NCT07206849

Study of Tovorafenib in High-Grade Glioma and Diffuse Intrinsic Pontine Glioma (DIPG)

A Phase 2 Study of Tovorafenib in Pediatric and Young Adult Patients Newly Diagnosed With High-Grade Glioma (HGG), Including Diffuse Intrinsic Pontine Glioma (DIPG), Which Harbor Alterations in the Mitogen-Activated Protein Kinase (MAPK) Pathway

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 79 (estimated)
• Sponsor: Nationwide Children's Hospital · Academic / Other
• Sex: All
• Age: 12 Months – 39 Years
• Healthy volunteers: Not accepted

Summary

The goal of this study is to determine the efficacy of the study drugs tovorafenib to treat pediatric and young adult patients newly diagnosed with a high-grade glioma (HGG), including DIPG, that have genetic changes in pathways (MAPK) that this drug targets. The main question the study aims to answer is whether tovorafenib can prolong the life of patients diagnosed with HGG, including DIPG.

Detailed description

In this phase 2 study, pediatric, adolescent, and young adult patients with newly-diagnosed HGG and DIPG harboring alterations in the MAPK pathway will be treated with tovorafenib following initial standard-of-care treatment with radiotherapy (RT). The objectives of the trial are to assess the progression free survival (PFS) and overall survival (OS) distribution for patients with newly diagnosed HGG. This trial will include three strata. Stratum A will evaluate PFS and OS in newly diagnosed patients with HGG harboring a BRAFV600 mutation. Stratum B will evaluate PFS and OS in newly- diagnosed patients with DIPG/DMG, primary spinal cord HGG with MAPK alterations, and other MAPK alterations will be descriptively analyzed. In Stratum C, metastatic patients will be assessed for feasibility of treatment with tovorafenib post craniospinal irradiation. Tovorafenib has previously been studied in pediatrics. The recommended pediatric dosing of tovorafenib is 380mg/m2 every week (QW) and will be used as the starting dose in all strata of this study. We hypothesize that tovorafenib will improve PFS in newly-diagnosed HGG.

Conditions

• High Grade Glioma (HGG) of the Brain With BRAF Aberration
• High Grade Glioma (III or IV)
• Diffuse Intrinsic Pontine Glioma
• High Grade Glioma
• WHO Grade 3 Glioma
• WHO Grade 4 Glioma
• Metastatic Brain Tumor

Interventions

Type	Name	Description
DRUG	Tovorafenib	Tovorafenib will be given orally once weekly (QW) throughout each cycle.

Timeline

• Start date: 2026-05-01
• Primary completion: 2030-05-01
• Completion: 2037-05-01
• First posted: 2025-10-03
• Last updated: 2026-04-08

Regulatory

• FDA-regulated drug study