DAY101 vs. Standard of Care Chemotherapy in Pediatric Participants With Low-Grade Glioma Requiring First-Line Systemic Therapy (LOGGIC/FIREFLY-2)

LOGGIC/FIREFLY-2: A Phase 3, Randomized, International Multicenter Trial of DAY101 Monotherapy Versus Standard of Care Chemotherapy in Patients With Pediatric Low-Grade Glioma Harboring an Activating RAF Alteration Requiring First-Line Systemic Therapy

This is a 2-arm, randomized, open-label, multicenter, global, Phase 3 trial to evaluate the efficacy, safety, and tolerability of tovorafenib monotherapy versus standard of care (SoC) chemotherapy in participants with pediatric low-grade glioma (LGG) harboring an activating rapidly accelerated fibrosarcoma (RAF) alteration requiring first-line systemic therapy.

Study Overview

• Status: Active, not recruiting
• Conditions: Low-grade Glioma; Pediatric Low-grade Glioma; Rapidly Accelerated Fibrosarcoma (RAF) Altered Glioma
• Intervention / Treatment: Drug: Chemotherapeutic Agent; Drug: Tovorafenib

Detailed Description

Approximately 400 treatment-naïve LGG participants will be randomized 1:1 to either tovorafenib (Arm 1) or an Investigator's choice of SoC chemotherapy (Arm 2).

Arm 1 (tovorafenib): Treatment cycles will repeat every 28 days in the absence of disease progression. Participants will continue tovorafenib until any of the following occurs: disease progression, unacceptable toxicity, withdrawal of consent to treatment, or end of study.

Arm 2 (Investigator's Choice of SoC Chemotherapy): Participants will receive one of 4 SoC chemotherapy options selected by the treating Investigator: Children's Oncology Group - Vincristine/Carboplatin (COG-V/C) regimen, International Society for Paediatric Oncology - Low-Grade Glioma Vincristine/Carboplatin (SIOPe-LGG-V/C) regimen, vinblastine (VBL) regimen, or monthly carboplatin. The choice of SoC chemotherapy regimen will be selected prior to participant randomization. Treatment will continue until completion of therapy or until any of the following occurs: disease progression, unacceptable toxicity, withdrawal of consent to treatment, or end of study.

Participants who discontinue treatment due to disease progression will have (1) radiographic evidence of disease progression, as determined by the Investigator, or (2) clinical progression, as determined by the Investigator. Investigators are encouraged to discuss cases of clinical progression and early radiographic progression without clinical symptoms with the Sponsor Medical Monitor prior to treatment discontinuation or initiation of a different form of treatment for the malignancy. Participants may continue therapy beyond progressive disease (PD).

• Study Type: Interventional
• Enrollment (Actual): 418
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Nedlands, Australia, 6009
    • Perth Children's Hospital
  • North Adelaide, Australia, 5006
    • Women's and Children's Health Network
  • Parkville, Australia, 3052
    • The Royal Children's Hospital - Children's Cancer Centre
  • Randwick, Australia, 2031
    • Sydney Children's Hospital - Randwick
  • Westmead, Australia, 2145
    • Children's Hospital at Westmead
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Children's Health Queensland Hospital and Health Service
• Austria
  • Vienna, Austria, 1090
    • Medizinische Universität Wien
  • Tyrol
    • Innsbruck, Tyrol, Austria, 6020
      • Medizinische Universität Innsbruck
• Belgium
  • Brussels, Belgium, 1200
    • Cliniques universitaires Saint-Luc
  • Ghent, Belgium, 9000
    • Universitair Ziekenhuis Gent
  • Leuven, Belgium, 3000
    • Universitair Ziekenhuis Leuven - Campus Gasthuisberg
• Brazil
  • São Paulo, Brazil, 04039-001
    • Grupo de Apoio ao Adolescente e à Criança com Câncer (GRAACC)
• Canada
  • Québec, Canada, G1V 4G2
    • Centre Hospitalier de l'Université Laval et Centre Mère-Enfant Soleil
  • Toronto, Canada, M5G 1X8
    • SickKids - The Hospital for Sick Children
  • Alberta
    • Calgary, Alberta, Canada, T3B 6A8
      • Alberta Children's Hospital
    • Edmonton, Alberta, Canada, T6G 2B7
      • Stollery Children's Hospital
  • British Columbia
    • Vancouver, British Columbia, Canada, V6H 3N1
      • British Columbia Children's Hospital
  • Ontario
    • Hamilton, Ontario, Canada, L8S 4L8
      • McMaster Children's Hospital
    • London, Ontario, Canada, N6A 5W9
      • Children's Hospital London Health Sciences Centre
    • Ottawa, Ontario, Canada, K1H 8L1
      • Children's Hospital of Eastern Ontario
  • Quebec
    • Montreal, Quebec, Canada, H3T IC5
      • CHU Sainte-Justine
    • Montreal, Quebec, Canada, H4A 3J1
      • The Montreal Children's Hospital
• Czechia
  • Brno, Czechia, 625 00
    • Fakultní Nemocnice Brno - D?tská Nemocnice
  • Prague, Czechia, 5 150 06
    • Motol University Hospital
• Denmark
  • Copenhagen, Denmark, 2100
    • Rigshospitalet
  • Central Jutland
    • Aarhus, Central Jutland, Denmark, 8200
      • Aarhus Universitetshospital
• Egypt
  • Cairo Governorate
    • Cairo, Cairo Governorate, Egypt, 11441
      • CCHE
• Finland
  • Helsinki, Finland, FI-00290
    • Helsingin yliopistollinen sairaala (HUS)
  • Tampere, Finland, 33520
    • Tampereen yliopistollinen sairaala
• France
  • Lille, France, 59020
    • Centre de Lutte contre le Cancer - Centre Oscar Lambret
  • Lyon, France, 69008
    • Centre Leon Berard
  • Marseille, France, 13005
    • Hôpital de la Timone
  • Paris, France, 75248
    • Institut Curie
  • Villejuif, France, 94805
    • Gustave Roussy
• Germany
  • Berlin, Germany, 13353
    • Charite Universitatsmedizin Berlin
  • Bielefeld, Germany, 33617
    • Evangelische Klinikum Bethel (EvKB)
  • Hamburg, Germany, 20246
    • Universitätsklinikum Hamburg-Eppendorf
  • Heidelberg, Germany, 69120
    • Universitatsklinikum Heidelberg
  • Tübingen, Germany, 72076
    • Universitätsklinikum Tübingen
  • Baden-Wurttemberg
    • Freiburg im Breisgau, Baden-Wurttemberg, Germany, 79106
      • Universitätsklinikum Freiburg
  • Bavaria
    • Augsburg, Bavaria, Germany, 86156
      • Universitätsklinikum Augsburg
    • Erlangen, Bavaria, Germany, 91054
      • Universitätsklinikum Erlangen
    • Würzburg, Bavaria, Germany, 97080
      • Universitatsklinikum Wurzburg
  • Hesse
    • Frankfurt am Main, Hesse, Germany, 60590
      • Universitätsklinikum Frankfurt
  • Lower Saxony
    • Hanover, Lower Saxony, Germany, 30625
      • Medizinische Hochschule Hannover
  • North Rhine-Westphalia
    • Essen, North Rhine-Westphalia, Germany, 45147
      • Universitaetsklinikum Essen
  • Saxony
    • Leipzig, Saxony, Germany, 4103
      • Universitatsklinikum Leipzig
• Greece
  • Athens, Greece, 11527
    • Aghia Sofia General Children's Hospital
  • Athens, Greece, 11527
    • Athens General Children's Hospital
• Hungary
  • Budapest, Hungary, 1094
    • Semmelweis Egyetem Tűzoltó utcai II. Sz. Gyermekgyógyászati Kliniká
• Ireland
  • Dublin
    • Crumlin, Dublin, Ireland, D12 N512
      • Children's Health Ireland at Crumlin
• Israel
  • Petah Tikva, Israel, 49202
    • Schneider Children's Medical Center of Israel
  • Ramat Gan, Israel, 5265601
    • The Edmond and Lily Safra Children's Hospital
• Italy
  • Bari, Italy, 70124
    • Azienda Universitaria Ospedaliera Consorziale - Policlinico di Bari
  • Florence, Italy, 50139
    • Azienda Ospedaliera U. Meyer
  • Genova, Italy, 16147
    • Istituto Giannina Gaslini
  • Naples, Italy, 80131
    • Azienda Ospedaliera di Rilievo Nazional Santobono Pausilipon
  • Padova, Italy, 35128
    • Azienda Ospedale Università di Padova
  • Udine, Italy, 33100
    • Azienda Sanitaria Universitaria Friuli Centrale - P.O. Santa Maria della Misericordia
  • Milan
    • Milan, Milan, Italy, 20133
      • Fondazione IRCCS - Istituto Nazionale dei Tumori
  • Rome
    • Roma, Rome, Italy, 00165
      • Ospedale Pediatrico Bambino Gesù
  • Turin
    • Torino, Turin, Italy, 10126
      • Ospedale Infantile Regina Margherita
• Jordan
  • Muhafazat al-Asima
    • Amman, Muhafazat al-Asima, Jordan, 11941
      • King Hussein Cancer Foundation - King Hussein Cancer Center
• Netherlands
  • Utrecht, Netherlands, 3584 CS
    • Prinses Maxima Centrum Kinderoncologie
• New Zealand
  • Grafton, New Zealand, 1023
    • Starship Paediatric Blood & Cancer Center
• Norway
  • Oslo, Norway, 372
    • Oslo universitetssykehus
  • Troms
    • Tromsø, Troms, Norway, 9038
      • Universitetssykehuset Nord-Norge - Tromsø
• Qatar
  • Doha, Qatar, 26999
    • Sidra Medicine
• Singapore
  • Singapore, Singapore, 229899
    • SingHealth Group - KK Women's and Children's Hospital
• Slovenia
  • Ljubljana, Slovenia, 1000
    • Univerzitetni Klinini Center Ljubljana
• South Korea
  • Seoul, South Korea, 03080
    • Seoul National University Hospital
  • Seoul, South Korea, 03722
    • Severance Hospital
• Spain
  • Barakaldo, Spain, 48903
    • Hospital Universitario Cruces
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain, 08950
    • Hospital Sant Joan de Deu Barcelona
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Madrid, Spain, 28009
    • Hospital Infantil Universitario Nino Jesus
  • Seville, Spain, 41013
    • Hospital Universitario Virgen del Rocio
  • Valencia, Spain, 46026
    • Hospital Universitari i Politecnic La Fe
• Sweden
  • Gothenburg, Sweden, 416 85
    • Drottning Silvias barn- och ungdomssjukhus
  • Lund, Sweden, 221 85
    • Skånes Universitetssjukhus - Lund
  • Stockholm, Sweden, 171 77
    • Astrid Lindgrens Barnsjukhus Solna
• Switzerland
  • Lausanne, Switzerland, 1011
    • Centre Hospitalier Universitaire Vaudois Lausanne
  • Zurich, Switzerland, 8032
    • Universitaets - Kinderspital Zürich
• Taiwan
  • Taipei, Taiwan, 110
    • Taipei Medical University Hospital
  • Taoyuan, Taiwan, 333
    • Chang Gung Memorial Hospital - Linkou Branch
• United Kingdom
  • Bristol, United Kingdom, BS2 8HW
    • University Hospitals Bristol and Weston NHS Foundation Trust
  • Cambridge, United Kingdom, CB2 0QQ
    • Cambridge University Hospitals NHS Foundation Trust
  • Manchester, United Kingdom, M20 4BX
    • The Christie Hospital
  • England
    • Birmingham, England, United Kingdom, B4 6NH
      • Birmingham Women's and Children's NHS Foundation Trust
    • Leeds, England, United Kingdom, LS1 3EX
      • Leeds Teaching Hospital NHS Trust
    • Liverpool, England, United Kingdom, L12 2AP
      • Alder Hey Children's NHS Foundation Trust
    • Manchester, England, United Kingdom, M13 PWL
      • Manchester University NHS Foundation Trust
    • Newcastle upon Tyne, England, United Kingdom, NE1 4LP
      • The Newcastle Upon Tyne Hospitals NHS Foundation Trust
    • Oxford, England, United Kingdom, WC1N 3JH
      • Great Ormond Street Hospital for Children
  • Hampshire
    • Southampton, Hampshire, United Kingdom, SO16 6YD
      • University Hospital Southampton NHS Foundation Trust
  • Northern Ireland
    • Belfast, Northern Ireland, United Kingdom, BT9 7AB
      • Royal Belfast Hospital for Sick Children
  • Scotland
    • Glasgow, Scotland, United Kingdom, G51 4TF
      • NHS Greater Glasgow and Clyde
  • South Yorkshire
    • Sheffield, South Yorkshire, United Kingdom, S10 2TH
      • Sheffield Children's Hospital
  • Surrey
    • Sutton, Surrey, United Kingdom, SM2 5PT
      • The Royal Marsden NHS Foundation Trust
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Children's of Alabama
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Phoenix Children's Hospital
  • California
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles
    • Orange, California, United States, 92868
      • Children's Hospital of Orange County Main Campus - Orange
    • Palo Alto, California, United States, 94304
      • Packard Children's Hospital Stanford
    • San Francisco, California, United States, 94158
      • UCSF Benioff Children's Hospital
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado
  • Connecticut
    • Hartford, Connecticut, United States, 06106-3322
      • Connecticut Children's Medical Center
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20010
      • Children's National Medical Center
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida Health
    • Miami, Florida, United States, 33155
      • Nicklaus Children's Hospital
    • Orlando, Florida, United States, 32806
      • Arnold Palmer Hospital for Children
    • St. Petersburg, Florida, United States, 33701
      • Johns Hopkins All Children's Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Children's Healthcare of Atlanta
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann & Robert H. Lurie Children's Hospital of Chicago
    • Chicago, Illinois, United States, 60637
      • University of Chicago
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Riley Hospital for Children at Indiana University Health
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals Clinics
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Norton Children's Hospital
  • Maine
    • Scarborough, Maine, United States, 04074
      • Maine Children's Cancer Program
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan - - C.S. Mott Children's Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Children's Minnesota
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • Childrens MS Cncr Ctr Bld Dsr
  • Missouri
    • St Louis, Missouri, United States, 63110
      • St. Louis Children's Hospital
  • Nebraska
    • Omaha, Nebraska, United States, 68198-6878
      • University of Nebraska Medical Center
  • New York
    • Albany, New York, United States, 12208
      • Albany Medical Center
    • New York, New York, United States, 10032
      • Columbia University
    • New York, New York, United States, 10016
      • New York University Langone Health
    • Rochester, New York, United States, 14642
      • University of Rochester
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke Cancer Institute
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Main Campus
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health Science University
  • Texas
    • Austin, Texas, United States, 78723
      • Dell Children's Medical Center of Central Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Children's Hospital
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin - Madison

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 25 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Less than 25 years of age with LGG with known activating RAF alteration.
• Histopathologic diagnosis of glioma or glioneuronal tumor.
• At least one measurable lesion as defined by RANO criteria.
• Meet indication for first-line systemic therapy.

Exclusion Criteria:

• Participant has any of the following tumor-histological findings:

  1. Schwannoma
  2. Subependymal giant cell astrocytoma (Tuberous Sclerosis)
  3. Diffuse intrinsic pontine glioma, even if histologically diagnosed as World Health Organization (WHO) Grade I-II
• Participant's tumor has additional pathogenic molecular alterations, including but not limited to a) isocitrate dehydrogenase (IDH) 1/2 mutation, b) Histone H3 mutation, and c) neurofibromatosis Type 1 (NF-1) loss of function alteration.
• Known or suspected diagnosis of NF-1/ neurofibromatosis Type 2 (NF-2).
• Prior or ongoing nonsurgical anticancer therapy for this indication (eg, chemotherapy, oral/IV targeted therapy) including radiation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tovorafenib	Drug: Tovorafenib; Oral Tablet Powder for Oral Suspension; Other Names: DAY101, Ojemda
Active Comparator: Investigator's choice of Standard of care therapy	Drug: Chemotherapeutic Agent; Intravenous solution for injection; Other Names: Carboplatin; VBL; COG-V/C; SIOPe-LGG-V/C

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR) of tovorafenib monotherapy versus SoC chemotherapy	ORR assessed per Response Assessment in Pediatric Neuro Oncology (RAPNO) criteria by Independent Review Committee (IRC), and defined as the proportion of participants with overall confirmed response of complete response (CR), partial response (PR), or minor response (MR).	Up to 60 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS) of tovorafenib monotherapy versus SoC chemotherapy	PFS assessed per RAPNO criteria by IRC, and defined as time from randomization to PD or death from any cause, whichever comes first.	Up to 60 months
Event-free survival (EFS) of tovorafenib monotherapy versus SoC chemotherapy	EFS assessed per RAPNO criteria by IRC, defined as time from randomization to PD, death from any cause, or initiation of any new anticancer therapy, whichever comes first.	Up to 60 months
Overall survival (OS) of tovorafenib monotherapy versus SoC chemotherapy	Overall survival is defined as time from randomization up to death from any cause.	Up to 60 months
Number of participants with any treatment-emergent adverse events, and Serious adverse events	Type, frequency, and severity of adverse events of tovorafenib monotherapy versus SoC chemotherapy will be assessed.	Up to 60 months
. Number of participants with clinically significant vital signs and laboratory abnormalities findings	Type, frequency, and severity of vital signs and laboratory abnormalities of tovorafenib monotherapy versus SoC chemotherapy will be assessed.	Up to 60 months
Change from baseline in Adaptive Behavior Composite Score (ABS) of tovorafenib monotherapy versus SoC chemotherapy	Adaptive behavior Composite Score will be evaluated using domain scores collected from the comprehensive Vineland III Adaptive Behavior Scale (VABS).	Baseline, Year 1, 2 and 5
Change from baseline in the Motor Skills Domain Score of tovorafenib monotherapy versus SoC chemotherapy	The motor skills (gross and fine) will be assessed using the Motor Skills Score domain of the VABS in pediatric participants.	Baseline, Year 1, 2 and 5
Change from baseline in the Daily Living Domain Score of tovorafenib monotherapy versus SoC chemotherapy	The daily living (personal, domestic and community) will be assessed using Daily Living Domain Score of VABS.	Baseline, Year 1, 2 and 5
Change from baseline in the Communication Domain Score of tovorafenib monotherapy versus SoC chemotherapy	The communication skills (receptive, expressive and written) will be assessed using Communication Domain Score of VABS.	Baseline, Year 1, 2 and 5
Change from baseline in the Socialization Domain Score of tovorafenib monotherapy versus SoC chemotherapy	The socialization skills (Interpersonal relationships, play and leisure time and coping skills) will be assessed using Socialization Domain Score of VABS.	Baseline, Year 1, 2 and 5
Change in age-adjusted visual acuity (VA) of tovorafenib monotherapy versus SoC chemotherapy in optic pathway glioma (OPG) participants aged < 3 years	Visual acuity testing using current age-appropriate testing methodology will be performed for all participants at Screening. For participants with OPG or an underlying visual deficit related to the primary malignancy, visual acuity testing will be performed every time participants have a radiographic response assessment. Assessments will be performed in each eye separately at a recommended testing distance of 3 meters.	Baseline and up to 5 years
Change in best corrected visual acuity of tovorafenib monotherapy versus SoC chemotherapy in OPG participants aged ≥ 3 years	Visual acuity assessments to be performed by an ophthalmologist or another qualified site clinical personnel.	Baseline and up to 5 years
Visual progression-free survival (v-PFS) of tovorafenib monotherapy versus SoC chemotherapy	Visual progression-free survival is defined as the time from start of treatment to visual event for OPG participants aged ≥ 3 years.	Up to 60 months
ORR of tovorafenib monotherapy versus SoC chemotherapy	ORR, defined as the proportion of participants with overall confirmed response per Response Assessment in Neuro-Oncology for High-Grade Glioma (RANO-HGG) criteria (CR or PR) and RANO-LGG criteria (CR, PR, or MR), as applicable.	Up to 60 months
Clinical benefit rate (CBR) of tovorafenib monotherapy versus SoC chemotherapy	CBR, defined as the proportion of participants with radiological tumor stabilization or regression per RANO-LGG (CR, PR, MR, or SD lasting 12 months or more), RANO-HGG (CR, PR, or SD lasting 12 months or more) or RAPNO criteria (CR, PR, MR or SD lasting 12 months or more), as applicable.	Up to 60 months
Time to response (TTR) of tovorafenib monotherapy versus SoC chemotherapy	TTR, measured by the time following randomization to first imaging of tumor response that was subsequently confirmed per RANO-HGG criteria (CR or PR), RANO-LGG criteria (CR, or PR, or MR), or RAPNO criteria (CR, PR, or MR), as applicable.	Up to 60 months
PFS of tovorafenib monotherapy versus SoC chemotherapy	PFS per RANO-HGG or RANO-LGG criteria (as applicable), defined as time from randomization to PD or death from any cause, whichever occurs first.	Up to 60 months
EFS of tovorafenib monotherapy versus SoC chemotherapy	EFS per RANO-HGG or RANO-LGG criteria (as applicable), defined as time from randomization to PD, death from any cause, or initiation of any new anticancer therapy, whichever comes first.	Up to 60 months
Duration of response (DOR) of tovorafenib monotherapy versus SoC chemotherapy	DOR, defined as time from first imaging of tumor response per RANO-LGG, RANO-HGG or RAPNO criteria, as applicable, that was subsequently confirmed to radiographic PD or death from any cause, whichever comes first.	Up to 60 months
Change from Baseline in health-related quality of life (HRQoL) total score of tovorafenib monotherapy versus SoC chemotherapy	The Patient-Reported Outcomes Measurement Information System (PROMIS®) Pediatric/Parent Proxy Profile 49 v2.0 will be used to assess mental and social HRQoL.	Baseline, Year 1, 2 and 5

Collaborators and Investigators

• Sponsor: Day One Biopharmaceuticals, Inc.
• Collaborators: SIOPe Brain Tumor Group LOGGIC Consortium

Publications and helpful links

General Publications

• van Tilburg CM, Kilburn LB, Perreault S, Schmidt R, Azizi AA, Cruz-Martinez O, Zapotocky M, Scheinemann K, Meeteren AYNS, Sehested A, Opocher E, Driever PH, Avula S, Ziegler DS, Capper D, Koch A, Sahm F, Qiu J, Tsao LP, Blackman SC, Manley P, Milde T, Witt R, Jones DTW, Hargrave D, Witt O. LOGGIC/FIREFLY-2: a phase 3, randomized trial of tovorafenib vs. chemotherapy in pediatric and young adult patients with newly diagnosed low-grade glioma harboring an activating RAF alteration. BMC Cancer. 2024 Jan 30;24(1):147. doi: 10.1186/s12885-024-11820-x.

Study record dates

Study Major Dates

• Study Start (Actual): February 27, 2023
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2031

Study Registration Dates

• First Submitted: September 16, 2022
• First Submitted That Met QC Criteria: October 3, 2022
• First Posted (Actual): October 4, 2022

Study Record Updates

• Last Update Posted (Actual): May 14, 2026
• Last Update Submitted That Met QC Criteria: May 12, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Rapidly accelerated fibrosarcoma; RAF alteration glioma; Glioneural tumor; Ojemda
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Sarcoma; Neoplasms, Connective and Soft Tissue; Neoplasms, Connective Tissue; Neoplasms, Fibrous Tissue; Noonan Syndrome 5; Organic Chemicals; Pharmacologic Actions; Chemical Actions and Uses; Therapeutic Uses; Coordination Complexes; Carboplatin; Antineoplastic Agents; tovorafenib
• Other Study ID Numbers: DAY101-002; 2022-001363-27 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No