The standard care for head and neck squamous cell carcinoma includes chemotherapy, cetuximab and immunotherapy. The response rates of these agents are in the range of 13-16%, and typically the overall survival is 6–12 months. Tipifarnib is a selective inhibitor of farsenyl transferase (FT). It blocks farsenylation of HRAS, thus HRAS cannot become its membrane-bound active form, and the HRAS signaling pathway is inactivated. In a phase II trial, patients with HRAS-mutant relapsed or refractory squamous cell head and neck cancer who did not respond to prior chemotherapy, cetuximab and/or immunotherapy were treated with tipifarnib. The primary endpoint is when 4 out of 18 subjects confirmed RECIST 1.1 partial responses. Before the completion of enrollment, four of the first six HRAS mutant HNSCC patients enrolled in the study confirmed partial responses to achieve its primary endpoint. According to this positive phase II data, the pharmaceutical company is now preparing for advancing tipifarnib to pivotal phase III studies.