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.
- Histological diagnosis of squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx
- Available tumor samples for submission or willing to undergo further tumor biopsies
- HPV negative disease, Stage III, IVa, IVb or Non oropharyngeal HPV positive disease, Stage III, IVa, IVb or HPV positive oropharyngeal disease T4, N2c, or N3
- 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.
- Diagnosis of any other malignancy within 5 years prior to randomization, except for 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 in situ carcinoma of the breast that has completed curative treatment, adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix or bladder.
- Active autoimmune disease
Eligible subjects will be assigned by chance (like the flip of a coin) to receive either avelumab or matching placebo, along with SoC chemoradiotherapy. You will have a 50% (1 in 2) chance of receiving either avelumab or matching placebo. Regardless of assignment subjects will receive the SoC chemoradiotherapy of cisplatin and radiotherapy.
Study participation lasts approximately 15 months, with a maintenance phase of 12 months.
After completing the treatment, subjects will be seen regularly approximately every 4 months by the study doctor, which is a part of regular follow-up care for this type of cancer.
Research CT scans of the head and neck are to be done every 16 weeks for 48 months (208 weeks), and every 24 weeks thereafter until disease progression. This would be 13 CT scans of the head and neck during the 48 months and about 2 CT scans of the head and neck per year until disease progression. Another CT scan of the head and neck would be done at the End of Treatment/Withdrawal Visit.
The total volume of blood that will be collected during the screening visit is approximately 4 teaspoons (20 milliliters). The total volume of blood that will be collected for study-related analysis will be approximately 128 teaspoons (423 milliliters). This is an estimated amount based on subjects remaining on study treatment which depends on the subject’s ability to safely tolerate the treatment, on how the cancer responds to the treatment, and on the subject’s and/or the study doctor’s decision to continue receiving treatment.
Besides blood work and imaging, subjects will undergo ECG testing, physical examinations and will be asked to complete questionnaires to record symptoms and side effects.