Neodjuvant Nivolumab and Lirilumab, Followed by Surgery, Followed by Adjuvant Nivolumab and Lirilumab, in SCCHN

This research study is a Phase II clinical trial. Phase II clinical trials test the safety
and effectiveness of an investigational drug or combination of drugs to learn whether it
works in treating a specific disease. "Investigational" means that the drug/s is being
studied.

The purpose of this study is to evaluate effectiveness (how well the drug/s work) of
nivolumab in combination with lirilumab in participants with SCCHN.

Nivolumab and lirilumab are types of immunotherapy. Immunotherapy works by encouraging the
body's own immune system to attack cancer cells. Both nivolumab and lirilumab have been
demonstrated to activate the immune system to attack cancer cells in participants with
different types of cancers.

In November, 2016, the Food and Drug Administration (FDA) approved nivolumab for the
treatment of participants with recurrent or metastatic squamous cell carcinoma of the head
and neck (SCCHN). Lirilumab is not FDA approved as of now.

Inclusion Criteria:

- Subject must have histologically or cytologically confirmed locoregionally recurrent
squamous cell carcinoma of the head and neck (including any primary site, such as oral
cavity, oropharynx, larynx or hypopharynx, and nasopharyngeal carcinoma)

- Must be a candidate for salvage surgery

- Willing to provide blood and tissue from diagnostic biopsy and at the time of surgery

- Has documented disease-free interval (DFI) > 8 weeks after completion of initial
therapy; DFI is from the time of completion of initial treatment to the diagnosis of
local or locoregional recurrence

- Any HPV status or smoking history is permitted. Oropharyngeal cancer patients are
required to undergo HPV testing with p16 immunohistochemistry and/or confirmatory HPV
PCR or ISH testing

- Age 18 years or older

- ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A)

- Participant must have normal organ and marrow function as defined below within 21 days
prior to study registration:

- leukocytes ≥3,000/mcL

- absolute neutrophil count ≥1,500/mcL

- platelets ≥100,000/mcL

- total bilirubin ≤2.0 g/dL

- AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal

- creatinine within normal institutional limits OR

- creatinine clearance ≥60 mL/min/1.73 m2 for participants with creatinine levels
above institutional normal

- Ability to understand and the willingness to sign a written informed consent document

- Women of childbearing potential (WOCBP) must agree to use appropriate method(s) of
contraception. WOCBP should plan to use an adequate method to avoid pregnancy for 5
months (30 days plus the time required for nivolumab to undergo five half-lives) after
the last dose of investigational drug

- Women of childbearing potential must have a negative serum or urine pregnancy test
(minimum sensitivity 25 iu/l or equivalent units of hcg) within 24 hours prior to the
start of nivolumab

- "Women of childbearing potential (WOCBP)" is defined as any female who has experienced
menarche and who has not undergone surgical sterilization (hysterectomy or bilateral
oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12
months of amenorrhea in a woman over 45 in the absence of other biological or
physiological causes. In addition, women under the age of 55 must have a documented
serum follicle stimulating hormone (FSH) level less than 40 mIU/mL

- Men who are sexually active with WOCBP must agree to use any contraceptive method with
a failure rate of less than 1% per year. Men who are sexually active with WOCBP will
be instructed to adhere to contraception for a period of 7 months after the last dose
of investigational product. Women who are not of childbearing potential (ie, who are
postmenopausal or surgically sterile as well as azoospermic men) do not require
contraception

Exclusion Criteria:

- Existing significant autoimmune conditions. Patients with a history of Hashimoto
thyroiditis who are stable on replacement hormone therapy are not excluded. Patients
cannot be on long-term (> 4 weeks) corticosteroids at doses exceeding prednisone 20 mg
(or its equivalent) prior to enrollment. Short-term corticosteroid dosing is permitted
as long as steroids are discontinued within 2 weeks of study enrollment.

- Subject who has had chemotherapy or radiotherapy within 4 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to entering the study or those who have not
recovered from adverse events due to agents administered more than 4 weeks earlier.

- Subject who has been treated with immunotherapy. This includes prior treatment with
anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug
specifically targeting T-cell co-stimulation or checkpoint pathways

- Subject with known brain metastases should be excluded from this clinical trial
because of their poor prognosis and because they often develop progressive neurologic
dysfunction that would confound the evaluation of neurologic and other adverse events.
However, baseline brain imaging is not required prior to enrollment in the study if
patients are asymptomatic.

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements.

- Known human immunodeficiency virus carrier or a diagnosis of immunodeficiency. Any
positive test result for hepatitis B virus or hepatitis C virus indicating presence of
virus, eg, Hepatitis B surface antigen (HBsAg, Australia antigen) positive, or
Hepatitis C antibody (anti-HCV) positive (except if HCV-RNA negative).

- Known non-infectious pneumonitis or any history of interstitial lung disease.

- Receipt of a live vaccine within 30 days of start of study treatment