A Study of CDX-3379 and Cetuximab and in Patients With Advanced Head and Neck Squamous Cell Carcinoma

Inclusion Criteria: 1. Histologically or cytologically confirmed head and neck squamous cell carcinoma. 2. Human papilloma virus (HPV) negative tumor. 3. Prior treatment with a check-point inhibitor targeting PD-1, unless not a candidate. 4. Prior treatment with cetuximab with tumor progression during or within 6 months after completing treatment. 5. Measurable disease. 6. Life expectancy ≥ 12 weeks. 7. If of childbearing potential (male or female), agrees to practice an effective form of contraception during study treatment and for at least 6 months following last treatment. 8. Willingness to undergo a tumor biopsy prior to starting treatment (or if biopsy is not feasible, provide archival tissue). Exclusion Criteria: 1. Previous treatment with CDX-3379 or other anti-ErbB3 targeted agents. 2. Nasal, paranasal sinus, or nasopharyngeal carcinoma, aside from WHO Type I and II (keratinizing, non-EBV positive) nasopharyngeal carcinoma which will be allowed. 3. Major surgery within 4 weeks prior to first dose of study treatment. 4. Chemotherapy within 21 days or at least 5 half-lives (whichever is shorter) prior to first dose of study treatment. 5. Monoclonal based therapies within 4 weeks (excluding cetuximab) and all other immunotherapy within 2 weeks prior to first dose of study treatment. 6. Other prior malignancy, active within 3 years, except for localized prostate cancer, cervical carcinoma in situ, non-melanomatous carcinoma of the skin, stage 1 differentiated thyroid cancer or ductal carcinoma in situ of the breast. 7. Active, untreated central nervous system metastases. 8. Active autoimmune disease or documented history of autoimmune disease. 9. Significant cardiovascular disease including CHF or poorly controlled hypertension.