GBM AGILE: A global, phase 2/3 adaptive platform trial to evaluate multiple regimens in newly diagnosed and recurrent glioblastoma.

TPS2074 Background: GBM AGILE, Glioblastoma Adaptive, Global, Innovative Learning Environment, is an international, multi-arm, seamless phase 2/3 response adaptive randomization platform trial designed to evaluate multiple therapies in newly diagnosed (ND) and recurrent glioblastoma (GBM) with the goal of identifying effective therapies matching them accurately to different patient subtypes in an accelerated manner. It is a collaboration between academic investigators, patient organizations and industry to support new drug applications for newly diagnosed and recurrent GBM. Methods: The primary objective of GBM AGILE is to identify therapies that effectively improve 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. Operating under a Master Protocol, GBM AGILE allows multiple drugs from different pharmaceutical companies to be evaluated simultaneously and/or over time against a common standard of care control. Based on performance, a drug may graduate and move to a rapid stage 2 (phase 3) within the trial, and the totality of the data can be used for a new drug application. An active pipeline is critical to the ongoing success of GBM AGILE. With the leadership of the trial’s Arm Selection Committee, uniform processes for including new drugs have been established to ensure a consistent review of drugs/drug combinations over the course of the trial. Factors considered include relevant pre-clinical data, preliminary evidence for antitumor activity. pharmacokinetic data to support proposed drug dosing and administration, and potential biomarkers helpful for the development of a drug. GBM AGILE provides an efficient mechanism to screen and develop robust information regarding the efficacy of proposed novel therapeutics and associated biomarkers for GBM and to quickly move therapies and biomarkers into clinic. GBM AGILE received IND approval from the FDA in April 2019, screening its first patient in June 2019. Site activation is ongoing in the US, with over 35 active sites and over 425 patients screened (as of February 2021). Expansion to Canada, Europe and China are under progress. Clinical trial information: NCT03970447.

Duke Scholars

Author Mustafa Khasraw Neurosurgery