Non-randomized, Open-label Study of Intralesional Nivolumab for High Risk Oral Premalignant Lesions

Subject Inclusion Criteria:

In order to be eligible for this trial, the subject must:

1. Presence of a treatment naïve, biopsy proven, intraoral premalignant lesion visiblefrom oral cavity.

2. Be willing and able to provide written informed consent for the trial.

3. Be >/= 18 years of age on day of signing informed consent.

4. Be willing to provide tissue, either archive or from a newly obtained oral biopsy.

5. Have a performance status of 0-2 on the ECOG Performance Scale.

6. Demonstrate adequate organ function as defined in Table 1 Table 1 Adequate Organ Function Laboratory Values Hematological Absolute neutrophilcount (ANC) ≥1,000 /mcL Platelets ≥75,000 / mcL Hepatic Serum total bilirubin ≤ 1.5X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULNAST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN

7. Female subject of childbearing potential should have a negative urine or serumpregnancy test within 72 hours prior to receiving the first dose of studymedication. If the urine test is positive or cannot be confirmed as negative, aserum pregnancy test will be required.

8. Female subjects of childbearing potential should be willing to use 2 methods ofbirth control or be surgically sterile or abstain from heterosexual activity for thecourse of study therapy through 120 days after the last dose of Nivolumab. Subjectsof childbearing potential are those who have not been surgically sterilized or havenot been free from menses for > 1 year.

9. Male subjects should agree to use an adequate method of contraception starting withthe first dose of study therapy through 120 days after the last dose of studytherapy.

Subject Exclusion Criteria:

The subject must be excluded from the trial if the subject:

1. Is currently participating and receiving study therapy with potentialanti-neoplastic activity or has participated in a study of an investigational agentand received study therapy with potential anti-neoplastic activity within 4 weeks ofthe first dose of treatment.

2. Has a known history of active TB (Bacillus Tuberculosis)

3. Hypersensitivity to nivolumab or any of its excipients.

4. Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to studyDay 1 or who has not recovered (i.e., ≤ Grade 2 or at baseline) from adverse eventsdue to agents administered more than 4 weeks earlier.

5. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapywithin 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 2 or atbaseline) from adverse events due to a previously administered agent.

6. Has a known additional malignancy that is progressing or requires active treatmentother than adjuvant hormonal therapy. Exceptions include basal cell carcinoma of theskin or squamous cell carcinoma of the skin or in situ cervical cancer.

7. Has known history of, or any evidence of active, non-infectious pneumonitis.

8. Has an active infection requiring systemic therapy.

9. Has a history or current evidence of any condition, therapy, or laboratoryabnormality that might confound the results of the trial, interfere with thesubject's participation for the full duration of the trial, or is not in the bestinterest of the subject to participate, in the opinion of the treating investigator.

10. Has known psychiatric or substance abuse disorders that would interfere withcooperation with the requirements of the trial.

11. Is pregnant or breastfeeding or expecting to conceive or father children within theprojected duration of treatment with pembrolizumab, starting with the pre-screeningor screening visit through 120 days after the last dose of trial treatment.

12. Has received a live vaccine within 30 days of planned start of study therapy.

Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live