Nivolumab combined with hypofractionated stereotactic irradiation (HFSRT) for patients with recurrent high grade gliomas: A phase I trial (NCT02829931).

TPS2084Background: Nivolumab is an IgG4 monoclonal antibody that targets the PD-1 immune checkpoint pathway and prevents binding of PD-1 with PD-L1 and PD-L2. Expression of PD-1 and PD-L1 is found in the microenvironment of high grade gliomas and correlates with worse outcome providing a rationale for investigating nivolumab in this group of patients (pts) with very limited treatment options. Nivolumab monotherapy is well tolerated in recurrent glioblastoma pts. Preclinical studies have demonstrated that radiotherapy synergizes with anti PD-1/PD-L1 blockade and produces tumor regression and long-term survival in orthotopic murine models of glioma. This report describes an ongoing phase I trial of nivolumab in combination with HFSRT in pts with recurrent WHO grade III or IV gliomas. Methods: This phase I study includes a safety cohort of 6 pts followed by dose expansion cohort of 20 pts (NCT02829931). Pts with bevacizumab naive recurrent WHO grade III or IV gliomas (maximum diameter of enhancing brain lesi...