Study on the Efficacy of Treatment by Radiotherapy and Pembrolizumab in Newly Diagnosed Metastatic Head & Neck Cancers

Prior treatment

• Prior radiotherapy in the head and neck region
• Any prior or current non-surgical treatment for invasive head and neck cancer. (except for pembrolizumab +/- chemotherapy for the current cancer for a maximum of 6 cycles). This will include but is not limited to: prior tyrosine kinase inhibitors, any monoclonal antibody, chemotherapy, anti-PD-1/PD-L1 and CTLA-4, prior radiotherapy (RT), or use of any investigational agent. Loco-regional recurrent or second primary head and neck cancer after prior surgical treatment alone in the head and neck region could be eligible.
• Patient having received live attenuated vaccine within 28 days prior to enrolment
• Active immunodeficiency or ongoing immunosuppressive therapy
• Prior organ transplantation including allogenic stem-cell transplantation
• Patient who have taken any investigational medicinal product or have used an investigational device within 30 days prior to study inclusion

Other illness

• History of another malignancy within 2 years prior to study inclusion, with the exception of completely resected basal or squamous cell skin cancer, or successfully treated in-situ carcinoma
• Known Acquired Immune Deficiency Syndrome (AIDS)
• Known currently active infection including hepatitis B or hepatitis C
• Active autoimmune disease except vitiligo, type-1 diabetes, hypothyroid stabilized with hormonal substitution, or psoriasis which do not require systemic treatment
• Active symptomatic interstitial lung disease
• 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

Lab values

• 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

Other

• Symptomatic central nervous system (CNS) metastases and / or carcinomatous meningitis
• Pregnant or breast feeding woman
• Any social, personal, medical, geographic 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
• Person deprived of their liberty or under protective custody or guardianship

• Patient must have signed a written informed consent form prior to any study specific procedures. When the patient is physically unable to give their written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in writing the patient's consent.
• Histologically confirmed squamous cell carcinoma of head and neck (oral cavity, oropharynx, hypopharynx, and larynx) including unknown primary head and neck lymph nodes with distant metastases at presentation (T1-4 N0-3 M1). Histological confirmation is required in case of a single metastatic lesion.
• Eligible for treatment by pembrolizumab according to the European Marketing Authorization
• Patient ≥18 years old
• Performance status: 0-1 (WHO)
• Combined Positive Score (CPS) ≥1 for primary tumor (as determined per local practice)
• Subjects must have at least one measurable lesion as per RECIST v1.1 to assess efficacy
• Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 14 days prior to randomization:
  • If randomization is done before treatment start: i. Absolute neutrophil count ≥1.5 × 10⁹/L ii. Platelet ≥100 × 10⁹/L iii. Hemoglobin ≥90 g/L iv. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT), ≤3 × upper limit of normal (ULN), (unless documented liver metastases where ≤5 x ULN is permitted) v. Bilirubin ≤1.5 × ULN. vi. Serum albumin ≥25 g/L vii. Creatinine clearance ≥30 mL/min (calculated per institutional guidelines or by Cockcroft-Gault or Modification of Diet in Renal Disease (MDRD) formula) viii. Corrected serum calcium of ≤11.5 mg/dL or ≤2.6 mmol/L. b. If randomization if done after treatment start i. Absolute neutrophil count ≥1.0 × 10⁹/L ii. Platelet ≥75 × 10⁹/L iii. Hemoglobin ≥85 g/L
• Patient must agree to use adequate contraception methods for the duration of the study treatment and up to 4 months after the last dose of pembrolizumab administration
• Patients must be affiliated to a Social Security System (or equivalent)
• No disease progression during systemic treatment if the randomization is done after the start of pembrolizumab for the current disease