The Global Coalition for Adaptive Research (GCAR) announced an agreement to evaluate AZD1390, an ataxia telangiectasia mutant (ATM) kinase inhibitor developed by AstraZeneca, in GCAR’s Glioblastoma Adaptive Global Innovative Learning Environment trial (GBM AGILE; ClinicalTrials.gov identifier NCT03970447). The AZD1390 arm will be assessed for the treatment of newly diagnosed glioblastoma, with recruitment of patients expected to begin in early 2025.
AZD1390 is brain-penetrant compound that blocks ATM-dependent signaling and repair of DNA double-strand breaks in the genome. Preclinically, AZD1390 has exhibited activity in combination with agents such as irradiation that induce double-strand breaks.
The novel agent has also been shown to achieve clinically relevant concentrations in resected glioblastoma tissue and suppress the natural repair of the DNA damage that is mediated by radiation. In an oral presentation at the American Association for Cancer Research (AACR) Annual Meeting 2024, AZD1390 with radiotherapy showed a manageable safety profile and preliminary efficacy for patients with glioblastoma in a phase I trial.
About GBM AGILE
GBM AGILE is an international phase II/III response-adaptive randomization platform trial of treatments in newly diagnosed and recurrent glioblastoma. It is designed to allow multiple therapies or combinations of therapies from different pharmaceutical companies to be evaluated simultaneously against a common control arm. Since launching in July 2019, the GBM AGILE trial has evaluated several therapies and has screened over 2,000 patients at trial locations in six countries.
Anthony Chalmers, PhD, FRCR, MRCP, Chair of Clinical Oncology at the University of Glasgow and Patrick Wen, MD, 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 AZD1390's evaluation in GBM AGILE. Timothy Cloughesy, MD, 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.
“There is an urgent need for new, tolerable and effective therapies to treat glioblastoma. GBM AGILE is a revolutionary, patient-centered, potentially registration-enabling, adaptive platform trial for glioblastoma,” said Dr. Wen. “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.”
