Pembrolizumab, Aspirin, and Clopidogrel Bisulfate in Treating Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

Inclusion Criteria

• Subject has pathologic confirmation of recurrent or metastatic HNSCC, regardless of human papillomavirus (HPV) status
• Subject has tumor that expresses PD-L1 (combined positive score [CPS] >= 1) as determined by a Food and Drug Administration (FDA)-approved test or subject has experienced disease progression on or after platinum-containing chemotherapy
• Subject’s scans have been reviewed at head and neck tumor board to assess tumor involvement
• Subject has measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1; tumor lesions situated in previously irradiated areas are considered measurable if progression has been demonstrated in such lesions
• Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
• Subject has estimated life expectancy of at least 3 months
• ANC >= 1000 K/CUMM
• Hemoglobin >= 8.0 grams/dL
• Platelets >= 75,000 K/CUMM
• International normalized ratio (INR) =< 1.7
• Estimated creatinine clearance > 30 mL/min according to the Cockcroft-Gault formula
• Total bilirubin =< 1.5 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN
• Female and male subjects of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study medication; effective forms of contraception include abstinence, hormonal contraceptive in conjunction with a barrier method, or a double barrier method; women of non-child-bearing potential may be included if they are either surgically sterile or have been post-menopausal for > 1 year * Note: Female subjects of childbearing potential must have a negative urine or serum pregnancy test within 14 days prior to registration; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required

Exclusion Criteria

• Subject is receiving concomitant immunosuppressive therapy, defined as: * Immunosuppressants, including: tacrolimus, sirolimus, everolimus, cyclosporine, azathioprine, mycophenolate mofetil, antithymocyte globulin, basiliximab, belatacept * Systemic corticosteroids (except for short team treatment of allergic reactions or for treatment of immune related adverse events [irAE]); steroids with no or minimal systemic effect (topical, inhalation) are allowed * Chemotherapy * Immunotherapy * Monoclonal antibodies
• Concurrent anticancer treatment within 14 days before the start of trial treatment
• Subject has had major surgery within the last 28 days
• Subject has an underlying bleeding disorder
• Subjects requiring re-irradiation to head and neck.
• Subject is receiving anticoagulation; subjects must have a washout period of 7 days from registration
• Subject has HNSCC with abutment or encasement of the internal carotid artery, external carotid artery or common carotid artery or any of the arterial branches.
• Subject has a draining fistula or wound in the head/neck.
• Subject with known aneurysm or pseudoaneurysm of the head/neck related to surgery.
• Subject has uncontrolled central nervous system (CNS) metastases. Subjects with previously treated brain metastases will be allowed if the brain metastases have been stable without CNS-directed therapy (such as radiation or surgery) or steroid treatment for at least 4 weeks prior to registration
• Receipt of any organ transplantation
• Active or history of any autoimmune disease (except type I diabetes mellitus [DM], vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment, which are allowed) or immunodeficiencies
• Known severe hypersensitivity reactions to monoclonal antibodies (grade >= 3 National Cancer Institute-Common Terminology Criteria for Adverse Events [NCI-CTCAE] version [v]4.0), any history of anaphylaxis or uncontrolled asthma
• Subjects who have a hypersensitivity to aspirin or non-steroidal anti-inflammatory drugs (NSAIDs)
• Concurrent NSAID therapy; subjects must have washout period of 7 days from registration
• Subjects with an acute gastrointestinal ulcer
• Subjects with active hemorrhagic diathesis
• Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (New York Heart Association [NYHA] class >= II), or serious uncontrolled cardiac arrhythmia
• All other significant diseases, which in the opinion of the investigator, may impair the subject’s tolerance of trial treatment
• Vaccination within 4 weeks of the 1st dose of pembrolizumab and while on study is prohibited EXCEPT for administration of inactivated vaccines (e.g. inactivated influenza vaccine)
• Women who are pregnant or nursing