500TiP - Update on GBM AGILE: A global, phase II/III adaptive platform trial to evaluate multiple regimens in newly diagnosed and recurrent glioblastoma

Background

GBM AGILE (Glioblastoma Adaptive, Global, Innovative Learning Environment, NCT03970447) is a biomarker based, multi-arm, international, seamless phase II/III platform trial designed to continuously add new arms and to rapidly identify experimental (exp.) therapies that improve overall survival (OS) and confirm efficacious exp. therapies and associated biomarker signatures to support new drug approvals and registration. It is estimated that about 25% of glioblastoma (GBM) patients that enroll in clinical trials in the US participate in GBM AGILE. Given the evergreen nature of GBM AGILE, with arms entering and exiting over time, combined with the high enrollment rate, there is commitment to providing regular updates on the progress of the trial to the GBM community. Furthermore, GBM AGILE also continues to add new design innovations, including more recently, dose finding (DF) and enhanced safety management (ESM) components.

Trial design

The primary objective of GBM AGILE is to identify therapies that improve the OS in patients with newly diagnosed or recurrent GBM. Bayesian response adaptive randomization is used within subtypes of GBM to assign participants to investigational arms based on performance. GBM AGILE operates under a Master Protocol allowing multiple drugs to be evaluated simultaneously and/or over time against a common control. New exp. therapies are added as potential new drugs are identified, while therapies are removed as they complete their evaluation. Six investigational arms have been included to date. Evaluation of the first three arms has been completed. Enrollment in GBM AGILE continues to be robust. Over 2000 patients have been screened for the trial since its launch in July 2019. Innovations include DF and ESM, a seamless process for the introduction of new arms that have modest safety data to accelerate, supplement and support their inclusion in the GBM AGILE trial by conducting a limited safety assessment followed directly by the full evaluation within the program. UGBM AGILE continues to support efficient incorporation and evaluation of new exp. therapies for patients with GBM and continues to be an effective model for phase III drug development.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Global Coalition for Adaptive Research.

Funding

Cure Brain Cancer Foundation, National Brain Tumor Society, National Foundation for Cancer Research, Asian Fund for Cancer Research Ltd, Global Coalition for Adaptive Research, Bayer, Kintara therapeutics, Kazia therapeutics, Vigeo Therapeutics, Biohaven Pharmaceuticals, Polaris Pharmaceuticals.

Disclosure

M. Weller: Financial Interests, Institutional, Other, Research grant: Novartis, Querics, Versameb; Financial Interests, Personal, Advisory Board: Bayer, Medac, Novartis, Orbus, Philogen, Anheart, Neurosense, Pfizer, Roche, Servier; Financial Interests, Personal, Invited Speaker: Novocure; Financial Interests, Institutional, Other, DSMB: Curevac. D.A. Berry: Financial Interests, Personal, Ownership Interest: Berry Consultants; Financial Interests, Personal and Institutional, Funding: NIH; Financial Interests, Personal, Full or part-time Employment: Berry Consultants; Financial Interests, Personal, Advisory Board, He has been a consultant and a member of advisory boards as part of companies’ contracts with Berry Consultants: Berry Consultants. M. Buxton: Financial Interests, Personal, Full or part-time Employment: Global Coalition for Adaptive Research. H. Colman: Financial Interests, Institutional, Funding: Orbus; Financial Interests, Personal and Institutional, Other, Leadership, Principal investigator: GCAR; Financial Interests, Institutional, Other, Research grant: Bayer, CNS Pharma, Sumimoto Dainippon Pharma Oncology, Samus Therapeutics, Erasca; Financial Interests, Institutional, Other: AnHeart Therapeutics; Financial Interests, Personal, Advisory Board: Best Doctors/Teladoc, Orbus Therapeutics, PPD, Chimerix, AnHeart Therapeutics, Alpha Biopharma, Sumitomo Pharma Oncology, Novartis, Servier. J.F. de Groot: Financial Interests, Personal, Advisory Board: Kintara Pharmaceuticals, Kazia, MundiPharma, Insightech, Monteris, Samus, Sapience, DSP Pharma, Telix, Servier, Alpha Pharmaceuticals, CapitalOne; Financial Interests, Personal, Other, DSMB: Chimerix, VBI; Financial Interests, Personal, Other, Spouse stock ownership: Brii Biosciences. B. Ellingson: Financial Interests, Personal and Institutional, Research Grant: Neosoma, Siemens; Financial Interests, Personal, Advisory Board: Medicenna, Voiant, Servier, Janssen, Imaging Endpoints, Kazia, Chimerix, Sumitomo Dainippon Pharma Oncology, ImmunoGenesis, Ellipses Pharma, Monteris, Neosoma, Alpheus Medical, Curtana Pharma, Sagimet Biosciences, Third Rock Ventures. G. Gordon: Financial Interests, Personal, Full or part-time Employment: Enzyme by Design; Financial Interests, Personal, Other, Ownership Interest (stock, stock options, patent or other intellectual property): Abbot, AbbVie, Pfizer, Medtronics, Crisper, Editas, Intellia, PhotonPharma. A.B. Lassman: Financial Interests, Personal and Institutional, Other, Research Grant (principal investigator, collaborator or consultant and pending grants as well as grants already received): AstraZeneca, Genentech/Roche, Millenium, Pfizer, Aeterna, Karyopharm, Keryx, Servier, QED/Helsinn, Chimerix, VBI Vaccines, Beigene, Bayer, AbbVie, RTOG-Foundation, Kadmon, NextSource, DelMar, Corden, Kazia, BMS, Semus, Orbus, GCAR; Financial Interests, Institutional, Other, Research Support (supplies, equipment, receipt of drugs or other in-kind support):: AbbVie, Chimerix, Karyopharm, Novartis, QED/Helsinn, VBI Vaccines, Novocure, Orbus, Pfizer, GCAR, OligoNation; Financial Interests, Personal, Speaker’s Bureau: Clinical Care Options; Financial Interests, Personal, Other, DSMB: BMS; Financial Interests, Personal, Advisory Board: Karyopharm, Novocure, Orbus, Sapience, Vivacitas. E. Lee: Financial Interests, Institutional, Other, Clinical trial support: Biohaven; Financial Interests, Personal, Other, Honorarium: Springer; Financial Interests, Personal, Royalties: Wolters Kluwer; Financial Interests, Personal, Advisory Board: GCAR. M. Lim: Financial Interests, Personal and Institutional, Other, Research Support (supplies, equipment, receipt of drugs or other in-kind support): Arbor, BMS, Tocagen, Kyrin-Kyowa, Biohaven, Urogen; Financial Interests, Personal, Other, Ownership Interest (stock, stock options, patent or other intellectual property): Egret Therapeutics, Pyramid Bio; Financial Interests, Personal, Advisory Board: VBI, InCephalo Therapeutics, Insightec, Biohaven, Sanianoia, Noxon, Hemispherian, Novocure, InCando, Black Diamond Therapeutics, Century Therapeutics. I. Mellinghoff: Financial Interests, Personal, Full or part-time Employment: MSK; Financial Interests, Personal, Speaker’s Bureau: Prelude Therapeutics, Roche, Black Diamond Therapeutics; Financial Interests, Personal, Advisory Board: Agios, Black Diamond Therapeutics, Debiopharm Group, Puma Biotechnology, Novartis, Servier Pharmaceuticals, Voyager Therapeutics, Vigeo Therapeutics, DC Europa Ltd, Kazia Therapeutics, Cardinal Health, Roche, Samus Therapeutics. J. Perry: Financial Interests, Personal, Advisory Board: Global Coalition for Adaptive Research. E. Sulman: Financial Interests, Personal and Institutional, Funding: Novocure; Financial Interests, Personal and Institutional, Other, Research Support (supplies, equipment, receipt of drugs or other in-kind support): Novocure; Financial Interests, Personal, Speaker’s Bureau: Novocure, Zai Lab. P. Wen: Financial Interests, Personal and Institutional, Research Grant: AstraZeneca, Black Diamond, Bristol Myers Squibb, Chimerix, Eli Lily, Erasca, MediciNova, Kazia, MediciNova, Global Coalition for Adaptive Research, Merck, Novartis, Quadriga, VBI Vaccines, Servier; Financial Interests, Personal, Advisory Board: Anheart, AstraZeneca, Black Diamond Therapeutics, Day One Bio, Celularity, Novocure, Novartis, Spacience, Kintara, Merck, Genenta, Mundipharma, Tango, Telix, GSK, Servier, Symbio. T. Cloughesy: Financial Interests, Personal, Other, Stock options, Stock, milestones, royalties, Patent: Katmai Phramaceuticals; Financial Interests, Personal, Other, Stock, milestones, royalties: Chimerix; Financial Interests, Personal, Stocks/Shares, Consultant/Advisory Board: Erasca; Financial Interests, Personal, Advisory Board, Consultant/Advisory Board: BlueRock, Vida Ventures, Lisat Therapeutics, Stemline, Jubilant, Servier, Sagimet, Clinical Care Options, Ideology Health, Sapience, Sonalasense, BrainStorm, Gan & Lee, InVivo, Vigeo Therapeutics, Katmai, DNATrix, Thyme, SDP, Roche, Novarits, Kintara, Bayer, Merck, Boehinger Ingelheim, VBL, Amgen, Kiyatec, Odonate Therapeutics QED, Pfizer, Tocagen, Medefield, Pascal Biosciences, Karyopharm, AbbVie, GW Pharma, VBI, Deciphera, Agios, Genocea, Calgene, Puma, Lilly, BMS, Cortice, Novocure, Novogen, Wellcome Trust, Boston Medical, Medscape, Insys, Sunovio, Human Longevity, Global Coalition for Adaptive Research, ProNai, Break Through Cancer, Katmai; Financial Interests, Personal and Institutional, Other, The Regents of the University of California (T.F.C. employer) has licensed intellectual property co-invented by TFC to Katmai Pharmaceuticals: Katmai. All other authors have declared no conflicts of interest.