A Phase I Study of PLX8394 Plus Ritonavir in Children with Recurrent or Progressive BRAF Activated Gliomas

Principal Institutions: Children’s Hospital of Los Angeles in partnership with the Pediatric Brain Tumor Consortium (PBTC) – This trial launches the first combinatorial drug agent trial for children with BRAF mutations. The majority of LGG have abnormal signaling through the mitogen-activated protein kinase (MAPK) pathway, usually due to activation of BRAF. The most common activating BRAF alteration in LGG is a tandem duplication that results in BRAF-KIAA1549 fusion, which is seen in 70-84% of pilocytic astrocytomas, the most common  subtype of pediatric LGG. The BRAFV600e point mutation is another activating alteration seen in 10% of pilocytic astrocytomas and up to 66% of pleomorphic xanthroastrocytomas.  LGG with BRAF activation have shown…