AZD-1390

AstraZeneca's AZD1390 to Join GBM AGILE, a Registrational-Intent Phase 2/3 Adaptive Platform Trial for Patients with Glioblastoma AZD1390 Arm Will Recruit Patients with Newly Diagnosed Glioblastoma LARKSPUR, Calif., Nov. 22, 2024 /PRNewswire/ -- The Global Coalition for Adaptive Research (GCAR) today announced that they have executed an agreement with AstraZeneca for the evaluation of AstraZeneca's compound, AZD1390, in GBM AGILE (Glioblastoma Adaptive Global Innovative Learning Environment - NCT03970447), the world's first global adaptive platform trial for glioblastoma. The AZD1390 arm will be evaluated for the treatment of newly diagnosed glioblastoma, with recruitment of patients expected to begin by Q2 2025. Continue Reading GBM AGILE Adaptive Global Innovative Learning Environment Glioblastoma is the most aggressive and common form of primary brain cancer. Treatment options and patient outcomes have seen little progress over the past several decades. Since launching in July 2019, the GBM AGILE trial has evaluated multiple therapies and has screened over 2000 patients at trial locations in six countries. GBM AGILE is designed to more rapidly identify and confirm effective therapies for patients with glioblastoma through response adaptive randomization and a seamless phase 2/3 design. Conceived by over 130 key opinion leaders, GBM AGILE 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. 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 AZD1390's evaluation in GBM AGILE. 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. "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. Patrick 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." AZD1390 is brain penetrant ataxia telangiectasia mutant (ATM) kinase inhibitor that blocks ATM-dependent signaling and repair of DNA double strand breaks (DSBs) in the genome. Preclinically, AZD1390 exhibits activity in combination with agents such as irradiation that induce DSBs. AZD1390 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. Furthermore, 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. "GCAR is committed to accelerating the development of life-changing treatments for patients with rare and deadly diseases such as glioblastoma. We believe that adaptive platform trials have the potential to achieve that mission and make a profound difference for patients," said Dr. Meredith Buxton, Chief Executive Officer and President of GCAR. "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." About Global Coalition for Adaptive Research (GCAR) Global Coalition for Adaptive Research (GCAR) is a 501(c)(3) non-profit corporation uniting physicians, clinical researchers, advocacy and philanthropic organizations, biotech/pharma companies, health authorities, and other key stakeholders in healthcare to expedite the discovery and development of treatments for patients with rare and deadly diseases. As the sponsor of innovative trials, including master protocols and adaptive platform trials, GCAR is dedicated to the advancement of science by modernizing clinical trials that support more efficient, less costly drug development. To learn more about GCAR and its initiatives, visit gcaresearch.org and follow us on social media @GCAResearch. CONTACT: Global Coalition for Adaptive Research Rachel Rosenstein-Sisson [email protected] SOURCE Global Coalition for Adaptive Research WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

AstraZeneca's investigational ATM kinase inhibitor AZD1390, when given with standard-of-care radiotherapy, demonstrated a manageable safety profile and preliminary efficacy in patients with glioblastoma (GBM) in a Phase I trial.Scientists presenting at the American Association for Cancer Research (AACR) annual meeting said AZD1390 demonstrated a manageable safety profile in patients with recurrent or newly diagnosed GBM when given in combination with Intensity-modulated radiation therapy (IMRT) and showed preliminary efficacy in patients with recurrent GBM."Glioblastoma is a lethal cancer with the majority of patients not surviving past two years from diagnosis. Despite efforts to improve survival, the current standard of care continues to be a backbone of radiotherapy with or without temozolomide [Temodar] without much innovation in the past two decades," said Jonathan T. Yang, of Memorial Sloan Kettering Cancer Center, who presented the results.The study assessed the safety, tolerability, early efficacy and maximum tolerated dose of AZD1390 with IMRT in 115 patients, including 75 with recurrent GBM in arm A and 36 patients with newly diagnosed, MGMT unmethylated GBM in arm C.  All patients received escalating once-daily doses of AZD1390. Patients in arm A were given 35 Gy of IMRT in 10 fractions over two weeks while those in arm C were given 60 Gy of IMRT in 30 fractions over six weeks. All patients were given adjuvant AZD1390 for two weeks following the completion of IMRT.Maximum tolerated doses identifiedOf the 115 patients, 15.7% had an AZD1390-related adverse event (AE) of a grade 3 or 4, and 4.3% of patients discontinued AZD1390 due to an AE related to AZD1390 only. The researchers identified 400 mg and 300 mg in arms A and C as the maximum tolerated doses of AZD1390. An overall survival (OS) of 12.7 months was observed in arm A while the OS data for arm C is still maturing."Most adverse effects experienced by patients during the study were low grade, readily manageable, and reversible,” Yang said. "If the preliminary efficacy benefit observed in this trial is proven in a pivotal study, it would be a critical, biologically supported approach to address the high unmet need in GBM."