MAPK Inhibition Combined With Anti-PD1 Therapy for BRAF-altered Pediatric Gliomas

This is a pilot study evaluating the toxicity and early efficacy of dabrafenib and/or trametinib combined with nivolumab for the treatment of BRAF-altered or NF altered gliomas. While dabrafenib, trametinib, and nivolumab have been used for pediatric gliomas in previous studies, this will be the first pediatric study evaluating the combination of these agents. This study will evaluate the use of dabrafenib, trametinib, and nivolumab in patients in recurrent, refractory, or progressive low grade gliomas harboring BRAFV600 mutations who have previously been treated with MAPK inhibition alone. The same combination will be explored in newly diagnosed or recurrent BRAFV600 mutant high grade glioma. This study will also evaluate the use of trametinib and nivolumab in patients with recurrent, refractory, or progressive low grade gliomas harboring a KIAA1549 BRAF fusion who have previously been treated with MAPK inhibition alone. The same combination will be explored in NF altered transforming or high grade glioma or high grade glioma harboring a KIAA1549 BRAF fusion. The objective of this study is to understand the safety and tolerability of the combination of dabrafenib, trametinib, and/or nivolumab in pediatrics. Secondarily, this study will evaluate for an early efficacy signal of the combination therapy and compare to historical treatment response to MAPK inhibition alone.