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

NCT05566795 | Active Not Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: DAY101-0022022-001363-27
• Study Type: interventional
• Target: 418
• Locations: 29 countries
• Sites: 132

Brief 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) alteration requiring first-line systemic therapy.

Conditions

Low-grade Glioma; Rapidly Accelerated Fibrosarcoma (RAF) Altered Glioma; Pediatric Low-grade Glioma

Keywords

Rapidly accelerated fibrosarcoma; RAF alteration glioma; Glioneural tumor; Ojemda

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (20)

• Progression-free survival (PFS) of tovorafenib monotherapy versus SoC chemotherapy

  Up to 60 months

• Event-free survival (EFS) of tovorafenib monotherapy versus SoC chemotherapy

  Up to 60 months

• Overall survival (OS) of tovorafenib monotherapy versus SoC chemotherapy

  Up to 60 months

• Number of participants with any treatment-emergent adverse events, and Serious adverse events

  Up to 60 months

• . Number of participants with clinically significant vital signs and laboratory abnormalities findings

  Up to 60 months

Study Arms (2)

Tovorafenib

EXPERIMENTAL

Drug: Tovorafenib

Investigator's choice of Standard of care therapy

ACTIVE COMPARATOR

Drug: Chemotherapeutic Agent

Interventions

Tovorafenib DRUG

Oral Tablet Powder for Oral Suspension

Also known as: DAY101, Ojemda

Tovorafenib

Chemotherapeutic Agent DRUG

Intravenous solution for injection

Also known as: COG-V/C, SIOPe-LGG-V/C, VBL, Carboplatin

Investigator's choice of Standard of care therapy

Eligibility Criteria

• Age: Up to 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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, 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.

Sponsors & Collaborators

• Day One Biopharmaceuticals, Inc.: lead
• SIOPe Brain Tumor Group LOGGIC Consortium: collaborator

Study Sites (138)

Children's of Alabama

Birmingham, Alabama, 35233, United States

Location

Phoenix Children's Hospital

Phoenix, Arizona, 85016, United States

Location

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Children's Hospital of Orange County Main Campus - Orange

Orange, California, 92868, United States

Location

Packard Children's Hospital Stanford

Palo Alto, California, 94304, United States

Location

UCSF Benioff Children's Hospital

San Francisco, California, 94158, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Connecticut Children's Medical Center

Hartford, Connecticut, 06106-3322, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

University of Florida Health

Gainesville, Florida, 32610, United States

Location

Nicklaus Children's Hospital

Miami, Florida, 33155, United States

Location

Arnold Palmer Hospital for Children

Orlando, Florida, 32806, United States

Location

Johns Hopkins All Children's Hospital

St. Petersburg, Florida, 33701, United States

Location

Children's Healthcare of Atlanta

Atlanta, Georgia, 30322, United States

Location

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Riley Hospital for Children at Indiana University Health

Indianapolis, Indiana, 46202, United States

Location

University of Iowa Hospitals Clinics

Iowa City, Iowa, 52242, United States

Location

Norton Children's Hospital

Louisville, Kentucky, 40202, United States

Location

Maine Children's Cancer Program

Scarborough, Maine, 04074, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Michigan - - C.S. Mott Children's Hospital

Ann Arbor, Michigan, 48109, United States

Location

Children's Minnesota

Minneapolis, Minnesota, 55404, United States

Location

Childrens MS Cncr Ctr Bld Dsr

Jackson, Mississippi, 39216, United States

Location

St. Louis Children's Hospital

St Louis, Missouri, 63110, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198-6878, United States

Location

Albany Medical Center

Albany, New York, 12208, United States

Location

New York University Langone Health

New York, New York, 10016, United States

Location

Columbia University

New York, New York, 10032, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

Duke Cancer Institute

Durham, North Carolina, 27705, United States

Location

Cleveland Clinic Main Campus

Cleveland, Ohio, 44195, United States

Location

Oregon Health Science University

Portland, Oregon, 97239, United States

Location

Dell Children's Medical Center of Central Texas

Austin, Texas, 78723, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

University of Wisconsin - Madison

Madison, Wisconsin, 53792, United States

Location

Children's Health Queensland Hospital and Health Service

South Brisbane, Queensland, 4101, Australia

Location

Perth Children's Hospital

Nedlands, 6009, Australia

Location

Women's and Children's Health Network

North Adelaide, 5006, Australia

Location

The Royal Children's Hospital - Children's Cancer Centre

Parkville, 3052, Australia

Location

Sydney Children's Hospital - Randwick

Randwick, 2031, Australia

Location

Children's Hospital at Westmead

Westmead, 2145, Australia

Location

Medizinische Universität Innsbruck

Innsbruck, Tyrol, 6020, Austria

Location

Medizinische Universität Wien

Vienna, 1090, Austria

Location

Cliniques Universitaires Saint-Luc

Brussels, 1200, Belgium

Location

Universitair Ziekenhuis Gent

Ghent, 9000, Belgium

Location

Universitair Ziekenhuis Leuven - Campus Gasthuisberg

Leuven, 3000, Belgium

Location

Grupo de Apoio ao Adolescente e à Criança com Câncer (GRAACC)

São Paulo, 04039-001, Brazil

Location

Alberta Children's Hospital

Calgary, Alberta, T3B 6A8, Canada

Location

Stollery Children's Hospital

Edmonton, Alberta, T6G 2B7, Canada

Location

British Columbia Children's Hospital

Vancouver, British Columbia, V6H 3N1, Canada

Location

McMaster Children's Hospital

Hamilton, Ontario, L8S 4L8, Canada

Location

Children's Hospital London Health Sciences Centre

London, Ontario, N6A 5W9, Canada

Location

Children's Hospital of Eastern Ontario

Ottawa, Ontario, K1H 8L1, Canada

Location

CHU Sainte-Justine

Montreal, Quebec, H3T IC5, Canada

Location

The Montreal Children's Hospital

Montreal, Quebec, H4A 3J1, Canada

Location

Centre Hospitalier de l'Université Laval et Centre Mère-Enfant Soleil

Québec, G1V 4G2, Canada

Location

SickKids - The Hospital for Sick Children

Toronto, M5G 1X8, Canada

Location

Fakultní Nemocnice Brno - D?tská Nemocnice

Brno, 625 00, Czechia

Location

Motol University Hospital

Prague, 5 150 06, Czechia

Location

Aarhus Universitetshospital

Aarhus, Central Jutland, 8200, Denmark

Location

Rigshospitalet

Copenhagen, 2100, Denmark

Location

CCHE

Cairo, Cairo Governorate, 11441, Egypt

Location

Helsingin yliopistollinen sairaala (HUS)

Helsinki, FI-00290, Finland

Location

Tampereen Yliopistollinen Sairaala

Tampere, 33520, Finland

Location

Centre de Lutte contre le Cancer - Centre Oscar Lambret

Lille, 59020, France

Location

Centre Léon Bérard

Lyon, 69008, France

Location

Hôpital de la Timone

Marseille, 13005, France

Location

Institut Curie

Paris, 75248, France

Location

Gustave Roussy

Villejuif, 94805, France

Location

Universitätsklinikum Freiburg

Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

Location

Universitätsklinikum Augsburg

Augsburg, Bavaria, 86156, Germany

Location

Universitätsklinikum Erlangen

Erlangen, Bavaria, 91054, Germany

Location

Universitätsklinikum Würzburg

Würzburg, Bavaria, 97080, Germany

Location

Universitätsklinikum Frankfurt

Frankfurt am Main, Hesse, 60590, Germany

Location

Medizinische Hochschule Hannover

Hanover, Lower Saxony, 30625, Germany

Location

Universitaetsklinikum Essen

Essen, North Rhine-Westphalia, 45147, Germany

Location

Universitätsklinikum Leipzig

Leipzig, Saxony, 4103, Germany

Location

Charité Universitätsmedizin Berlin

Berlin, 13353, Germany

Location

Evangelische Klinikum Bethel (EvKB)

Bielefeld, 33617, Germany

Location

Universitätsklinikum Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

Universitätsklinikum Heidelberg

Heidelberg, 69120, Germany

Location

Universitätsklinikum Tübingen

Tübingen, 72076, Germany

Location

Aghia Sofia General Children's Hospital

Athens, 11527, Greece

Location

Athens General Children's Hospital

Athens, 11527, Greece

Location

Semmelweis Egyetem Tűzoltó utcai II. Sz. Gyermekgyógyászati Kliniká

Budapest, 1094, Hungary

Location

Children's Health Ireland at Crumlin

Crumlin, Dublin, D12 N512, Ireland

Location

Schneider Children's Medical Center of Israel

Petah Tikva, 49202, Israel

Location

The Edmond and Lily Safra Children's Hospital

Ramat Gan, 5265601, Israel

Location

Fondazione IRCCS - Istituto Nazionale dei Tumori

Milan, Milan, 20133, Italy

Location

Ospedale Pediatrico Bambino Gesù

Roma, Rome, 00165, Italy

Location

Ospedale Infantile Regina Margherita

Torino, Turin, 10126, Italy

Location

Azienda Universitaria Ospedaliera Consorziale - Policlinico di Bari

Bari, 70124, Italy

Location

Azienda Ospedaliera U. Meyer

Florence, 50139, Italy

Location

Istituto Giannina Gaslini

Genova, 16147, Italy

Location

Azienda Ospedaliera di Rilievo Nazional Santobono Pausilipon

Naples, 80131, Italy

Location

Azienda Ospedale Università di Padova

Padova, 35128, Italy

Location

Azienda Sanitaria Universitaria Friuli Centrale - P.O. Santa Maria della Misericordia

Udine, 33100, Italy

Location

King Hussein Cancer Foundation - King Hussein Cancer Center

Amman, Muhafazat al-Asima, 11941, Jordan

Location

Prinses Maxima Centrum Kinderoncologie

Utrecht, 3584 CS, Netherlands

Location

Starship Paediatric Blood & Cancer Center

Grafton, 1023, New Zealand

Location

Universitetssykehuset Nord-Norge - Tromsø

Tromsø, Troms, 9038, Norway

Location

Oslo Universitetssykehus

Oslo, 372, Norway

Location

Sidra Medicine

Doha, 26999, Qatar

Location

SingHealth Group - KK Women's and Children's Hospital

Singapore, 229899, Singapore

Location

Univerzitetni Klinini Center Ljubljana

Ljubljana, 1000, Slovenia

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Severance Hospital

Seoul, 03722, South Korea

Location

Hospital Universitario Cruces

Barakaldo, 48903, Spain

Location

Hospital Universitari Vall d'Hebrón

Barcelona, 08035, Spain

Location

Hospital Sant Joan de Déu Barcelona

Barcelona, 08950, Spain

Location

Hospital Infantil Universitario Niño Jesús

Madrid, 28009, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, 41013, Spain

Location

Hospital Universitari i Politècnic La Fe

Valencia, 46026, Spain

Location

Drottning Silvias barn- och ungdomssjukhus

Gothenburg, 416 85, Sweden

Location

Skånes Universitetssjukhus - Lund

Lund, 221 85, Sweden

Location

Astrid Lindgrens Barnsjukhus Solna

Stockholm, 171 77, Sweden

Location

Centre Hospitalier Universitaire Vaudois Lausanne

Lausanne, 1011, Switzerland

Location

Universitaets - Kinderspital Zürich

Zurich, 8032, Switzerland

Location

Taipei Medical University Hospital

Taipei, 110, Taiwan

Location

Chang Gung Memorial Hospital - Linkou Branch

Taoyuan, 333, Taiwan

Location

Birmingham Women's and Children's NHS Foundation Trust

Birmingham, England, B4 6NH, United Kingdom

Location

Leeds Teaching Hospital NHS Trust

Leeds, England, LS1 3EX, United Kingdom

Location

Alder Hey Children's NHS Foundation Trust

Liverpool, England, L12 2AP, United Kingdom

Location

Manchester University NHS Foundation Trust

Manchester, England, M13 PWL, United Kingdom

Location

The Newcastle Upon Tyne Hospitals NHS Foundation Trust

Newcastle upon Tyne, England, NE1 4LP, United Kingdom

Location

Great Ormond Street Hospital for Children

Oxford, England, WC1N 3JH, United Kingdom

Location

University Hospital Southampton NHS Foundation Trust

Southampton, Hampshire, SO16 6YD, United Kingdom

Location

Royal Belfast Hospital for Sick Children

Belfast, Northern Ireland, BT9 7AB, United Kingdom

Location

NHS Greater Glasgow and Clyde

Glasgow, Scotland, G51 4TF, United Kingdom

Location

Sheffield Children's Hospital

Sheffield, South Yorkshire, S10 2TH, United Kingdom

Location

The Royal Marsden NHS Foundation Trust

Sutton, Surrey, SM2 5PT, United Kingdom

Location

University Hospitals Bristol and Weston NHS Foundation Trust

Bristol, BS2 8HW, United Kingdom

Location

Cambridge University Hospitals NHS Foundation Trust

Cambridge, CB2 0QQ, United Kingdom

Location

The Christie Hospital

Manchester, M20 4BX, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 38291372 DERIVED

MeSH Terms

Conditions

Noonan Syndrome 5

Interventions

tovorafenib; Antineoplastic Agents; Carboplatin

Intervention Hierarchy (Ancestors)

Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses; Coordination Complexes; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Tovorafenib versus standard of care chemotherapy

Study Record Dates

• First Submitted: September 16, 2022
• First Posted: October 4, 2022
• Study Start: February 27, 2023
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2031
• Last Updated: May 14, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

IT (9); QA (1); BE (3); DK (2); NL (1); US (38); SL (1); BR (1); GB (14); NO (2); EG (1); ES (7); FR (5); IL (2); NZ (1); KR (2); CA (10); HU (1); IE (1); SE (3); CZ (2); TW (2); GR (2); SG (1); FI (2); JO (1); CH (2); DE (13); AU (2)