DAY101 vs. Standard of Care Chemotherapy in Pediatric Patients 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 DAY101 monotherapy versus standard of care (SoC) chemotherapy in patients with pediatric low-grade glioma (LGG) harboring an activating rapidly accelerated fibrosarcoma (RAF) alteration requiring front-line systemic therapy.

Study Overview

• Status: Recruiting
• Conditions: Low-grade Glioma
• Intervention / Treatment: Drug: DAY101; Drug: Chemotherapeutic Agent

Detailed Description

Approximately 400 treatment-naïve low-grade glioma patients will be randomized 1:1 to either DAY101 (Arm 1) or an Investigator's choice of SoC chemotherapy (Arm 2).

Arm 1 (DAY101): treatment cycles will repeat every 28 days in the absence of disease progression. Patients will continue DAY101 until any of the following occurs: radiographic progression based on Response Assessment in Neuro-Oncology (RANO) criteria as determined by the Investigator and confirmed by the Independent Review Committee (IRC), unacceptable toxicity, withdrawal of consent to treatment, or end of study.

Arm 2 (Investigator's Choice of SoC Chemotherapy): patients will receive one of 3 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, or vinblastine (VBL) regimen. The choice of SoC chemotherapy regimen will be selected prior to patient randomization. Treatment will continue until completion of therapy or until any of the following occurs: radiographic progression based on RANO criteria as determined by the Investigator and confirmed by the IRC, unacceptable toxicity, withdrawal of consent to treatment, or end of study.

During treatment phase, patients who demonstrate radiographic progression per RANO criteria as determined by the Investigator and confirmed by IRC in Arm 1 (DAY101) may be allowed to continue DAY101 if, in the opinion of the Investigator, the patient is deriving clinical benefit from continuing study treatment and approved by the Sponsor. Patients who demonstrate radiographic progression per RANO criteria as determined by the Investigator and confirmed by IRC during the treatment phase in Arm 2 (SoC chemotherapy) and discontinue treatment may be eligible to receive DAY101 at the same treatment and assessment schedule. In addition, Arm 2 patients who demonstrate radiographic progression after completion of chemotherapy [ie, during long-term follow-up (LTFU)] may be eligible to receive DAY101.

• Study Type: Interventional
• Enrollment (Estimated): 400
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Day One Clinical Trials Information; Phone Number: 650-484-0899; Email: clinicaltrials@dayonebio.com

Study Locations

• Australia
  • Nedlands, Australia, 6009
    • Recruiting
    • Perth Children's Hospital
  • North Adelaide, Australia, 5006
    • Recruiting
    • Women's and Children's Health Network
  • Parkville, Australia, 3052
    • Recruiting
    • The Royal Children's Hospital - Children's Cancer Centre
  • Randwick, Australia, 2031
    • Recruiting
    • Sydney Children's Hospital - Randwick
  • Westmead, Australia, 2145
    • Recruiting
    • Children's Hospital at Westmead
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Recruiting
      • Children's Health Queensland Hospital and Health Service
• Austria
  • Innsbruck, Austria, 6020
    • Recruiting
    • Medizinische Universität Wien
• Belgium
  • Brussel, Belgium, 1200
    • Recruiting
    • Cliniques Universitaires Saint-Luc
  • Ghent, Belgium, 9000
    • Recruiting
    • Universitair Ziekenhuis Gent
  • Leuven, Belgium, 3000
    • Recruiting
    • Universitair Ziekenhuis Leuven - Campus Gasthuisberg
• Canada
  • Québec, Canada, G1V 4G2
    • Recruiting
    • Centre Hospitalier de l'Université Laval et Centre Mère-Enfant Soleil
  • Toronto, Canada, M5G 1X8
    • Recruiting
    • SickKids - The Hospital for Sick Children
  • Alberta
    • Calgary, Alberta, Canada, T3B 6A8
      • Recruiting
      • Alberta Children's Hospital
  • British Columbia
    • Vancouver, British Columbia, Canada, V6H 3N1
      • Recruiting
      • British Columbia Children's Hospital
  • Quebec
    • Montréal, Quebec, Canada, H3T IC5
      • Recruiting
      • CHU Sainte-Justine
    • Montréal, Quebec, Canada, H4A 3J1
      • Recruiting
      • The Montreal Children's Hospital
• Czechia
  • Brno, Czechia, 625 00
    • Recruiting
    • Fakultní Nemocnice Brno - D?tská Nemocnice
  • Prague, Czechia, 5 150 06
    • Recruiting
    • Motol University Hospital
• Denmark
  • Copenhagen, Denmark, 2100
    • Recruiting
    • Rigshospitalet
• Finland
  • Helsinki, Finland, FI-00290
    • Recruiting
    • Helsingin yliopistollinen sairaala (HUS)
  • Tampere, Finland, 33520
    • Recruiting
    • Tampereen yliopistollinen sairaala
• France
  • Lyon, France, 69008
    • Recruiting
    • Centre LEON BERARD
  • Marseille, France, 13005
    • Recruiting
    • Hopital de La Timone
  • Paris, France, 75248
    • Recruiting
    • Institut Curie
  • Villejuif, France, 94805
    • Recruiting
    • Gustave Roussy
• Germany
  • Berlin, Germany, 13353
    • Recruiting
    • Charite Universitatsmedizin Berlin
  • Bielefeld, Germany, 33617
    • Recruiting
    • Evangelische Klinikum Bethel (EvKB)
  • Hamburg, Germany, 20246
    • Recruiting
    • Universitätsklinikum Hamburg-Eppendorf
  • Heidelberg, Germany, 69120
    • Recruiting
    • Universitätsklinikum Heidelberg
  • Tübingen, Germany, 72076
    • Recruiting
    • Universitätsklinikum Tübingen
  • Ulm, Germany, 89075
    • Recruiting
    • Universitätsklinikum Erlangen
  • Baden-Württemberg
    • Freiburg, Baden-Württemberg, Germany, 79106
      • Recruiting
      • Universitatsklinikum Freiburg
  • Bayern
    • Augsburg, Bayern, Germany, 86156
      • Recruiting
      • Universitatsklinikum Augsburg
    • Würzburg, Bayern, Germany, 97080
      • Recruiting
      • Universitätsklinikum Würzburg
  • Hessen
    • Frankfurt, Hessen, Germany, 60590
      • Recruiting
      • Universitatsklinikum Frankfurt
  • Sachsen
    • Leipzig, Sachsen, Germany, 4103
      • Recruiting
      • Universitatsklinikum Leipzig
• Greece
  • Athens, Greece, 11527
    • Recruiting
    • Aghia Sofia General Children's Hospital
  • Athens, Greece, 11527
    • Recruiting
    • Athens General Children's Hospital
• Hungary
  • Budapest, Hungary, 1094
    • Recruiting
    • Semmelweis Egyetem Tűzoltó utcai II. Sz. Gyermekgyógyászati Kliniká
• Ireland
  • Dublin
    • Crumlin, Dublin, Ireland, D12 N512
      • Recruiting
      • Children's Health Ireland at Crumlin
• Israel
  • Petah tikva, Israel, 49202
    • Recruiting
    • Schneider Children's Medical Center of Israel
  • Ramat Gan, Israel, 5265601
    • Recruiting
    • The Edmond and Lily Safra Children's Hospital
• Italy
  • Genova, Italy, 16147
    • Recruiting
    • Istituto Giannina Gaslini
  • Napoli, Italy, 80131
    • Recruiting
    • Azienda Ospedaliera di Rilievo Nazional Santobono Pausilipon
  • Padova, Italy, 35128
    • Recruiting
    • Azienda Ospedale Università di Padova
  • Milan
    • Milano, Milan, Italy, 20133
      • Recruiting
      • Fondazione IRCCS - Istituto Nazionale dei Tumori
  • Rome
    • Roma, Rome, Italy, 00165
      • Recruiting
      • Ospedale Pediatrico Bambino Gesù
  • Turin
    • Torino, Turin, Italy, 10126
      • Recruiting
      • Ospedale Infantile Regina Margherita
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Recruiting
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 03722
    • Recruiting
    • Severance Hospital
• Netherlands
  • Utrecht, Netherlands, 3584 CS
    • Recruiting
    • Prinses Maxima Centrum Kinderoncologie
• New Zealand
  • Grafton, New Zealand, 1023
    • Recruiting
    • Starship Paediatric Blood & Cancer Center
• Norway
  • Oslo, Norway, 372
    • Recruiting
    • Oslo Universitetssykehus
  • Troms
    • Tromsø, Troms, Norway, 9038
      • Recruiting
      • Universitetssykehuset Nord-Norge - Tromsø
• Singapore
  • Singapore, Singapore, 229899
    • Recruiting
    • SingHealth Group - KK Women's and Children's Hospital
• Slovenia
  • Ljubljana, Slovenia, 1000
    • Recruiting
    • Univerzitetni Klinini Center Ljubljana
• Spain
  • Barakaldo, Spain, 48903
    • Recruiting
    • Hospital Universitario Cruces
  • Barcelona, Spain, 08035
    • Recruiting
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain, 08950
    • Recruiting
    • Hospital Sant Joan de Déu Barcelona
  • Madrid, Spain, 28046
    • Recruiting
    • Hospital Universitario La Paz
  • Madrid, Spain, 28009
    • Recruiting
    • Hospital Infantil Universitario Nino Jesus
  • Sevilla, Spain, 41013
    • Recruiting
    • Hospital Universitario Virgen del Rocio
  • Valencia, Spain, 46026
    • Recruiting
    • Hospital Universitari I Politecnic La Fe
• Sweden
  • Göteborg, Sweden, 416 85
    • Recruiting
    • Drottning Silvias barn- och ungdomssjukhus
  • Lund, Sweden, 221 85
    • Recruiting
    • Skånes Universitetssjukhus - Lund
  • Stockholm, Sweden, 171 77
    • Recruiting
    • Astrid Lindgrens Barnsjukhus Solna
• Switzerland
  • Lausanne, Switzerland, 1011
    • Recruiting
    • Centre Hospitalier Universitaire Vaudois Lausanne
  • Zurich, Switzerland, 8032
    • Recruiting
    • Universitaets - Kinderspital Zürich
• United Kingdom
  • Bristol, United Kingdom, BS2 8HW
    • Recruiting
    • University Hospitals Bristol and Weston NHS Foundation Trust
  • Cambridge, United Kingdom, CB2 0QQ
    • Recruiting
    • Cambridge University Hospitals NHS Foundation Trust
  • England
    • Leeds, England, United Kingdom, LS1 3EX
      • Recruiting
      • Leeds Teaching Hospital NHS Trust
    • Newcastle Upon Tyne, England, United Kingdom, NE1 4LP
      • Recruiting
      • The Newcastle Upon Tyne Hospitals NHS Foundation Trust
    • Oxford, England, United Kingdom, WC1N 3JH
      • Recruiting
      • Great Ormond Street Hospital for Children
  • Scotland
    • Glasgow, Scotland, United Kingdom, G51 4TF
      • Recruiting
      • NHS Greater Glasgow and Clyde
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Recruiting
      • Children's of Alabama
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Recruiting
      • Phoenix Children's Hospital
  • California
    • Los Angeles, California, United States, 90027
      • Recruiting
      • Children's Hospital Los Angeles
    • San Francisco, California, United States, 94158
      • Recruiting
      • UCSF Benioff Children's Hospital
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • Children's Hospital Colorado
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Recruiting
      • Children's National Medical Center
  • Florida
    • Orlando, Florida, United States, 32806
      • Recruiting
      • Arnold Palmer Hospital for Children
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Children's Healthcare of Atlanta
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Ann & Robert H. Lurie Children's Hospital of Chicago
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Recruiting
      • Riley Hospital for Children at Indiana University Health
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Dana-Farber Cancer Institute
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Recruiting
      • University of Michigan - - C.S. Mott Children's Hospital
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Recruiting
      • St. Louis Children's Hospital
  • New York
    • New York, New York, United States, 10016
      • Recruiting
      • New York University Langone Health
    • Rochester, New York, United States, 14642
      • Recruiting
      • University of Rochester
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Recruiting
      • Duke Cancer Institute
  • Texas
    • Dallas, Texas, United States, 75390
      • Recruiting
      • University of Texas Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • Recruiting
      • Texas Children's Hospital
  • Washington
    • Seattle, Washington, United States, 98105
      • Recruiting
      • Seattle Children's Hospital

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:

• Patient 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
• Patient's tumor has additional activating molecular alterations
• Known or suspected diagnosis of neurofibromatosis Type 1 or 2 (NF-1/NF-2)
• Prior or ongoing nonsurgical anticancer therapy for this indication (eg, chemotherapy, oral/intravenous 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: Arm #1; DAY101	Drug: DAY101; Oral pan-RAF inhibitor; Other Names: tovorafenib
Active Comparator: Arm #2; Investigator's choice of one of the following current standard of care for pediatric patients with low-grade gliomas: Children's Oncology Group - Vincristine/Carboplatin (COG-V/C); International Society for Paediatric Oncology - Low-Grade Glioma Vincristine/Carboplatin (SIOPe-LGG-V/C); Vinblastine (VBL)	Drug: Chemotherapeutic Agent; Intravenous solution for injection; Other Names: VBL; COG-V/C; SIOPe-LGG-V/C

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compare the objective response rate (ORR) assessed per RANO criteria by independent review committee (IRC) of DAY101 monotherapy versus standard of care (SoC) chemotherapy	ORR, per RANO criteria, defined as the proportion of patients with overall confirmed response of complete response (CR) or partial response (PR)	Up to 60 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compare the progression-free survival (PFS) assessed by IRC of DAY101 monotherapy versus SoC chemotherapy per RANO criteria	PFS per RANO criteria, defined as time from randomization to PD or death from any cause	Up to 60 months
Compare the duration of response (DOR) assessed by IRC of DAY101 monotherapy versus SoC chemotherapy per RANO criteria	DOR per RANO criteria, defined as time from confirmed response to PD or death from any cause for patients with confirmed response	Up to 60 months
Compare the overall survival (OS) of DAY101 monotherapy versus SoC chemotherapy	OS, defined as time from randomization up to death from any cause	Up to 60 months
Compare the safety and tolerability of DAY101 monotherapy versus SoC chemotherapy	Type, frequency, and severity of treatment-emergent adverse events	Up to 60 months
Compare the safety and tolerability of DAY101 monotherapy versus SoC chemotherapy	Measured by incidence of clinically significant laboratory abnormalities	Up to 60 months
Compare changes in neurological function between DAY101 versus SoC	Change from baseline in the Vineland Adaptive Behavior Composite Scales [age-adjusted standard scores range between 20 to 140, with a mean of 100 and standard deviation of 15, and lower scores indicate worse functional outcomes]	Up to 60 months
Compare changes in visual function outcomes of DAY101 monotherapy versus SoC chemotherapy in patients with optic pathway glioma (OPG)	Measured by Teller Acuity Cards® or alternative	Up to 60 months
Compare the ORR of DAY101 monotherapy versus SoC chemotherapy as assessed by IRC per RANO criteria	ORR, defined as the proportion of patients with overall confirmed response per RANO	Up to 60 months
Compare the ORR of DAY101 monotherapy versus SoC chemotherapy as assessed by IRC per Response Assessment in Pediatric Neuro-Oncology (RAPNO) criteria	ORR, defined as the proportion of patients with overall confirmed response per RAPNO	Up to 60 months
Compare the clinical benefit rate (CBR) of DAY101 monotherapy versus SoC chemotherapy as assessed by IRC per RANO and RAPNO criteria	CBR, defined as the proportion of patients with radiological tumor stabilization or regression per RANO or RAPNO criteria, as applicable	Up to 60 months
Compare time to response (TTR) of DAY101 monotherapy versus SoC chemotherapy as assessed by IRC per RANO and RAPNO criteria	Measured by the time to first response following initiation of therapy in patients with best overall confirmed response per RANO or RAPNO criteria, as applicable	Up to 60 months
Compare the PFS of DAY101 monotherapy versus SoC chemotherapy as assessed by IRC per RAPNO and RANO criteria	PFS per RANO or RAPNO (as applicable), defined as time from randomization to progressive disease (PD) or death from any cause	Up to 60 months
Compare the DOR of DAY101 monotherapy versus SoC chemotherapy as assessed by IRC per RAPNO and RANO criteria	DOR, defined as time from confirmed response to PD or death from any cause for patients with confirmed response per RANO or RAPNO criteria, as applicable	Up to 60 months

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): February 27, 2023
• Primary Completion (Estimated): February 1, 2026
• Study Completion (Estimated): March 1, 2030

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): April 8, 2024
• Last Update Submitted That Met QC Criteria: April 5, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioma; Antineoplastic Agents
• Other Study ID Numbers: DAY101-002

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No