Durable responses to long-term selumetinib in Chinese pediatric NF1 patients with inoperable plexiform neurofibromas.

Background: This study provides the first long-term efficacy and safety data of selumetinib in Chinese pediatric patients with inoperable symptomatic plexiform neurofibromas (PN) associated with neurofibromatosis type 1 (NF1). Methods: In this single-center Phase I clinical trial(NCT04590235), we enrolled children with NF1-related PN aged 3 to <18 years and treated them with selumetinib at a dose of 25 mg/m Results: A total of 16 children were enrolled (median age 11 years; range 4-16) . At the final DCO, the median follow-up duration was 25 cycles (range, 24-33). With extended follow-up at the latest DCO, patients received treatment for a median of 45 cycles (range, 20-52). The objective response rate (ORR) remained 81.3% (95% CI, 54.4%-96.0%) at both the final and latest DCOs, demonstrating durable tumor responses over long-term treatment. At Cycle 42 (predefined assessment timepoint at the latest DCO), the median best percentage reduction in target PN volume was 47.3%. All patients experienced at least one adverse event (AE), while 12 of 16 patients (75.0%) experienced at least one treatment-related adverse event (TRAE). Most TRAEs were Grade 1-2 and consistent with the known safety profile of selumetinib. No Grade ≥3 TRAEs were observed. Treatment was associated with improvements in pain and HRQoL scores. Exploratory analyses suggested increased growth velocity and reduced café-au-lait macule pigmentation in prepubertal patients. Conclusions: Long-term selumetinib treatment in Chinese pediatric patients with NF1-related PN resulted in durable tumor responses and sustained pain improvement. No new safety signals were identified, although ongoing monitoring of known adverse events remains warranted. Trial Registration: NCT04590235, registered at ClinicalTrials.gov, URL: https://clinicaltrials.gov/study/NCT04590235?term=NCT04590235&rank=1.