Kura Oncology Inc., a clinical-stage biopharma company focused on the development of precision medicines, has announced positive top-line results from a Phase 2 trial for its lead candidate, tipifarnib, in patients with HRAS-mutant relapsed or refractory squamous cell head and neck cancer (HNSCC). The Phase 2 trial achieved its primary endpoint prior to the completion of enrolment.
Tipifarnib is a selective nonpeptidomimetic competitive inhibitor of farsenyltransferase (FT). Currently, the asset is in Phase 2 development for the development of solid tumors, HNSCC (including salivary gland cancer), and thyroid cancer with HRAS mutations. The drug was originally developed by Johnson & Johnson (J&J) under the brand name Zarnestra, but was denied approval by the FDA for acute myeloid leukemia (AML) in 2005. In 2015, Kura entered into an agreement with J&J for an exclusive license to develop and commercialise tipifarnib in oncology, specifically HRAS-mutant HNSCC patients. HRAS is a proto-oncogene that has been implicated in the development and progression of HNSCC. The recurrent/metastatic patient population for HNSCC is an area of significantly high unmet need. The patient population typically has an overall survival (OS) of 6–12 months with the current standard of care, and the estimated incident population for HNSCC with HRAS mutations in the US is 2,800–3,400 patients.
The Phase 2 study (NCT02383927) investigated the antitumor activity of tipifarnib in subjects with locally-advanced and relapsed metastatic tumors, as well as HRAS mutations that had no curative therapy. The primary endpoint of the study was objective response rate (ORR). Subjects (n=36) were enrolled into two non-randomised cohorts: malignant thyroid tumors with HRAS and HNSCC with HRAS. Subjects with HNSCC received tipifarnib orally at a dose of 900mg twice daily on days 1–21 of a 28 day cycle. All the subjects had to consent to show at least 10 tumor slides from a diagnostic biopsy for retrospective testing of the HRAS gene status. A total of four out of 18 subjects were required to meet the primary endpoint of ORR. Out of the first six evaluable subjects, partial responses—as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria—were observed in four subjects, and two subjects achieved disease stabilisation. Among these patients, objective responses were observed in two patients for over one year. Tipifarnib’s safety profile appears to be relatively benign and was consistent with the known safety profile. The most common adverse events (AEs) seen during the study (based on 472 solid tumor patients) were myelosuppression, fatigue, nausea, diarrhea, and vomiting. Notably, patients who did not respond to prior chemotherapy, cetuximab and/or immunotherapy, did respond to tipifarnib. Having revealed positive Phase 2 data, Kura is now preparing to advance tipifarnib to pivotal Phase 3 studies, which are estimated to commence at the end of 2018.
The outlook for Kura appears positive, and the data provided on tipifarnib has heightened physician expectations for the other three Phase 2 trials currently taking place. Kura’s recent focus on intellectual property (IP) protection has led to its US exclusivity for tipifarnib use in the HRAS-mutant HNSCC indication until August 2036. Additionally, Kura has a second product candidate that is currently undergoing an open-label Phase I study for patients with locally advanced and relapsed metastatic HNSCC: KO-947, a potent and selective small-molecule extracellular signal-regulated kinase-1 (ERK) inhibitor. In terms of Kura’s financial position, the company has managed to raise a total of $62.25M in cash as of August 10, 2017, placing the biopharma in a strong position to continue with the development of its pipeline assets. The outcome of the company’s upcoming Phase 3 pivotal trial may lead to an approval for HRAS HNSCC patients in the years to come. GlobalData expects that Kura Oncology will emerge as a dominant contender in the precision medicine arena in the coming years.