Kura Oncology Completes Enrollment in Ziftomenib Trial for NPM1-Mutant AML

Kura Oncology, Inc., a clinical-stage biopharmaceutical company focused on precision medicines for cancer treatment, has successfully completed patient enrollment in the Phase 2 portion of the KOMET-001 clinical trial. This trial aims to evaluate the efficacy of ziftomenib (KO-539), a menin inhibitor, in patients suffering from relapsed or refractory (R/R) NPM1-mutant acute myeloid leukemia (AML). The company has enrolled 85 patients in less than 16 months and anticipates reporting topline data by early 2025.

The completion of enrollment marks a significant milestone for Kura Oncology. Troy Wilson, Ph.D., J.D., President and CEO of Kura Oncology, expressed enthusiasm for this development, emphasizing the potential of ziftomenib to become a leading treatment for genetically defined acute leukemias. The company’s confidence is bolstered by the recent Breakthrough Therapy Designation granted by the U.S. Food and Drug Administration (FDA), which aims to expedite the review process for ziftomenib as the company prepares for a New Drug Application submission.

The Phase 2 portion of the KOMET-001 trial began dosing patients in February 2023. This study is designed to assess the clinical activity, safety, and tolerability of ziftomenib in patients with R/R NPM1-mutant AML, with the primary endpoint being a complete response. Enrollment of the necessary 85 patients to support this primary endpoint analysis has now been completed.

Eunice Wang, M.D., Chief of the Leukemia Service at Roswell Park Comprehensive Cancer Center and principal investigator of the trial, highlighted the urgency for more effective AML treatments and the potential for ziftomenib to fulfill this unmet need. NPM1-mutant AML accounts for about 30% of new AML cases each year and currently lacks approved targeted therapies. Dr. Wang noted that the safety profile and clinical activity demonstrated by ziftomenib offer hope for transforming the standard of care for these patients.

Acute myeloid leukemia (AML) is the most common form of acute leukemia in adults and originates in the bone marrow. Despite various treatment options, the prognosis for AML patients remains grim, creating a substantial need for new therapies. NPM1 mutations are prevalent in about 30% of AML cases and contribute to poor survival outcomes, especially in the relapsed or refractory setting. These mutations often coexist with other genetic alterations such as FLT3, DNMT3A, and IDH1/2, further complicating the disease prognosis. Currently, there are no FDA-approved therapies specifically targeting NPM1-mutant AML.

Ziftomenib, an oral investigational drug, targets the menin-KMT2A/MLL interaction crucial for the proliferation of genetically defined AML cells. In the Phase 1 portion of the KOMET-001 study, ziftomenib showed encouraging safety and tolerability, with a 35% complete remission rate observed in 20 patients treated at the 600 mg daily dose. The drug has received Breakthrough Therapy Designation from the FDA for treating R/R NPM1-mutant AML.

Kura Oncology's broader pipeline includes small molecule drug candidates aimed at cancer signaling pathways. The company is also evaluating ziftomenib in combination with standard care treatments for newly diagnosed and R/R NPM1-mutant and KMT2A-rearranged AML. Additionally, their portfolio includes Tipifarnib, a farnesyl transferase inhibitor in Phase 1/2 trials for PIK3CA-dependent head and neck squamous cell carcinoma, and KO-2806, a next-generation inhibitor under evaluation in a Phase 1 dose-escalation trial.

Kura Oncology continues to make strides in the field of precision oncology, aiming to bring innovative treatments to patients with significant unmet medical needs.