Novel applications for immune checkpoint blockers in head and neck cancer

Durvalumab has shown activity in squamous cell carcinoma of the head and neck. Locally advanced resectable cancers of this type represent a challenge, as the majority of these patients still die from this disease in spite of surgery, radio- and chemotherapy. Checkpoint inhibitors have proven to prolong life in recurrent/metastatic SCCHN, and several molecules are currently tested in clinical trials in this indication, including PD-1, PD-L1, and CTLA-4 antibodies, either as single agent or in combination. These compounds might represent a valuable treatment for SCCHN patients in the adjuvant setting, given the favorable toxicity profile. Combination of durvalumab (PD-L1 inhibition) and tremelimumab (CTLA-4 inhibition) is currently tested in recurrent/metastatic head and neck cancer, and compared to durvalumab as single agent, and to standard of care chemotherapy.

In this study both options, i.e. durvalumab as a single agent or durvalumab in combination with tremelimumab, will be tested. Newly diagnosed patients with SCCHN of the oral cavity, will be treated with a single dose of durvalumab with or without tremelimumab two weeks before scheduled surgery. When patients are first diagnosed with a resectable oral SCC, a biopsy is taken to confirm the diagnosis, and surgery is planned. This standard practice thus involves sequential tissue harvesting, both at the time of biopsy as well as the final resection specimen, making it possible to observe hallmarks of immune response when patients are treated once with durvalumab with or without tremelimumab after confirmation of the diagnosis on biopsy, but before surgery.