Inclusion Criteria:

          1. Subjects must have signed and dated an IRB/IEC approved written informed consent form
             in accordance with regulatory and institutional guidelines. This must be obtained
             before the performance of any protocol related procedures that are not part of normal
             subject care.

          2. Subjects must be willing and able to comply with scheduled visits, treatment schedule,
             laboratory tests and other requirements of the study.

          3. Men and women >/= 18 years of age.

          4. Eastern Cooperative Oncology Group (ECOG) performance status of </= 1.

          5. Subjects with histologically- or cytologically-documented incurable Human
             Papillomavirus (HPV)-positive OPSCC. HPV-16 serotype will be assessed by Cervista
             assay.

          6. Subjects can be treatment naïve or may have had two prior regimens for recurrent
             cancer. They must be naive to treatment with PD-1/L1 or CTLA-4 inhibitors.

          7. Subjects must have progression within 6 months of platin exposure during definitive or
             palliative therapy.

          8. Subjects must have measurable disease by CT or MRI per RECIST 1.1 criteria;
             Radiographic Tumor Assessment performed within 28 days of study inclusion.

          9. Target lesions may be located in a previously irradiated field if there is documented
             (radiographic) disease progression in that site.

         10. Subject entering the study will need to consent for mandatory biopsy at study entrance
             and as an optional procedure prior to C3 for biomarker evaluation. Biopsy should be
             excisional, incisional or core needle. Fine needle aspiration is insufficient.

         11. Prior chemotherapy, monoclonal antibody therapy, must have been completed at least 4
             weeks prior to start. Radiotherapy or radiosurgery must have been completed at least 2
             weeks prior to start.

         12. All baseline laboratory requirements will be assessed and should be obtained within
             -14 days of study registration. Screening laboratory values must meet the following
             criteria i) White blood cells (WBCs) >/= 2000/microL ii) Neutrophils >/= 1500/microL
             iii) Platelets >/= 100 x 10^3/microL iv) Hemoglobin >/= 9.0 g/dL Patients must not be
             transfused for at least 14 days prior to study entry v) Serum creatinine of </=1.5 x
             upper limit of normal(ULN) or creatinine clearance(CrCl) > 50 mL/minute (using
             Cockcroft/Gault formula) Female CrCl= 0.85 x [(140 - age in years) x weight in kg]/(72
             x serum creatinine in mg/dL) Male CrCl= 1.00 x [(140 - age in years) x weight in
             kg]/(72 x serum creatinine in mg/dL) vi) AST </= 2.5 x ULN vii) ALT </= 2.5 x ULN
             viii) Total bilirubin</= 1.5 x ULN (except subjects with Gilbert Syndrome who must
             have total bilirubin <3.0 mg/dl).

         13. Women of childbearing potential (WOCBP) must use method(s) of contraception for 30
             days + 5 half-lives (60 days) of the study drugs. For a teratogenic study drug and/or
             when there is insufficient information to assess teratogenicity (preclinical studies
             have not been done), a highly effective method(s) of contraception (failure rate of
             less than 1% per year) is required. Highly effective birth control in this study is
             defined as a double barrier method. Examples include a condom (with spermicide) in
             combination with a diaphragm, cervical cap, or intrauterine device (IUD). The
             individual methods of contraception should be determined in consultation with the
             investigator.

         14. WOCBP 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 investigational
             product.

         15. Women must not be breastfeeding.

         16. Men who are sexually active with WOCBP must use any contraceptive method with a
             failure rate of less than 1% per year. The investigator shall review contraception
             methods and the time period that contraception must be followed. Men that are sexually
             active with WOCBP must follow instructions for birth control for a period of 90 days
             plus the time required for the investigational drug to undergo 5 half- lives (60
             days).

        Exclusion Criteria:

          1. Subjects with active CNS metastases are excluded. Subjects are eligible if CNS
             metastases are adequately treated and subjects are neurologically returned to baseline
             (except for residual signs or symptoms related to the CNS treatment) for at least 4
             weeks prior to enrollment. In addition, subjects must be either off corticosteroids,
             or on a stable or decreasing dose of </= 10 mg daily prednisone (or equivalent) for 2
             weeks.

          2. Subjects with carcinomatous meningitis.

          3. Subjects with active, known or suspected systemic autoimmune disease. Subjects with
             vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune
             thyroiditis only requiring hormone replacement, or conditions not expected to recur in
             the absence of an external trigger are permitted to enroll.

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

          5. Prior therapy with anti-CD137 or ISA101.

          6. Subjects with a history of interstitial lung disease.

          7. Other active malignancy requiring concurrent intervention.

          8. Subjects with previous malignancies (except non-melanoma skin cancers, and the
             following in situ cancers: bladder, gastric, colon, endometrial, cervical/dysplasia,
             melanoma, or breast) are excluded unless a complete remission was achieved at least 2
             years prior to study entry AND no additional therapy is required during the study
             period.

          9. Subjects with toxicities attributed to prior anti-cancer therapy other than alopecia
             and fatigue that have not resolved to grade 1 (NCI CTCAE version 4.03) or baseline
             before administration of study drug.

         10. Subjects who have not recovered from the effects of major surgery or significant
             traumatic injury at least 14 days before the first dose of study treatment.

         11. Treatment with any investigational agent within 28 days of first administration of
             study treatment.

         12. Known history of testing positive for human immunodeficiency virus (HIV) or known
             acquired immunodeficiency syndrome (AIDS).

         13. Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus
             ribonucleic acid (HCV RNA) indicating acute or chronic infection.

         14. History of allergy or intolerance (unacceptable adverse event) to study drugs
             components.

         15. WOCBP who are pregnant or breastfeeding.

         16. Women with a positive pregnancy test at enrollment or prior to administration of study
             medication.

         17. Any other serious or uncontrolled medical disorder, active infection, physical exam
             finding, laboratory finding, altered mental status, or psychiatric condition that, in
             the opinion of the investigator, would limit a subject's ability to comply with the
             study requirements, substantially increase risk to the subject, or impact the
             interpretability of study results.

         18. Prisoners or subjects who are involuntarily incarcerated.

         19. Subjects who are compulsorily detained for treatment of either a psychiatric or
             physical (eg, infectious disease) illness.