Two phase-II clinical trials are currently evaluating the clinical efficacy of alpelisib as monotherapy in HPV-positive HNSCC (NCT03601507) and alpelisib in combination with the farnesyltransferase inhibitor tipifarnib in HRAS- and PIK3CA-mutant HNSCC (NCT04997902). The gene discussed is HRAS; the disease is head and neck squamous cell carcinoma.