AstraZeneca's ataxia telangiectasia mutant (ATM) kinase inhibitor, AZD1390, is set to be evaluated in the Glioblastoma Adaptive Global Innovative Learning Environment (GBM AGILE) trial, as announced by the Global Coalition for Adaptive Research (GCAR). This global phase II/III adaptive platform trial aims to assess the drug's efficacy in treating newly diagnosed glioblastoma, with patient recruitment expected to begin in early 2025.
AZD1390 is designed to penetrate the brain and block ATM-dependent signaling, thereby inhibiting the repair of DNA double-strand breaks. Preclinical studies have indicated that AZD1390 exhibits activity when combined with agents like irradiation that induce such double-strand breaks.
Clinical Data and Rationale
Data presented at the American Association for Cancer Research (AACR) Annual Meeting 2024 highlighted that AZD1390, when administered with radiotherapy, demonstrated a manageable safety profile and showed preliminary efficacy in glioblastoma patients in a phase I trial. The compound has also been shown to achieve clinically relevant concentrations in resected glioblastoma tissue and suppress the natural repair of DNA damage mediated by radiation.
GBM AGILE Trial Design
GBM AGILE is an international response-adaptive randomization platform trial evaluating treatments for both newly diagnosed and recurrent glioblastoma. The trial allows for the simultaneous evaluation of multiple therapies or combinations from different pharmaceutical companies against a common control arm. Since its launch in July 2019, GBM AGILE has screened over 2,000 patients across trial locations in six countries and has evaluated several therapies.
Expert Perspectives
Anthony Chalmers, PhD, FRCR, MRCP, Chair of Clinical Oncology at the University of Glasgow, and Patrick Wen, MD, Director of the 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 within GBM AGILE. Timothy Cloughesy, MD, 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.
"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."
