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

TPS2084 Background: 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 naïve recurrent WHO grade III or IV gliomas (maximum diameter of enhancing brain lesion ≤ 4 cm) are eligible. An interval of at least 6 months after the end of prior radiation therapy is required unless there is a new recurrence outside of the previous radiotherapy treatment field. Eligible patients will be treated with HFSRT to the recurrent tumor (30 Gy delivered in 5 fractions). Nivolumab will be started 5 days after HFSRT. It will be administered intravenously every 2 weeks (at 240 mg flat dose) for 4 months. After 4 months, nivolumab will be administered every 4 weeks at 480 mg flat dose. The primary study objectives are to determine safety and tolerability of nivolumab administered in combination with HFSRT to recurrent high grade gliomas. Secondary endpoints include determination of the preliminary antitumor activity (response rate, 6-months survival and 9-months survival rates), and exploring tissue and imaging biomarkers. Study Progress: At deadline for abstract submission, 5 patients have been treated on this study. Clinical trial information: NCT02829931.