Immunotherapy (Nivolumab) for the Treatment of Untreated or Recurrent Head and Neck Cancer in Patients Undergoing Surgery

Inclusion Criteria

• Cohort 1: Subjects must have histologically confirmed previously untreated squamous cell carcinoma of the head and neck that is amenable to surgical resection as part of standard of care
• Cohort 2: Subjects must have histologically confirmed recurrent squamous cell carcinoma of head and neck, that is amenable for salvage surgery. Sites of recurrence may either be locoregional and/or distant. Distant metastatic disease is permissible in this cohort and can be addressed at an interval with systemic therapy (e.g., chemotherapy, targeted therapies), or local therapies (e.g. radiation, metastatectomy) as clinically indicated
• The primary site should be a head and neck squamous cell carcinoma (including, but not limited to oral cavity, oropharynx, hypopharynx, or larynx, paranasal sinuses, nasal cavity). Squamous cell carcinoma of unknown primary, diagnosed in lymph nodes in neck, can be included but should be tested for p16 and confirmed HPV specific assay (testing NOT required for enrollment; can be done at an interval)
• Subjects with oropharyngeal primary tumors must have confirmation of HPV tumor status per clinical standards, although not necessary at enrollment
• Subjects must have been determined to be candidates for surgical resection by a multidisciplinary team including a surgeon, a medical oncologist and a radiation oncologist
• Subjects must have at least one lesion that can be biopsied (or has been) at baseline
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
• Life expectancy of greater than 6 months
• Leukocytes >= 1,500/mcL
• Absolute neutrophil count >= 1,000/mcL
• Platelets >= 100,000/mcL
• Total bilirubin =< 1.5 x institutional upper limit of normal (except subjects with Gilbert syndrome, who can have total bilirubin < 3.0 mg/dL)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x institutional upper limit of normal
• Creatinine within normal institutional limits OR creatinine clearance >= 40 mL/min (using modified Cockcroft-Gault formula) for patients with creatinine levels above institutional normal
• The effects of nivolumab on the developing human fetus are unknown * Women of childbearing potential (WOCBP) must have a negative urine or serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 24 hours prior to the start of study treatment * Women must not be breastfeeding * Women of childbearing potential (WOCBP) must agree to follow instructions for method(s) of contraception for the duration of treatment with study treatment and for 5 months post-treatment completion. Women should use an adequate method(s) of contraception * Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study treatment(s) and 7 months post-treatment completion. In addition, male participants must be willing to refrain from sperm donation during this time. Men who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception
• Patient understands the study regimen, its requirements, risks and discomforts and is able and willing to sign the informed consent form. Voluntary signed and dated Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written informed consent form in accordance with regulatory and institutional guidelines must be obtained before the performance of any protocol related procedures that are not part of normal patient care. Subjects must be competent to report adverse events (AEs), understand the drug dosing schedule and use of medications to control AEs
• Measurable disease – either radiologically (per Response Evaluation Criteria in Solid Tumors [RECIST]) or clinically measurable on exam in order to assess treatment response

Exclusion Criteria

• Any active history of a known autoimmune disease. Subjects with vitiligo, type 1 diabetes mellitus, residual hypothyroidism requiring hormone replacement, or conditions not expected to recur in the absence of an external trigger are permitted to enroll
• Patients who have had prior chemotherapy for newly diagnosed (cohort 1) or recurrent (cohort 2) head and neck cancer. In cohort 2 only, previous perioperative chemotherapy or chemoradiation for the management of localized or locally advanced disease permitted
• Patients who received prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, antiCD137, anti-CTLA-4 antibody therapies, any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
• Any live / attenuated vaccine (e.g. varicella, zoster, yellow fever, rotavirus, oral polio and measles, mumps, rubella [MMR]) within 30 days of first treatment
• Patients with uncontrolled brain metastases. Patients with brain metastases must have stable neurologic status following local therapy (surgery and/or radiation) for at least 2 weeks without the use of steroids or on stable or decreasing dose of =< 10 mg daily prednisone (or equivalent), and must be without neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Patients with a history of carcinomatous meningitis are not eligible
• Patients who have an active concurrent malignancy that is not controlled/cured and could impact life expectancy within the next 3 years. E.g. patients with localized cutaneous squamous cell carcinoma or basal cell carcinoma or treated prostate cancer with no evidence of disease progression may be allowed to enroll after review by the study team and principal investigator
• Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, myocardial infarction or new onset angina within six months of enrollment, or psychiatric illness/social situations that would limit compliance with study requirements
• Women who are pregnant or nursing
• Men with female partners who are not willing to use contraception
• Active infection with hepatitis B or hepatitis C (active infection is defined by abnormal liver function tests (= elevated AST/ALT) or ongoing use of an antiviral hepatitis treatment). Patients with normal liver function tests (defined by normal AST/ALT) per definition do not have an active infection and are eligible to enroll without additional testing
• Patients with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization. However, inhaled or topical steroids and adrenal replacement steroid doses =< 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease
• Epstein-Barr virus (EBV) positive (+) head and neck cancer (e.g. EBV[+] nasopharyngeal carcinoma)
• Patients with human immunodeficiency virus (HIV) are excluded given the unknown risk of interaction with highly active antiretroviral therapy (HAART) and the unknown benefit of immunotherapy in this population