Losartan, Pembrolizumab and Stereotactic Body Radiation Therapy for the Treatment of Patients With Locally Recurrent, Refractory or Oligometastatic Head and Neck Squamous Cell Carcinoma

Exclusion Criteria

• •Nasopharyngeal carcinoma, salivary gland carcinoma or primary skin squamous cell carcinoma (SCC)
• •Prior treatment with an anti-PD-1, anti-PD-L1, or anti-PD-L2 antibody
• •Chemotherapy or other anti-cancer therapy within 3 weeks prior to study day 1
• •Hypersensitivity to losartan or any component of the formulation
• •Radiation therapy within 6 months prior to study day 1
• •Patients with disease surrounding \> 50% of the carotid
• •Participant who has not recovered to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade ≤ 1 from an adverse event (AE) due to previous cancer therapeutics (i.e., chemotherapy, radiation therapy, biologic therapy, and/or experimental therapy) with the exception of alopecia
• •Major surgery as assessed by the investigator (with the exception of diagnostic biopsy) within ≤ 28 days prior to study day 1 (patients must have completely recovered from any previous surgery prior to study day 1)
• •Clinically significant bleeding ≤ 4 weeks prior to study day 1
• •Requirement for parenteral antibiotics, or any active infection requiring parenteral antibiotic therapy within 4 weeks prior to study day 1
• •Clinically significant or uncontrolled diabetes mellitus (hemoglobin A1C ≤ 8.5%). Patients with diabetes mellitus treated with aliskiren ≤ 7 days prior to study day 1 are excluded
• •Active autoimmune disorders that have required systemic treatment with disease modifying agents, corticosteroids, or immunosuppressive drugs in the past 2 years are excluded. Patients with autoimmune disorder or well-managed or inactive autoimmune disorders, such as Hashimoto's thyroiditis, may be allowed at the discretion of the PI
• •Current use of systemic corticosteroids equivalent to \>10 mg of prednisone per day
• •Current use of angiotensin receptor blockers (ARBs) or angiotensin converting enzyme (ACE) inhibitors for management of hypertension
• •Clinically significant cardiovascular, pulmonary, endocrine, neurologic, gastrointestinal or genitourinary disease unrelated to underlying solid tumor that in the judgment of the investigator should preclude treatment with losartan
• •Any other active malignancy except for low-risk prostate cancer previously treated or under active surveillance, uncomplicated and cured basal cell carcinoma, or squamous cell carcinoma of the skin within 5 years of study entry
• •Known history of positive hepatitis C (HCV) antibody, hepatitis B (HBV) surface antigen (HbsAg and HBV core Ab positive), or human immunodeficiency virus (HIV) antibody results. Patients with positive antibody tests are eligible with negative viral loads
• •Administration of live, attenuated vaccine ≤ 28 days prior to study day 1. Administration of inactivated flu vaccines is allowed
• •Any prior treatment with losartan or other specific TGF-β-directed therapy
• •Treatment with another investigational drug or device, or approved therapy for investigational use ≤ 28 days prior to study day 1, or if the half-life of the previous product is known, within 5 times the half-life prior to study day 1, whichever may be longer
• •Pregnant or breast feeding
• •Any condition that in the opinion of the investigator would interfere with the participant's safety, compliance while on trial, or understanding or rendering of informed consent