Preoperative Immune Checkpoint Inhibitor for Patients With Recurrent or Metastatic SCCHN Undergoing Surgical Salvage

This research is being done to see if it is safe and feasible to give the investigational
drugs, nivolumab (also known as BMS-936558) before surgery to people with newly diagnosed or
recurrent squamous cell carcinoma of head and neck (SCCHN). Patients with recurrent disease
may have a limited number of sites of metastatic (spread) squamous cell carcinoma of head and
neck. Another goal of this study is to learn how nivolumab impacts the immune system's
ability to treat the cancer. While nivolumab is approved by the U. S. Food and Drug
Administration (FDA) for the treatment of patients with metastatic SCCHN with progression on
or after platinum-based chemotherapy, the word "investigational" in this context means that
the study drugs are not approved by the FDA for the treatment of head and neck cancers prior
to surgery and thus is still being tested in research studies. However, the FDA is allowing
the use of nivolumab in this study.

This study will have two arms. Cohort (arm) 1 will examine one dose of nivolumab given about
4 weeks before surgical resection (removal) of a newly diagnosed SCCHN. Twelve patients will
be enrolled to this arm. Cohort 2 will examine one dose of nivolumab given about 4 weeks
before surgical resection (removal) of SCCHN which has recurred and possibly spread to
distant sites, but still can be resected with one surgery. Twelve patients will be enrolled
to this arm.

Inclusion:

Cohort 1: Subjects must have histologically confirmed previously untreated locally advanced
squamous cell carcinoma of the head and neck which is amenable to surgical resection

Cohort 2: Subjects must have histologically confirmed recurrent squamous cell carcinoma of
head and neck, which is amenable for salvage surgery. Sites of recurrence may either be
locoregional or distant (non-CNS site) if resection can be done in one surgical field.

- The primary site should be oral cavity, oropharynx, hypopharynx, or larynx. Squamous
cell carcinoma of unknown primary, diagnosed in lymph nodes in neck, can be included
but should be tested for HPV by DNA or RNA in situ hybridization (ISH).

- Subjects must have confirmation of HPV status by DNA or RNA ISH if the primary site is
oropharynx.

- Subjects must have at least one lesion that can be biopsied at baseline.

- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.

- Age >18 years.

- Life expectancy of greater than 6 months.

- Patients must have normal organ and marrow function as defined below:

- 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)

- AST(SGOT)/ALT(SGPT) ≤ 3 X institutional upper limit of normal

- Creatinine OR creatinine clearance within normal institutional limits OR ≥ 40
mL/min (using modified Cockcroft-Gault formula) for patients with creatinine
levels above institutional normal.

- Resting and walking O2 saturation must remain above 90% at the time of screening

- Women of childbearing potential (WOCBP) must have a negative urine or serum pregnancy
test (minimum sensitivity 25 IU/L or equivalent units of 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 (Refer to nivolumab IB for WOCBP and methods of contraception to be
provided)

- Males who are sexually active with WOCBP must agree to follow instructions for
method(s) of contraception (Refer to protocol appendix E) 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 IRB/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 AEs,
understand the drug dosing schedule and use of medications to control AEs.

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 had prior surgical resection of distant metastasis (metastatectomy)
within 6 months of enrollment.

- Patients who received prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti
CD137, anti-CTLA-4 antibody therapies, any other antibody or drug specifically
targeting T-cell co-stimulation or checkpoint pathways. Any live / attenuated vaccine
(eg varicella, zoster, yellow fever, rotavirus, oral polio and measles, mumps, rubella
(MMR)) during treatment and until 100 days post last dose.

- Patients with uncontrolled brain metastases

- Patients with brain metastases must have stable neurologic status following local
therapy (surgery or radiation) for at least 2 weeks without the use of steroids or on
stable or decreasing dose of < 10mg 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. Patients with localized cutaneous
squamous cell carcinoma or basal cell carcinoma which is completely excised are
allowed to enroll.

- Uncontrolled inter-current illness including, but not limited to, ongoing or active
infection, administration of live vaccination in the prior 3 months, 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 defined as positive tests for
hepatitis B surface antigen or hepatitis C ribonucleic acid (RNA).

- Patients with a condition requiring systemic treatment with either corticosteroids
(>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14
days of randomization. Inhaled or topical steroids and adrenal replacement steroid
doses < 10 mg daily prednisone equivalent, are permitted in the absence of active
autoimmune disease.

- Patients with nasopharynx carcinoma

- Patient with HIV are excluded given the unknown risk of interaction with HAART and the
unknown benefit of immunotherapy in this population.

- Participants who have received a live / attenuated vaccine within 30 days of first
treatment.