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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04775485




Registration number
NCT04775485
Ethics application status
Date submitted
3/02/2021
Date registered
1/03/2021
Date last updated
27/12/2023

Titles & IDs
Public title
A Study to Evaluate DAY101 in Pediatric and Young Adult Patients With Relapsed or Progressive Low-Grade Glioma and Advance Solid Tumors
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
Secondary ID [1] 0 0
DAY101-001/PNOC026
Universal Trial Number (UTN)
Trial acronym
FIREFLY-1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Low-grade Glioma 0 0
Advanced Solid Tumor 0 0
Condition category
Condition code
Cancer 0 0 0 0
Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - DAY101

Experimental: Arm #1 - Pediatric patients with low-grade glioma treated with DAY101 (Registrational Arm)

Experimental: Arm #2 - Expanded access arm of pediatric patients with low-grade glioma treated with DAY101

Experimental: Arm #3 - Pediatric patients with advanced solid tumors treated with DAY101


Treatment: Drugs: DAY101
DAY101 is an oral pan-RAF inhibitor provided as an immediate-release tablet (100 mg) or powder for reconstitution (25 mg/mL).
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Arm 1: Overall response rate (ORR) by independent radiology review committee (IRC) based on RANO criteria
Timepoint [1] 0 0
Up to 48 months
Primary outcome [2] 0 0
Arm 2: Assess the safety and tolerability of DAY101
Timepoint [2] 0 0
Up to 48 months
Primary outcome [3] 0 0
Arm 3: Overall response rate (ORR) by independent radiology review committee (IRC) based on RECIST v1.1 criteria
Timepoint [3] 0 0
Up to 48 months
Secondary outcome [1] 0 0
Relationship between pharmacokinetics (PK) and drug effects
Timepoint [1] 0 0
Up to 48 months
Secondary outcome [2] 0 0
Effect on electrocardiogram (ECG) and QT interval corrected for heart rate by Fridericia's formula (QTcF) prolongation
Timepoint [2] 0 0
Up to 48 months
Secondary outcome [3] 0 0
ORR by Investigator
Timepoint [3] 0 0
Up to 48 months
Secondary outcome [4] 0 0
Evaluate the concordance of prior local laboratory BRAF molecular profiling with a central BRAF alteration assay being evaluated by the Sponsor
Timepoint [4] 0 0
Up to 48 months
Secondary outcome [5] 0 0
Arm 1: Evaluate visual acuity (VA) outcomes compared with baseline
Timepoint [5] 0 0
Up to 48 months
Secondary outcome [6] 0 0
Arms 1 & 2: ORR by IRC and Investigator using RAPNO criteria
Timepoint [6] 0 0
Up to 48 months
Secondary outcome [7] 0 0
Arms 1 & 2: Progression free survival (PFS) using RANO and RAPNO criteria by 1) an IRC and 2) the treating Investigator (RANO only)
Timepoint [7] 0 0
Up to 48 months
Secondary outcome [8] 0 0
Arms 1 & 2: Duration of response (DOR) with best overall response of CR or PR using RANO and RAPNO criteria by 1) an IRC and 2) the treating Investigator (RANO only)
Timepoint [8] 0 0
Up to 48 months
Secondary outcome [9] 0 0
Arms 1 & 2: Time to response following initiation of DAY101
Timepoint [9] 0 0
Up to 48 months
Secondary outcome [10] 0 0
Arms 1 & 2: Clinical benefit rate based on the proportion of patients with best overall response using RANO or RAPNO criteria
Timepoint [10] 0 0
Up to 48 months
Secondary outcome [11] 0 0
Arms 1 & 3: Assess the safety and tolerability of DAY101
Timepoint [11] 0 0
Up to 48 months
Secondary outcome [12] 0 0
Arm 3: Duration of response (DOR) with best overall response of CR or PR using RECIST v1.1 criteria by 1) an IRC and 2) the treating Investigator
Timepoint [12] 0 0
Up to 48 months
Secondary outcome [13] 0 0
Arm 3: Time to response following initiation of DAY101
Timepoint [13] 0 0
Up to 48 months
Secondary outcome [14] 0 0
Arm 3: Clinical benefit rate based on the proportion of patients with best overall response using RECIST v1.1 criteria
Timepoint [14] 0 0
Up to 48 months

Eligibility
Key inclusion criteria
- Age 6 months to 25 years with:

1. Arms 1 & 2: a relapsed or progressive LGG with documented known activating BRAF
alteration

2. Arm 3: locally advanced or metastatic solid tumor with documented known or
expected to be activating RAF fusion

- Confirmation of histopathologic diagnosis of LGG and molecular diagnosis of activating
BRAF alteration

- Must have received at least one line of systemic therapy and have 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
Minimum age
6 Months
Maximum age
25 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Patient's tumor has additional previously-known activating molecular alterations

- Patient has symptoms of clinical progression in the absence of radiographic
progression

- Known or suspected diagnosis of neurofibromatosis type 1 (NF-1)

- Other inclusion/exclusion criteria as stipulated by protocol may apply

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
22/04/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
10/06/2024
Actual
Sample size
Target
140
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Queensland Children's Hospital - Brisbane
Recruitment hospital [2] 0 0
Royal Children's Hospital - Parkville
Recruitment hospital [3] 0 0
Perth Children's Hospital - Perth
Recruitment hospital [4] 0 0
Sydney Children's Hospital - Randwick
Recruitment hospital [5] 0 0
The Children's Hospital at Westmead - Westmead
Recruitment postcode(s) [1] 0 0
4101 - Brisbane
Recruitment postcode(s) [2] 0 0
3052 - Parkville
Recruitment postcode(s) [3] 0 0
WA 6009 - Perth
Recruitment postcode(s) [4] 0 0
NSW 2031 - Randwick
Recruitment postcode(s) [5] 0 0
2145 - Westmead
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
District of Columbia
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Maryland
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
Missouri
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
North Carolina
Country [10] 0 0
United States of America
State/province [10] 0 0
Oregon
Country [11] 0 0
United States of America
State/province [11] 0 0
Pennsylvania
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
United States of America
State/province [13] 0 0
Utah
Country [14] 0 0
United States of America
State/province [14] 0 0
Washington
Country [15] 0 0
Canada
State/province [15] 0 0
Quebec
Country [16] 0 0
Denmark
State/province [16] 0 0
Copenhagen
Country [17] 0 0
Germany
State/province [17] 0 0
Berlin
Country [18] 0 0
Germany
State/province [18] 0 0
Heidelberg
Country [19] 0 0
Israel
State/province [19] 0 0
Haifa
Country [20] 0 0
Israel
State/province [20] 0 0
Petah Tikva
Country [21] 0 0
Israel
State/province [21] 0 0
Ramat Gan
Country [22] 0 0
Korea, Republic of
State/province [22] 0 0
Seoul
Country [23] 0 0
Netherlands
State/province [23] 0 0
Utrecht
Country [24] 0 0
Singapore
State/province [24] 0 0
Singapore
Country [25] 0 0
Switzerland
State/province [25] 0 0
Zürich
Country [26] 0 0
United Kingdom
State/province [26] 0 0
London
Country [27] 0 0
United Kingdom
State/province [27] 0 0
Newcastle Upon Tyne

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Day One Biopharmaceuticals, Inc.
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Pacific Pediatric Neuro-Oncology Consortium
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
FIREFLY-1 is an ongoing, Phase 2, multi center, open-label study to evaluate the safety and
efficacy of oral pan-RAF inhibitor DAY101 in pediatric, adolescent, and young adult patients
with recurrent or progressive low-grade glioma or an advanced solid tumor harboring a known
RAF alteration.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04775485
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Day One Biopharmaceuticals
Address 0 0
Country 0 0
Phone 0 0
650-484-0899
Fax 0 0
Email 0 0
firefly-1@dayonebio.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04775485