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RECRUITING
NCT06712875
PHASE1/PHASE2

MAPK Inhibition Combined With Anti-PD1 Therapy for BRAF-altered Pediatric Gliomas

Sponsor: Ann & Robert H Lurie Children's Hospital of Chicago

View on ClinicalTrials.gov

Summary

Pediatric gliomas harboring BRAF-alterations, commonly BRAFV600 mutation or KIAA1549-BRAF fusion, are currently treated with either chemotherapy or mitogen activated protein kinase (MAPK) inhibitors, such as, dabrafenib and/or trametinib. Unfortunately, some BRAF-altered gliomas can progress or have rebound growth after discontinuation of therapy. Data from BRAFV600E-mutant melanoma has shown potential synergy between MAPK inhibition and anti-programmed cell death 1 (anti-PD1) checkpoint blockade. Anti-PD1 therapy, such as, nivolumab can block the PD1 receptor on T cells, a marker of T cell exhaustion, allowing a continued or more robust anti-tumor immune response. Here, investigators will combine MAPK inhibition with anti-PD1 therapy in recurrent, refractory low grade BRAF-altered glioma and newly diagnosed or recurrent BRAF-altered or NF-altered high grade glioma.

Official title: A Pilot Study Evaluating the Toxicity and Clinical Benefit of Mitogen-activated Protein Kinase (MAPK) Pathway Inhibition Combined With Programmed Cell Death-1 Checkpoint Blockade (Anti-PD1) for the Treatment of BRAF-altered Pediatric Gliomas

Key Details

Gender

All

Age Range

1 Year - 26 Years

Study Type

INTERVENTIONAL

Enrollment

27

Start Date

2025-04-01

Completion Date

2029-06

Last Updated

2025-05-29

Healthy Volunteers

No

Interventions

DRUG

Trametinib and Nivolumab

Trametinib combined with nivolumab (Cohort A)

DRUG

Dabrafenib, trametinib, nivolumab

Dabrafenib + trametinib combined with nivolumab (Cohort B)

Locations (3)

Children's National Hospital

Washington D.C., District of Columbia, United States

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States