LGG-46. TRAMETINIB THERAPY IN PEDIATRIC PATIENTS WITH LOW-GRADE GLIOMAS (LGG) WITH BRAF GENE FUSION; A DISEASE-SPECIFIC COHORT IN THE FIRST PEDIATRIC TESTING OF TRAMETINIB

LGG is the most prevalent childhood brain tumor. BRAF fusions drive constitutive activation of BRAF and tumorigenesis. We report results of trametinib, a MEK1/2 inhibitor, in pediatric patients with LGG with BRAF fusion.

This phase 1/2 trial (NCT02124772) enrolled pediatric patients (≤18 y) with refractory/recurrent tumors. We report results from interim analysis of pediatric patients with LGG harboring BRAF fusion. Trametinib was dosed at 4 dose levels in part A (0.0125, 0.025, 0.04, and 0.032 mg/kg/d) and at 0.025 mg/kg/day in the expansion cohort. Tumor assessments were performed every 8 weeks by MRI, including T2-FLAIR sequences, using RANO criteria.

Twenty-three patients were enrolled across cohorts. Median age of patients was 8 y (range, 2-18) and 13 of 23 were male. At data cutoff, 15 patients were ongoing. One patient discontinued with progressive disease (PD) at 35 weeks, 4 due to adverse events (AEs), 2 per investigator discretion, and 1 per consent withdrawal. The most common treatment-related AEs were diarrhea (14), rash (13), paronychia (9), and maculopapular rash (8). There were no deaths on study. Confirmed partial responses were observed in 3 patients by investigator and 1 patient by independent review. No patients had best response of PD. All responses were ongoing at the data cutoff (all >1 y), and 12 patients had ongoing stable disease (49-121 weeks).

In pediatric patients with pretreated LGG and BRAF fusion, trametinib was well tolerated, with 1 independently confirmed RANO response, and most patients were without PD >1 y.