Tolerance and Efficacy of Pembrolizumab or Cetuximab Combined With RT in Patients With Locally Advanced HNSCC

Inclusion Criteria: 1. Written informed consent 2. Age ≥18 ≤ 80 years. 3. Performance Status ECOG 0-1 4. Histologically confirmed diagnosis of previously untreated locally advanced HNSCC (Stage III, IVa and IVb according to the American Joint Committee on Cancer Staging System) of one or more of the following sites: oral cavity, oropharynx, hypopharynx and larynx 5. Availability of pre-treatment tumour tissue (for biomarker analysis, PD -L1, TILs and immune-monitoring) 6. p16 expression from tumor sample (immunohistochemistry) 7. Recording of the smoking history 8. No viral infection (HIV, Hepatitis B/C) 9. No autoimmune disease 10. No immunodeficiency or immunosuppressive therapy 11. No active CNS disease 12. No interstitial lung disease 13. No active infection 14. Women of child-bearing potential: negative serum pregnancy test at screening and use of appropriate contraception methods from study entry 15. Patients not proposed cisplatin-based chemotherapy because of age, general condition, if medically unfit or patient refusal. 16. Adequate organ laboratory values 17. Health insurance coverage Exclusion Criteria: 1. Nasopharyngeal, paranasal sinuses, nasal cavity tumours or thyroid cancers; 2. Squamous cell cancer involving cervical neck nodes with unknown primary site; 3. Metastatic disease; 4. 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, prior neoadjuvant therapy, prior surgical resection, or use of any investigational agent; 5. Weight loss of \>10% during the last 3 weeks prior the screening visit; 6. Concurrent treatment with any other systemic anti-cancer therapy that is not specified in the protocol; 7. Concomitant treatment with any drug on the prohibited medication list such as live vaccines (for details, see the protocol); 8. History of another malignancy within the last 3 years (exception of in situ carcinoma and skin carcinomas); 9. If female, pregnant or lactating; 10. 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. 11. Known hypersensitivity reaction to study medication; 12. 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.