The Global Coalition for Adaptive Research (GCAR) and AstraZeneca have announced an agreement to evaluate AZD1390, AstraZeneca's compound, within the GBM AGILE (Glioblastoma Adaptive Global Innovative Learning Environment) trial. This Phase 2/3 adaptive platform trial (NCT03970447) is designed for patients with glioblastoma, the most aggressive and common form of primary brain cancer, where treatment options have seen limited progress in recent decades. The AZD1390 arm will focus on patients with newly diagnosed glioblastoma, with recruitment slated to begin by Q2 2025.
GBM AGILE, launched in July 2019, is designed to expedite the identification and confirmation of effective glioblastoma therapies through response adaptive randomization and a seamless Phase 2/3 design. The trial, conceived by over 130 key opinion leaders, operates under a master protocol, allowing simultaneous evaluation of multiple therapies or combinations from different pharmaceutical companies against a common control arm. Data from GBM AGILE can potentially support new drug applications (NDA) and biologics license applications (BLA) submissions to regulatory bodies like the US FDA.
Professor Anthony Chalmers, Chair of Clinical Oncology at the University of Glasgow, and Dr. Patrick Wen, Director, Center for Neuro-Oncology at Dana-Farber Cancer Institute and Professor of Neurology at Harvard Medical School, will serve as arm Principal Investigators for the AZD1390 evaluation. Dr. Timothy Cloughesy, Director, Neuro-Oncology Program and Distinguished Professor of Neurology at the University of California, Los Angeles, is the Global Principal Investigator for the overall study.
Rationale for AZD1390 in GBM AGILE
"There is an urgent need for new, tolerable and effective therapies to treat glioblastoma," said Dr. Patrick Wen. "GBM AGILE is a revolutionary, patient-centered, potentially registration-enabling, adaptive platform trial for glioblastoma. 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."
AZD1390 is a brain-penetrant ataxia-telangiectasia mutant (ATM) kinase inhibitor that blocks ATM-dependent signaling and repair of DNA double-strand breaks (DSBs) in the genome. Preclinical studies indicate that AZD1390 exhibits activity in combination with agents like irradiation that induce DSBs. The drug has also demonstrated clinically relevant concentrations in resected glioblastoma tissue and suppresses the natural repair of DNA damage mediated by radiation. Phase I trial data presented at the American Association for Cancer Research (AACR) Annual Meeting 2024 indicated that AZD1390 with radiotherapy showed a manageable safety profile and preliminary efficacy in glioblastoma patients.
GCAR's Perspective
"GCAR is committed to accelerating the development of life-changing treatments for patients with rare and deadly diseases such as glioblastoma," said Dr. Meredith Buxton, Chief Executive Officer and President of GCAR. "We believe that adaptive platform trials have the potential to achieve that mission and make a profound difference for patients. We are delighted to collaborate with AstraZeneca and look forward to expediting the evaluation of AZD1390 in GBM AGILE for the treatment of glioblastoma, a devastating disease with a critical need for more effective treatments."
Since its launch, the GBM AGILE trial has screened over 2000 patients across trial locations in six countries, evaluating multiple therapies in the ongoing effort to combat glioblastoma.
