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.
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.
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.
Single group
Tovorafenib
DrugTovorafenib is an oral Type II RAF kinase inhibitor available in 100 mg immediate-release tablet or 25 mg/milliliter (mL) powder for reconstitution.
Arm 1: Overall response rate
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.
Arm 2: Number of participants reporting adverse events
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.
Arm 2: Number of participants with clinically significant changes in clinical chemistry parameters
Arm 2: Number of participants with clinically significant changes in hematology parameters
Arm 1 and 3: Number of participants reporting adverse events
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.
Arm 1 and 3: Number of participants with clinically significant changes in clinical chemistry parameters
Arm 1 and 3: Number of participants with clinically significant changes in hematology parameters
Arm 1: Area under the concentration-time curve (AUC) of Tovorafenib
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Day One Biopharmaceuticals, Inc.
Lead sponsor
Pacific Pediatric Neuro-Oncology Consortium
Collaborator
