Durvalumab With Radiotherapy for Adjuvant Treatment of Intermediate Risk SCCHN

Inclusion Criteria: * Written informed consent obtained to participate in the study and HIPAA authorization for release of personal health information. Consent for the use of any residual material from biopsy (archival tissue) and serial blood draws will be required for enrollment. * Age ≥ 18 years of age on day of signing informed consent * ECOG Performance Status of 0 or 1 (See Appendix 12.4: ECOG Performance Status) * Histologically confirmed squamous cell carcinoma of the head and neck, including the following subtypes: oral cavity, oropharynx, hypopharynx, larynx * Must have undergone gross total resection of the primary tumor with curative intent within the past 8 weeks with surgical pathology demonstrating ≥ 1 of the following criteria for "intermediate" risk of recurrence: * perineural invasion * lymphovascular invasion * single lymph node \> 3 cm or at least 2 nodes without evidence of extracapsular extension * close margins defined as \< 5 mm but not frankly positive (in the case of ambiguous, controversial, or superseded margins, final clinical assessment regarding margin status will prevail) * pathologically confirmed T3 or T4 primary tumor * No prior therapy to primary tumor prior to surgical resection (no induction therapy or recurrent disease). * Demonstrated adequate organ function as defined in the protocol * Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days prior to treatment. NOTE: Females are considered of child bearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months. Documentation of postmenopausal status must be provided. * WOCBP must be willing to abstain from heterosexual activity or to use at least 1 highly effective method of contraception from the time of informed consent until 90 days after durvalumab monotherapy treatment is discontinued (whichever is longer). See section 5.6 of the protocol for additional details on contraception requirements for WOCBP and male participants in this trial. * Male patients with female partners must have had a prior vasectomy or agree to use an adequate method of contraception (i.e., double barrier method: condom plus spermicidal agent) starting with the first dose of study therapy through 90 days after durvalumab monotherapy is discontinued. * Subjects must be willing and able to comply with study procedures based on the judgment of the investigator or protocol designee. Exclusion Criteria: Subjects meeting any of the following exclusion criteria will not be able to participate in this study: * Is currently participating in or has participated in a study of an investigational agent or an investigational device within 4 weeks of the first dose of treatment. * Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study. * Has evidence of metastatic disease at time of diagnosis * Is receiving concurrent chemotherapy, investigational drug, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable. * Treatment with any investigational drug within 28 days or 5 half-lives of Day 1 of treatment on this study, whichever is shortest. * Has not received any antibiotics \<7 days prior to 1st dose of durvalumab. If the patient receives either IV antibiotics or \>5 day treatment course (oral or IV), then the 1st durvalumab dose should not be given until 14 days of last antibiotic dose. During eligibility screening, subjects who receive any antibiotics within 30 days prior to the proposed initial infusion of durvalumab should be flagged and reviewed by the site's Principle Investigator to determine if the subject is a good candidate to receive durvalumab. * Known allergy or hypersensitivity to durvalumab or any of the study drug excipients. * Prior randomization or treatment in a previous durvalumab clinical study regardless of treatment arm assignment. * Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion: * Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection) * Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent * Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication) * Has received systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. * Active infection requiring systemic therapy including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). * Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \[anti-HBc\] and absence of HBsAg) are eligible. * Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA. * Has a known contraindication to radiation therapy, including inherited syndromes associated with hypersensitivity to ionizing radiation such as Ataxia-Telangiectasia and Nijmegen Breakage Syndrome * Has a history of uncontrolled liver disease (including but not limited to cirrhosis). * Subjects with baseline weight ≤ 40kg (88 lbs). * Female patients who are pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study) or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab monotherapy. * History of another primary malignancy except for. * Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of IP and of low potential risk for recurrence * Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease * Adequately treated carcinoma in situ without evidence of disease * History of leptomeningeal carcinomatosis. * Has an active autoimmune disease (or inflammatory disorders) requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]). The following are exceptions to this criterion: * Subjects with vitiligo or alopecia or resolved childhood asthma/atopy * Subjects who require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. * Subjects with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement or with Sjorgen's syndrome will not be excluded from the study * Any chronic skin condition that does not require systemic therapy * Subjects without active HNSCC disease in the last 5 years may be included but only after consultation with the study physician * Subjects with celiac disease controlled by diet alone * Has a history of non-infectious pneumonitis that required steroids or evidence of interstitial lung disease or current active, non-infectious pneumonitis. * Major surgical procedure (as defined by the Investigator) within 21 days prior to the first dose of investigational product (IP). Note: Local surgery of isolated lesions for palliative intent is acceptable. * Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent. * Receipt of live attenuated vaccine within 30 days prior to the first dose of study drug. Note: Patients, if enrolled, should not receive live vaccine whilst receiving study treatment and up to 30 days after the last dose of study treatment.