Randomized Pre-surgical Window-of-Opportunity Trial of TTI-101 in Patients With Stage II-IV Resectable HPV-negative Squamous Cell Carcinoma of the Head and Neck

Inclusion Criteria: Patients must meet the following criteria for study entry: * Biopsy-proven primary Stage II-IV squamous cell carcinoma of the head and neck * For oropharyngeal cancer patients: HPV-negative by p16 and/or direct high-risk HPV assessment * Surgical resection must be planned as primary therapy with or without adjuvant radiation therapy. * Signed Informed Consent Form (ICF). * Ability and willingness to comply with the requirements of the study protocol. * Ability to swallow study drug. * Age years of 18 years. * Measurable disease per RECIST v1.1 (see Appendix 2) and/or per direct clinical measurements. * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 (see Appendix 4) * Adequate hematologic and hepatorenal function, defined by the following laboratory results obtained within 4 weeks prior to study entry: * ANC 1500 cells/L * Platelet count 100,000/L; * Hemoglobin 9.0 g/dL * Total bilirubin 1.5 upper limit of normal (ULN) with the following exception: Patients with known Gilbert disease who have serum bilirubin level 3 ULN may be enrolled. * AST and ALT 2.5 ULN * Alkaline phosphatase 2.5 ULN * Serum creatinine clearance ≥60 mL/min, measured or calculated per institutional standard protocol • INR and aPTT 1.5 ULN * This applies only to patients who do not receive therapeutic anticoagulation; patients receiving therapeutic anticoagulation (such as low-molecular-weight heparin or warfarin) should be on a stable dose. * N…