Low-grade GliomaPhase 3NCT05566795
DAY101 vs. Standard of Care Chemotherapy in Pediatric Participants With Low-Grade Glioma Requiring First-Line Systemic Therapy (LOGGIC/FIREFLY-2)
A Phase 3 study testing Tovorafenib and Chemotherapeutic Agent in people with Low-grade Glioma and Rapidly Accelerated Fibrosarcoma (RAF) Altered Glioma, run by Day One Biopharmaceuticals, Inc. at 138 sites in 30 countries.
Trial summary
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)… Read more about this study
- Who is it for?
- Ages Up to 25 years
- Conditions the study is for
- Low-grade Glioma, Rapidly Accelerated Fibrosarcoma (RAF) Altered Glioma, Pediatric Low-grade Glioma
- What is being tested?
- Tovorafenib and Chemotherapeutic Agent
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 418 participants
- Where
- 138 sitesin 30 countries
- Study dates
- 27 Feb 2023to Jun 2031
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 25 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Less than 25 years of age with LGG harboring a documented known activating RAF alteration, as identified through molecular assays performed at Clinical Laboratory Improvement Amendments (CLIA) or other similarly certified laboratories.
- Histopathologic diagnosis of glioma or glioneuronal tumor.
- At least one measurable T2/FLAIR lesion that can be reproducibly measured in at least 2 dimensions of at least 10 millimetres (mm), visible on 2 or more axial slices that are preferably, at most, 5 mm apart with 0-mm skip.
- Meet indication for first-line systemic therapy.
Who cannot join
- Participant has any of the following tumor-histological findings:
- Schwannoma
- Subependymal giant cell astrocytoma (Tuberous Sclerosis)
- Diffuse intrinsic pontine glioma, even if histologically diagnosed as World Health Organization (WHO) Grade I-II
- Participant's tumor has additional pathogenic molecular alterations, (even if histologically low-grade) including but not limited to any of the following: 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) via genetic testing or current diagnostic clinical criteria.
- Prior or ongoing nonsurgical anticancer therapy for this indication (eg, chemotherapy, oral/IV targeted therapy) including radiation.
Trial locations and contacts
138 sites in 30 countries.
138 sites in 30 countries
United States38 sites
Albany Medical Center
Albany, New York, 12208
University of Michigan - - C.S. Mott Children's Hospital
Ann Arbor, Michigan, 48109
Children's Healthcare of Atlanta
Atlanta, Georgia, 30322
Children's Hospital Colorado
Aurora, Colorado, 80045
Dell Children's Medical Center of Central Texas
Austin, Texas, 78723
Children's of Alabama
Birmingham, Alabama, 35233
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611
University of Chicago
Chicago, Illinois, 60637
Cleveland Clinic Main Campus
Cleveland, Ohio, 44195
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
Duke Cancer Institute
Durham, North Carolina, 27705
University of Florida Health
Gainesville, Florida, 32610
Connecticut Children's Medical Center
Hartford, Connecticut, 06106-3322
Texas Children's Hospital
Houston, Texas, 77030
Riley Hospital for Children at Indiana University Health
Indianapolis, Indiana, 46202
University of Iowa Hospitals Clinics
Iowa City, Iowa, 52242
Childrens MS Cncr Ctr Bld Dsr
Jackson, Mississippi, 39216
Children's Hospital Los Angeles
Los Angeles, California, 90027
Norton Children's Hospital
Louisville, Kentucky, 40202
University of Wisconsin - Madison
Madison, Wisconsin, 53792
Nicklaus Children's Hospital
Miami, Florida, 33155
Children's Minnesota
Minneapolis, Minnesota, 55404
New York University Langone Health
New York, New York, 10016
Columbia University
New York, New York, 10032
University of Nebraska Medical Center
Omaha, Nebraska, 68198-6878
Children's Hospital of Orange County Main Campus - Orange
Orange, California, 92868
Arnold Palmer Hospital for Children
Orlando, Florida, 32806
Packard Children's Hospital Stanford
Palo Alto, California, 94304
Phoenix Children's Hospital
Phoenix, Arizona, 85016
Oregon Health Science University
Portland, Oregon, 97239
University of Rochester
Rochester, New York, 14642
UCSF Benioff Children's Hospital
San Francisco, California, 94158
Maine Children's Cancer Program
Scarborough, Maine, 04074
Seattle Children's Hospital
Seattle, Washington, 98105
St. Louis Children's Hospital
St Louis, Missouri, 63110
Johns Hopkins All Children's Hospital
St. Petersburg, Florida, 33701
Children's National Medical Center
Washington D.C., District of Columbia, 20010
United Kingdom14 sites
Royal Belfast Hospital for Sick Children
Belfast, Northern Ireland, BT9 7AB
Birmingham Women's and Children's NHS Foundation Trust
Birmingham, England, B4 6NH
University Hospitals Bristol and Weston NHS Foundation Trust
Bristol, BS2 8HW
Cambridge University Hospitals NHS Foundation Trust
Cambridge, CB2 0QQ
NHS Greater Glasgow and Clyde
Glasgow, Scotland, G51 4TF
Leeds Teaching Hospital NHS Trust
Leeds, England, LS1 3EX
Alder Hey Children's NHS Foundation Trust
Liverpool, England, L12 2AP
Manchester University NHS Foundation Trust
Manchester, England, M13 PWL
The Christie Hospital
Manchester, M20 4BX
The Newcastle Upon Tyne Hospitals NHS Foundation Trust
Newcastle upon Tyne, England, NE1 4LP
Great Ormond Street Hospital for Children
Oxford, England, WC1N 3JH
Sheffield Children's Hospital
Sheffield, South Yorkshire, S10 2TH
University Hospital Southampton NHS Foundation Trust
Southampton, Hampshire, SO16 6YD
The Royal Marsden NHS Foundation Trust
Sutton, Surrey, SM2 5PT
Germany13 sites
Universitätsklinikum Augsburg
Augsburg, Bavaria, 86156
Charité Universitätsmedizin Berlin
Berlin, 13353
Evangelische Klinikum Bethel (EvKB)
Bielefeld, 33617
Universitätsklinikum Erlangen
Erlangen, Bavaria, 91054
Universitaetsklinikum Essen
Essen, North Rhine-Westphalia, 45147
Universitätsklinikum Frankfurt
Frankfurt am Main, Hesse, 60590
Universitätsklinikum Freiburg
Freiburg im Breisgau, Baden-Wurttemberg, 79106
Universitätsklinikum Hamburg-Eppendorf
Hamburg, 20246
Medizinische Hochschule Hannover
Hanover, Lower Saxony, 30625
Universitätsklinikum Heidelberg
Heidelberg, 69120
Universitätsklinikum Leipzig
Leipzig, Saxony, 4103
Universitätsklinikum Tübingen
Tübingen, 72076
Universitätsklinikum Würzburg
Würzburg, Bavaria, 97080
Canada10 sites
Alberta Children's Hospital
Calgary, Alberta, T3B 6A8
Stollery Children's Hospital
Edmonton, Alberta, T6G 2B7
McMaster Children's Hospital
Hamilton, Ontario, L8S 4L8
Children's Hospital London Health Sciences Centre
London, Ontario, N6A 5W9
CHU Sainte-Justine
Montreal, Quebec, H3T IC5
The Montreal Children's Hospital
Montreal, Quebec, H4A 3J1
Children's Hospital of Eastern Ontario
Ottawa, Ontario, K1H 8L1
Centre Hospitalier de l'Université Laval et Centre Mère-Enfant Soleil
Québec, G1V 4G2
SickKids - The Hospital for Sick Children
Toronto, M5G 1X8
British Columbia Children's Hospital
Vancouver, British Columbia, V6H 3N1
Italy9 sites
Azienda Universitaria Ospedaliera Consorziale - Policlinico di Bari
Bari, 70124
Azienda Ospedaliera U. Meyer
Florence, 50139
Istituto Giannina Gaslini
Genova, 16147
Fondazione IRCCS - Istituto Nazionale dei Tumori
Milan, Milan, 20133
Azienda Ospedaliera di Rilievo Nazional Santobono Pausilipon
Naples, 80131
Azienda Ospedale Università di Padova
Padova, 35128
Ospedale Pediatrico Bambino Gesù
Roma, Rome, 00165
Ospedale Infantile Regina Margherita
Torino, Turin, 10126
Azienda Sanitaria Universitaria Friuli Centrale - P.O. Santa Maria della Misericordia
Udine, 33100
Spain7 sites
Hospital Universitario Cruces
Barakaldo, 48903
Hospital Universitari Vall d'Hebrón
Barcelona, 08035
Hospital Sant Joan de Déu Barcelona
Barcelona, 08950
Hospital Infantil Universitario Niño Jesús
Madrid, 28009
Hospital Universitario La Paz
Madrid, 28046
Hospital Universitario Virgen del Rocío
Seville, 41013
Hospital Universitari i Politècnic La Fe
Valencia, 46026
Australia6 sites
Perth Children's Hospital
Nedlands, 6009
Women's and Children's Health Network
North Adelaide, 5006
The Royal Children's Hospital - Children's Cancer Centre
Parkville, 3052
Sydney Children's Hospital - Randwick
Randwick, 2031
Children's Health Queensland Hospital and Health Service
South Brisbane, Queensland, 4101
Children's Hospital at Westmead
Westmead, 2145
France5 sites
Centre de Lutte contre le Cancer - Centre Oscar Lambret
Lille, 59020
Centre Léon Bérard
Lyon, 69008
Hôpital de la Timone
Marseille, 13005
Institut Curie
Paris, 75248
Gustave Roussy
Villejuif, 94805
Belgium3 sites
Cliniques Universitaires Saint-Luc
Brussels, 1200
Universitair Ziekenhuis Gent
Ghent, 9000
Universitair Ziekenhuis Leuven - Campus Gasthuisberg
Leuven, 3000
Sweden3 sites
Drottning Silvias barn- och ungdomssjukhus
Gothenburg, 416 85
Skånes Universitetssjukhus - Lund
Lund, 221 85
Astrid Lindgrens Barnsjukhus Solna
Stockholm, 171 77
Austria2 sites
Medizinische Universität Innsbruck
Innsbruck, Tyrol, 6020
Medizinische Universität Wien
Vienna, 1090
Czechia2 sites
Fakultní Nemocnice Brno - D?tská Nemocnice
Brno, 625 00
Motol University Hospital
Prague, 5 150 06
Denmark2 sites
Aarhus Universitetshospital
Aarhus, Central Jutland, 8200
Rigshospitalet
Copenhagen, 2100
Finland2 sites
Helsingin yliopistollinen sairaala (HUS)
Helsinki, FI-00290
Tampereen Yliopistollinen Sairaala
Tampere, 33520
Greece2 sites
Aghia Sofia General Children's Hospital
Athens, 11527
Athens General Children's Hospital
Athens, 11527
Israel2 sites
Schneider Children's Medical Center of Israel
Petah Tikva, 49202
The Edmond and Lily Safra Children's Hospital
Ramat Gan, 5265601
Norway2 sites
Oslo Universitetssykehus
Oslo, 372
Universitetssykehuset Nord-Norge - Tromsø
Tromsø, Troms, 9038
South Korea2 sites
Seoul National University Hospital
Seoul, 03080
Severance Hospital
Seoul, 03722
Switzerland2 sites
Centre Hospitalier Universitaire Vaudois Lausanne
Lausanne, 1011
Universitaets - Kinderspital Zürich
Zurich, 8032
Taiwan2 sites
Taipei Medical University Hospital
Taipei, 110
Chang Gung Memorial Hospital - Linkou Branch
Taoyuan, 333
Brazil1 site
Grupo de Apoio ao Adolescente e à Criança com Câncer (GRAACC)
São Paulo, 04039-001
Hungary1 site
Semmelweis Egyetem Tűzoltó utcai II. Sz. Gyermekgyógyászati Kliniká
Budapest, 1094
Jordan1 site
King Hussein Cancer Foundation - King Hussein Cancer Center
Amman, Muhafazat al-Asima, 11941
Singapore1 site
SingHealth Group - KK Women's and Children's Hospital
Singapore, 229899
About this study
Official title: 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.
Read the 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).
- Conditions
- Low-grade Glioma, Rapidly Accelerated Fibrosarcoma (RAF) Altered Glioma, Pediatric Low-grade Glioma
- Being tested
- Tovorafenib, Chemotherapeutic Agent
- Keywords
- Rapidly accelerated fibrosarcoma, RAF alteration glioma, Glioneural tumor, Ojemda
- Medical subject headings
- Noonan Syndrome 5
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TovorafenibDrug
Also called DAY101, Ojemda
Oral Tablet Powder for Oral Suspension
Chemotherapeutic AgentDrug
Also called COG-V/C, SIOPe-LGG-V/C, VBL, Carboplatin
Intravenous solution for injection
| Study group | Role | What they receive |
|---|---|---|
| Tovorafenib | Experimental | Not described Receives: Drug: Tovorafenib |
| Investigator's choice of Standard of care therapy | Active comparator | Not described Receives: Drug: Chemotherapeutic Agent |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Up to 60 months
Secondary outcomes (4)
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.
Measured: 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.
Measured: Up to 60 months
Time to next treatment (TTNT) of tovorafenib monotherapy versus SoC chemotherapy
Time to next treatment is defined as time from randomization to initiation of any new anticancer treatment or death from any cause, whichever occurs first.
Measured: 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.
Measured: Up to 60 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Oct 2022
- Study start27 Feb 2023
- Primary completionJun 2027 (estimated)
- Study completionJun 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Low-grade GliomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Tovorafenib versus standard of care chemotherapy
- Masking
- None (open label)
- Enrolment
- 418 participants (actual)
Sponsor and investigators
- Lead sponsor
- Day One Biopharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- SIOPe Brain Tumor Group LOGGIC Consortium
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05566795
- Sponsor's protocol ID
- DAY101-002
- Other IDs
- 2022-001363-27
- Status last verified
- Oct 2026
- First submitted
- 16 Sep 2022
- Last updated
- 19 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Amayiri N, Mushtaq N, Ghalibafian M, Bouffet E. Management of pediatric brain tumors in low- and middle-income countries. Adv Cancer Res. 2025;167:427-453. doi: 10.1016/bs.acr.2025.08.004. Epub 2025 Sep 9.
PubMed 41198344van 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.
PubMed 38291372