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