Pediatric low-grade glioma (pLGG) is the most prevalent childhood brain tumor. Patients with V600 mutation-positive pLGG may benefit from treatment with dabrafenib. Part 2 of a phase I/IIa study, open-label study (NCT01677741) explores the activity and safety of dabrafenib treatment in these patients. Patients ages 1 to <18 years who had V600-mutant solid tumors (≥1 evaluable lesion) with recurrent, refractory, or progressive disease after ≥1 standard therapy were treated with oral dabrafenib 3.0 to 5.25 mg/kg/day (part 1) or at the recommended phase II dose (RP2D; part 2). Primary objectives were to determine the RP2D (part 1, results presented in a companion paper) and assess clinical activity (part 2). Here, we report the clinical activity, including objective response rates (ORRs) using Response Assessment in Neuro-Oncology criteria and safety across parts 1 and 2. Overall, 32 patients with pLGG were enrolled (part 1, = 15; part 2, = 17). Minimum follow-up was 26.2 months. Among all patients, the ORR was 44% 95% confidence interval (CI), 26-62 by independent review. The 1-year progression-free survival rate was 85% (95% CI, 64-94). Treatment-related adverse events (AE) were reported in 29 patients (91%); the most common was fatigue (34%). Grade 3/4 treatment-related AEs were reported in 9 patients (28%). Dabrafenib demonstrated meaningful clinical activity and acceptable tolerability in patients with V600-mutant pLGG.