without minimal residual disease, duration of remission, transfusion independence, event-free survival, and overall survival.

Patients with NPM1 mutations or KMT2A rearrangements, an ECOG performance status of 0 to 2, a life expectancy of at least 2 months, and adequate liver and kidney function are eligible for participation in the study. Patients who have active central nervous system leukemia, grade 2 or higher graft-vs-host disease, or not had adequate hematologic recovery following stem cell transplantation are not eligible for study participation.

The trial is estimated to be completed by mid-2024.1

Ziftomenib is also being investigated as a combination therapy with venetoclax (Venclexta) and azacitidine or cytarabine plus daunorubicin in NPM1-mutant and KMT2A-rearranged AML in the KOMET-007 study (NCT05735184). KOMET-008 (NCT05735184) is looking at gilteritinib (Xospata) and fludarabine, cytarabine, idarubicin, and granulocyte colony stimulating factor or low-dose cytarabine in KMT2A-rearranged AML.

1. Kura Oncology receives breakthrough therapy designation for ziftomenib in NPM1-mutant AML. News release. Kura Oncology. April 22, 2024. Accessed April 22, 2024. https://tinyurl.com/2tjjb824
2. First in human study of ziftomenib in relapsed or refractory acute myeloid leukemia. ClinicalTrials.gov. Updated March 15, 2024. Accessed April 22, 2024. https://clinicaltrials.gov/study/NCT04067336
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