Trametinib Dimethyl Sulfoxide

This phase I/II study established pediatric dosing for trametinib (0.032 mg/kg/day for age <6 years, 0.025 mg/kg/day for ≥6 years) with or without dabrafenib in relapsed/refractory BRAF V600‑mutant low‑grade glioma. Objective response rates were 15% for monotherapy (n=13) and 25% for combination (n=36). Treatment discontinuations due to adverse events were more common with monotherapy (54% vs. 22%). The combination achieved target concentrations with manageable safety and demonstrated clinical efficacy, supporting its use in pediatric BRAF‑mutant low‑grade glioma.

Fig. 1 Duration of exposure to study treatment and best percentage change from baseline in measurable lesions by independent review in patients with BRAF V600–mutant LGGa. (Bouffet E, et al., 2023)

A preterm infant with Noonan syndrome (PTPN11 class 5 variant), congenital pulmonary lymphangiectasis, chylothorax, and refractory respiratory failure was treated with trametinib (max 0.025 mg/kg/day for 5 weeks). The chylothorax resolved, pulmonary function improved, and the infant was discharged home. A systematic review of 16 published cases showed short‑term symptom improvement in all, with three deaths unrelated to trametinib and moderate side effects in a subset. Trametinib is promising for severe Noonan syndrome manifestations, but clinical trials are urgently needed to establish safety and standardized protocols.

Fig. 2 Simplified representation of the RAS-MAPK pathway, genes affected by variants in noonan syndrome, and downstream effects of variants and trametinib. (De Brouchoven I, et al., 2025)