Pdct-24. a Phase I Dose Escalation Trial of the Mek1/2 Inhibitor Mek162 (binimetinib) in Children With Low-grade Gliomas and Other Ras-raf Pathway-activated Tumors: Initial Report
Year: 2017
Type: conference-abstract
Abstract: Ras/Raf/MEK/ERK pathway activation is the primary driver of most pediatric low-grade gliomas (LGG), the most common brain tumor in children. Unresectable LGG are associated with multiple recurrences and significant long-term morbidity. MEK162 is an orally bioavailable inhibitor of MEK1/2 and potently inhibits the Ras/Raf/MEK/ERK pathway. The primary objective of this first-in-children multi-institutional open-label phase I dose-escalation trial was to determine the maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) of MEK162 oral suspension administered on a continuous twice daily dosing schedule in children with recurrent, refractory or progressive tumors. Secondary objectives included characterization of safety and tolerability, assessment of pharmacokinetic profile, and preliminary assessment of anti-tumor activity. Children aged 1-18 years with recurrent, refractory or progressive LGG and other non-hematologic malignancies associated with activation of the Ras/Raf pathway were enrolled according to a 3 + 3 dose escalation design, with a starting dose of 16mg/m2 twice daily. Dose level (MTD and/or RP2D), toxicity, pharmacokinetic, and preliminary response data will be presented.
Source: Neuro-Oncology
Authors: Nathan Robison, Jasmine Pauly, Jemily Malvar, Mariella Filbin, Rebecca Loret de Mola, Kathleen Dorris, Anne Bendel, Daniel Bowers, Miriam Bornhorst, Karen Gauvain, Sarah Leary, Tobey MacDonald, Sharon Gardner, Alyssa Reddy, Patricia Diaz, Yi Juin Tan, Claire Sinai, Tom Davidson, Nicole Ullrich, Ashley Margol, Girish Dhall, Mark Borchert, Keith Ligon, Richard Sposto, Mark Kieran
Institutions: University of Southern California, Children's Hospital of Los Angeles, Broad Institute, Oregon Health & Science University, Children's Hospital Colorado, Children's Minnesota, The University of Texas Southwestern Medical Center, Children's National, Washington University in St. Louis, Fred Hutch Cancer Center, Emory University, Winship Cancer Institute, New York University, University of Alabama at Birmingham, Dana-Farber Cancer Institute, University of California, Los Angeles, Boston Children's Hospital
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2767262472