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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT04775485
Registration number
NCT04775485
Ethics application status
Date submitted
3/02/2021
Date registered
1/03/2021
Date last updated
10/04/2025
Titles & IDs
Public title
A Study to Evaluate Tovorafenib in Pediatric and Young Adult Participants With Relapsed or Progressive Low-Grade Glioma and Advance Solid Tumors
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Scientific title
FIREFLY-1: 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
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Secondary ID [1]
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DAY101-001/PNOC026
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Universal Trial Number (UTN)
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Trial acronym
FIREFLY-1
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Low-grade Glioma
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Advanced Solid Tumor
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Condition category
Condition code
Cancer
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Brain
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Tovorafenib
Experimental: Arm 1: Low-Grade Glioma - Participants with recurrent or progressive low-grade glioma will receive 420 milligrams/meters square (mg/m\^2) of tovorafenib weekly according to dose rounding guidelines and according to their baseline body surface area (BSA).
Experimental: Arm 2: Low-Grade Glioma Expanded Access - Participants with recurrent or progressive low-grade glioma will receive 420 mg/m\^2 of tovorafenib weekly according to dose rounding guidelines and according to their baseline BSA.
Experimental: Arm 3: Advanced Solid Tumor - Participants with advanced solid tumors will receive 420 mg/m\^2) of tovorafenib weekly according to dose rounding guidelines and according to their baseline BSA.
Treatment: Drugs: Tovorafenib
Tovorafenib is an oral Type II RAF kinase inhibitor available in 100 mg immediate-release tablet or 25 mg/milliliter (mL) powder for reconstitution.
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Arm 1: Overall response rate
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Assessment method [1]
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ORR is defined as percentage of participants with best overall confirmed response of complete response (CR) or partial response (PR) by the Response Assessment in Neuro-Oncology - high-grade glioma (RANO-HGG) criteria.
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Timepoint [1]
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Up to 48 months
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Primary outcome [2]
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Arm 2: Number of participants reporting adverse events
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Assessment method [2]
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An adverse event (AE) is any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
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Timepoint [2]
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Up to 48 months
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Primary outcome [3]
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Arm 2: Number of participants with clinically significant changes in clinical chemistry parameters
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Assessment method [3]
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Timepoint [3]
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Up to 48 months
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Primary outcome [4]
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Arm 2: Number of participants with clinically significant changes in hematology parameters
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Assessment method [4]
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Timepoint [4]
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Up to 48 months
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Primary outcome [5]
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Arm 3: Overall response rate
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Assessment method [5]
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Determined by the treating investigator and measured by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or RANO-HGG criteria, as appropriate.
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Timepoint [5]
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Up to 48 months
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Secondary outcome [1]
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Arm 1 and 3: Number of participants reporting adverse events
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Assessment method [1]
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An adverse event (AE) is any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
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Timepoint [1]
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Up to 48 months
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Secondary outcome [2]
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Arm 1 and 3: Number of participants with clinically significant changes in clinical chemistry parameters
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Assessment method [2]
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Timepoint [2]
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Up to 48 months
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Secondary outcome [3]
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Arm 1 and 3: Number of participants with clinically significant changes in hematology parameters
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Assessment method [3]
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Timepoint [3]
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Up to 48 months
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Secondary outcome [4]
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Arm 1: Area under the concentration-time curve (AUC) of Tovorafenib
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Assessment method [4]
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Timepoint [4]
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Cycle 1: Day 1 and Day 15; Cycles 2, 4, 7, 10 and 13: Day 1
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Secondary outcome [5]
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Arm 1: Minimum drug concentration (Cmin)
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Assessment method [5]
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Timepoint [5]
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Cycle 1: Day 1 and Day 15; Cycles 2, 4, 7, 10 and 13: Day 1
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Secondary outcome [6]
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Arm 1: Change from Baseline QT interval corrected for heart rate by Fridericia's formula (?QTcF)
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Assessment method [6]
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Timepoint [6]
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Baseline to 48 months
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Secondary outcome [7]
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Arm 1: Change from Baseline PR interval (?PR)
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Assessment method [7]
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Timepoint [7]
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Baseline to 48 months
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Secondary outcome [8]
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Arm 1: Change from Baseline QRS interval (?QRS)
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Assessment method [8]
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Timepoint [8]
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Baseline to 48 months
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Secondary outcome [9]
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Arm 1: Change from baseline heart rate (?HR)
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Assessment method [9]
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Timepoint [9]
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Baseline to 48 months
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Secondary outcome [10]
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Arm 1: Change in electrocardiogram (ECG) waveform morphology
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Assessment method [10]
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Timepoint [10]
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Baseline to 48 months
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Secondary outcome [11]
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Arm 1 and Arm 2: Overall response rate
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Assessment method [11]
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ORR is defined as percentage of participants with best overall confirmed response of CR or PR by the RANO-HGG criteria.
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Timepoint [11]
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Up to 48 months
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Secondary outcome [12]
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Arm 1, Arm 2 and Arm 3: Overall response rate in Pediatric participants
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Assessment method [12]
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ORR is defined as percentage of participants with best overall confirmed response of CR or PR or minor response (MR) by Response Assessment in Pediatric Neuro-Oncology (RAPNO) criteria.CR or PR by RECIST v1.1 criteria.
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Timepoint [12]
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Up to 48 months
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Secondary outcome [13]
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Arm 1, Arm 2 and Arm 3: duration of progression-free survival (PFS)
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Assessment method [13]
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PFS as defined by the time following initiation of tovorafenib to progression or death in participants treated with tovorafenib measured by RECIST v1.1, RAPNO, or RANO-HGG criteria as determined by the treating investigator and an IRC.
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Timepoint [13]
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Up to 48 months
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Secondary outcome [14]
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Arm 1, Arm 2 and Arm 3: Duration of response (DOR)
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Assessment method [14]
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DOR as defined by the length of response in participants with best overall confirmed response of CR or PR or MR and measured by RANO-HGG, RAPNO, and/or RECIST v1.1 criteria, as applicable.
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Timepoint [14]
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Up to 48 months
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Secondary outcome [15]
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Arm 1, Arm 2 and Arm 3: Time to response (TTR)
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Assessment method [15]
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TTR as defined as the time to first response following initiation of tovorafenib in participants with best overall confirmed response of CR or PR measured by RECIST v1.1 or RANO-HGG criteria, as applicable.
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Timepoint [15]
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Up to 48 months
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Secondary outcome [16]
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Arm 1, Arm 2 and Arm 3: Clinical benefit rate (CBR)
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Assessment method [16]
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CBR as defined as participants with BOR of CR, PR or stable disease (SD) measured by RECIST v1.1 or RANO-HGG, as applicable, and lasting 12 months or more following initiation of tovorafenib.
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Timepoint [16]
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Up to 48 months
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Secondary outcome [17]
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Arm 1 and Arm 2: Duration of overall survival
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Assessment method [17]
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Overall survival as defined by the time following initiation of tovorafenib to death of any cause in participants treated with tovorafenib.
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Timepoint [17]
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Up to 48 months
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Secondary outcome [18]
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Arm 1: Change from baseline in best corrected visual acuity (BCVA) outcomes
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Assessment method [18]
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Timepoint [18]
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Baseline to 48 months
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Secondary outcome [19]
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Arm 1: Changes in molecular analysis of cells obtained from archival tissue
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Assessment method [19]
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Timepoint [19]
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At Screening
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Eligibility
Key inclusion criteria
* Low Grade Glioma & Low-Grade Glioma Extension: a relapsed or progressive LGG with documented known activating BRAF alteration.
* Advanced Solid Tumor: locally advanced or metastatic solid tumor with documented known or expected to be activating RAF fusion.
* Participants must have histopathologic verification of malignancy at either original diagnosis or relapse.
* Must have received at least one line of prior systemic therapy and have documented evidence of radiographic progression.
* Must have at least 1 measurable lesion as defined by RANO (Arms 1 & 2) or RECIST v1.1 (Arm 3) criteria
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Minimum age
6
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Maximum age
25
Years
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
* Participant's tumor has additional previously-known activating molecular alterations.
* Participant has symptoms of without radiographically recurrent or radiographically progressive disease.
* Known or suspected diagnosis of neurofibromatosis type 1 (NF-1) via genetic testing or current diagnostic criteria.
Other inclusion/exclusion criteria as stipulated by protocol may apply
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Non-randomised trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Single group
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Other design features
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Phase
Phase 2
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Recruiting
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
22/04/2021
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
31/05/2027
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Actual
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Sample size
Target
141
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Accrual to date
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Final
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Recruitment in Australia
Recruitment state(s)
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Recruitment hospital [1]
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Queensland Children's Hospital - Brisbane
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Recruitment hospital [2]
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Royal Children's Hospital - Parkville
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Recruitment hospital [3]
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Perth Children's Hospital - Perth
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Recruitment hospital [4]
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Sydney Children's Hospital - Randwick
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Recruitment hospital [5]
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The Children's Hospital at Westmead - Westmead
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Recruitment postcode(s) [1]
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4101 - Brisbane
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Recruitment postcode(s) [2]
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3052 - Parkville
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Recruitment postcode(s) [3]
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WA 6009 - Perth
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Recruitment postcode(s) [4]
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NSW 2031 - Randwick
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Recruitment postcode(s) [5]
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2145 - Westmead
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Recruitment outside Australia
Country [1]
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United States of America
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State/province [1]
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California
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Country [2]
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United States of America
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State/province [2]
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District of Columbia
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Country [3]
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United States of America
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State/province [3]
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Illinois
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Country [4]
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United States of America
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State/province [4]
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Maryland
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Country [5]
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United States of America
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State/province [5]
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Massachusetts
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Country [6]
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United States of America
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State/province [6]
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Michigan
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Country [7]
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United States of America
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State/province [7]
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Missouri
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Country [8]
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United States of America
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State/province [8]
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New York
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Country [9]
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United States of America
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State/province [9]
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North Carolina
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Country [10]
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United States of America
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State/province [10]
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Oregon
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Country [11]
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United States of America
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State/province [11]
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Pennsylvania
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Country [12]
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United States of America
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State/province [12]
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Texas
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Country [13]
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United States of America
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State/province [13]
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Utah
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Country [14]
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United States of America
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State/province [14]
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Washington
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Country [15]
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Canada
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State/province [15]
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Quebec
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Country [16]
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Denmark
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State/province [16]
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Copenhagen
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Germany
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State/province [17]
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Berlin
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Country [18]
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Germany
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State/province [18]
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Heidelberg
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Country [19]
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Israel
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State/province [19]
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Haifa
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Israel
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State/province [20]
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Petah Tikva
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Israel
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State/province [21]
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Ramat Gan
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Country [22]
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Korea, Republic of
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State/province [22]
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Seoul
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Netherlands
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State/province [23]
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Utrecht
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Country [24]
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Singapore
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State/province [24]
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Singapore
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Switzerland
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State/province [25]
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Zürich
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United Kingdom
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State/province [26]
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London
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Country [27]
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United Kingdom
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State/province [27]
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Newcastle Upon Tyne
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
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Name
Day One Biopharmaceuticals, Inc.
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Address
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Country
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Other collaborator category [1]
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Other
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Name [1]
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Pacific Pediatric Neuro-Oncology Consortium
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Address [1]
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Ethics approval
Ethics application status
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Summary
Brief summary
This is a Phase 2, multi center, open-label study to evaluate the safety and efficacy of Type II RAF (tovorafenib) in pediatric participants with low-grade glioma or advanced solid tumors. Qualifying genomic alterations will be identified through molecular assays as routinely performed at Clinical Laboratory Improvement Amendments (CLIA) of 1988 or other similarly certified laboratories prior to enrollment into any of the arms. The study will consist of a screening period, a treatment period, a long-term extension phase, end of treatment (EOT) visit(s), a safety follow-up visit, and long-term follow-up assessments.
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Trial website
https://clinicaltrials.gov/study/NCT04775485
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Address
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Day One Biopharmaceuticals, Inc.
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Address
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Country
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Phone
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650-484-0899
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Fax
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Email
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[email protected]
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Contact person for scientific queries
No information has been provided regarding IPD availability
What supporting documents are/will be available?
No Supporting Document Provided
Type
Other Details
Attachment
Study protocol
https://cdn.clinicaltrials.gov/large-docs/85/NCT04775485/Prot_000.pdf
Statistical analysis plan
https://cdn.clinicaltrials.gov/large-docs/85/NCT04775485/SAP_001.pdf
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results not provided in
https://clinicaltrials.gov/study/NCT04775485
Download to PDF