A Phase Ib Study of Neoadjuvant of Cetuximab Plus Motolimod and Cetuximab Plus Motolimod Plus Nivolumab

Inclusion Criteria:

* Previously untreated stage II, III, or IVA histologically or cytologically confirmed squamous cell carcinoma of the head and neck
* Primary tumors of the oral cavity, oropharynx, hypopharynx, or larynx
* Macroscopic complete resection of the primary tumor must be planned
* Age ≥ 18 years
* ECOG performance status 0-1
* Adequate hematologic, renal and hepatic function
* Have signed written informed consent

Exclusion Criteria:

* Subjects who fail to meet inclusion criteria
* Primary tumors of the sinuses, paranasal sinuses, or nasopharynx, or unknown primary tumors
* Prior severe infusion reaction to a monoclonal antibody
* Pregnancy or breastfeeding
* Evidence of distant metastasis
* Any other malignancy active within 5 years except for non-melanoma skin cancer or carcinoma in situ of the cervix, DCIS or LCIS of the breast
* Prior history of head and neck cancer
* Prior therapy with motolimod, nivolumab, or other agents targeting PD-1/PD-L1
* Prior therapy targeting the EGFR pathway
* Acute hepatitis, known HIV, or active uncontrolled infection
* Patients with active autoimmune disease
* History of uncontrolled cardiac disease within prior 6 months
* Uncontrolled peptic or gastric ulcer disease, or gastrointestinal bleeding within prior 6 months
* Active alcohol abuse or other illness or circumstance that carries a likelihood of inability to comply with study treatment and follow-up or otherwise compromise the study's objectives
* Treatment with a non-approved or investigational drug within 30 days prior to Day 1 of study treatment
* Live vaccine within 30 days of planned start of study therapy
* History of pneumonitis or interstitial lung disease
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to nivolumab