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

NCT05566795 | Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: DAY101-0022022-001363-27
• Study Type: interventional
• Target: 400
• Locations: 29 countries
• Sites: 136

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

RECRUITING

Phoenix Children's Hospital

Phoenix, Arizona, 85016, United States

RECRUITING

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

RECRUITING

Children's Hospital of Orange County Main Campus - Orange

Orange, California, 92868, United States

RECRUITING

Packard Children's Hospital Stanford

Palo Alto, California, 94304, United States

RECRUITING

UCSF Benioff Children's Hospital

San Francisco, California, 94158, United States

RECRUITING

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

RECRUITING

Connecticut Children's Medical Center

Hartford, Connecticut, 06106-3322, United States

RECRUITING

Children's National Medical Center

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

RECRUITING

University of Florida Health

Gainesville, Florida, 32610, United States

RECRUITING

Nicklaus Children's Hospital

Miami, Florida, 33155, United States

RECRUITING

Arnold Palmer Hospital for Children

Orlando, Florida, 32806, United States

RECRUITING

Johns Hopkins All Children's Hospital

St. Petersburg, Florida, 33701, United States

RECRUITING

Children's Healthcare of Atlanta

Atlanta, Georgia, 30322, United States

RECRUITING

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

Chicago, Illinois, 60611, United States

RECRUITING

University of Chicago

Chicago, Illinois, 60637, United States

RECRUITING

Riley Hospital for Children at Indiana University Health

Indianapolis, Indiana, 46202, United States

RECRUITING

University of Iowa Hospitals Clinics

Iowa City, Iowa, 52242, United States

RECRUITING

Norton Children's Hospital

Louisville, Kentucky, 40202, United States

RECRUITING

Maine Children's Cancer Program

Scarborough, Maine, 04074, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

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

Ann Arbor, Michigan, 48109, United States

RECRUITING

Children's Minnesota

Minneapolis, Minnesota, 55404, United States

RECRUITING

Childrens MS Cncr Ctr Bld Dsr

Jackson, Mississippi, 39216, United States

RECRUITING

St. Louis Children's Hospital

St Louis, Missouri, 63110, United States

RECRUITING

University of Nebraska Medical Center

Omaha, Nebraska, 68198-6878, United States

RECRUITING

Albany Medical Center

Albany, New York, 12208, United States

RECRUITING

New York University Langone Health

New York, New York, 10016, United States

RECRUITING

Columbia University

New York, New York, 10032, United States

RECRUITING

University of Rochester

Rochester, New York, 14642, United States

RECRUITING

Duke Cancer Institute

Durham, North Carolina, 27705, United States

RECRUITING

Cleveland Clinic Main Campus

Cleveland, Ohio, 44195, United States

RECRUITING

Oregon Health Science University

Portland, Oregon, 97239, United States

RECRUITING

Dell Children's Medical Center of Central Texas

Austin, Texas, 78723, United States

RECRUITING

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

RECRUITING

Texas Children's Hospital

Houston, Texas, 77030, United States

RECRUITING

Seattle Children's Hospital

Seattle, Washington, 98105, United States

RECRUITING

University of Wisconsin - Madison

Madison, Wisconsin, 53792, United States

RECRUITING

Children's Health Queensland Hospital and Health Service

South Brisbane, Queensland, 4101, Australia

RECRUITING

Perth Children's Hospital

Nedlands, 6009, Australia

RECRUITING

Women's and Children's Health Network

North Adelaide, 5006, Australia

RECRUITING

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

Parkville, 3052, Australia

RECRUITING

Sydney Children's Hospital - Randwick

Randwick, 2031, Australia

RECRUITING

Children's Hospital at Westmead

Westmead, 2145, Australia

RECRUITING

Medizinische Universität Innsbruck

Innsbruck, Tyrol, 6020, Austria

RECRUITING

Medizinische Universität Wien

Vienna, 1090, Austria

RECRUITING

Cliniques Universitaires Saint-Luc

Brussels, 1200, Belgium

RECRUITING

Universitair Ziekenhuis Gent

Ghent, 9000, Belgium

RECRUITING

Universitair Ziekenhuis Leuven - Campus Gasthuisberg

Leuven, 3000, Belgium

RECRUITING

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

São Paulo, 04039-001, Brazil

RECRUITING

Alberta Children's Hospital

Calgary, Alberta, T3B 6A8, Canada

RECRUITING

Stollery Children's Hospital

Edmonton, Alberta, T6G 2B7, Canada

RECRUITING

British Columbia Children's Hospital

Vancouver, British Columbia, V6H 3N1, Canada

RECRUITING

McMaster Children's Hospital

Hamilton, Ontario, L8S 4L8, Canada

RECRUITING

Children's Hospital London Health Sciences Centre

London, Ontario, N6A 5W9, Canada

RECRUITING

Children's Hospital of Eastern Ontario

Ottawa, Ontario, K1H 8L1, Canada

RECRUITING

CHU Sainte-Justine

Montreal, Quebec, H3T IC5, Canada

RECRUITING

The Montreal Children's Hospital

Montreal, Quebec, H4A 3J1, Canada

RECRUITING

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

Québec, G1V 4G2, Canada

RECRUITING

SickKids - The Hospital for Sick Children

Toronto, M5G 1X8, Canada

RECRUITING

Fakultní Nemocnice Brno - D?tská Nemocnice

Brno, 625 00, Czechia

RECRUITING

Motol University Hospital

Prague, 5 150 06, Czechia

RECRUITING

Aarhus Universitetshospital

Aarhus, Central Jutland, 8200, Denmark

RECRUITING

Rigshospitalet

Copenhagen, 2100, Denmark

RECRUITING

CCHE

Cairo, Cairo Governorate, 11441, Egypt

RECRUITING

Helsingin yliopistollinen sairaala (HUS)

Helsinki, FI-00290, Finland

RECRUITING

Tampereen Yliopistollinen Sairaala

Tampere, 33520, Finland

RECRUITING

Centre de Lutte contre le Cancer - Centre Oscar Lambret

Lille, 59020, France

RECRUITING

Centre Léon Bérard

Lyon, 69008, France

RECRUITING

Hôpital de la Timone

Marseille, 13005, France

RECRUITING

Institut Curie

Paris, 75248, France

RECRUITING

Gustave Roussy

Villejuif, 94805, France

RECRUITING

Universitätsklinikum Freiburg

Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

RECRUITING

Universitätsklinikum Augsburg

Augsburg, Bavaria, 86156, Germany

RECRUITING

Universitätsklinikum Erlangen

Erlangen, Bavaria, 91054, Germany

RECRUITING

Universitätsklinikum Würzburg

Würzburg, Bavaria, 97080, Germany

RECRUITING

Universitätsklinikum Frankfurt

Frankfurt am Main, Hesse, 60590, Germany

RECRUITING

Medizinische Hochschule Hannover

Hanover, Lower Saxony, 30625, Germany

RECRUITING

Universitaetsklinikum Essen

Essen, North Rhine-Westphalia, 45147, Germany

RECRUITING

Universitätsklinikum Leipzig

Leipzig, Saxony, 4103, Germany

RECRUITING

Charité Universitätsmedizin Berlin

Berlin, 13353, Germany

RECRUITING

Evangelische Klinikum Bethel (EvKB)

Bielefeld, 33617, Germany

RECRUITING

Universitätsklinikum Hamburg-Eppendorf

Hamburg, 20246, Germany

RECRUITING

Universitätsklinikum Heidelberg

Heidelberg, 69120, Germany

RECRUITING

Universitätsklinikum Tübingen

Tübingen, 72076, Germany

RECRUITING

Aghia Sofia General Children's Hospital

Athens, 11527, Greece

RECRUITING

Athens General Children's Hospital

Athens, 11527, Greece

RECRUITING

Semmelweis Egyetem Tűzoltó utcai II. Sz. Gyermekgyógyászati Kliniká

Budapest, 1094, Hungary

RECRUITING

Children's Health Ireland at Crumlin

Crumlin, Dublin, D12 N512, Ireland

RECRUITING

Schneider Children's Medical Center of Israel

Petah Tikva, 49202, Israel

RECRUITING

The Edmond and Lily Safra Children's Hospital

Ramat Gan, 5265601, Israel

RECRUITING

Fondazione IRCCS - Istituto Nazionale dei Tumori

Milan, Milan, 20133, Italy

RECRUITING

Ospedale Pediatrico Bambino Gesù

Roma, Rome, 00165, Italy

RECRUITING

Ospedale Infantile Regina Margherita

Torino, Turin, 10126, Italy

RECRUITING

Azienda Universitaria Ospedaliera Consorziale - Policlinico di Bari

Bari, 70124, Italy

RECRUITING

Azienda Ospedaliera U. Meyer

Florence, 50139, Italy

RECRUITING

Istituto Giannina Gaslini

Genova, 16147, Italy

RECRUITING

Azienda Ospedaliera di Rilievo Nazional Santobono Pausilipon

Naples, 80131, Italy

RECRUITING

Azienda Ospedale Università di Padova

Padua, 35128, Italy

RECRUITING

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

Udine, 33100, Italy

RECRUITING

King Hussein Cancer Foundation - King Hussein Cancer Center

Amman, Muhafazat al-Asima, 11941, Jordan

RECRUITING

Prinses Maxima Centrum Kinderoncologie

Utrecht, 3584 CS, Netherlands

RECRUITING

Starship Paediatric Blood & Cancer Center

Grafton, 1023, New Zealand

RECRUITING

Universitetssykehuset Nord-Norge - Tromsø

Tromsø, Troms, 9038, Norway

RECRUITING

Oslo Universitetssykehus

Oslo, 372, Norway

RECRUITING

Sidra Medicine

Doha, 26999, Qatar

RECRUITING

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

Singapore, 229899, Singapore

RECRUITING

Univerzitetni Klinini Center Ljubljana

Ljubljana, 1000, Slovenia

RECRUITING

Seoul National University Hospital

Seoul, 03080, South Korea

RECRUITING

Severance Hospital

Seoul, 03722, South Korea

RECRUITING

Hospital Universitario Cruces

Barakaldo, 48903, Spain

RECRUITING

Hospital Universitari Vall d'Hebrón

Barcelona, 08035, Spain

RECRUITING

Hospital Sant Joan de Déu Barcelona

Barcelona, 08950, Spain

RECRUITING

Hospital Infantil Universitario Niño Jesús

Madrid, 28009, Spain

RECRUITING

Hospital Universitario La Paz

Madrid, 28046, Spain

RECRUITING

Hospital Universitario Virgen del Rocío

Seville, 41013, Spain

RECRUITING

Hospital Universitari i Politècnic La Fe

Valencia, 46026, Spain

RECRUITING

Drottning Silvias barn- och ungdomssjukhus

Gothenburg, 416 85, Sweden

RECRUITING

Skånes Universitetssjukhus - Lund

Lund, 221 85, Sweden

RECRUITING

Astrid Lindgrens Barnsjukhus Solna

Stockholm, 171 77, Sweden

RECRUITING

Centre Hospitalier Universitaire Vaudois Lausanne

Lausanne, 1011, Switzerland

RECRUITING

Universitaets - Kinderspital Zürich

Zurich, 8032, Switzerland

RECRUITING

Taipei Medical University Hospital

Taipei, 110, Taiwan

RECRUITING

Chang Gung Memorial Hospital - Linkou Branch

Taoyuan District, 333, Taiwan

RECRUITING

Birmingham Women's and Children's NHS Foundation Trust

Birmingham, England, B4 6NH, United Kingdom

RECRUITING

Leeds Teaching Hospital NHS Trust

Leeds, England, LS1 3EX, United Kingdom

RECRUITING

Alder Hey Children's NHS Foundation Trust

Liverpool, England, L12 2AP, United Kingdom

RECRUITING

Manchester University NHS Foundation Trust

Manchester, England, M13 PWL, United Kingdom

RECRUITING

The Newcastle Upon Tyne Hospitals NHS Foundation Trust

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

RECRUITING

Great Ormond Street Hospital for Children

Oxford, England, WC1N 3JH, United Kingdom

RECRUITING

University Hospital Southampton NHS Foundation Trust

Southampton, Hampshire, SO16 6YD, United Kingdom

RECRUITING

Royal Belfast Hospital for Sick Children

Belfast, Northern Ireland, BT9 7AB, United Kingdom

RECRUITING

NHS Greater Glasgow and Clyde

Glasgow, Scotland, G51 4TF, United Kingdom

RECRUITING

Sheffield Children's Hospital

Sheffield, South Yorkshire, S10 2TH, United Kingdom

RECRUITING

The Royal Marsden NHS Foundation Trust

Sutton, Surrey, SM2 5PT, United Kingdom

RECRUITING

University Hospitals Bristol and Weston NHS Foundation Trust

Bristol, BS2 8HW, United Kingdom

RECRUITING

Cambridge University Hospitals NHS Foundation Trust

Cambridge, CB2 0QQ, United Kingdom

RECRUITING

The Christie Hospital

Manchester, M20 4BX, United Kingdom

RECRUITING

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

Central Study Contacts

Day One Clinical Trials Information

CONTACT

650-484-0899; clinicaltrials@dayonebio.com

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: March 2, 2026

Record last verified: 2026-02

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 (6)