Kura Oncology Doses First Patient in Phase 1b Expansion Cohorts With Menin Inhibitor KO-539

Kura Oncology, Inc. recently announced the first patient has been dosed in the Phase 1b portion of KOMET-001, a Phase 1/2 clinical trial of the company’s oral, potent and selective menin inhibitor, KO-539, in patients with relapsed or refractory acute myeloid leukemia (AML).

KO-539 demonstrated a wide therapeutic window in the Phase 1a dose-escalation portion of KOMET-001, with promising single-agent activity from 50 mg to 800 mg in an all-comer population of patients with relapsed or refractory AML, including patients with NPM1 mutations and KMT2A rearrangements. The Phase 1b portion of the study is designed to determine the lowest dose of KO-539 that provides maximum biologic and clinical effect in two expansion cohorts – a low dose (200 mg) and a high dose (600 mg) – each enriched with NPM1-mutant and KMT2A-rearranged relapsed/refractory AML patients. Both doses have demonstrated preliminary evidence of biologic and clinical activity and were determined to be safe and well tolerated in the Phase 1a portion of the study.

Kura expects to enroll at least 12 patients in each of the Phase 1b expansion cohorts and assess those patients for safety and tolerability, pharmacokinetics, pharmacodynamics and efficacy in order to determine the recommended Phase 2 dose. In addition, the Phase 1b gives the company flexibility to enroll up to 18 additional patients per cohort, as appropriate. Kura believes that data from patients enrolled in the cohort selected as the recommended Phase 2 dose can be included as part of the registration-directed portion of the KOMET-001 trial.

“We believe KO-539 has the potential to be both a first-in-class and a best-in-class menin inhibitor,” said Stephen Dale, MD, Chief Medical Officer of Kura Oncology. “We intend to conduct a comprehensive clinical development plan for KO-539, both as a monotherapy and in front-line combination studies. A critical component of this plan is the determination of an optimal dose, particularly given the compelling efficacy, safety and wide therapeutic window of KO-539. These Phase 1b expansion cohorts enable us to gather a more robust dataset in our targeted populations and help refine selection of a recommended dose for Phase 2 and beyond, while maintaining an aggressive development timeline for the program. We look forward to presenting data at a future medical meeting.”

In December 2020, Kura reported preliminary clinical data from the KOMET-001 clinical trial of KO-539 at the American Society of Hematology Annual Meeting. These data were highlighted by single-agent activity in patients with relapsed or refractory AML, including patients with NPM1 mutations and KMT2A rearrangements. KO-539 also demonstrated a favorable safety and tolerability profile, with no drug discontinuations due to treatment-related adverse events and no evidence of QTc prolongation.

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, especially in the relapsed/refractory setting. More than 50% of patients with AML who achieve a CR after induction therapy relapse within one to three years, and less than 10% of those with relapsed/refractory AML are alive at three years. Prognosis is poor in patients with KMT2A rearrangements and in those with co-mutations that may include NPM1.

KOMET-001 (Kura Oncology Menin Inhibitor Trial) is a Phase 1/2, first-in-human, open-label trial to determine the safety, tolerability, and anti-tumor activity of KO-539 in patients with refractory or relapsed AML. The Phase 1b portion is currently open to enroll patients with NPM1 mutations or KMT2A-rearrangments. A Phase 2 registration-enabling expansion portion is planned following determination of the optimal Phase 2 dose. Additional information about KOMET-001 can be found at kuraoncology.com/clinical-trials-komet.

KO-539 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 preclinical models, KO-539 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. KO-539 has received Orphan Drug Designation from the U.S. Food and Drug Administration for the treatment of AML.

Kura Oncology is a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer. The Company’s pipeline consists of small molecule drug candidates that target cancer signaling pathways. KO-539, a potent and selective menin inhibitor, is currently in a Phase 1/2 clinical trial (KOMET-001) and targeting patients with relapsed/refractory acute myeloid leukemia, including patients with NPM1 mutations or KMT2A rearrangements. Tipifarnib, a potent, selective and orally bioavailable farnesyl transferase inhibitor, has received Breakthrough Therapy Designation for the treatment of patients with HRAS mutant head and neck squamous cell carcinoma and is currently in a registration-directed study (AIM-HN) in patients with this devastating disease. Kura is also developing a next-generation farnesyl transferase inhibitor, which is intended to target innovative biology and larger oncology indications through rational combinations. For more information, visit www.kuraoncology.com.