FDA Steps Up Review of Tipifarnib for Treatment of Certain Patients with Head and Neck Cancer

The Food and Drug Administration (FDA) granted fast track designation to the investigational therapy tipifarnib for the treatment of patients with HRAS mutant head and neck squamous cell carcinomas (HNSCC) after their progression on platinum-based chemotherapy.

“We are very encouraged by our growing body of clinical data for tipifarnib in HRAS mutant HNSCC and believe that the FDA’s fast track designation puts us one step closer to delivering a precision medicine treatment for patients with this devastating disease,” Dr. Antonio Gualberto, head of development and chief medical officer of Kura Oncology, said in a press release.

A fast track designation is granted by the FDA when the administration determines the drug can treat a serious condition and fills an unmet medical need. This allows for closer interaction between the drug manufacturer and the FDA in order to get the drug out to patients sooner and acquire the necessary data faster. In the case of tipifarnib, it is meant for patients with HRAS mutant HNSCC that have failed previous treatment, meaning their options in the current landscape are not as robust as other patients with head and neck cancers.

Tipifarnib is a potent inhibitor of farnesyl transferase that targets a wide range of proteins, including those in the RAS family like the H-Ras protein created by the HRAS gene. These proteins play a vital role in normal cell division, but when HRAS is mutated this causes normal cells to become cancerous.

Tipifarnib has previously been studied in more than 5,000 patients with different cancers including those with relapsed or refractory peripheral t-cell lymphoma, myelomonocytic leukemia, as well as patients with HRAS mutant HNSCC. The drug demonstrated compelling anti-cancer activity in multiple patient subsets, however, a molecular mechanism of action has yet to be identified to explain its clinical activity, according to Kura Oncology.

In a previous phase 2 study of tipifarnib in patients with HNSCC, researchers studied overall response rate and median progression-free survival, the time during or after treatment a patient lives without the disease worsening. Thirty-three patients were enrolled­, 23 of which had HNSCC, and the overall response for this patient group was 53%. Median progression-free survival was 5.4 months.

“These results are very gratifying, considering our trial is targeting patients who have stopped responding to other treatments,” said Dr. Alan L. Ho, a medical oncologist at Memorial Sloan Kettering Cancer Center in New York City, in the initial press release regarding the phase 2 trial data of tipifarnib presented at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics. “Tipifarnib is safe and well-tolerated even in patients who have received multiple lines of previous therapies,” he explained.

Kura Oncology continues to enroll patients in its ongoing trial of tipifarnib in patients with recurrent or metastatic HRAS mutant HNSCC. This global multi-center trial was originally initiated in November 2018 and expects to fulfill enrollment in early 2021 in more than 81 clinical sites across the United States, Europe, and Asia. With the fast track designation now granted, the data from this trial will be shared with the FDA more readily, potentially leading to a faster approval process for tipifarnib.

“Although we experienced some delays in site activation, we’re encouraged to have the vast majority of the participating sites now open, with a corresponding increase in the rate of screening,” Kathleen Ford, chief operating officer of Kura Oncology, said in a press release. “Enrollment in (the trial) remains our top priority and we remain steadfast in our commitment to bring tipifarnib to patients with HRAS mutant HNSCC for whom no treatment options are specifically indicated.”

A clinical trial on the safety and efficacy of tipifarnib for this patient population remains open as well.