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)

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).