Dose Finding Study of Zanzalintinib With Pembrolizumab and Cetuximab in Head and Neck SCC

Inclusion Criteria

• •Histologically or cytologically confirmed recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M HNSCC), which is considered incurable by local therapies.
• •Primary tumor locations: oropharynx, oral cavity, hypopharynx, larynx, nasopharynx, and sinonasal. Unknown primary is also eligible.
• •Age: Participants must be at least 18 years old.
• •ECOG Performance Status: Must be 0-1.
• •Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.
• •For oropharyngeal cancer: HPV (p16) testing is required. p16 Immunohistochemistry (IHC) is sufficient for Human Papillomavirus (HPV) testing.
• •Programmed cell death ligand 1 (PD-L1) combined positive score (CPS) : For patients with previously untreated R/M disease, a combined positive score (CPS) of 1 or greater is required. There is no PD-L1 restriction for patients who have previously received anti-PD(L)1 therapy.
• •Recovery to baseline or ≤ Grade 1 severity (CTCAE v5) from any adverse events (AEs), including immune-related AEs from prior treatments.
• •Adequate organ and marrow function, including:
• •Absolute neutrophil count (ANC) ≥ 1500/mm3.
• •Platelets ≥ 100,000/mm3.
• •Hemoglobin ≥ 9 g/dL.
• •Normal liver and kidney function.
• •Capable of understanding and complying with the protocol requirements and must have signed the informed consent document.
• •Contraception: Sexually active fertile subjects must agree to use a highly effective method of contraception during the study and for 2 months after the last dose of cetuximab and 4 months after the last dose of pembrolizumab.