Combination Trial of Tipifarnib and Alpelisib in Adult Recurrent/ Metastatic Head and Neck Squamous Cell Carcinoma (R/M HNSCC)

Prior treatment

• Ongoing treatment with certain anticancer agents.
• Prior treatment (at least 1 full treatment cycle) with an FTI or PI3K, mTOR, or AKT inhibitor.
• Received treatment for unstable angina, myocardial infarction, and/or cerebro-vascular attack within the prior 6 months.
• Major surgery, other than diagnostic surgery, within 2 weeks prior to Cycle 1 Day 1, without complete recovery.

Other illness

• Active, uncontrolled bacterial, viral, or fungal infections requiring systemic therapy.
• Participant with an established diagnosis of diabetes mellitus Type 1 or not controlled Type 2.
• Participant has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the trial drugs based on Investigator discretion.
• Participant has currently documented pneumonitis/interstitial lung disease.
• Participant has a history of severe cutaneous reaction, such as Stevens-Johnson Syndrome (SJS), Erythema Multiforme (EM), Toxic Epidermal Necrolysis (TEN), or Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS).

Other

• Histologically confirmed salivary gland, thyroid, (primary) cutaneous squamous or nonsquamous histologies (eg, mucosal melanoma).
• Non-tolerable Grade 2, or ≥ Grade 3 neuropathy or evidence of unstable neurological symptoms within 4 weeks of Cycle 1 Day 1.
• Other protocol defined exclusion criteria may apply.

• At least 18 years of age.
• Histologically confirmed head and neck cancer of squamous histology not amenable to local therapy with curative intent (surgery or radiation therapy with or without chemotherapy).
• Documented treatment failure from at least 1 prior systemic therapy in the R/M setting, unless determined not appropriate.
• Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
• Has a tumor that is dependent upon HRAS and/or PIK3CA.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Acceptable liver, renal, endocrine, and hematologic function.
• Must be able to swallow alpelisib whole tablet or oral suspension containing crushed tablets. Feeding tube may not be used for alpelisib administration.
• Other protocol defined inclusion criteria may apply.