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

Low-grade Glioma Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05566795
• Other study ID #: DAY101-002
• Status: Recruiting
• Phase: Phase 3
• Start date: February 27, 2023
• Est. completion date: March 2030

Study information

• Verified date: June 2024
• Source: Day One Biopharmaceuticals, Inc.
• Contact: Day One Clinical Trials Information
• Phone: 650-484-0899
• Email: clinicaltrials[@]dayonebio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 patients with pediatric low-grade glioma (LGG) harboring an activating rapidly accelerated fibrosarcoma (RAF) alteration requiring front-line systemic therapy.

Description:

Approximately 400 treatment-naïve low-grade glioma patients 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. Patients will continue tovorafenib until any of the following occurs: disease progression based on Response Assessment in Neuro-Oncology (RANO-LGG) criteria, 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: disease progression based on RANO-LGG criteria, unacceptable toxicity, withdrawal of consent to treatment, or end of study.

Patients who discontinue treatment due to disease progression will have (1) radiographic evidence of progressive disease based on RANO-LGG, as determined by the Investigator and confirmed by the IRC, or (2) clinical progression based on RANO-LGG criteria determined by the Investigator. Investigators are encouraged to discuss cases of clinical progression and early radiographic progression without clinical symptom with the Sponsor Medical Monitor prior to treatment discontinuation or initiation of a different form of treatment for the malignancy. Patients may continue therapy beyond progressive disease

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 400
• Est. completion date: March 2030
• Est. primary completion date: February 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 25 Years

Eligibility

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 pathogenic molecular alterations, including but not limited to a) IDH 1/2 mutation, b) Histone H3 mutation, and c) NF-1 loss of function alteration.

• 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

Related Conditions & MeSH terms

• Glioma
• Low-grade Glioma

Intervention

Drug:
• Tovorafenib
Oral type II RAF kinase inhibitor
• Chemotherapeutic Agent
Intravenous solution for injection

Locations

Country	Name	City	State
Australia	Perth Children's Hospital	Nedlands
Australia	Women's and Children's Health Network	North Adelaide
Australia	The Royal Children's Hospital - Children's Cancer Centre	Parkville
Australia	Sydney Children's Hospital - Randwick	Randwick
Australia	Children's Health Queensland Hospital and Health Service	South Brisbane	Queensland
Australia	Children's Hospital at Westmead	Westmead
Austria	Medizinische Universität Wien	Innsbruck
Belgium	Cliniques Universitaires Saint-Luc	Brussel
Belgium	Universitair Ziekenhuis Gent	Ghent
Belgium	Universitair Ziekenhuis Leuven - Campus Gasthuisberg	Leuven
Canada	Alberta Children's Hospital	Calgary	Alberta
Canada	CHU Sainte-Justine	Montréal	Quebec
Canada	The Montreal Children's Hospital	Montréal	Quebec
Canada	Centre Hospitalier de l'Université Laval et Centre Mère-Enfant Soleil	Québec
Canada	SickKids - The Hospital for Sick Children	Toronto
Canada	British Columbia Children's Hospital	Vancouver	British Columbia
Czechia	Fakultní Nemocnice Brno - D?tská Nemocnice	Brno
Czechia	Motol University Hospital	Prague
Denmark	Aarhus Universitetshospital	Aarhus	Midtjylland
Denmark	Rigshospitalet	Copenhagen
Finland	Helsingin yliopistollinen sairaala (HUS)	Helsinki
Finland	Tampereen Yliopistollinen Sairaala	Tampere
France	Centre Léon Bérard	Lyon
France	Hôpital de la Timone	Marseille
France	Institut Curie	Paris
France	Gustave Roussy	Villejuif
Germany	Universitätsklinikum Augsburg	Augsburg	Bayern
Germany	Charité Universitätsmedizin Berlin	Berlin
Germany	Evangelische Klinikum Bethel (EvKB)	Bielefeld
Germany	Universitätsklinikum Frankfurt	Frankfurt	Hessen
Germany	Universitätsklinikum Freiburg	Freiburg	Baden-Württemberg
Germany	Universitätsklinikum Hamburg-Eppendorf	Hamburg
Germany	Universitätsklinikum Heidelberg	Heidelberg
Germany	Universitätsklinikum Leipzig	Leipzig	Sachsen
Germany	Universitätsklinikum Tübingen	Tübingen
Germany	Universitätsklinikum Erlangen	Ulm
Germany	Universitätsklinikum Würzburg	Würzburg	Bayern
Greece	Aghia Sofia General Children's Hospital	Athens
Greece	Athens General Children's Hospital	Athens
Hungary	Semmelweis Egyetem Tuzoltó utcai II. Sz. Gyermekgyógyászati Kliniká	Budapest
Ireland	Children's Health Ireland at Crumlin	Crumlin	Dublin
Israel	Schneider Children's Medical Center of Israel	Petah tikva
Israel	The Edmond and Lily Safra Children's Hospital	Ramat Gan
Italy	Azienda Universitaria Ospedaliera Consorziale - Policlinico di Bari	Bari
Italy	Istituto Giannina Gaslini	Genova
Italy	Fondazione IRCCS - Istituto Nazionale dei Tumori	Milano	Milan
Italy	Azienda Ospedaliera di Rilievo Nazional Santobono Pausilipon	Napoli
Italy	Azienda Ospedale Università di Padova	Padova
Italy	Ospedale Pediatrico Bambino Gesù	Roma	Rome
Italy	Ospedale Infantile Regina Margherita	Torino	Turin
Italy	Azienda Sanitaria Universitaria Friuli Centrale - P.O. Santa Maria della Misericordia	Udine
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital	Seoul
Netherlands	Prinses Maxima Centrum Kinderoncologie	Utrecht
New Zealand	Starship Paediatric Blood & Cancer Center	Grafton
Norway	Oslo Universitetssykehus	Oslo
Norway	Universitetssykehuset Nord-Norge - Tromsø	Tromsø	Troms
Singapore	SingHealth Group - KK Women's and Children's Hospital	Singapore
Slovenia	Univerzitetni Klinini Center Ljubljana	Ljubljana
Spain	Hospital Universitario Cruces	Barakaldo
Spain	Hospital Sant Joan de Déu Barcelona	Barcelona
Spain	Hospital Universitari Vall d'Hebrón	Barcelona
Spain	Hospital Infantil Universitario Niño Jesús	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Virgen del Rocío	Sevilla
Spain	Hospital Universitari i Politècnic La Fe	Valencia
Sweden	Drottning Silvias barn- och ungdomssjukhus	Göteborg
Sweden	Skånes Universitetssjukhus - Lund	Lund
Sweden	Astrid Lindgrens Barnsjukhus Solna	Stockholm
Switzerland	Centre Hospitalier Universitaire Vaudois Lausanne	Lausanne
Switzerland	Universitaets - Kinderspital Zürich	Zurich
United Kingdom	Birmingham Women's and Children's NHS Foundation Trust	Birmingham	England
United Kingdom	University Hospitals Bristol and Weston NHS Foundation Trust	Bristol
United Kingdom	Cambridge University Hospitals NHS Foundation Trust	Cambridge
United Kingdom	NHS Greater Glasgow and Clyde	Glasgow	Scotland
United Kingdom	Leeds Teaching Hospital NHS Trust	Leeds	England
United Kingdom	Manchester University NHS Foundation Trust	Manchester	England
United Kingdom	The Newcastle Upon Tyne Hospitals NHS Foundation Trust	Newcastle Upon Tyne	England
United Kingdom	Great Ormond Street Hospital for Children	Oxford	England
United Kingdom	The Royal Marsden NHS Foundation Trust	Sutton	Surrey
United States	University of Michigan - - C.S. Mott Children's Hospital	Ann Arbor	Michigan
United States	Children's Healthcare of Atlanta	Atlanta	Georgia
United States	Children's Hospital Colorado	Aurora	Colorado
United States	Children's of Alabama	Birmingham	Alabama
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	Cleveland Clinic Main Campus	Cleveland	Ohio
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Duke Cancer Institute	Durham	North Carolina
United States	Texas Children's Hospital	Houston	Texas
United States	Riley Hospital for Children at Indiana University Health	Indianapolis	Indiana
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	New York University Langone Health	New York	New York
United States	Arnold Palmer Hospital for Children	Orlando	Florida
United States	Phoenix Children's Hospital	Phoenix	Arizona
United States	University of Rochester	Rochester	New York
United States	St. Louis Children's Hospital	Saint Louis	Missouri
United States	UCSF Benioff Children's Hospital	San Francisco	California
United States	Seattle Children's Hospital	Seattle	Washington
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Day One Biopharmaceuticals, Inc.	SIOPe Brain Tumor Group LOGGIC Consortium

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Canada,  Czechia,  Denmark,  Finland,  France,  Germany,  Greece,  Hungary,  Ireland,  Israel,  Italy,  Korea, Republic of,  Netherlands,  New Zealand,  Norway,  Singapore,  Slovenia,  Spain,  Sweden,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Compare the objective response rate (ORR) assessed per RANO-LGG criteria by Independent Review Committee (IRC) of tovorafenib monotherapy versus standard of care (SoC) chemotherapy	ORR, per RANO-LGG criteria, defined as the proportion of patients with overall confirmed response of complete response (CR) or partial response (PR)	Up to 60 months
Secondary	Compare the progression-free survival (PFS) assessed by IRC of tovorafenib monotherapy versus SoC chemotherapy per RANO-LGG criteria	PFS per RANO-LGG criteria, de?ned as time from randomization to PD or death from any cause	Up to 60 months
Secondary	Compare the duration of response (DOR) assessed by IRC of tovorafenib monotherapy versus SoC chemotherapy per RANO-LGG criteria	DOR per RANO-LGG criteria, de?ned as time from confirmed response to PD or death from any cause for patients with confirmed response	Up to 60 months
Secondary	Compare the overall survival (OS) of tovorafenib monotherapy versus SoC chemotherapy	OS, defined as time from randomization up to death from any cause	Up to 60 months
Secondary	Compare the safety and tolerability of tovorafenib monotherapy versus SoC chemotherapy	Type, frequency, and severity of treatment-emergent adverse events	Up to 60 months
Secondary	Compare the safety and tolerability of tovorafenib monotherapy versus SoC chemotherapy	Measured by incidence of clinically significant laboratory abnormalities	Up to 60 months
Secondary	Evaluate changes in neurological function and adaptive behavior between tovorafenib 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
Secondary	Compare changes in visual function outcomes of tovorafenib monotherapy versus SoC chemotherapy in patients with optic pathway glioma (OPG)	Measured by Teller Acuity Cards® or alternative	Up to 60 months
Secondary	Compare the ORR of tovorafenib monotherapy versus SoC chemotherapy as assessed by IRC per RANO-HGG and Response Assessment in Pediatric Neuro-Oncology (RAPNO-LGG) criteria	ORR, de?ned as the proportion of patients with overall con?rmed response per RANO-HGG, RANO-LGG, or RAPNO-LGG criteria.	Up to 60 months
Secondary	Compare the clinical bene?t rate (CBR) of tovorafenib monotherapy versus SoC chemotherapy as assessed by IRC per RANO-LGG, RANO-HGG and RAPNO-LGG criteria	CBR, de?ned as the proportion of patients with radiological tumor stabilization or regression per RANO-LGG, RANO-HGG or RAPNO-LGG criteria, as applicable	Up to 60 months
Secondary	Compare time to response (TTR) of tovorafenib monotherapy versus SoC chemotherapy as assessed by IRC per RANO-LGG, RANO-HGG and RAPNO-LGG criteria	Measured by the time to ?rst response following initiation of therapy in patients with best overall con?rmed response per RANO-LGG, RANO-HGG or RAPNO-LGG criteria, as applicable	Up to 60 months
Secondary	Compare the PFS of tovorafenib monotherapy versus SoC chemotherapy as assessed by IRC per RAPNO-LGG and RANO-HGG criteria	PFS per RANO-HGG or RAPNO-LGG (as applicable), de?ned as time from randomization to progressive disease (PD) or death from any cause	Up to 60 months
Secondary	Compare the DOR of tovorafenib monotherapy versus SoC chemotherapy as assessed by IRC per RAPNO-LGG and RANO-HGG criteria	DOR, de?ned as time from con?rmed response to PD or death from any cause for patients with confirmed response per RANO or RAPNO criteria, as applicable	Up to 60 months
Secondary	Evaluate the health-related quality of life (HRQoL) in tovorafenib versus SoC chemotherapy using Patient-Reported Outcomes Measurement Information System (PROMIS) test battery	Measured by change from baseline in Total Score at 1, 2, 5 years	Up to 60 months