The Global Coalition for Adaptive Research (GCAR) has announced a collaboration with AstraZeneca to evaluate AZD1390 in the GBM AGILE (Glioblastoma Adaptive Global Innovative Learning Environment) trial, a Phase 2/3 adaptive platform trial for patients with glioblastoma. The AZD1390 arm will focus on treating newly diagnosed glioblastoma, with patient recruitment slated to begin in Q2 2025.
GBM AGILE: An Innovative Approach to Glioblastoma Treatment
Glioblastoma, the most aggressive and common primary brain cancer, has seen limited progress in treatment options and patient outcomes over the past few decades. GBM AGILE, launched in July 2019, aims to address this challenge by rapidly identifying and confirming effective therapies through response adaptive randomization and a seamless phase 2/3 design. The trial has already screened over 2000 patients across six countries and evaluated multiple therapies.
GBM AGILE operates under a master protocol, allowing simultaneous evaluation of multiple therapies or combinations from different pharmaceutical companies against a common control arm. This innovative design and efficient operational infrastructure could potentially provide the data needed for new drug applications (NDA) and biologics license applications (BLA) submissions to regulatory bodies like the US FDA.
AZD1390: Targeting DNA Damage Repair
AZD1390 is a brain-penetrant ataxia telangiectasia mutant (ATM) kinase inhibitor. It functions by blocking ATM-dependent signaling and the repair of DNA double-strand breaks (DSBs) in the genome. Preclinical studies have demonstrated AZD1390's activity in combination with agents like irradiation that induce DSBs. The drug has also been shown to achieve clinically relevant concentrations in resected glioblastoma tissue and suppress the natural repair of DNA damage mediated by radiation.
Data presented at the American Association for Cancer Research (AACR) Annual Meeting 2024 indicated that AZD1390, when combined with radiotherapy, exhibited a manageable safety profile and showed preliminary efficacy in glioblastoma patients in a Phase I trial. "We are excited to include AZD1390 in GBM AGILE, based on encouraging data from previous studies, showing encouraging preliminary efficacy in heavily treated recurrent glioblastoma patients and potential for AZD1390 to act as a radiosensitizer. This investigational drug has the potential to support improved outcomes for glioblastoma patients," said Dr. Patrick Wen, Director, Center for Neuro-Oncology at Dana-Farber Cancer Institute.
Leadership and Commitment
Professor Anthony Chalmers from the University of Glasgow and Dr. Patrick Wen will serve as arm Principal Investigators for the AZD1390 evaluation in GBM AGILE. Dr. Timothy Cloughesy from the University of California, Los Angeles, is the Global Principal Investigator for the overall study.
"GCAR is committed to accelerating the development of life-changing treatments for patients with rare and deadly diseases such as glioblastoma. We believe that adaptive platform trials have the potential to achieve that mission and make a profound difference for patients," said Dr. Meredith Buxton, Chief Executive Officer and President of GCAR.
