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 immunotherapy-drugs-are-boosting-survival/" >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).