Study To Compare Avelumab In Combination With Standard of Care Chemoradiotherapy (SoC CRT) Versus SoC CRT for Definitive Treatment In Patients With Locally Advanced Squamous Cell Carcinoma Of The Head And Neck (JAVELIN HEAD AND NECK 100)

• Drug: Avelumab
  
  Avelumab + SOC Chemoradiation
• Other: Chemoradiation
  
  Cisplatin + Radiation Therapy

• Experimental: Avelumab + SOC Chemoradiation Therapy
  
  • Avelumab 10 mg/kg IV: Day 1 of the Lead-in Phase; Days 8, 25, and 39 of the CRT Phase; and Q2W for 12 months during the Maintenance Phase
  • Cisplatin 100 mg/m2 IV: Days 1, 22, and 43 of the CRT Phase
  • Intensity Modulated Radiation Therapy (IMRT) 70 Gy/35 fractions/7 weeks; 1 fraction per day, 5 fractions/week for 7 weeks during the CRT Phase
  Intervention: Drug: Avelumab
• Placebo Comparator: Placebo + SOC CRT
  
  • Placebo IV matching avelumab: Days 1 of the Lead-in Phase; Days 8, 25, and 39 of the CRT Phase; Q2W for 12 months during the Maintenance Phase
  • Cisplatin 100 mg/m2 IV: Days 1, 22, and 43 of the CRT Phase
  • IMRT 70 Gy/35 fractions/7 weeks; 1 fraction per day, 5 fractions/week for 7 weeks during the CRT Phase
  Intervention: Other: Chemoradiation

INCLUSION CRITERIA

• Histological diagnosis of squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx
• HPV negative disease, Stage III, IVa, IVb; non-oropharyngeal HPV positive disease Stage III, IVa, IVb, HPV positive oropharyngeal disease T4 or N2c or N3
• No prior therapy for advanced stage SCCHN; eligible for definitive CRT with curative intent.
• Available tumor samples for submission or willing to undergo further tumor biopsies:
• Age ?18 years (?19 in Korea;20 years in Japan and Taiwan).
• ECOG Performance Status 0 or 1
• Adequate bone marrow function
• Adequate renal function
• Adequate liver function
• Pregnancy test (for patients of childbearing potential) negative at screening

EXCLUSION CRITERIA

• Prior immunotherapy with an anti PD 1, anti PD L1, anti PD L2, anti CD137, or anti CTLA 4 antibody (including ipilimumab), or any other antibody or drug specifically targeting T cell co stimulation or immune checkpoint pathways.
• Major surgery 4 weeks prior to randomization.
• Prior malignancy requiring tumor-directed therapy within the last 2 years prior to enrollment, or concurrent malignancy associated with clinical instability. Exceptions for disease within the 2 years are superficial esophageal cancer (TIS or T1a) fully resected by endoscopy, prostate cancer (Gleason score 6) either curatively treated or deemed to not require treatment, ductal IS carcinoma of the breast that has completed curative treatment, adequately treated basal cell or squamous cell skin cancer.
• Active autoimmune disease
• Any of the following in the 6 months prior to randomization: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, or symptomatic pulmonary embolism.
• Active infection requiring systemic therapy.
• Use of immunosuppressive medication at time of randomization
• Prior organ transplantation including allogenic stem-cell transplantation.
• Diagnosis of prior immunodeficiency or known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness.
• Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
• Vaccination within 4 weeks prior to randomization.
• Current use of or anticipated need for treatment with other anti-cancer drugs.
• Pregnant female patients, breastfeeding female patients, and male patients able to father children 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 60 days after the last dose of avelumab/placebo (whichever is later).