Kura Oncology Begins Phase 1 Trial of Ziftomenib for Advanced GIST Treatment

Kura Oncology, a clinical-stage biopharmaceutical company, has commenced a Phase 1 clinical trial named KOMET-015. This trial involves the investigation of ziftomenib, a selective oral menin inhibitor, in combination with imatinib for patients with gastrointestinal stromal tumors (GIST) who have experienced treatment failure with imatinib. Ziftomenib had already shown promising results in patients with certain genetic mutations in acute myeloid leukemia (AML), prompting Kura Oncology to explore its potential in other cancer treatments.

GIST, primarily characterized by KIT-dependent solid tumors, is a type of sarcoma with about 4,000 to 6,000 new diagnoses in the United States annually. Despite initial control of the disease with imatinib, frontline treatment, approximately 60% of patients develop resistance within two years. This resistance highlights the urgent need for new therapeutic strategies.

In preclinical studies, the combination of ziftomenib and imatinib demonstrated significant antitumor activity. The rationale behind this combination is a synthetic lethal interaction where ziftomenib targets the weaknesses in GIST tumors, exacerbated by tyrosine kinase inhibitors (TKIs) like imatinib, even when they become less effective. Encouraging results from these studies indicate ziftomenib might delay or overcome resistance to imatinib, offering hope for improved treatment outcomes.

Dr. Mollie Leoni, Chief Medical Officer at Kura Oncology, emphasized the potential impact of menin inhibitors like ziftomenib in cancer treatment. The limited therapeutic options for advanced GIST patients underscore the importance of exploring new treatment combinations. The anticipated success of the KOMET-015 trial could revolutionize how GIST is treated by combining targeted therapies to overcome drug resistance.

Dr. Mrinal Gounder, a specialist in sarcoma and early-phase drug development at Memorial Sloan Kettering Cancer Center, acknowledged the importance of the KOMET-015 trial. The study aims to evaluate safety, tolerability, and preliminary antitumor activity of the ziftomenib-imatinib combination in adults with advanced GIST who have shown disease progression after prior imatinib treatment. Following the dose-escalation phase, expansion cohorts will further assess these parameters to determine the recommended Phase 2 dose.

Dr. Shreyaskumar Patel from The University of Texas MD Anderson Cancer Center pointed out the limitations of existing therapies like TKIs, which target KIT mutations. The clinical advancement of ziftomenib, backed by substantial preclinical data, offers promise for those with imatinib-resistant genotypes. The trial's initiation is a crucial milestone for addressing the significant unmet needs in this patient population.

Ziftomenib, administered once daily, is also being developed for genetically defined AML with unmet needs. It received Breakthrough Therapy Designation from the FDA for relapsed or refractory NPM1-mutant AML due to positive results from Kura's KOMET-001 trial. The company, in collaboration with Kyowa Kirin Co., continues to explore ziftomenib's potential across various cancer-related conditions.

The KOMET-015 trial stands out as no other clinical studies have assessed the combination of a menin inhibitor with standard GIST therapies. With its innovative approach, Kura Oncology aims to redefine treatment pathways for patients with advanced GIST, potentially improving survival rates and quality of life for those affected by this challenging disease.