Kura Oncology's Menin Inhibitor Ziftomenib Receives FDA IND Clearance for Advanced GIST
Key Insights
Kura Oncology announced FDA clearance of its IND application for ziftomenib to treat advanced gastrointestinal stromal tumors (search) (GIST (search)).
A Phase 1 study of ziftomenib combined with imatinib in advanced GIST (search) patients is planned for early 2025.
Preclinical data suggests ziftomenib may resensitize patients to imatinib, potentially inducing durable responses in resistant cases.
Kura Oncology, Inc. (Nasdaq: KURA) has received FDA clearance for its Investigational New Drug (IND) application for ziftomenib, a selective menin inhibitor, in the treatment of advanced gastrointestinal stromal tumors (search) (GIST (search)). The company plans to initiate a Phase 1 clinical trial combining ziftomenib with imatinib in early 2025.
This clearance marks the first IND approval for a menin inhibitor targeting GIST (search), a solid tumor with limited options for patients with advanced disease. According to Kura Oncology's President and CEO, Troy Wilson, Ph.D., J.D., many GIST patients develop resistance to imatinib, the frontline treatment. Preclinical data suggests ziftomenib could resensitize these patients to imatinib, potentially leading to durable responses.
Addressing Imatinib Resistance in GIST
GIST (search), the most common sarcoma, is characterized by KIT (search)-dependent solid tumors. Imatinib, a KIT inhibitor, is the standard of care, but resistance often develops, leaving patients with limited subsequent treatment options that have moderate efficacy and tolerability. The menin-MLL (search) complex regulates KIT expression in GIST cells, and preclinical data indicates that menin inhibitors display additive therapeutic activity with imatinib in imatinib-sensitive GIST models. Furthermore, ziftomenib, combined with imatinib, has shown potential to resensitize patients to imatinib and induce durable responses in imatinib-resistant PDX models.
Clinical Trial Plans
The planned Phase 1 study will evaluate the combination of ziftomenib and imatinib in patients with advanced GIST (search) who have experienced imatinib failure. This proof-of-concept study aims to assess the safety and efficacy of the combination therapy in this patient population with limited treatment alternatives.
Ziftomenib: A Precision Medicine Approach
Ziftomenib is an oral drug candidate targeting the menin-KMT2A (search) protein-protein interaction. It has already received Breakthrough Therapy Designation for relapsed/refractory NPM1-mutant acute myeloid leukemia (search) (AML (search)). Kura Oncology has completed enrollment in a Phase 2 registration-directed trial of ziftomenib in R/R NPM1-mutant AML (KOMET-001) and is conducting clinical trials to evaluate ziftomenib in combination with standard of care treatments in newly diagnosed and R/R NPM1-mutant and KMT2A-rearranged AML.