TRLS-10. ROVER: A PHASE 1/2 STUDY OF AVAPRITINIB IN PEDIATRIC PATIENTS WITH SOLID TUMORS DEPENDENT ON KIT OR PDGFRA SIGNALING

Abstract Pediatric patients with advanced relapsed/refractory (R/R) solid (including central nervous system [CNS]) tumors have poor prognoses. KIT alterations are common in germ cell and high-grade glioma (HGG); platelet-derived growth factor receptor alpha (PDGFRA) sarcoma HGG. Diffuse midline gliomas H3K27-altered (DMG-H3K27-altered) depend on PDGFRA signaling for tumor growth. However, no KIT-/PDGFRA-targeted therapies currently approved pediatric R/R or CNS tumors, including DMG-H3K27-altered. The selective inhibitor avapritinib has demonstrated potent activity against activation-loop (exon 17) juxtamembrane 11) mutants (IC50<2 nM), (D842V) (IC50=0.24 nM). Cellular IC50 of wild-type was 95 nM. penetration preclinical models (steady-state brain-to-plasma ratios from 0.74–1.00) indicates potential antitumor activity. Avapritinib is to treat adults systemic mastocytosis the USA, Europe after ≥1 prior therapy. also treatment unresectable/metastatic gastrointestinal stromal harboring exon 18 mutations D842V) D842V Europe. ROVER, a 2-part phase 1/2, multicenter, open-label study (NCT04773782), investigating aged 2 <18 years dependent signaling, Objectives include safety, efficacy, pharmacokinetics. Part 1 will enroll ≥12 patients; primary endpoint determine recommended dose (RP2D). ≥25 at RP2D; objective response rate per RECIST v1.1 Response Assessment Neuro-Oncology tumors. once daily be administered continuous 28-day cycles. Study enrollment planned 26 sites 9 countries, North America, Europe, Asia/Pacific.