P11.29.B UPDATE ON GBM AGILE: A GLOBAL, PHASE 2/3 ADAPTIVE PLATFORM TRIAL TO EVALUATE MULTIPLE REGIMENS IN NEWLY DIAGNOSED AND RECURRENT GLIOBLASTOMA
Authors: Weller M , Alexander B , Berry D , Blondin N , Buxton M , Cavenee W , Colman H , de Groot J , de la Fuente M , Ducray F , Ellingson B , Gordon G , Hyddmark E M V , Khasraw M , Lassman A , Lee E , Lim M , Mellinghoff I , Mikkelsen T , Perry J , Sulman E , Tanner K , Wen P , Wick A , Yung A , Cloughesy T 
Published: September 2023

Abstract

BACKGROUND
GBM AGILE (Glioblastoma Adaptive, Global, Innovative Learning Environment) is a biomarker based, multi-arm, international, seamless Phase 2/3 platform trial designed to rapidly identify experimental therapies that improve overall survival and confirm efficacious experimental therapies and associated biomarker signatures to support new drug approvals and registration. GBM AGILE is a collaboration between academic investigators, patient organizations and industry to support new drug applications for newly diagnosed (ND) and recurrent GBM.

METHODS
The primary objective of GBM AGILE is to identify therapies that effectively improve the overall survival in patients with ND or recurrent GBM. Bayesian response adaptive randomization is used within subtypes of the disease to assign participants to investigational arms based on their performance. New experimental therapies are added as information about promising new drugs is identified, while therapies are removed as they complete their evaluation. GBM AGILE has screened over 1400 patients and enrollment rates are 3 to 4 times greater than traditional GBM trials, with active sites averaging 0.75 to 1 patients/site/month. There are 41 active sites in the US, 4 active sites in Canada and 3 active sites in Europe with a total of 15 sites planned for Switzerland, France and Germany. Expansion to Australia is currently underway. GBM AGILE operates under a Master Protocol which allows multiple drugs from different pharmaceutical/biotech companies to be evaluated simultaneously and/or over time against a common control. Along with an adaptive trial design, shared control arm and operational processes to serve the goal of helping patients receive optimal care in a fast and efficient manner, GBM AGILE incorporates new design and operational elements to enhance efficiencies, including more recently dose finding and enhanced safety management components. The dose finding phase allows for an initial evaluation of the experimental study drug in combination with radiotherapy and temozolomide, and/or lomustine in a limited number of patients at a select number of study sites within the trial in order to ensure that there are no critical safety signals before expansion to a larger subset of patients for enhanced safety monitoring followed by broader inclusion of the combination at all global study sites. The investigational drugs that have employed the dose finding phase and enhanced safety monitoring process have tolerable safety profile with toxicities that are monitorable, reversible, and not related to the control arm treatments. Through the use of improved and flexible processes, GBM AGILE continues to serve as a global trial that supports the efficient and rapid incorporation and evaluation of new experimental therapies for patients with GBM. Clinical trial information: NCT03970447.