AstraZeneca's AZD1390, a brain-penetrant ataxia telangiectasia mutant (ATM) kinase inhibitor, is set to be evaluated in the Glioblastoma Adaptive Global Innovative Learning Environment (GBM AGILE) trial. The trial, a Phase 2/3 adaptive platform, aims to assess the drug's efficacy in patients with newly diagnosed glioblastoma. Patient recruitment for the AZD1390 arm is anticipated to begin by the second quarter of 2025.
Glioblastoma remains a formidable challenge in oncology, being the most aggressive and common form of primary brain cancer. Despite decades of research, treatment options and patient outcomes have seen limited progress. The GBM AGILE trial, launched in July 2019, seeks to address this unmet need by evaluating multiple therapies simultaneously through a master protocol.
GBM AGILE's adaptive design allows for more rapid identification and confirmation of effective therapies. The trial employs response adaptive randomization and a seamless Phase 2/3 design. Over 2000 patients have already been screened at trial locations across six countries. Data from GBM AGILE can potentially support new drug applications (NDA) and biologics license applications (BLA) submissions to regulatory bodies such as the US FDA.
AZD1390: Mechanism of Action and Prior Studies
AZD1390 functions by blocking ATM-dependent signaling and the repair of DNA double-strand breaks (DSBs) in the genome. Preclinical studies have demonstrated its 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 DNA damage repair 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 preliminary efficacy in glioblastoma patients during a Phase I trial.
Leadership and Collaboration
Professor Anthony Chalmers from the University of Glasgow and Dr. Patrick Wen from Dana-Farber Cancer Institute will serve as arm Principal Investigators for the AZD1390 evaluation. Dr. Timothy Cloughesy from the University of California, Los Angeles, is the Global Principal Investigator for the overall study.
Dr. Wen emphasized the urgent need for new glioblastoma therapies, stating, "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."
About GBM AGILE
GBM AGILE was conceived by over 130 key opinion leaders and is conducted under a master protocol, allowing multiple therapies or combinations of therapies from different pharmaceutical companies to be evaluated simultaneously against a common control arm. With its innovative design and efficient operational infrastructure, data from GBM AGILE can potentially be used as the foundation for a new drug application (NDA) and biologics license application (BLA) submissions and registrations to the US FDA and other health authorities.
