Maintenance Immune Check-point Inhibitor Following Post-operative Chemo-radiation in Subjects With HPV-negative HNSCC

Inclusion Criteria: * Patients with squamous cell carcinoma of the oral cavity (excluding lip), larynx, hypopharynx or p16-negative oropharynx (p16 determined locally) * Surgical treatment no more than 4 weeks prior randomization (which may include revisions, secondary flaps etc., VACs) with completed wound healing no later than 4 weeks after the initial procedure * At high risk of locoregional recurrence based on extranodal extension (ENE) and/or R1 resection margin \< 1 mm, as documented in the pathology report of surgery. * With postoperative pathology stage III or IV or stage II but with positive margins (based on AJCC 8th edition) * Availability of FFPE tumor tissue block from the resection specimen * Availability of operative and pathology report and preoperative diagnostic images for retrospective review * ECOG Performance status 0-1 * Age ≥ 18 years * Adequate bone marrow, liver and renal functions within 7 days from randomization * Audiogram must be within normal range * Chemoradiation planned to start within maximum of 2 weeks from randomization. Whenever indicated, dental extraction should be carried out at least 10 days before the start of CRT. * Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients within 72 hours prior to randomization. * Patients of childbearing / reproductive potential must agree to use highly effective methods of contraception based on the Clinical trials Facilitation Group (CFTG) guidance from randomization up to 90 days after the last dose of Durvalumab/placebo (Appendix I) or 6 months after the last CRT, whichever is longer. * Female subjects who are breast feeding should discontinue nursing prior to randomization to 90 days after the last dose of Durvalumab. * Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up. * Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with CRT or Durvalumab may be included only after consultation with the clinical research physician * Before patient randomization, written informed consent must be given according to ICH/GCP, and national/local regulations Exclusion Criteria: * Evidence of distant metastases before and after surgery * Any evidence of early locoregional recurrence after surgery * Any prior treatment with chemotherapy, radiotherapy or cetuximab * Any previous treatment with a PD1 or PD-L1 inhibitor, including Durvalumab, a CTLA-4 inhibitor including tremelimumab or other checkpoint inhibitors or other immunotherapy during the last 12 months * Any contraindication to cisplatin and radiotherapy * Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria. * Body weight \</=30 kg * Any concurrent chemotherapy, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable. * Current or prior use of immunosuppressive medication within 14 days prior to enrollment, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid, or steroids as premedication for hypersensitivity reactions (eg, CT scan premedication) * History of allogenic organ transplantation * Receipt of live attenuated vaccination within 30 days prior to enrollment Note: Patients, if enrolled, should not receive live vaccine whilst receiving Durvalumab and up to 30 days after the last dose of Durvalumab. * Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis, systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.). Following disorders are acceptable: * Vitiligo or alopecia * Hypothyroidism (e.g. following Hashimoto syndrome) stable on hormone replacement * Any chronic skin condition that does not require systemic therapy * Active disease in the last 5 years may be included but only after consultation with the treating physician * Celiac disease controlled by diet alone * Diverticulosis * Known allergy or hypersensitivity to cisplatin and Durvalumab or any of its excipients * Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension (defined as blood pressure above 160/90 mm Hg despite medication), unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, active peptic ulcer disease or gastritis, liver cirrhosis CHILD B+, C, active bleeding diatheses * History of active primary immunodeficiency * Active infection 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. * History of another primary malignancy with the exception of: * Malignancy treated with curative intent and with no known active disease ≥5 years before enrollment 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 symptomatic brain metastases and leptomeningeal carcinomatosis * Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study * Female subjects who are pregnant or male or female subjects of reproductive potential who are not willing to employ effective birth control from randomisation to 90 days after the last dose of Durvalumab * Any psychological, familial, sociological or geographical condition that could increase risk of incurring AEs or compromise the ability of the patient to give written informed consent, or hamper compliance with the study protocol and follow-up schedule; these conditions should be discussed with the patient before registration in the trial