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Video

Clinical trials: Non-immunologic

Session: Plenary I

CTNI-37 - Clinical activity of RAF inhibitor tovorafenib according to prior MAPK inhibitor treatment in the registrational pediatric low-grade glioma arm of the phase 2 FIREFLY-1 (PNOC026) study

Friday, November 17, 2023
10:25 AM – 10:35 AM PT
Location: Exhibit Hall C
Non-CME

    Author(s)

  • DK

    Dong-Anh Khuong-Quang

    The Royal Children's Hospital Melbourne
    Melbourne, Victoria, Australia

    • Author(s)

  • Karsten Nysom

    Department of Pediatrics and Adolescent Medicine, Copenhagen University Hospital - Rigshospitalet
    Copenhagen, Denmark

    • Plenary Abstract Presenter(s)

  • Daniel B. Landi

    Duke University
    Durham, North Carolina, United States

    • Author(s)

  • David S. Ziegler

    Kids Cancer Centre, Sydney Children’s Hospital
    Randwick, New South Wales, Australia

  • PH

    Pablo Hernáiz Driever

    German HIT-LOGGIC-Registry for LGG in children and adolescents, Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
    Berlin, Germany

  • Sarah E. S. Leary

    Cancer and Blood Disorders Center, Seattle Children's
    Seattle, Washington, United States

  • SB

    Simon Bailey

    Great North Childrens Hospital and Newcastle University
    Newcastle upon Tyne, United Kingdom

  • Jasper van der Lugt

    Princess Máxima Center for Pediatric Oncology
    Utrecht, Utrecht, Netherlands

  • Sébastien Perreault

    CHU Sainte Justine
    Montréal, Quebec, Canada

  • AW

    Angela J. Waanders

    Ann & Robert H Lurie Children's Hospital
    Chicago, Illinois, United States

  • PB

    Patricia A. Baxter

    Texas Children's Cancer Center, Texas Children's Hospital
    Houston, Texas, United States

  • OW

    Olaf Witt

    Hopp Children’s Cancer Center Heidelberg (KiTZ), Heidelberg University Hospital and German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT)
    Heidelberg, Germany

  • DH

    Darren Hargrave

    UCL Great Ormond Street Institute of Child Health
    London, England, United Kingdom

  • GM

    Geoffrey McCowage

    Sydney Children’s Hospitals Network
    Westmead, New South Wales, Australia

  • JH

    Jordan R. Hansford

    Children's Cancer Centre, Royal Children’s Hospital Melbourne
    Parkville, Victoria, Australia

  • HT

    Helen Toledano

    Schneider Children’s Medical Center of Israel
    Petach Tikva, Israel

  • LO

    Liat Oren

    Rambam Healthcare Campus
    Haifa, Israel

  • ET

    Enrica E. K. Tan

    KK Women's and Children's Hospital
    Singapore, Singapore

  • NG

    Nicolas Gerber

    University Children's Hospital
    Zurich, Switzerland

  • HK

    Hyoung Jin Kang

    Department of Pediatrics, Seoul National University College of Medicine, Seoul National University Cancer Research Institute, Seoul National University Children’s Hospital
    Seoul, Republic of Korea

  • VL

    Valérie Larouche

    CHU de Québec-Université Laval (CHUL)
    Québec City, Quebec, Canada

  • MA

    Mohamed S. S. Abdelbaki

    St. Louis Children's Hospital (NCH)
    St. Louis, Missouri, United States

  • IC

    Izzy Cornelio

    Day One Biopharmaceuticals
    Brisbane, California, United States

  • YK

    Yeonhee Kim

    Day One Biopharmaceuticals
    Brisbane, California, United States

  • AW

    Ashley Walter

    Day One Biopharmaceuticals
    Brisbane, California, United States

  • PM

    Peter Manley

    Day One Biopharmaceuticals
    Brisbane, California, United States

  • Lindsay B. Kilburn

    Children’s National Hospital
    Washington, District of Columbia, United States


Background: Pediatric low-grade glioma (pLGG) is the most common childhood brain tumor. Genomic alterations of RAF are common oncogenic drivers in pLGG. Tovorafenib is an investigational, selective, CNS-penetrant, type II RAF inhibitor.

Methods: FIREFLY-1 (NCT04775485) is a phase 2 study evaluating tovorafenib monotherapy. Registrational arm 1 enrolled patients aged 6 months–25 years of age with recurrent or progressive LGG harboring an activating BRAF alteration. Tovorafenib 420 mg/m2 (600 mg max) was administered weekly (tablet or liquid suspension). Independently assessed overall response rate (ORR), as defined by RANO-HGG and RANO-LGG criteria, are primary and exploratory endpoints.

Results: As of December 22 2022, 69 (RANO-HGG) and 76 (RANO-LGG) of 77 patients in arm 1 were evaluable at baseline and had ≥9 months of follow-up. Median age at enrollment was 8 years (range 2–21), and 60% (n=46) patients had received prior MAPK inhibitor (MAPKi) therapy. Among the evaluable patients, the ORR was 62% (RANO-HGG, n= 69) and 45% (RANO-LGG, n=76), respectively. The ORR in patients previously treated with MAPKis (n=41 [RANO-HGG]; n=45 [RANO-LGG]) was 68% (4 CRs; 24 PRs) (RANO-HGG) and 44% (5 PRs; 15 MRs) (RANO-LGG). In MAPKi-naïve patients (28 [RANO-HGG]; 31 [RANO-LGG]), the ORR was 54% (15 PRs) (RANO-HGG) and 45% (7 PRs; 7 MRs) (RANO-LGG). Among 136 patients in arms 1 and 2 of FIREFLY-1, the most common treatment-related adverse events (TRAEs) of any grade were hair color changes (71%), fatigue (40%) and maculopapular rash (38%). Tovorafenib dose modifications occurred in 39 (29%) and discontinuations in 4 (3%) patients due to TRAEs.

Conclusions: Tovorafenib provided clinically meaningful tumor responses, including those with a best response reported of SD or PD using another MAPKi, in patients with BRAF-altered pLGG regardless of prior MAPKi therapy, and has a manageable safety profile.