Tadalafil and Pembrolizumab in Recurrent or Metastatic Head and Neck Cancer

Selected Inclusion Criteria: * Patients (at least 18 years of age) must have recurrent or metastatic squamous cell carcinoma of the head and neck. * Presence of measurable disease. * Life expectancy of greater than 12 weeks * Patients must have normal organ and marrow function Selected Exclusion Criteria: * Prior therapy with an PD-1 or PD-L1 inhibitor in the recurrent or metastatic setting * Uncontrolled central nervous system metastases (stable metastases permitted) * Active autoimmune disease * Chemotherapy ≤28 days prior to first administration of study treatment and/or monoclonal antibody ≤8 weeks prior to first administration of study treatment. * Prior daily use of tadalafil or other long-acting PDE5 inhibitors for one month or greater within 3 months of trial enrollment * Current use of all other long-acting PDE5 inhibitors. * Known severe hypersensitivity to tadalafil or any of the excipients of this product * Current treatment with nitrates * Current systemic treatment with a potent cytochrome P450 3A4 (CYP3A4) inhibitor such as ketoconazole or ritonavir. * Current treatment with guanylate cyclase (GC) stimulators such as riociguat. * History of hypotension and/or blindness and/or sensorineural hearing loss during prior treatment with tadalafil or other PDE-5 inhibitors * History of known hereditary degenerative retinal disorders, including retinitis pigmentosa * Prior history of non-arteritic anterior ischemic optic neuropathy * Pregnant or breastfeeding; a negative pregnancy test is required within 14 days of randomization for all women of childbearing potential. * History of stroke within prior 6 months. * History of acute myocardial infarction within prior 3 months, uncontrolled angina, uncontrolled arrhythmia, or uncontrolled congestive heart failure * Left ventricular outflow obstructions, such as aortic stenosis and idiopathic hypertrophic subaortic stenosis * Angina requiring treatment with long-acting nitrates * Angina requiring treatment with short-acting nitrates within 90 days of planned tadalafil administration * Unstable angina within 90 days of visit 1 (Braunwald 1989) * Positive cardiac stress test without documented evidence of subsequent, effective cardiac intervention * History of any of the following coronary conditions within 90 days of planned tadalafil administration: * Myocardial Infarction * Coronary artery bypass graft surgery * Percutaneous coronary intervention (for example, angioplasty or stent placement) * Any evidence of heart disease (NYHA ≥ Class II as defined in Protocol Attachment LVHG.3) within 6 months of planned tadalafil administration * Concurrent systemic immunosuppressant therapy (e.g., cyclosporine A, tacrolimus, etc., or chronic administration of \>10 mg/day of prednisone or equivalent) * Prior organ transplantation * Known history of human immunodeficiency virus (HIV) or active infection with hepatitis C virus (HCV) or hepatitis B virus (HBV).