On February 26, 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 that the first patient has been dosed in KOMET-008, the Company’s Phase 1 trial of its menin inhibitor ziftomenib, in combination with gilteritinib, FLAG-IDA or LDAC for the treatment of NPM1-mutant or KMT2A-rearranged acute myeloid leukemia (AML) (Press release, Kura Oncology, FEB 26, 2024, View Source [SID1234640455]).
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
"Roughly half of patients with relapsed or refractory NPM1-mutant AML have co-occurring FLT3 mutations, and the prognosis for these patients is particularly poor," said Stephen Dale, M.D., Chief Medical Officer of Kura Oncology. "Given the potential best-in-class safety and tolerability profile as well as the robust monotherapy activity observed in our Phase 1 study of ziftomenib, we believe an all-oral combination of ziftomenib and gilteritinib may provide an attractive treatment option for these patients."
KOMET-008 is a Phase 1 study designed to assess safety and tolerability, pharmacokinetics and evidence of clinical activity of ziftomenib in combination with gilteritinib, FLAG-IDA or LDAC for two genetically defined cohorts, NPM1-mutant AML and KMT2A-rearranged AML, in the relapsed/refractory setting. Trial participants will be enrolled in one of five dose escalation cohorts, including a cohort of NPM1-mutant AML patients with a documented FLT3 co-mutation, who will be treated in combination with the FLT3 inhibitor gilteritinib. For more information regarding KOMET-008, please visit www.clinicaltrials.gov (identifier: NCT06001788).
Kura is conducting a series of studies to evaluate ziftomenib in combination with current standards of care in earlier lines of therapy and across multiple patient populations. In July, the Company began dosing patients in the first of these studies, KOMET-007, in combination with venetoclax and azacitidine in patients with relapsed/refractory NPM1-mutant and KMT2A-rearranged AML or in combination with standard induction cytarabine/daunorubicin chemotherapy (7+3) in patients with previously untreated NPM1-mutant and KMT2A-rearranged AML. Kura reported positive preliminary data from 20 patients in KOMET-007 on January 30, 2024.
Preclinical data for menin inhibitors in combination with multiple FLT3 inhibitors demonstrate strong synergistic effects compared to either single agent alone. Currently there are no other actively recruiting clinical trials evaluating the combination of a menin inhibitor with a FLT3 inhibitor for the treatment of AML.
About Acute Myeloid Leukemia
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 and KMT2A rearrangements represent approximately 5-10% 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. Adult patients with KMT2A-r AML have a poor prognosis with high rates of resistance and relapse following standard of care, with median overall survival for this patient population of only 6 months following 2nd line and 2.4 months following 3rd line2. No FDA-approved therapies targeting NPM1-m and KMT2A-r AML currently exist.
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. Ziftomenib inhibits the KMT2A/MLL protein complex and exhibits downstream effects on HOXA9/MEIS1 expression and potent anti-leukemic activity in genetically defined preclinical models of AML. Ziftomenib has received Orphan Drug Designation from the U.S. Food and Drug Administration for the treatment of AML. Additional information about clinical trials for ziftomenib can be found at kuraoncology.com/clinical-trials/#ziftomenib.