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

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).

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/m² twice daily in 28-day cycles until disease progression or intolerance. The study consisted of a predefined treatment phase, with a final data cutoff (DCO) on August 15, 2023, followed by an extended follow-up period with a latest DCO on March 1, 2025. Tumor response was assessed by volumetric MRI using Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) criteria. Safety was evaluated per CTCAE v5.0. Patient-reported outcomes included pain, health-related quality of life (HRQoL), and exploratory growth and dermatologic assessments. Prior PK data have been reported.

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.

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.

NCT04590235, registered at ClinicalTrials.gov, URL: https://clinicaltrials.gov/study/NCT04590235?term=NCT04590235&rank=1.