Kura Oncology and Kyowa Kirin are advancing ziftomenib, a selective oral menin inhibitor, into Phase 3 trials following positive topline results from the Phase 2 KOMET-001 trial. The drug is being developed for patients with relapsed/refractory (R/R) NPM1-mutant acute myeloid leukemia (AML). The KOMET-001 trial achieved its primary endpoint of complete remission (CR) plus CR with partial hematological recovery (CRh), demonstrating a statistically significant outcome and a favorable benefit-risk profile.
The companies plan to submit a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) in the second quarter of 2025 for ziftomenib in R/R NPM1-m AML. This follows the FDA's Breakthrough Therapy Designation (BTD) granted to ziftomenib in April 2024, the first investigational therapy to receive this designation for this specific AML subtype.
Phase 3 Trial Designs
Building on the Phase 2 results and positive interactions with the FDA, Kura and Kyowa Kirin are initiating a single protocol, KOMET-017, encompassing two independently powered, randomized, double-blind, placebo-controlled Phase 3 trials. These trials will evaluate ziftomenib in combination with both intensive and non-intensive combination regimens in patients with newly diagnosed NPM1-m and KMT2A-rearranged (KMT2A-r) AML.
The KOMET-017-IC trial will assess ziftomenib in combination with induction chemotherapy (7+3) in newly diagnosed NPM1-m and KMT2A-r AML patients. The dual-primary endpoints are minimum residual disease (MRD) negative complete response (CR) and event-free survival (EFS), designed to support potential U.S. accelerated approval and full approval, respectively. The KOMET-017-NIC trial will evaluate ziftomenib with venetoclax plus azacitidine in newly diagnosed NPM1-m patients unfit for intensive chemotherapy. The dual-primary endpoints here are CR and overall survival (OS), also intended to support accelerated and full approval pathways.
Clinical Significance
AML is a challenging hematological malignancy, with approximately 20,000 Americans diagnosed each year. NPM1 mutations or KMT2A rearrangements are found in about 35% of cases. Despite available treatments, relapse is common, and the 5-year survival rate is only 31.9%, dropping to 11.2% for patients older than 65.
According to Mollie Leoni, M.D., Chief Medical Officer of Kura Oncology, "Even with approved therapies, up to 70% of patients who achieve a first CR will see their AML return within 3 years... Given this urgent need, we are pleased with the outcome of these FDA interactions and look forward to initiating our Phase 3 trials to establish the benefit-risk profile of ziftomenib in both the intensive and non-intensive chemotherapy settings."
Strategic Collaboration
In November 2024, Kura Oncology and Kyowa Kirin entered a global strategic collaboration to develop and commercialize ziftomenib. Under the agreement, Kura received an upfront payment of $330 million and is eligible for up to $1.161 billion in milestone payments. Kura will lead development, regulatory, and commercial strategy in the U.S., while Kyowa Kirin will lead these activities outside the U.S.
