Kura Oncology Gets FDA Nod for Menin Inhibitor Ziftomenib in Advanced GIST

Kura Oncology, Inc. has received U.S. Food and Drug Administration (FDA) approval for its Investigational New Drug (IND) application for ziftomenib. This advancement marks the initiation of a Phase 1 study to evaluate ziftomenib combined with imatinib in treating advanced gastrointestinal stromal tumors (GIST). The study is expected to begin in the first half of 2025.

Dr. Troy Wilson, CEO of Kura Oncology, highlighted the significance of this milestone, noting that it is the first time a menin inhibitor has been approved to treat GIST, a condition with few treatment options for advanced stages. Imatinib is currently the frontline treatment for GIST, but resistance often develops over time. Preclinical data indicates that ziftomenib could resensitize patients to imatinib, potentially inducing lasting responses.

GIST, the most prevalent form of sarcoma, is characterized by KIT-dependent tumors. KIT inhibitors have shown positive outcomes for GIST patients, with imatinib being the standard treatment. However, once patients develop resistance to imatinib, alternative treatments are limited and often come with challenging side effects. The menin-MLL complex's role in regulating KIT expression in GIST cells suggests that menin inhibitors could provide additional therapeutic benefits when used with imatinib in GIST models sensitive to the drug.

Kura's preclinical studies also indicate that ziftomenib could work synergistically with imatinib to combat resistance in imatinib-resistant GIST models. The combination of these two drugs has the potential to re-sensitize patients to imatinib and achieve durable responses. Kura plans to launch a proof-of-concept study for this combination treatment in patients with advanced GIST who have not responded to imatinib.

Kura Oncology is focused on developing precision medicines to treat cancer. Their pipeline includes small molecule drug candidates aimed at cancer signaling pathways. Ziftomenib, an oral drug taken once daily, targets the menin-KMT2A protein-protein interaction. It has already been granted Breakthrough Therapy Designation for treating relapsed or refractory (R/R) NPM1-mutant acute myeloid leukemia (AML). The company has completed enrollment for a Phase 2 trial of ziftomenib in R/R NPM1-mutant AML (KOMET-001) and is conducting further studies to evaluate its effectiveness in combination with existing treatments for newly diagnosed and R/R NPM1-mutant and KMT2A-rearranged AML.

Additionally, Kura is investigating Tipifarnib, a selective farnesyl transferase inhibitor (FTI), in a Phase 1/2 trial combined with alpelisib for patients with PIK3CA-dependent head and neck squamous cell carcinoma (KURRENT-HN). They are also evaluating KO-2806, a next-generation FTI, both as a monotherapy and in combination with targeted therapies in a Phase 1 dose-escalation trial (FIT-001).

Kura Oncology remains committed to advancing precision medicine in cancer treatment through rigorous clinical trials and development of targeted therapies.