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GBM AGILE is the glioblastoma trial that never ends: new drugs enter, are tested against the same standard treatment in newly diagnosed and recurrent patients at once, and either graduate to a confirmatory stage or are dropped. Its first drug, regorafenib, did not help, which the trial established faster and more cheaply than a stand-alone study would have.
GBM AGILE was designed between 2015 and 2018 by a consortium of neuro-oncologists and statisticians, including Timothy Cloughesy, Brian Alexander, Meredith Buxton and Donald Berry, and is sponsored by the Global Coalition for Adaptive Research, a non-profit created to run it. The design paper appeared in Clinical Cancer Research in 2018 and the trial opened in July 2019 in the United States, since extended to Canada, Europe and China. Patients with newly diagnosed glioblastoma, split by MGMT promoter methylation, and patients with recurrent disease all enter one protocol; the control arm receives temozolomide with radiotherapy (newly diagnosed) or lomustine or another standard (recurrent). Randomisation is response-adaptive within each population, overall survival is the endpoint, and an arm that reaches a pre-set probability of success moves seamlessly into a second, confirmatory stage sized to support approval.
The first experimental arm, regorafenib, enrolled from 2019 and its results were reported at the 2024 European neuro-oncology meeting and published in the Journal of Clinical Oncology in 2026: regorafenib did not improve overall survival in any of the populations, closing the question raised by the small REGOMA trial. Paxalisib and VAL-083 completed their first stages without meeting the graduation criteria. Troriluzole, VT1021 and azeliragon entered later, and the platform continues to add arms.
GBM AGILE has changed how glioblastoma drugs are tested: companies can enter a single arm without building their own registration trial, patients in newly diagnosed and recurrent settings are studied together, and negative answers arrive in about two years. Whether a graduated arm will be accepted for approval on platform data alone is the test the trial has not yet faced, and the JCO editorial on its regorafenib experience debates how much a shared, evolving control can be trusted over a decade.
One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.
One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.
One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.
Shares Interim analysis, readout and data cut-off, Seamless, adaptive and Bayesian trial designs, Master protocol (platform, basket and umbrella trials), Trial design, endpoints and cost.
Shares Lomustine (CCNU), Brain and spinal cord tumours (all types), Glioma & glioblastoma.
Shares Interim analysis, readout and data cut-off, Seamless, adaptive and Bayesian trial designs, Master protocol (platform, basket and umbrella trials), Trial design, endpoints and cost.
Shares Lomustine (CCNU), Temozolomide, Glioma & glioblastoma.
Shares Lomustine (CCNU), Temozolomide, Glioma & glioblastoma.
Shares Lomustine (CCNU), Brain and spinal cord tumours (all types), Glioma & glioblastoma.
Shares Brain and spinal cord tumours (all types), Temozolomide, Glioma & glioblastoma.