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OncoMatch/Clinical Trials/NCT06712875

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

Is NCT06712875 recruiting? Yes, currently enrolling (May 2026). This Phase 1/2 trial studies multiple treatments including Trametinib and Nivolumab and Dabrafenib, trametinib, nivolumab for low grade glioma.

Phase 1/2RecruitingAnn & Robert H Lurie Children's Hospital of ChicagoNCT06712875Data as of May 2026

Treatment: Trametinib and Nivolumab · Dabrafenib, trametinib, nivolumabPediatric 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.

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Extracted eligibility criteria

Cancer type

Glioblastoma

Biomarker criteria

Required: BRAF KIAA1549-BRAF fusion

harboring a KIAA1549-BRAF fusion

Required: NF1 NF1-associated glioma or NF1-altered glioma

Patients with NF1-associated gliomas or NF1-altered glioma

Required: BRAF V600 mutation

harboring BRAFV600 mutation

Prior therapy

Must have received: BRAF inhibitor — Low Grade Glioma only

Patients must have received a prior BRAF inhibitor (first or second generation), MEK inhibitor, or a combination. The response to this therapy must be known and information provided at study enrollment.

Must have received: MEK inhibitor — Low Grade Glioma only

Patients must have received a prior BRAF inhibitor (first or second generation), MEK inhibitor, or a combination. The response to this therapy must be known and information provided at study enrollment.

Must have received: radiation therapy — High Grade Glioma only

Patients must have received prior radiotherapy >12 weeks prior to enrollment.

Cannot have received: MAPK inhibitor and checkpoint blockade combination therapy

Patients who have received MAPK inhibitor and checkpoint blockade combination therapy.

Cannot have received: BRAF inhibitor

Exception: if discontinued due to grade 3 or higher toxicity or clinically significant grade 2 toxicity requiring discontinuation

Patients who previously discontinued BRAF inhibitor (type 1 inhibitor or dimer inhibitor, such as, DAY101), MEK inhibitor, or the combination because of grade 3 or higher toxicity or clinically significant grade 2 toxicity requiring discontinuation of therapy are not eligible.

Cannot have received: MEK inhibitor

Exception: if discontinued due to grade 3 or higher toxicity or clinically significant grade 2 toxicity requiring discontinuation

Patients who previously discontinued BRAF inhibitor (type 1 inhibitor or dimer inhibitor, such as, DAY101), MEK inhibitor, or the combination because of grade 3 or higher toxicity or clinically significant grade 2 toxicity requiring discontinuation of therapy are not eligible.

Lab requirements

Blood counts

adequate organ and bone marrow function required

Kidney function

adequate organ and bone marrow function required

Liver function

adequate organ and bone marrow function required

Patients must have adequate organ and bone marrow function

Structured fields extracted by AI. May contain errors — verify against the official protocol.

US trial sites

  • Children's National Hospital · Washington D.C., District of Columbia
  • Ann & Robert H. Lurie Children's Hospital of Chicago · Chicago, Illinois
  • Memorial Sloan Kettering Cancer Center · New York, New York

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