FDA Grants Breakthrough Therapy Designation to Tipifarnib for Treatment of HRAS-Mutant HNSCC


The FDA has granted breakthrough therapy designation to the investigational drug tipifarnib for the treatment of patients with recurrent or metastatic HRAS-mutant head and neck squamous cell carcinoma (HNSCC) with variant allele frequency of at least 20% following disease progression on platinum-based chemotherapy, according to the drug’s developer, Kura Oncology.1

The designation was based on preliminary activity reported in the phase 2 RUN-HN clinical trial (NCT02383927), which evaluated tipifarnib in patients with recurrent or metastatic HRAS-mutant HNSCC. Data from this trial were presented at the American Society of Clinical Oncology (ASCO) Virtual Scientific Program in June 2020.2

In this study, all patients had RECIST v1.1 measurable disease at study entry. Participants received a starting dose of either 600 mg or 900 mg of tipifarnib administered orally twice daily on days 1 through 7 and 15 through 21 of 28-day treatment cycles until progression of disease (PD) or unacceptable toxicity.

The study’s primary end point was objective response rate (ORR). Key secondary end points included safety and tolerability. Moreover, the exploratory end points were progression-free survival (PFS) and duration of response (DOR).

As of September 30, 2019, tipifarnib had demonstrated an ORR of 50% among 18 evaluable patients. The median DOR was 14.7 months. Median PFS was 5.9 months with tipifarnib compared with 2.8 months with last prior line of therapy. Median overall survival was 15.4 months.

Currently, tipifarnib is being studied in the ongoing international, multicenter, open-label, 2 cohort, non-comparative, pivotal phase 2 AIM-HN study (NCT03719690) for this indication. In this study, investigators will evaluate the ORR of tipifarnib in patients with HNSCC with HRAS mutations.

“We are very pleased that the FDA has awarded breakthrough therapy designation to tipifarnib, and we appreciate the agency’s affirmation of its potential to treat this devastating disease,” Troy Wilson, PhD, JD, president and chief executive officer of Kura Oncology, said in a press release. “We remain focused on conducting our AIM-HN registration-directed trial and look forward to working closely with the FDA to bring this therapy to patients as soon as possible.”

Tipifarnib was previously granted fast track designation by the FDA for the treatment of patients with HRAS-mutant HNSCC. In addition to HNSCC, tipifarnib has demonstrated encouraging clinical activity in a number of other genetically defined tumor types. Kura Oncology has also received multiple issued patents for tipifarnib.


1. Kura Oncology Receives FDA Breakthrough Therapy Designation for Tipifarnib in Head and Neck Squamous Cell Carcinoma. News release. Kura Oncology. Published February 24, 2021. Accessed February 24, 2021. https://www.globenewswire.com/news-release/2021/02/24/2181242/0/en/Kura-Oncology-Receives-FDA-Breakthrough-Therapy-Designation-for-Tipifarnib-in-Head-and-Neck-Squamous-Cell-Carcinoma.html

2. Loh Ho A, Hanna GJ, Scholz CR, Gualberto A, Hoon Park S. Preliminary activity of tipifarnib in tumors of the head and neck, salivary gland and urothelial tract with HRAS mutations. J Clin Oncol. 2020;38(suppl 15):6504. doi: 10.1200/JCO.2020.38.15_suppl.6504

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