TRLS-11. A PHASE 1 STUDY OF SAVOLITINIB IN RECURRENT, PROGRESSIVE, OR REFRACTORY MEDULLOBLASTOMA, HIGH-GRADE GLIOMA, DIFFUSE INTRINSIC PONTINE GLIOMA, AND CENTRAL NERVOUS SYSTEM (CNS) TUMORS HARBORING MET ABERRATIONS: A PEDIATRIC BRAIN TUMOR CONSORTIUM TRIAL

Abstract Aberrant mesenchymal epithelial transition receptor (MET) activation leads to neoplasia, promotes invasive tumor growth, angiogenesis, and metastasis. Deregulation of MET signaling pathway is frequently observed in pediatric CNS tumors making inhibition a potential therapeutic target this patient population. A phase 1 first-in-children trial the inhibitor savolitinib was performed children with recurrent, progressive or refractory medulloblastoma, high-grade glioma (HGG), diffuse intrinsic pontine (DIPG), other harboring aberrations. The study sought determine maximum tolerated dose (MTD) recommended 2 (RP2D) using Rolling-6 design given orally once daily continuously, describe its toxicity profile pharmacokinetics (PK). Once MTD established, PK expansion cohort opened enrollment. This will be followed by an efficacy for patients whose harbor activating genomic Tumor tissue blood were collected as part correlative studies consenting subjects. Twenty-eight enrolled (median age:12 years; range: 6-21); one deemed ineligible, 22 evaluable finding. MTD/RP2D 350 mg/m2 (dose level 3). Two limiting toxicities reported subjects consisted grade 3 fatigue ALT elevation. most common 3/4 were: neutropenia (7.7%) lymphopenia (7.7%). One partial response recurrent HGG on (150 mg/m2). As recent data freeze, had completed 35 treatment courses. Sustained stable disease experienced DIPG who remained median 9 cycles (range: 4-24). Correlative are ongoing presented. Savolitinib well-tolerated mg/m2. Antitumor activity observed.