Kura Oncology has dosed the first subject in the Phase I/II KURRENT clinical trial of its oral experimental drug candidate, tipifarnib, plus alpelisib in HRAS-dependent and/or PIK3CA-dependent head and neck squamous cell carcinoma (HNSCC) patients.

Tipifarnib is an orally bioavailable farnesyl transferase inhibitor while Novartis’ alpelisib is an inhibitor of phosphatidylinositol-3-kinase (PI3K).

A biomarker-defined cohort, open-label trial, KURRENT will analyse the safety, identify the combination dose and evaluate initial anti-tumour activity of tipifarnib, along with alpelisib to treat subjects with HRAS- and/or PIK3CA-dependent HNSCC.

The preliminary arm of the trial enrolled subjects with PIK3CA-dependent HNSCC.

Kura and Novartis signed a clinical partnership in July 2021 to assess tipifarnib plus alpelisib in HNSCC patients.

According to the deal, Kura holds worldwide development and marketing rights to tipifarnib.

Kura Oncology president and CEO Troy Wilson said: “Despite the approval of immunotherapy, the treatment of recurrent and metastatic HNSCC remains a significant unmet need.

“The KURRENT trial builds on the impressive clinical activity reported for tipifarnib as a monotherapy in HRAS mutant HNSCC and represents an opportunity to significantly expand the potential patient population and target mechanisms of drug resistance.”

According to preclinical data, HRAS and PI3kα are mutually-dependent oncogenes in HNSCC and the combination of tipifarnib and a PI3Kα inhibitor could potentially offer improved antitumor activity as against hindering each target alone.

Last month, the US Food and Drug Administration placed a partial clinical hold on Kura Oncology’s Phase Ib KOMET-001 trial of KO-539 to treat in relapsed or refractory acute myeloid leukaemia.

The move comes after a Grade 5 serious adverse event of patient death probably linked to differentiation syndrome was reported in the trial.