Skip to main content
SNO 28th Annual Meeting Main banner
Final Program


Program
Icon Legend
Presentation Icons
CME
CME
Non-CME
Non-CME
ISS CME
ISS CME
Named Award Winner
Named Award Winner
Award Winner
Award Winner
Poster Award Winner
Poster Award Winner
Back
Video

Clinical trials: Non-immunologic

Session: Town Hall: Debating Unanswered Questions in Neuro-Oncology

CTNI-51 - A randomized double-blind Phase 3 study of vorasidenib vs placebo in patients with mutant IDH1/2 diffuse glioma (INDIGO): exploratory analysis of variant allele frequency and progression-free survival

Saturday, November 18, 2023
2:53 PM – 3:01 PM PT
Location: Exhibit Hall C
Non-CME

    Plenary Abstract Presenter(s)

  • Timothy F. Cloughesy

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

    • Author(s)

  • Ingo K. Mellinghoff

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

  • Martin J. van den Bent

    Erasmus MC Cancer Institute
    Rotterdam, Netherlands

  • DB

    Deborah T. Blumenthal

    Tel Aviv Medical Center, Tel Aviv University
    Tel Aviv, Tel Aviv, Israel

  • Mehdi Touat

    Pitié Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP) Sorbonne Université
    Paris, Massachusetts, France

  • Katherine B. Peters

    Duke University Medical Center
    Durham, North Carolina, United States

  • Jennifer L. Clarke

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

  • JM

    Joe Mendez

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

  • Shlomit Yust-Katz

    Davidoff Cancer Center at Rabin Medical Center
    Petach Tikva, HaMerkaz, Israel

  • WM

    Warren P. Mason

    Princess Margaret Cancer Centre
    Toronto, Canada

  • Francois Ducray

    Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Centre de Recherche en Cancérologie de Lyon
    Lyon, France

  • Yoshie Umemura

    Ivy Brain Tumor Center at Barrow Neurological Institute
    Phoenix, Arizona, United States

  • LN

    L. Burt Nabors

    University of Alabama at Birmingham
    Birmingham, Alabama, United States

  • Matthias Holdhoff

    Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
    Baltimore, Maryland, United States

  • AH

    Andreas F. Hottinger

    University Hospital of Lausanne
    Lausanne, Switzerland

  • Yoshiki Arakawa

    Department of Neurosurgery, Kyoto University Graduate School of Medicine
    Kyoto, Kyoto, Japan

  • JS

    Juan M. Sepúlveda

    Hospital Universitario 12 de Octubre
    Madrid, Spain

  • Wolfgang Wick

    Universitatsklinikum Heidelberg
    Heidelberg, Baden-Wurttemberg, Germany

  • Riccardo Soffietti

    University of Turin
    Torino, Piemonte, Italy

  • James Perry

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

  • PG

    Pierre Giglio

    The Ohio State University Wexner Medical Center
    Columbus, Ohio, United States

  • Macarena I. de la Fuente

    Sylvester Comprehensive Cancer Center
    Miami, Florida, United States

  • EM

    Elizabeth A. Maher

    University of Texas Southwestern Medical Center
    Dallas, Texas, United States

  • SC

    Sung Choe

    Servier Pharmaceuticals
    Boston, Massachusetts, United States

  • DZ

    Dan Zhao

    Servier Pharmaceuticals
    Boston, Massachusetts, United States

  • SP

    Shuchi S. Pandya

    Servier Pharmaceuticals
    Boston, Massachusetts, United States

  • LS

    Lori Steelman

    Servier Pharmaceuticals
    Boston, Massachusetts, United States

  • IH

    Islam Hassan

    Servier Pharmaceuticals
    Boston, Massachusetts, United States

  • AT

    Adriana E. Tron

    Servier Pharmaceuticals
    Boston, Massachusetts, United States

  • Patrick Y. Wen

    Dana-Farber Cancer Institute
    Boston, Massachusetts, United States


Introduction: Vorasidenib is an oral, brain-penetrant, inhibitor of mutant isocitrate dehydrogenase (mIDH) 1/2 enzymes. The INDIGO study (NCT04164901) showed significantly improved radiographic progression-free survival (PFS) by blinded independent review committee (BIRC) with vorasidenib, compared with placebo, in patients with mIDH1/2 adulttype diffuse glioma (hazard ratio [HR] 0.39, 95% CI 0.27–0.56; one-sided P= 0.000000067 [Mellinghoff N Engl J Med 2023]). The key secondary endpoint of time-to-next-intervention was also met.

Methods: In this double-blind Phase 3 study, patients aged ≥ 12 years with residual/recurrent grade 2 mIDH1/2 oligodendroglioma or astrocytoma, measurable non-enhancing disease, and no prior treatment for glioma were randomized 1:1 to receive vorasidenib 40 mg or placebo daily in 28-day cycles. An investigational clinical trial assay centrally confirmed IDH1 R132H/C/G/S/L or IDH2 R172K/M/W/S/G mutation variants. Pretreatment (archival) tumor tissue was analyzed by next-generation sequencing for CDKN2A/B homozygous deletion and other co-mutations (ACE Extended Cancer Panel).

Results: As of Sep 6, 2022 (preplanned second interim analysis), 168 patients were randomized to vorasidenib and 163 to placebo (median age, 40.0 years; Karnofsky performance scale= 100, 53.5%; oligodendroglioma, 172; astrocytoma, 159; mIDH1, 315; mIDH2, 16). Two patient subgroups were defined by baseline IDH1/2 variant allele frequency (VAF): lower/higher than the median value (0.377). The median PFS results favored vorasidenib over placebo in both subgroups (low VAF, one-sided P= 0.0116; high VAF, one-sided P < 0.0001). Vorasidenib and placebo groups had similar and a low number of co-mutations in known/likely oncogenic genes at baseline (median number of co-mutations across both groups was 4). CDKN2A homozygous deletion was detected in only two participants (both in the placebo group). Additional data will be presented.

Conclusion: In the first randomized Phase 3 study of a targeted therapy in grade 2 mIDH1/2 glioma, vorasidenib prolonged median PFS by BIRC, relative to placebo, irrespective of IDH1/2 VAF.