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

NCT07206849 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: CONNECT TarGeT-BR01FD008167
• Study Type: interventional
• Target: 79
• Locations: 0 countries
• Sites: N/A

Brief 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.

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

Keywords

tovorafenib; high grade glioma

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival Stratum A

  Estimate the progression-free survival (PFS) distribution for pediatric and young adult patients (age: ≥12 months and ≤39 years) with newly-diagnosed BRAFV600 mutant HGG (Stratum A) who receive tovorafenib monotherapy post RT compared to molecularly-stratified, matched historical controls.

  6 years

Secondary Outcomes (12)

• Overall Survival Stratum A

  6 years

• OS Stratum B

  6 years

• PFS Stratum B

  6 years

• OS Stratum B

  6 years

• Establish the RP2D of tovorafenib - Stratum C

  At the end of Cycle 1 (each cycle is 28 days)

Study Arms (3)

Stratum A - localized HGG

EXPERIMENTAL

Patients with intracranial, localized, non-pontine, and non-thalamic HGG harboring a BRAFV600 mutation (who do not meet criteria for Strata B or C).

Drug: Tovorafenib

Stratum B - DIPG

EXPERIMENTAL

Patients with DIPG/DMG as defined in Section 4.1.3 OR patients with localized, non-pontine, non-thalamic HGG harboring a MAPK alteration not included in Stratum A (KIAA1549:BRAF fusion, KRAS/NRAS, CRAF/RAF1, other RAF mutation, or FGFR alteration) OR patients with primary spinal tumors.

Drug: Tovorafenib

Stratum C - metastatic HGG

EXPERIMENTAL

Patients with metastatic HGG (including metastatic DIPG/DMG) harboring a MAPK alteration (BRAFV600, KIAA1549:BRAF fusion, KRAS/NRAS, CRAF/RAF1, other RAF mutation, or FGFR alteration).

Drug: Tovorafenib

Interventions

Tovorafenib DRUG

Tovorafenib will be given orally once weekly (QW) throughout each cycle.

Stratum A - localized HGG; Stratum B - DIPG; Stratum C - metastatic HGG

Eligibility Criteria

• Age: 12 Months - 39 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patient must have previously enrolled on TarGeT-SCR.
• Age Patients must be ≥12 months and ≤39 years of age at the time of enrollment on TarGeT-SCR.
• Body Surface Area (BSA) Patients must have a BSA \>0.3m2.
• Diagnosis:
• Patients with a newly-diagnosed HGG, including DIPG, which harbor alterations in the MAPK pathway are eligible. All patients must have tumor tissue from diagnostic biopsy or resection. The diagnosis of HGG, including DIPG, must have been confirmed through TarGeT-SCR.
• For the diagnosis of DIPG, patients must have a tumor with pontine epicenter and diffuse involvement of at least 2/3 of the pons, with histopathology consistent with diffuse WHO Grade 2-4 glioma.
• All other HGGs must be WHO Grade 3 or 4.
• Disease Status
• Patients must be newly diagnosed and enroll and start treatment within 35 days of completion of radiotherapy.
• Measurable disease is not required. Patients without measurable disease are eligible.
• Patients with primary spinal tumors are eligible.
• Patients with secondary or radiation-induced HGG are eligible.
• TarGeT-B Strata Definitions
• Patients must be able to be assigned to one of the strata below:
• Stratum A: Patients with intracranial, localized, non-pontine, and non-thalamic HGG harboring a BRAFV600 mutation (who do not meet criteria for Strata B or C).

You may not qualify if:

• Pregnancy or breastfeeding.
• Patients with neurofibromatosis type 1 (NF-1) are not eligible for this study.
• Infection: Patients who have an uncontrolled infection are not eligible.
• Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study are not eligible.
• Patients with uncontrolled GI disease or other condition that could affect absorption or predispose participant to gastrointestinal ulceration are not eligible.
• Concomitant Medications • Corticosteroids: Patients receiving corticosteroids are eligible, but the use of corticosteroids must be reported.
• Investigational Agents/Drugs: Patients who are currently receiving another investigational drug are not eligible. This includes targeted agents, monoclonal antibodies, herbal supplements, or other investigational agents other than tovorafenib.
• Anti-cancer Agents: Patients who are currently receiving other anti-cancer agents are not eligible with the exception of temozolomide given concurrently with radiotherapy.
• Anticonvulsants: Patients who are receiving enzyme-inducing anticonvulsants as listed in Appendix II, are not eligible.
• Patients who are receiving medications known to prolong QTc interval as listed in Appendix III are not eligible.
• As tovorafenib is a substrate of CYP2C8, patients should not take strong inhibitors or inducers of CYP2C8 (See Appendix VI), as they could alter the drug's pharmacokinetics. Medications that are substrates of CYP2C8 or CYP3A4 are allowed but should be used with caution.
• Medications that are substrates of breast cancer resistance protein (BCRP) with a narrow therapeutic index are prohibited during this study (Appendix IV).
• Patients who are receiving duloxetine, alosetron, or theophylline (CYP1A2 inhibitors) are not eligible.
• Patients on beta-blockers are not eligible.
• Selective serotonin reuptake inhibitors (SSRIs) such as citalopram (Celexa), escitalopram (Lexapro), Fluoxetine (Prozac), fluvoxamine (Luvox), paroxetine (Paxil), sertraline (Zoloft) should be used with caution but are not contraindicated.

Sponsors & Collaborators

• Day One Biopharmaceuticals, Inc.: collaborator
• Nationwide Children's Hospital: lead

MeSH Terms

Conditions

Glioma; Diffuse Intrinsic Pontine Glioma; Brain Neoplasms

Interventions

tovorafenib

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Brain Stem Neoplasms; Infratentorial Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Central Study Contacts

Kelsey H Troyer, PhD

CONTACT

16147223284; kelsey.troyer@nationwidechildrens.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Tovorafenib

Study Record Dates

• First Submitted: September 18, 2025
• First Posted: October 3, 2025
• Study Start: May 1, 2026
• Primary Completion (Estimated): May 1, 2030
• Study Completion (Estimated): May 1, 2037
• Last Updated: April 8, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share