On September 30, 2024 Kura Oncology, Inc. (Nasdaq: KURA), a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer, reported the publication of its KOMET-001 Phase 1 study manuscript in The Lancet Oncology journal (Press release, Kura Oncology, SEP 30, 2024, View Source [SID1234646927]). The paper, entitled "Ziftomenib in relapsed/refractory acute myeloid leukaemia (KOMET-001): results from an open-label, multi-cohort, phase 1a/1b trial," is now available on The Lancet Oncology website and in the Scientific Manuscripts section on Kura’s website.
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"The results from the KOMET-001 Phase 1 study are encouraging as they demonstrate meaningful benefit of ziftomenib in NPM1-mutant acute myeloid leukemia (AML), and publication of these data expands the growing evidence supporting the efficacy and safety of ziftomenib in a disease indication of unmet need," said Ghayas C. Issa, M.D., assistant professor of Leukemia at The University of Texas MD Anderson Cancer Center. "We are thankful for the patients and their families for their participation in the KOMET-001 trial and for the scientific community who have contributed to this research to advance more tolerable and effective treatment options for AML patients."
The KOMET-001 study is a Phase 1/2 global, open-label, multi-cohort clinical trial evaluating the safety, tolerability and clinical activity of ziftomenib in relapsed/refractory (R/R) AML. In the Phase 1a dose escalation portion, patients received ziftomenib once daily in 28-day cycles and in the Phase 1b dose validation/expansion portion, patients were randomized to two parallel cohorts at 200 mg and 600 mg. As of the data cutoff on August 30, 2023, 83 patients received one or more doses of ziftomenib and the primary objective of this study was to determine the recommended phase 2 dose (RP2D) based on safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary activity. The results demonstrated promising clinical activity with manageable toxicity in heavily pretreated patients including marrow blast reduction, neutrophil and platelet recovery, transfusion independence, and clearance of measurable residual disease.
"Our Phase 1 study provided the critical safety and clinical activity data in order to determine the RP2D and support our pivotal Phase 2 registration-directed trial in patients with NPM1-mutant AML," said Stephen Dale, M.D., Chief Medical Officer of Kura Oncology. "These data reinforce our commitment to developing novel investigational therapies, including menin inhibitors, to realize the transformative value for patients with acute leukemias. The clinical data generated to date, including the insights gained from this study, demonstrate the potential for ziftomenib to become a cornerstone of AML therapy through monotherapy and combination approaches."
In May 2024, Kura Oncology announced completion of enrollment in the Phase 2 portion of KOMET-001, a registration-directed trial of ziftomenib in patients with R/R NPM1-mutant AML. Enrollment of the 85 patients in Phase 2 was completed in fewer than 16 months and the Company expects to report topline data from the trial in early 2025.
About NPM1-mutant AML
AML is the most common acute leukemia in adults and begins when the bone marrow makes abnormal myeloblasts (white blood cells), red blood cells or platelets. Despite the many available treatments for AML, prognosis for patients remains poor and a high unmet need remains. The menin pathway is considered a driver for multiple genetic alterations of the disease, of which NPM1 mutations are among the most common, representing approximately 30% of AML cases. While patients with NPM1-m AML have high response rates to frontline therapy, relapse rates are high and survival outcomes are poor, with only 30% overall survival at 12 months in the R/R setting. Additionally, NPM1 mutations frequently occur with co-mutations in other disease-associated genes, including FLT3, DNMT3A and IDH1/2, with prognosis heavily influenced by the presence of co-occurring mutations. Adult patients with NPM1-m AML and select co-mutations and/or R/R disease have a poor prognosis, with median overall survival of only approximately 7.8 months in 2nd line, 5.3 months in 3rd line, and 3.5 months following the 4th line1. There are currently no FDA-approved therapies targeting NPM1-m AML.
About Ziftomenib
Ziftomenib is a novel, once-daily, oral investigational drug candidate targeting the menin-KMT2A/MLL protein-protein interaction for treatment of genetically defined AML patients with high unmet need. In the KOMET-001 Phase 1 study, ziftomenib demonstrated encouraging safety and tolerability with reported events consistent with features and manifestations of underlying disease. Clinical activity of ziftomenib as a monotherapy was optimal at the 600 mg daily dose and a 35% complete remission rate was observed in 20 patients with NPM1-mutant AML treated at the recommended Phase 2 dose (600 mg). Ziftomenib has received Breakthrough Therapy Designation (BTD) from the U.S. Food and Drug Administration for the treatment of R/R NPM1-mutant AML. Additional information about clinical trials for ziftomenib can be found at kuraoncology.com/clinical-trials/#ziftomenib.