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

Starting soon · Phase 2

Conditions studied: 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

In brief

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.

Key facts

Study ID

NCT07206849

Run by

Nationwide Children's Hospital

People needed

79

Starts

2026-11-01

Expected to finish

2037-11-01

Last updated by the study team

2026-07-31

Who can join

Age: 1 and older, up to 39. Sex: any. Healthy volunteers: not accepted.

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).
• Stratum B: 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.
• Stratum C: 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).
• Presence of at least one relevant actionable somatic alteration:
• MAPK pathway alteration(s): BRAFV600 mutation (Strata A or C)
• KIAA1549:BRAF fusion (Strata B or C)
• KRAS/NRAS alteration (Strata B or C)
• CRAF/RAF1 alteration (Strata B or C)
• other RAF mutations (Strata B or C)
• FGFR alteration (Strata B or C)
• Performance Level:

You may not qualify if…

• Pregnancy or breastfeeding.
• Other Exclusion Criteria
• 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.
• Anticoagulants: patients who are receiving therapeutic anticoagulants including warfarin, low-molecular weight heparin are not eligible.
• Patients with prior or ongoing clinically significant medical or psychiatric condition that, in the investigator's opinion, could affect the safety of the participant, or could impair the assessment of study results are not eligible.

Full record on ClinicalTrials.gov

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