A Phase Ib Study of Neoadjuvant of Cetuximab Plus Motolimod and Cetuximab Plus Motolimod Plus Nivolumab
A Phase Ib Study of Neoadjuvant of Cetuximab Plus Motolimod and Cetuximab Plus Motolimod Plus Nivolumab
Protocol VRXP-A106 will enroll patients with Stage II-IVA head and neck cancer patients who
 will be treated with surgical resection. Cetuximab and motolimod (Cohort 1); and cetuximab,
 motolimod, and nivolumab (Cohort 2) will be administered for a 3-4 week period before
 surgery. The primary objective of the study is to determine the extent to which the
 administration of neoadjuvant motolimod plus cetuximab and motolimod plus cetuximab and
 nivolumab modulates immune biomarkers (NK, mDC and T cell activation as well as tumor
 infiltration and serum cytokines) in peripheral blood and head and neck cancer tumors. An
 exploratory objective of the study is to assess whether modulation of biomarkers as described
 above can predict anti-tumor response.
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