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Clinical trials: Non-immunologic

Session: Poster Session

CTNI-85 - GBM AGILE platform trial for newly diagnosed and recurrent GBM: results of first experimental arm, regorafenib

Friday, November 17, 2023
7:30 PM – 9:30 PM PT
Location: Exhibit Hall A/B
Non-CME

    Poster Presenter(s)

  • Patrick Y. Wen

    Dana-Farber Cancer Institute
    Boston, Massachusetts, United States

    • Author(s)

  • BA

    Brian Alexander

    Foundation Medicine
    Cambridge, Massachusetts, United States

  • DB

    Donald Berry

    Berry Consultants, LLC
    Austin, Texas, United States

  • MB

    Meredith Buxton

    Global Coalition for Adaptive Research
    Larkspur, California, United States

  • WC

    Webster Cavenee

    UCSD
    La Jolla, California, United States

  • Howard Colman

    Huntsman Cancer Institute, University of Utah
    Salt Lake City, Utah, United States

  • John F. de Groot

    University of California, San Francisco
    San Francisco, California, United States

  • Benjamin M. Ellingson

    UCLA Brain Tumor Imaging Laboratory, Department of Radiological Sciences, University of California Los Angeles
    Los Angeles, California, United States

  • GG

    Gary Gordon

    Global Coalition for Adaptive Research
    Larkspur, Illinois, United States

  • EH

    Emma Maria Viktoria Hyddmark

    Global Coalition for Adaptive Research
    Larkspur, California, United States

  • Mustafa Khasraw

    Duke Cancer Institute
    Durham, North Carolina, United States

  • Michael Lim

    Stanford University School of Medicine
    Stanford, California, United States

  • Ingo K. Mellinghoff

    Memorial Sloan Kettering Cancer Center
    New York, New York, United States

  • TM

    Tom Mikkelsen

    Henry Ford Hospital
    Detroit, Michigan, United States

  • James Perry

    Sunnybrook Health Sciences Centre, University of Toronto
    Toronto, Ontario, Canada

  • AP

    Ashley Powell

    Global Coalition for Adaptive Research
    Larkspur, California, United States

  • Erik P. Sulman

    New York University Grossman School of Medicine, Laura and Isaac Perlmutter Cancer Center at NYU Langone Health
    New York, New York, United States

  • KT

    Kirk Tanner

    National Brain Tumor Society
    Newton, Massachusetts, United States

  • Michael Weller

    Department of Neurology and Clinical Neuroscience Center, University Hospital and University of Zurich, Zurich, Switzerland
    Zurich, Zurich, Switzerland

  • WY

    W.K. Alfred Yung

    University of Texas MD Anderson Cancer Center
    Houston, Texas, United States

  • Nicolas Blondin

    Yale University
    New Haven, Alabama, United States

  • Andrew J. Brenner

    UT Health San Antonio Mays Cancer Center
    San Antonio, Texas, United States

  • Omar H. Butt

    Washington University
    Saint Louis, Missouri, United States

  • Macarena I. de la Fuente

    Sylvester Comprehensive Cancer Center
    Miami, Florida, United States

  • JD

    Jan Drappatz

    University of Pittsburgh Medical Center
    Pittsburgh, Pennsylvania, United States

  • FI

    Fabio M. Iwamoto

    Division of Neuro-Oncology, New York-Presbyterian/Columbia University Medical Center
    New York, New York, United States

  • LK

    Lyndon Kim

    Mount Sinai Beth Israel
    New York, New York, United States

  • Eudocia Q. Lee

    Dana-Farber Cancer Institute, Boston, MA
    Boston, Massachusetts, United States

  • MM

    Megan M. Mantica

    University of Pittsburgh Medical Center (UPMC) - Hillman Cancer Center
    Pittsburgh, United States

  • Burt Nabors

    Heersink School of Medicine
    Birmingham, Alabama, United States

  • HN

    Herbert B. Newton

    Brain Tumor and Neuro-Oncology Center, University Hospitals of Cleveland Medical Center, Seidman Cancer Center
    Cleveland, Ohio, United States

  • David Schiff

    University of Virginia School of Medicine
    Charlottesville,, Virginia, United States

  • Tobias Walbert

    Henry Ford Health
    Detroit, Michigan, United States

  • Shiao-Pei Weathers

    University of Texas MD Anderson Cancer Center
    Houston, Texas, United States

  • Timothy F. Cloughesy

    University of California Los Angeles
    Los Angeles, California, United States

  • Andrew B. Lassman

    Columbia University Vagelos College of Physicians and Surgeons and New York Presbyterian Hospital
    New York, New York, United States

GBM AGILE (NCT03970447;https://www.gcaresearch.org/research/gbm-agile) is a phase 3 Bayesian adaptive platform trial that efficiently tests multiple arms against common control, with 6 arms included to date. Primary endpoint is overall survival (OS). Stage 1 experimental arms are adaptively randomized against other arms. Demonstrated efficacy in stage 1 leads to fixed randomization stage 2. Stages 1 and 2 are combined for registration. Control randomization is fixed. Regorafenib, a multikinase-inhibitor, entered into GBM AGILE as the first arm and therefore was equally randomized against control. Regorafenib showed OS benefit in recurrent disease (RD) in randomized phase 2 REGOMA trial.

Methods: Patient subtypes in GBM AGILE are newly diagnosed unmethylated (NDU), RD, and—not considered for regorafenib—ND methylated (NDM). Arm indications (signatures) are combinations of subtypes. Control is temozolomide (ND) and lomustine (RD). Efficacy is assessed by OS hazard ratio(HR), arm/control. Efficacy is demonstrated when Bayesian probability of benefit (HR < 1.00) ≥ 98% (roughly analogous P-value: 0.02). Futility occurs at any monthly analysis when Bayesian predictive power (PP) is < 25% for all signatures. Follow-up continues for 12 months after arm’s accrual stops. RESULTS for regorafenib: When PP for all 3 pre-defined signatures was < 25%, regorafenib’s accrual was stopped for futility. Regorafenib/control sample sizes were 49/51, 126/128, 175/179 for signatures NDU, RD, and both. Respective PPs: 0.138, 0.030, 0.025—none close to 0.25. Respective mean HRs: 1.26, 1.25, 1.23. Probabilities of benefit (HR < 1.00): 0.35, 0.18, 0.17. At final analysis, mean HRs were 1.07, 1.12, 1.10 with final probabilities of benefit (HR < 1.00) equal to 0.43, 0.24, 0.24—none close to 0.98.

Conclusion: GBM AGILE efficiently and compellingly addressed regorafenib’s role in GBM, in RD and NDU. These findings are germane as they fail to confirm the REGOMA results in RD. GBM AGILE continues to efficiently assess other therapies, including utilizing concurrent and previously accrued controls.