Clinical trial NCT04775485: A Study to Evaluate Tovorafenib in Pediatric and Young Adult Participants With Relapsed or Progressive Low-Grade Glioma and Advance Solid Tumors
Official 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Low-grade Glioma
Advanced Solid Tumor
Keywords: Low-grade Glioma
Advanced Solid Tumor
FIREFLY-1
DAY101
Tovorafenib
Lead sponsor: Day One Biopharmaceuticals, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Pacific Pediatric Neuro-Oncology Consortium
First posted: 2021-03-01
Enrollment: 141
Sex: ALL
Minimum age (years): 6
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

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

Primary outcomes:
measure: Arm 1: Overall response rate
timeFrame: Up to 48 months
measure: Arm 2: Number of participants reporting adverse events
timeFrame: Up to 48 months
measure: Arm 2: Number of participants with clinically significant changes in clinical chemistry parameters
timeFrame: Up to 48 months
measure: Arm 2: Number of participants with clinically significant changes in hematology parameters
timeFrame: Up to 48 months
measure: Arm 3: Overall response rate
timeFrame: Up to 48 months
Secondary outcomes:
measure: Arm 1 and 3: Number of participants reporting adverse events
timeFrame: Up to 48 months
measure: Arm 1 and 3: Number of participants with clinically significant changes in clinical chemistry parameters
timeFrame: Up to 48 months
measure: Arm 1 and 3: Number of participants with clinically significant changes in hematology parameters
timeFrame: Up to 48 months
measure: Arm 1: Area under the concentration-time curve (AUC) of Tovorafenib
timeFrame: Cycle 1: Day 1 and Day 15; Cycles 2, 4, 7, 10 and 13: Day 1
measure: Arm 1: Minimum drug concentration (Cmin)
timeFrame: Cycle 1: Day 1 and Day 15; Cycles 2, 4, 7, 10 and 13: Day 1
measure: Arm 1: Change from Baseline QT interval corrected for heart rate by Fridericia's formula (ΔQTcF)
timeFrame: Baseline to 48 months
measure: Arm 1: Change from Baseline PR interval (ΔPR)
timeFrame: Baseline to 48 months
measure: Arm 1: Change from Baseline QRS interval (ΔQRS)
timeFrame: Baseline to 48 months
measure: Arm 1: Change from baseline heart rate (ΔHR)
timeFrame: Baseline to 48 months
measure: Arm 1: Change in electrocardiogram (ECG) waveform morphology
timeFrame: Baseline to 48 months
measure: Arm 1 and Arm 2: Overall response rate
timeFrame: Up to 48 months
measure: Arm 1, Arm 2 and Arm 3: Overall response rate in Pediatric participants
timeFrame: Up to 48 months
measure: Arm 1, Arm 2 and Arm 3: duration of progression-free survival (PFS)
timeFrame: Up to 48 months
measure: Arm 1, Arm 2 and Arm 3: Duration of response (DOR)
timeFrame: Up to 48 months
measure: Arm 1, Arm 2 and Arm 3: Time to response (TTR)
timeFrame: Up to 48 months
measure: Arm 1, Arm 2 and Arm 3: Clinical benefit rate (CBR)
timeFrame: Up to 48 months
measure: Arm 1 and Arm 2: Duration of overall survival
timeFrame: Up to 48 months
measure: Arm 1: Change from baseline in best corrected visual acuity (BCVA) outcomes
timeFrame: Baseline to 48 months
measure: Arm 1: Changes in molecular analysis of cells obtained from archival tissue
timeFrame: At Screening
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: UCSF Benioff Children's Hospital
state: California
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Chicago
country: United States
facility: Lurie Children's Hospital of Chicago
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: CS Mott Children's Hospital
state: Michigan
city: Saint Louis
country: United States
facility: St. Louis Children's Hospital
state: Missouri
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: Durham
country: United States
facility: Duke Cancer Center
state: North Carolina
city: Portland
country: United States
facility: Doernbecher Children's Hospital Oregon & Health Science University
state: Oregon
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Brisbane
country: Australia
facility: Queensland Children's Hospital
city: Parkville
country: Australia
facility: Royal Children's Hospital
city: Perth
country: Australia
facility: Perth Children's Hospital
city: Randwick
country: Australia
facility: Sydney Children's Hospital
city: Westmead
country: Australia
facility: The Children's Hospital at Westmead
city: Montreal
country: Canada
facility: Centre Hospitalier Universitaire Ste-Justine
state: Quebec
city: Montreal
country: Canada
facility: Montreal Children's Hospital
state: Quebec
city: Québec
country: Canada
facility: Centre Mère-Enfant Soleil du CHU
state: Quebec
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Berlin
country: Germany
facility: Charité Universitätsmedizin Berlin, Campus Virchow Klinikum, Otto-Heubner-Centrum für Kinder
city: Heidelberg
country: Germany
facility: Hopp-Kindertumorzentrum Heidelberg (KiTZ), KiTZ Clinical Trial Unit (ZIPO)
city: Haifa
country: Israel
facility: Rambam Health Care Campus
city: Petah Tikva
country: Israel
facility: Schneider Children's Medical Center of Israel
city: Ramat Gan
country: Israel
facility: The Chaim Sheba Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital - Yonsei University
city: Utrecht
country: Netherlands
facility: Princess Maxima Center for Pediatric Oncology
city: Singapore
country: Singapore
facility: KK Women's and Children's Hospital
city: Zürich
country: Switzerland
facility: Universitäts-Kinderspital Zürich - Eleonorenstiftung
city: London
country: United Kingdom
facility: UCL Great Ormond Street Institute of Child Health
city: Newcastle Upon Tyne
country: United Kingdom
facility: Newcastle University
Study officials:
References: