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

Inclusion Criteria: 1. Signed written and voluntary informed consent. 2. Patient must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures. 3. Age \> 18 years, male or female. Disease characteristics 4. Patient must be diagnosed with histologically confirmed squamous cell carcinoma of the oral cavity (SCCOC) (floor of mouth, anterior 2/3 tongue, buccal mucosa, upper and lower gingiva, and retromolar trigone) considered resectable by the head and neck surgical rounds (T2-4a, N0-2, M0; without evidence of distant metastasis). 5. Patient must be willing and able to provide up to 2 fresh tumor biopsies for histopathological and biomarker evaluation; first as pre-treatment baseline, and the second after treatment with mocetinostat but prior to treatment with durvalumab. * Patients who decline an in-house fresh pre-treatment tumor biopsy must give consent to provide a tumor block from an existing diagnostic primary tumor biopsy completed within 90 days of enrollment, which is of acceptable quality and quantity for analysis, as assessed by the study site correlatives team. 6. No anti-neoplastic treatment is allowed between the time from obtaining baseline tumor specimen and enrollment. Patient characteristics 7. ECOG performance status 0-1. 8. Patient must have adequate organ function as determined by the following: \- Renal function: i. Serum creatinine \< 1.5 ULN (upper limit of normal range) or a calculated creatinine clearance of \> 50mL/min using the following formula: Creatinine clearance = \[(140-age) x wt (kg) x Constant\*\] / creatinine (umol/L) \*Constant = 1.23 for men, and 1.04 for women \- Bone marrow function (without hematopoietic growth factors or transfusion): i. Absolute neutrophil count (ANC) \> 1.5 x 109/L ii. Leukocytes \> 3.0 x 109/L iii. Hemoglobin \> 90 g/L or \> 9g/dL iv. Platelets \> 100 x 109/L \- Liver function: i. Total bilirubin \< ULN ii. Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) \< 2.5 x ULN \- Cardiac function: i. A normal left ventricular ejection fraction (LVEF) of \> 50% and the absence of any clinically significant pericardial effusion, as evidenced by an echocardiogram performed within 4 weeks of the study commencement. 9. Evidence of post-menopausal status, or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply: * Women \<50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy). * Women ≥50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses \>1 year ago, had chemotherapy-induced menopause with last menses \>1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy). 10. Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up. 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.