On October 26, 2022 Kura Oncology, Inc. (Nasdaq: KURA), a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer, today reported proof of mechanism in KURRENT-HN, the Company’s Phase 1/2 clinical trial of tipifarnib in combination with alpelisib in patients with HRAS- and/or PIK3CA-dependent head and neck squamous cell carcinoma (HNSCC) (Press release, Kura Oncology, OCT 26, 2022, View Source [SID1234622405]). The preliminary data are being presented at the EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Molecular Targets and Cancer Therapeutics Symposium in Barcelona.
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In a poster entitled, "HNSCCs overexpressing wild-type HRAS are sensitive to combined tipifarnib and alpelisib treatment," Kura highlights a patient with stage III squamous cell carcinoma of the tonsil, including a PIK3CA mutation and HRAS overexpression, who has achieved a durable partial remission on study. The 35-year-old patient enrolled in KURRENT-HN after failing two prior treatments, experienced an 81% reduction in target lesions after one cycle of tipifarnib and alpelisib and an 84% reduction after three cycles. As of September 14, 2022, the patient continued on study for more than 27 weeks. Treatment-related adverse events in the study have been consistent with the known safety profiles of each drug and are manageable, with no dose-limiting toxicities reported to date. A copy of the poster is available at www.kuraoncology.com.
Although tipifarnib has shown single-agent clinical activity in a highly selected population of HRAS mutant HNSCC1, and alpelisib has shown single-agent clinical activity in patients with PIK3CA-mutant, ER-positive/HER2-negative breast cancer2, no objective responses have been observed with either agent as a monotherapy in patients with PIK3CA-mutant HNSCC.
"These preliminary data from KURRENT-HN are encouraging, supporting the biologic rationale that combining a farnesyl transferase inhibitor with a PI3Kα inhibitor can achieve meaningful clinical responses in PIK3CA-dependent HNSCC," said Stephen Dale, M.D., Chief Medical Officer of Kura Oncology. "In addition, our new preclinical data support the potential of this combination to address approximately 45% of HNSCC tumors that harbor an actionable HRAS and/or PIK3CA mutation or overexpression. We are now working to identify a recommended Phase 2 dose and schedule for the combination and remain committed to bringing this important new treatment option to patients with recurrent or metastatic HNSCC who are in dire need of better therapies."
About KURRENT-HN
The KURRENT-HN trial is a biomarker-defined cohort study designed to evaluate the safety, determine the recommended combination dosing and assess early anti-tumor activity of tipifarnib and alpelisib for the treatment of HNSCC patients whose tumors are dependent on HRAS and/or PI3Kα pathways. The initial cohort in the trial is comprised of patients who have PIK3CA-dependent HNSCC. In August, Kura announced the first patient was dosed in a second cohort comprised of patients with HRAS overexpression. For more information about the trial, refer to www.kuraoncology.com/kurrent/.
About HNSCC
Head and neck squamous cell carcinoma (HNSCC) is the seventh most common cancer worldwide, accounting for more than 500,000 new cases each year. Despite advances in immunotherapy, the prognosis for advanced HNSCC patients remains poor, with an estimated median overall survival of 13-15 months in patients when stratified by PD-L1 expression. Although the anti-epidermal growth factor receptor (EGFR) antibody, cetuximab, was approved more than a decade ago, development of biomarker-directed therapies in HNSCC has been stymied by the limited number of druggable targets in the genomic landscape and the challenge of managing drug refractory, recurrent/metastatic HNSCC.