TriangleNCT04775485 · CITED IN SOURCE DOCUMENTS
A Study to Evaluate Tovorafenib in Pediatric and Young Adult Participants With Relapsed or Progressive Low-Grade Glioma and Advance Solid Tumors
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE2
- Status at capture
- RECRUITING
- Registry last update
- 2025-04-10
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.
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
No posted result sections were captured. Registered plans do not establish that a treatment works.
Who could take part
- 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
- healthy Volunteers
- false
- maximum Age
- 25 Years
- minimum Age
- 6 Months
- sex
- ALL
- std Ages
- CHILD
- ADULT
Treatment arms and interventions
- arm Groups
- description
- 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).
- intervention Names
- Drug: Tovorafenib
- label
- Arm 1: Low-Grade Glioma
- type
- EXPERIMENTAL
- description
- 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.
- intervention Names
- Drug: Tovorafenib
- label
- Arm 2: Low-Grade Glioma Expanded Access
- type
- EXPERIMENTAL
- description
- 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.
- intervention Names
- Drug: Tovorafenib
- label
- Arm 3: Advanced Solid Tumor
- type
- EXPERIMENTAL
- interventions
- arm Group Labels
- Arm 1: Low-Grade Glioma
- Arm 2: Low-Grade Glioma Expanded Access
- Arm 3: Advanced Solid Tumor
- description
- Tovorafenib is an oral Type II RAF kinase inhibitor available in 100 mg immediate-release tablet or 25 mg/milliliter (mL) powder for reconstitution.
- name
- Tovorafenib
- other Names
- DAY101
- type
- DRUG
Study design
- allocation
- NON_RANDOMIZED
- intervention Model
- SINGLE_GROUP
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 141
- type
- ESTIMATED
Registered outcome plans (not posted results)
- primary Outcomes
- description
- 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.
- measure
- Arm 1: Overall response rate
- time Frame
- Up to 48 months
- description
- 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.
- measure
- Arm 2: Number of participants reporting adverse events
- time Frame
- Up to 48 months
- measure
- Arm 2: Number of participants with clinically significant changes in clinical chemistry parameters
- time Frame
- Up to 48 months
- measure
- Arm 2: Number of participants with clinically significant changes in hematology parameters
- time Frame
- Up to 48 months
- description
- Determined by the treating investigator and measured by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or RANO-HGG criteria, as appropriate.
- measure
- Arm 3: Overall response rate
- time Frame
- Up to 48 months
- secondary Outcomes
- description
- 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.
- measure
- Arm 1 and 3: Number of participants reporting adverse events
- time Frame
- Up to 48 months
- measure
- Arm 1 and 3: Number of participants with clinically significant changes in clinical chemistry parameters
- time Frame
- Up to 48 months
- measure
- Arm 1 and 3: Number of participants with clinically significant changes in hematology parameters
- time Frame
- Up to 48 months
- measure
- Arm 1: Area under the concentration-time curve (AUC) of Tovorafenib
- time Frame
- Cycle 1: Day 1 and Day 15; Cycles 2, 4, 7, 10 and 13: Day 1
- measure
- Arm 1: Minimum drug concentration (Cmin)
- time Frame
- 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)
- time Frame
- Baseline to 48 months
- measure
- Arm 1: Change from Baseline PR interval (ΔPR)
- time Frame
- Baseline to 48 months
- measure
- Arm 1: Change from Baseline QRS interval (ΔQRS)
- time Frame
- Baseline to 48 months
- measure
- Arm 1: Change from baseline heart rate (ΔHR)
- time Frame
- Baseline to 48 months
- measure
- Arm 1: Change in electrocardiogram (ECG) waveform morphology
- time Frame
- Baseline to 48 months
- description
- ORR is defined as percentage of participants with best overall confirmed response of CR or PR by the RANO-HGG criteria.
- measure
- Arm 1 and Arm 2: Overall response rate
- time Frame
- Up to 48 months
- description
- 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.
- measure
- Arm 1, Arm 2 and Arm 3: Overall response rate in Pediatric participants
- time Frame
- Up to 48 months
Full study description
- 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.
Source references
- references
- citation
- Kilburn LB, Khuong-Quang DA, Hansford JR, Landi D, van der Lugt J, Leary SES, Driever PH, Bailey S, Perreault S, McCowage G, Waanders AJ, Ziegler DS, Witt O, Baxter PA, Kang HJ, Hassall TE, Han JW, Hargrave D, Franson AT, Yalon Oren M, Toledano H, Larouche V, Kline C, Abdelbaki MS, Jabado N, Gottardo NG, Gerber NU, Whipple NS, Segal D, Chi SN, Oren L, Tan EEK, Mueller S, Cornelio I, McLeod L, Zhao X, Walter A, Da Costa D, Manley P, Blackman SC, Packer RJ, Nysom K. The type II RAF inhibitor tovorafenib in relapsed/refractory pediatric low-grade glioma: the phase 2 FIREFLY-1 trial. Nat Med. 2024 Jan;30(1):207-217. doi: 10.1038/s41591-023-02668-y. Epub 2023 Nov 17.
- pmid
- 37978284
- type
- DERIVED
Source notices and limitations
Discovery and provenance
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- 14 CLINICAL STUDIES The efficacy of OJEMDA was evaluated in a multicenter, open-label, single-arm clinical trial (FIREFLY-1; NCT04775485). Eligible patients (N=76) were required to have a relapsed or refractory pediatric low-grade glioma (LGG) harboring an activating BRAF alteration based on loc
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Preserved source evidence · Not medical advice