Trial of Nivolumab as a Novel Neoadjuvant Pre-Surgical Therapy for Locally Advanced Oral Cavity Cancer

OCC patients who are scheduled for surgery will be given Nivolumab prior to surgery to see if
there are any changes in surgical outcomes.

Inclusion Criteria:

- Newly diagnosed histologically proven locoregional OCSCC (T stage 2-4) without
evidence of distant metastases. OCSCC includes the subsites of oral tongue, floor of
mouth, gingiva, retromolar trigone, and buccal mucosa OR

Recurrent or persistent histologically proven locoregional OCSCC (recurrent T-stage 2-4)
that was initially treated with surgery alone. To allow sufficient tumor tissue for the
immunological analyses, patients with T1 OCSCC will be excluded. Eligibility criteria will
also include the following:

- Greater than or equal to 18 years of age

- ECOG performance status of 0 or 1

- Must meet screening lab criteria outlined in the protocol

- Reproductive Status:

WOCBP must use appropriate method(s) of contraception. WOCBP should use an adequate method
to avoid pregnancy for 23 weeks (30 days plus the time required for nivolumab to undergo
five half-lives) after the last dose of investigational drug.

Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere
to contraception with a failure rate of less than 1% per year for a period of 31 weeks
after the last dose of investigational product.

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 consecutive months of amenorrhea in a
woman over 45.

Women of childbearing potential must have a negative serum pregnancy test (minimum
sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to registration Women
who are not of childbearing potential (ie, who are postmenopausal or surgically sterile and
azoospermic men are not required to use contraception.

Exclusion Criteria:

- Prior immunotherapy or treatment with another anti PD 1 agent.

- Prior chemotherapy including Cetuximab or radiation therapy.

- Previous severe hypersensitivity reaction to another monoclonal antibody

- Women who are pregnant, lactating or expecting to conceive or father children within
the research period

- Known history of HIV or AIDS

- Positive test for HBV sAg or HCV antibody indicating acute or chronic infection

- Concomitant malignancies except cutaneous squamous cell carcinoma or basal cell
carcinoma

- Unresectable primary tumor or regional disease; presence of distant metastases.

- Active, known or suspected autoimmune disease. Note: Subjects are permitted to enroll
if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to
autoimmune condition only requiring hormone replacement, psoriasis not requiring
systemic treatment, or conditions not expected to recur in the absence of an external
trigger

- Presence of condition requiring systemic treatment with either corticosteroids (> 10
mg daily prednisone equivalents) or other immunosuppressive medications within 14 days
of study drug administration. Inhaled or topical steroids and adrenal replacement
doses > 10 mg daily prednisone equivalents are permitted in the absence of active
autoimmune disease.