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).