Perreault S, Larouche V, Tabori U, et al. - Assuming that up to 50% of pediatric low-grade gliomas (PLGG) are refractory to conventional chemotherapy and that the majority of PLGG have activation of the MAPK/ERK pathway, researchers sought to report on the efficacy of specific MEK inhibitors such as trametinib, which act further down in the molecular pathway, as a better treatment alternative for these patients. They investigate the objective response rate of trametinib as a single agent for the treatment of progressing/refractory tumors with MAPK/ERK pathway activation. In the TRAM-01 study, a phase II multicentric open-label basket trial, four groups are included: Group 1 comprises NF1 patients with progressing/refractory glioma; Group 2 comprises NF1 patients with plexiform neurofibroma; Group 3 comprises patients with progressing/refractory glioma with KIAA1549-BRAF fusion; Group 4 comprises other patients with progressing/refractory glioma with activation of the MAPK/ERK pathway. Eligible patients will be provided daily oral trametinib at full dose for a total of 18 cycles of 28 days. In seven Canadian centers, enrollment of a total of 150 patients will be done. The assessment of progression-free survival, overall survival, safety and tolerability of trametinib, serum levels of trametinib and evaluation of the quality of life during treatment are included as secondary objectives. As per expectations, trametinib will enable targeting directly and specifically the MAPK/ERK pathway. A significant response in most patients is expected.