REPORT

PI JA Kyte & Å Bratland

The phase I/II study REPORT investigate PD-1 blockade combined with radiotherapy (RT) in patients with recurrent head and neck cancer squamous cell carcinoma (HNSCC). Radiation therapy induces massive cell death and release of tumor antigens, accompanied by danger signals known to trigger the immune system. There is generally a high expression of PDL-1 in HNSCC, and the expression is enhanced by RT. HNSCC is among the most radiation sensitive cancers, and HNSCC with T-cell infiltration is more sensitive to radiotherapy. Nivolumab has been approved against HNSCC and has a favourable safety profile. We have allied with H&N surgeons so that tumor biopsies will be available for translational research. In REPORT, we integrate nivolumab into current 1^st line therapy for recurrent HNSCC, allowing the combination to be tested in patients that have not received multiple lines of therapy and ensuring that findings are relevant to clinical practice.

Study design and objectives

REPORT is a singel-arm, open label phase I/II study evaluating the safety and efficacy of nivolumab when combined with re-irradiation in 20 patients with recurrent HNSCC.

Primary objectives:

1. Safety and tolerability of nivolumab administered concomitant with re-irradiation in HNSCC
2. To determine a safe dose of nivolumab when administered concomitant with re-irradiation

Secondary objectives:

1. To evaluate progression-free survival after 12 months
2. To evaluate tumor response (ORR, DOR, DRR) and overall survival
3. To investigate the immune response induced by the study therapy
4. To investigate biomarkers for clinical response, toxicity and immune response
5. To investigate tumor evolution and changes in microenvironment during study therapy