Kura Oncology Publishes Ziftomenib Phase 1 Results in The Lancet Oncology

Kura Oncology, Inc., a clinical-stage biopharmaceutical company specializing in precision medicines for cancer treatment, has announced the publication of its KOMET-001 Phase 1 study in the esteemed journal, The Lancet Oncology. The study, titled "Ziftomenib in relapsed/refractory acute myeloid leukemia (KOMET-001): results from an open-label, multi-cohort, phase 1a/1b trial," is accessible on The Lancet Oncology website.

Dr. Ghayas C. Issa from The University of Texas MD Anderson Cancer Center expressed optimism about the KOMET-001 Phase 1 study results, highlighting the significant benefits of ziftomenib in treating NPM1-mutant acute myeloid leukemia (AML). He extended gratitude towards the patients and scientific community for their contributions to advancing more tolerable and effective treatment options for AML.

The KOMET-001 study is a global, open-label, multi-cohort clinical trial aimed at evaluating the safety, tolerability, and clinical activity of ziftomenib in patients with relapsed or refractory (R/R) AML. During the Phase 1a dose escalation part, patients received ziftomenib daily in 28-day cycles. In the Phase 1b dose validation/expansion part, patients were randomized into two cohorts receiving either 200 mg or 600 mg. By the data cutoff date of August 30, 2023, 83 patients had been dosed with ziftomenib. The study's primary goal was to determine the recommended Phase 2 dose (RP2D) by assessing safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary activity. The findings indicated promising clinical activity and manageable toxicity in heavily pretreated patients, noted by reductions in marrow blasts, recovery of neutrophils and platelets, transfusion independence, and clearance of measurable residual disease.

Dr. Stephen Dale, Chief Medical Officer of Kura Oncology, emphasized that the Phase 1 study was crucial for determining the RP2D and supporting the pivotal Phase 2 registration-directed trial for patients with NPM1-mutant AML. He reiterated Kura Oncology's dedication to developing innovative therapies, including menin inhibitors, to significantly impact the treatment of acute leukemias. The clinical data gathered so far suggest that ziftomenib has the potential to become a foundational AML therapy, both as a monotherapy and in combination treatments.

In May 2024, Kura Oncology completed enrollment for the Phase 2 portion of KOMET-001, which aims to register ziftomenib for patients with R/R NPM1-mutant AML. The enrollment of 85 patients was achieved in under 16 months, and the company expects to release top-line data from this trial in early 2025.

Acute myeloid leukemia (AML), the most common acute leukemia in adults, originates when bone marrow produces abnormal myeloblasts, red blood cells, or platelets. Despite numerous treatment options, the prognosis for AML patients remains poor, reflecting a high unmet need. The menin pathway, implicated in various genetic alterations of AML, includes NPM1 mutations, which occur in about 30% of AML cases. Although patients with NPM1-mutant AML show high response rates to initial therapies, relapse rates are significantly high, with only 30% overall survival at 12 months in the R/R setting. Furthermore, NPM1 mutations frequently co-occur with other genetic mutations like FLT3, DNMT3A, and IDH1/2, which worsen the prognosis. Adult patients with NPM1-mutant AML and additional co-mutations or R/R disease face a challenging prognosis, with median overall survival rates of approximately 7.8 months, 5.3 months, and 3.5 months in second, third, and fourth-line settings, respectively. Currently, there are no FDA-approved therapies specifically targeting NPM1-mutant AML.

Ziftomenib, an innovative, once-daily oral investigational drug, targets the menin-KMT2A/MLL protein-protein interaction for treating genetically defined AML patients with high unmet needs. In the KOMET-001 Phase 1 study, ziftomenib showcased encouraging safety and tolerability, with reported events aligning with underlying disease characteristics. As a monotherapy, its clinical activity was optimal at a 600 mg daily dose, achieving a 35% complete remission rate among 20 patients with NPM1-mutant AML treated at the recommended Phase 2 dose of 600 mg. Ziftomenib has earned Breakthrough Therapy Designation (BTD) from the U.S. Food and Drug Administration for treating R/R NPM1-mutant AML. 

Kura Oncology is a clinical-stage biopharmaceutical company focused on precision medicines for cancer treatment. Their pipeline includes small molecule drug candidates targeting cancer signaling pathways. Ziftomenib, a once-daily oral drug targeting the menin-KMT2A protein-protein interaction, has received BTD for R/R NPM1-mutant AML. Kura has completed Phase 2 registration-directed trial enrollment for ziftomenib in this patient group and is conducting various clinical trials to evaluate its efficacy in combination with existing standards of care for newly diagnosed and R/R NPM1-mutant and KMT2A-rearranged AML. Additional assessments are ongoing for KO-2806, a next-generation farnesyl transferase inhibitor (FTI), and Tipifarnib, a selective FTI in a Phase 1/2 trial for PIK3CA-dependent head and neck squamous cell carcinoma.

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