Pre-operative Mocetinostat (MGCD0103) and Durvalumab (MEDI4736) (PRIMED) for Squamous Cell Carcinoma of the Oral Cavity

Exclusion Criteria

• •1. Primary site of head and neck carcinoma unknown, lip, hard palate, skin, or outside the oral cavity.
• •2. Patients with tumors that invade major vessels, as shown unequivocally by imaging studies.
• •* For patients with tumors that do not invade major blood vessels but are within 3mm of the carotid artery or branches thereof, any anticoagulant therapy (including aspirin, non-steroidal anti-inflammatories, antiplatelet agents or other anti-coagulants) must be discontinued.
• •3. Patients with any prior history of bleeding related to the current head and neck cancer.
• •4. Patients with a history of gross hemoptysis (bright red blood of ½ teaspoon or more per episode of coughing) \< 3 months prior to enrollment.
• •5. Prior or concurrent radiation therapy to tumor at site of planned resection.
• •6. Any concurrent chemotherapy, biologic, immunologic or hormonal therapy for cancer treatment.
• •* Concurrent use of hormones for non-cancer-related conditions (eg, insulin for diabetes and hormone replacement therapy) is acceptable.
• •7. Current or prior use of immunosuppressive medication within 14 days prior to starting dosing. The following are exceptions to this criteria:
• •* Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra-articular injection).
• •* Systemic corticosteroids at physiologic doses not exceeding 10 mg/day of prednisone or equivalent.
• •* Steroids as premedication for hypersensitivity reactions (eg, computed tomography scan premedication).
• •8. Active or documented history of autoimmune disease within 2 years before screening, including:
• •* Active or prior documented inflammatory bowel disease (eg. Crohn's disease, ulcerative colitis).
• •* Patients with vitiligo, resolved childhood asthma/atopy, type I diabetes mellitus, Grave's disease, Hashimoto's disease, or psoriasis not requiring systemic treatment within the past 2 years, are not excluded.
• •9. History of primary immune deficiency.
• •10. History of organ transplant that requires use of immunosuppressive medications.
• •11. Use of any live vaccines against infectious diseases within 4 weeks of study treatment initiation.
• •12. Known allergy or reaction to any component of Mocetinostat and/or Durvalumab formulation.
• •13. Known history of tuberculosis.
• •14. Subjects who are known to be human immunodeficiency (HIV) positive.
• •15. Subjects who are known to be hepatitis B or C positive.
• •16. Female patients who are pregnant or breast-feeding.
• •17. Male or female patients of reproductive potential who are not willing to use effective birth control from screening to 180 days following the last dose of durvalumab.
• •18. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, unstable cardiac arrhythmia, active peptic ulcer disease or gastritis, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring adverse events from Mocetinostat or Durvalumab, or compromise the ability of the subject to give written informed consent.
• •19. Any condition that, in the opinion of the Investigator, would interfere with evaluation of the study regimen or interpretation of patient safety or study results.
• •20. Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab.
• •21. History of another primary malignancy, except for:
• •* Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of study drug and of low potential risk for recurrence,
• •* Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease,
• •* Adequately treated carcinoma in situ without evidence of disease.
• •22. Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of study medications.
• •23. Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE \>Grade 1.