Critères d'inclusion : - Age > 18 and < 75 years
- Performance Status (PS) ECOG 0-1 (Appendix 2)
- Written informed consent
- Recording of alcohol consumption and smoking history
- Stage III, stage IV (American Joint Committee on Cancer 7th edition) 38
- Oral cavity, oropharynx, hypopharynx or larynx
- Squamous cell carcinoma treated by primary surgery
- Recovery from the surgical procedure allowing for cisplatin-RT
- RT planned within 4 to 8 weeks after surgery
- Patient/tumor carrying a high risk of relapse with:
-> extra-capsular extension (ECE),
-> and/or positive margins (R1 or close margin ≤ 1 mm)
- Availability of surgical tumour specimen (PD-L1, TILs and immune landscape ...)
- For oropharyngeal tumor, known p16 status (by IHC)
- Determination of patient ability to receive cisplatin 100 mg/m2 for 3 cycles:
-> Calculated creatinine clearance ≥ 60 mL/min as determined by CKD-EPI method (Cockcroft and Gault or MDRD method allowed)
-> Absolute neutrophil count ≥1 500/μL, platelets ≥100 000/μL, haemoglobin ≥ 10 g/dL, aspartate (AST) and alanine transaminase (ALT) less than 2 times the upper limit of the normal range (ULN), total bilirubin ≤ 1.5 mg/dL, serum albumin >35 g/L
-> Peripheral neuropathy ≤ grade 1
-> Sensorineural hearing loss (confirmed by audiogram)
-> Cardiac function compatible with hyperhydration
-> No administration of prophylactic phenytoin
-> For patients aged 71-74 years, PS must be 0 and fit according to geriatric evaluation
Critères de non-inclusion : - Nasopharyngeal, paranasal sinuses, nasal cavity tumours or thyroid cancers
- Squamous cell carcinoma involving cervical neck nodes with unknown primary site
- Metastatic disease (stage IVc)
- Active viral infection (HIV, Hepatitis B/C) or known history of positive test for HIV
- Active autoimmune disease
- Active immunodeficiency or ongoing immunosuppressive therapy
- Active CNS disease
- Interstitial lung disease
- Active infection
- Any prior or current treatment for invasive head and neck cancer. This will include but is not limited to: prior tyrosine kinase inhibitors, any monoclonal antibody, induction chemotherapy, prior RT, or use of any investigational agent
- Concurrent treatment with any other systemic anti-cancer therapy that is not specified in the protocol
- Concomitant treatment with any drug on the prohibited medication list such as live vaccines. Live vaccines administered more than 30 days before study entry are permitted
- History of other malignancy within the last 3 years (exception of in situ carcinoma, thyroid papillary carcinoma, skin carcinomas, localized prostate carcinoma Gleason 6 and in situ breast carcinoma)
- Pregnant, breastfeeding patients, and female patients of childbearing potential who are unwilling or unable to use 2 highly effective methods of contraception as outlined in the protocol for the duration of the study and for at least 6 months after the last dose of cisplatin and 7 months after the last dose of nivolumab
- Significant disease which, in the judgment of the investigator, as a result of the medical interview, physical examinations, or screening investigations would make the patient inappropriate for entry into the trial
- Known hypersensitivity reaction to study drugs
- Any social, personal, medical and/or psychologic factor(s) that could interfere with the observance of the patient to the protocol and/or the follow-up and/or the signature of the informed consent
- Prior organ transplantation including allogenic stem-cell transplantation
- 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 Classification Class II), or serious cardiac arrhythmia requiring medication
- Persisting toxicity related to prior therapy or pre-existing conditions (NCI CTCAE v. 4.03 Grade > 1) 39
- Other severe acute or chronic medical conditions including colitis, pneumonitis, pulmonary fibrosis or psychiatric conditions including active suicidal ideation; or laboratory abnormalities that may increase the risk associated with study participation and, in the judgment of the investigator, would make the patient inappropriate for entry into this study
- Concurrent enrolment in another clinical trial using an investigational anti-cancer treatment within 28 days prior to the first dose of study treatment