Kura Oncology Reports Preclinical Data Supporting Opportunity for Ziftomenib in Treatment of Gastrointestinal Stromal Tumors (GIST)

Core Insights - Kura Oncology's menin inhibitor, ziftomenib, demonstrates strong and lasting antitumor activity when combined with imatinib in both imatinib-sensitive and resistant GIST models, indicating a promising therapeutic strategy for advanced gastrointestinal stromal tumors (GIST) [1][3][4] Group 1: Preclinical Data and Mechanism - Preclinical studies show that the combination of ziftomenib and imatinib significantly outperforms imatinib alone in patient-derived xenograft models of GIST [3] - The mechanism of action involves a synthetic lethal approach where ziftomenib targets an epigenetic vulnerability in GIST tumors, leading to reduced KIT expression and activity, and effectively silencing ERK and AKT/mTOR signaling pathways [3] Group 2: Clinical Development Plans - Kura Oncology plans to initiate a proof-of-concept study for ziftomenib in combination with imatinib in patients with advanced GIST who have failed imatinib treatment, expected to start in the first half of 2025 [1][4] - The FDA has cleared the Investigational New Drug (IND) application for ziftomenib, facilitating its clinical development for advanced GIST [4] Group 3: Background on GIST and Ziftomenib - GISTs are the most common form of sarcoma, primarily driven by KIT mutations, and while imatinib is the standard treatment, resistance often develops, necessitating new therapeutic options [5] - Ziftomenib is a selective oral menin inhibitor also being developed for acute myeloid leukemia (AML) and has received Breakthrough Therapy Designation from the FDA for this indication [6]