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)
Condition: Squamous Cell Carcinoma of the Head and Neck
MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck
Intervention: Avelumab; Chemoradiation
Intervention description: Avelumab + SOC Chemoradiation; Cisplatin + Radiation Therapy
Intervention MeSH terms: Avelumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 697.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a phase 3 randomized, placebo controlled study to evaluate the safety and anti-tumor
      activity of Avelumab in combination with standard of care chemoradiation (SoC CRT) versus SoC
      CRT alone in front-line treatment of patients with locally advanced head and neck cancer.
    

Eligibility criteria:

        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).