FIREFLY-1
Research type
Research Study
Full title
A Phase 2, Open-Label, Multicenter Study to Evaluate the Safety and Efficacy of the Oral Pan-RAF Inhibitor DAY101 in Pediatric Patients with RAF Altered, Recurrent or Progressive Low-Grade Glioma and Advanced Solid Tumors.
IRAS ID
288511
Contact name
Holly Spencer
Contact email
Sponsor organisation
Day One Biopharmaceuticals, Inc. (Day One)
Eudract number
2020-003657-30
Clinicaltrials.gov Identifier
108340, IND
Duration of Study in the UK
3 years, 5 months, 1 days
Research summary
This is a Phase 2, multicenter, multi-arm, open-label study evaluating DAY101 in pediatric patients with low-grade gliomas and advanced solid tumors.
The study will consist of three treatment arms:
• Arm 1 (Low-Grade Glioma): Patients aged 6 months to 25 years, inclusive, with recurrent or progressive low-grade glioma harboring a known activating BRAF alteration, including BRAF V600 mutations and KIAA1549:BRAF fusions.
• Arm 2 (Low-Grade Glioma Extension): Patients aged 6 months to 25 years, inclusive, with recurrent or progressive low-grade glioma harboring a known or expected to be activating RAF alteration. Opening of Arm 2 to enrollment will be based on the recommendation of the DSMB as described below in Section 3.1.2.
• Arm 3 (Advanced Solid Tumor): Patients aged 6 months to 25 years, inclusive, with advanced solid tumors harboring a known or expected to be activating RAF fusion.Low-Grade Gliomas (LGG) are the most common brain tumour diagnosed in children, they can occur anywhere within the central nervous system. These tumours are slow-growing, chronic and relentless. Despite being low-grade, LGGs are a serious medical condition with significant life-long effects such as motor (loss of function of body part) or visual impairment.
Within the body there is a signalling pathway called MAPK (mitogen-activated protein kinase). These pathways regulate cell growth, survival and differentiation. Genetic alterations of the MAPK pathway have been commonly found in LGG.
One of the most frequently altered genes in this pathway is called the BRAF gene. DAY101 is an oral, selective, small-molecule, Type II pan-RAF kinase inhibitor. DAY101 has been shown pre-clinically to inhibit BRAF alterations.
Extracranial tumors harboring RAF fusions are rare, but through recent publications (Coffin 2020, Rankin 2020, Penning 2021), more patients are being identified as more genomic sequencing data is generated from patient’s tumors. DAY101 could potentially serve a broader pediatric population with RAF fusions beyond just patients with pediatric LGG.Treatment of patients with LGG or advanced solid tumors with chemotherapy, radiation or removal via surgery can have serious side effects, particularly in younger patients, depending on the location of the tumour.
The purpose of this study is to evaluate the efficacy (ability for the study drug to produce the desired effect) and safety of DAY101 as monotherapy in pediatric and young patients with recurrent or progressive LGG harbouring a known activating BRAF alteration or with an advanced solid tumor with an activating RAF alteration.
This study is being sponsored by Day One Biopharmaceuticals, Inc. (“Day One”). It is planned to run in 8 countries and plans to recruit 140 participants.REC name
West Midlands - Edgbaston Research Ethics Committee
REC reference
21/WM/0012
Date of REC Opinion
15 Mar 2021
REC opinion
Further Information Favourable Opinion