Randomized trial evaluating the addition of nivolumab to cisplatin-radiotherapy combination for treatment of cancers of the head and neck

Prior treatment

• Incomplete macroscopic resection (R2), as stated in the surgical report
• 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
• Any prior treatment for the current head and neck cancer other than primary surgery. 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
• Clinically significant (i.e., active) cardiovascular disease: · Cerebral vascular accident/stroke (< 6 months prior to enrollment) or · Myocardial infarction (< 6 months prior to enrollment) or · unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II) or · Serious cardiac arrhythmia requiring medication

Other illness

• Nasopharyngeal, paranasal sinuses, nasal cavity tumours or thyroid cancers
• Active central nervous system disease
• Interstitial lung disease
• Active infection
• Metastatic disease
• Known active viral infection (Human Immunodeficiency Virus (HIV), Hepatitis B/C) or known history of positive test for HIV, active autoimmune disease and/or active immunodeficiency or ongoing immunosuppressive therapy
• 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)

Lab values

• Severe acute or chronic medical conditions including colitis, pneumonitis, pulmonary fibrosis, laboratory abnormalities or other 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

Other

• Squamous cell carcinoma involving cervical neck nodes with unknown primary site
• 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 5 months after the last dose of nivolumab
• Male patients who are unwilling or unable to use contraception methods for the duration of the study and for at least 6 months after the last dose of cisplatin.

• Age > 18 and < 75 years
• Squamous cell carcinoma of the head and neck treated by primary surgery
• Histopathological classification: pStage III or IV. However, Oropharyngeal Cancer pStage II p16 positive with pT3N1 or pT4N1 and tobacco consumption ≥20 packs/year are eligible. (American Joint Committee on Cancer 8th edition)
• Subject must have complete macroscopic resection.
• Subject must be free of disease
• Recovery from the surgical procedure allowing for cisplatin-Radiotherapy
• Radiotherapy planned to start within 4 to 9 weeks after surgery. However, a maximum of 1 additional week could be considered in case of delay due to healing or logistical problem
• Patient/tumor carrying a high risk of relapse with one or more following criteria: · Extra-capsular extension (ECE) · Multiple peri-neural invasion · Multiple nodal extension without ECE (≥ 4 nodes) · Positive margins (R1 or close margin ≤ 1 mm) R1 is microscopic residual disease and close margin is R0 with a minimum margin ≤ 1 mm in any direction.
• Adequate tumor specimen from archived or resected tissue available for PD-L1, TILs and immune landscape and other biomarker evaluation
• Performance Status (PS) ECOG 0-1
• Written informed consent
• Recording of alcohol consumption and smoking history
• Histologically proven squamous cell carcinoma of the head and neck from one or more of the following primary sites: oral cavity, oropharynx, hypopharynx or larynx