Pembrolizumab in Combination With Cisplatin and Intensity Modulated Radiotherapy (IMRT) in Head and Neck Cancer

Inclusion Criteria

• Written informed consent
• If a woman of childbearing potential, documentation of negative pregnancy
• Histologically-confirmed head and neck squamous cell carcinoma with no evidence of distant metastasis. The primary site may be the oral cavity, oropharynx, larynx, or hypopharynx. Patients with squamous cell carcinoma of unknown primary, metastatic to cervical lymph nodes, are permitted to enroll.
• High risk or intermediate risk disease, defined below. Staging evaluation should be determined by imaging studies and complete head and neck exam in accordance with the American Joint committee on Cancer Staging Manual, 7th edition.

o High risk patient must meet one of the following criteria:

• Surgically unresectable oral cavity. Patients who are technically resectable but refuse surgery due to morbidity (eg. total glossectomy) are also eligible. Medically inoperable patients are not eligible.
• Larynx: T4 any N; T2-3 and ≥ N2a
• Hypopharynx: T1-2N1-3 or T3-4N0-3
• Oropharynx: p16(-) AND T3-4 or ≥ N2a
• Unknown primary: p16(-) AND ≥ N2a

o Intermediate risk patients must meet one of the following criteria:

• Oropharynx: p16(+) AND one of the following
• T3 or ≥ N2a AND ≥ 10 pack-years tobacco exposure (see Tobacco Assessment Form, Appendix A)
• T4 or N3 disease irrespective of tobacco exposure
• Unknown primary: p16(+) AND one of the following
• ≥ N2a AND ≥ 10 pack-years tobacco exposure
• N3 disease irrespective of tobacco exposure
• Patients must be untreated with curative-intent surgery for current diagnosis of Stage III, IVa, or IVb disease. Diagnostic biopsy of primary tumor and/or nodal sites is permitted.
• Diagnostic simple tonsillectomy is permitted, provided patient has RECIST-measurable nodal disease.
• Patients with a second HNSCC primary tumor are eligible for this study, provided more than 2 years have elapsed since the first diagnosis of HNSCC, the original tumor was managed with surgery only (no adjuvant chemotherapy or radiotherapy), and has not recurred.
• Patients with simultaneous primaries or bilateral tumors are excluded, with the exception of patients with bilateral tonsil cancers or patients with T1-2, N0, M0 differentiated thyroid carcinoma (resected or management deferred), who are eligible.
• No prior systemic (chemotherapy or biologic/molecular targeted therapy) or radiation treatment for head and neck cancer.
• Patients may have received chemotherapy or radiation for a previous, curatively treated non-HNSCC malignancy, provided at least 2 years have elapsed.
• Patients must be untreated with radiation above the clavicles.
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
• Age ≥ 18
• Patients must have measurable disease according to RECIST 1.1
• Patients must demonstrate adequate organ function as defined.
• Sexually active patients must agree to use adequate contraceptive measures, while on study and for 30 days after the last dose of study drug.

Exclusion Criteria

• Nasopharyngeal primary site
• Current participation in or previous participation in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of study treatment.
• History of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the investigational agent.
• Distant metastatic disease including CNS or leptomeningeal metastases is not allowed.
• History of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• Received prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (i.e. ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
• History of second malignancy within 2 years prior to Study Day 1 (except for excised and cured non-melanoma skin cancer, carcinoma in situ of breast or cervix, superficial bladder cance