Immunotherapy is emerging as new treatment for a variety of malignancies, including pediatric DIPG and HGG. Immunotherapy uses one’s own anti-tumor immune capabilities and has gained recent attention as a complementary approach to traditional therapies like radiation. One protein called programmed cell death-1 (PD-1) can be made by tumor cells as a mechanism to shut off the body's immune response to tumor. PD-1 works by binding to the body’s T-cells and giving them a message to turn off. Preclinical studies looking at blocking PD-1 in brain tumors has shown that PD-1 blockade increases survival and leads to long-term responses in mice. Additionally, PD-1 blockade combined with radiation appears to heighten the local immune response and increase the number of active T-cells surrounding the tumor. Hypofractionated radiation (higher doses given over fewer days) may heighten the effects by further increasing local inflammation and leading to greater numbers and activation of tumor-associated immune cells. In DIPG, hypofractionated radiation may also improve quality of life by shortening radiation periods and decreasing time spent in the hospital. These findings have led to interest that PD-1 blockade combined with radiation, either standard or hypofractionated, could be a new way to treat brain tumors.
REGN2810 is a novel, human antibody directed at the PD-1 receptor that prevents PD-1 activation by blocking interaction with its signal proteins, PD-L1 and –L2. PNOC013 combines REGN2810 with radiation as a new treatment strategy for children and young adults with newly diagnosed DIPG, newly diagnosed, and recurrent HGG, as well as children with recurrent solid tumors. The study is a multi-arm clinical trial that will randomize patients with DIPG or HGG to different radiation schedules (standard or hypofractionated) to be given in combination with REGN2810. REGN2810 will then continue as monotherapy once radiation is complete. PNOC013 will evaluate the safety of this treatment approach, as well as look at the impact on survival and disease responses in patients treated on this study. Funding is provided by Regeneron Pharmaceuticals.