The Global Coalition for Adaptive Research (GCAR) announced today the activation of AstraZeneca's AZD1390 in the GBM AGILE trial, a groundbreaking adaptive platform study for glioblastoma. This marks the seventh investigational arm in the trial, which will evaluate the drug for adult patients with newly diagnosed glioblastoma across multiple international sites.
Glioblastoma remains the most aggressive and common form of primary brain cancer, with treatment options and patient outcomes showing minimal improvement over the past several decades. The addition of AZD1390 to the GBM AGILE platform represents a significant opportunity to address this critical unmet need.
Innovative Trial Design Accelerates Drug Development
GBM AGILE (Glioblastoma Adaptive Global Innovative Learning Environment – NCT03970447) employs a seamless Phase 2/3 design under a master protocol. This innovative approach allows multiple therapies from different pharmaceutical companies to be evaluated simultaneously against a common control arm.
Since its launch in 2019, the trial has evaluated multiple therapies and screened over 2,300 patients at trial locations across six countries. The platform's efficient operational infrastructure means data generated could potentially support new drug applications to the FDA and other regulatory authorities.
"GBM AGILE is designed to rapidly identify and confirm effective therapies for patients with glioblastoma through response adaptive randomization," explained Dr. Patrick Wen, Director of the Center for Neuro-Oncology at Dana-Farber Cancer Institute and Professor of Neurology at Harvard Medical School, who serves as one of the arm Principal Investigators.
Promising Mechanism of Action
AZD1390 is a brain-penetrant ataxia telangiectasia mutant (ATM) kinase inhibitor that blocks ATM-dependent signaling and repair of DNA double strand breaks in the genome. The drug has demonstrated activity in preclinical studies when combined with radiation therapy, which induces DNA damage in cancer cells.
Importantly, AZD1390 has been shown to achieve clinically relevant concentrations in resected glioblastoma tissue and suppress tumor cells' ability to repair radiation-induced DNA damage. Data from a Phase I trial presented at the American Association for Cancer Research (AACR) Annual Meeting 2024 showed a manageable toxicity profile and preliminary efficacy in patients with recurrent glioblastoma.
Professor Anthony Chalmers, Chair of Clinical Oncology at the University of Glasgow and co-Principal Investigator for the AZD1390 arm, expressed optimism about the drug's potential: "Glioblastoma is an invariably fatal cancer with few effective treatment options. There is an urgent need for better treatment options. We are excited to evaluate AZD1390 in GBM AGILE based on encouraging data from previous studies and the extensive evidence that AZD1390 can increase the effectiveness of radiation therapy. This investigational drug has clear potential to improve outcomes for glioblastoma patients."
Leadership and Collaboration
The trial brings together leading experts in neuro-oncology. In addition to Professor Chalmers and Dr. Wen serving as arm Principal Investigators for AZD1390's evaluation, Dr. Timothy Cloughesy, Director of the Neuro-Oncology Program and Distinguished Professor of Neurology at the University of California, Los Angeles, is the Global Principal Investigator for the overall study.
Dr. Meredith Buxton, CEO and President of GCAR, highlighted the importance of collaborative approaches in addressing rare and deadly diseases: "At GCAR, we're dedicated to accelerating the development of critically needed therapies for patients facing rare and deadly diseases like glioblastoma. We believe master protocols and adaptive platform trials are a powerful way to expedite that progress. We're excited to collaborate with AstraZeneca and look forward to rapidly advancing the development of AZD1390 in GBM AGILE to help address the urgent need for more effective glioblastoma therapies."
Implications for Glioblastoma Treatment Landscape
The addition of AZD1390 to the GBM AGILE platform represents a significant step forward in the search for effective glioblastoma treatments. By targeting the DNA damage response pathway, AZD1390 employs a mechanism distinct from many conventional therapies, potentially offering a new approach to treating this challenging malignancy.
If successful, this investigational therapy could provide a much-needed option for patients with newly diagnosed glioblastoma, a population with limited effective treatment alternatives. The adaptive trial design also means that promising signals of efficacy can be identified more quickly than in traditional clinical trials, potentially accelerating the path to regulatory approval.
The Global Coalition for Adaptive Research continues to demonstrate the value of innovative trial designs in addressing challenging diseases with high unmet needs. As a 501(c)(3) non-profit organization, GCAR unites physicians, researchers, advocacy groups, pharmaceutical companies, and other stakeholders to expedite treatment development through more efficient, less costly clinical trial approaches.
