A single center, single arm, prospective clinical study initiated by a researcher on the efficacy and safety of FCN-159 in the treatment of pediatric patients with type 1 neurofibromatosis associated with symptomatic and inoperable plexiform neurofibromatosis: Mid-term study report.

Abstract

e22013 Background: Data from some clinical studies have shown that MEK inhibitors have obtained effective results in the treatment of patients with inoperable Type I neurofibromatosis-related plexiform neurofibroma (NF1-PN). The aim of this study was to evaluate the efficacy and safety of the MEK inhibitor FCN-159 in pediatric type I neurofibromatosis-related plexiform neurofibroma. Methods: The study is a single-center, single-arm, prospective study to enroll 20 subjects, who will be given 5 mg/m 2 FCN-159 orally daily according to their body surface area, and the primary follow-up indicator will be the reduction in tumor volume of the children as assessed by MRI technique every 4 months, and other indicators will include pain, motor function, safety, and adverse events. Results: This study was conducted from 2023-10 onwards. All 20 subjects have been enrolled to date, with 19 subjects having valid follow-up data. The mean age of subjects at registration was 94.8 months (30-191 months), the mean volume of selected target tumors at follow-up was 89.8 cm 3 (11.4-257.7 cm 3 ), and the current median follow-up time was 8 months (2-14 months). After completing MRI after the appropriate time, 79% (15/19) of patients showed a shrinking or shrinking trend in the target tumor, with a median percent reduction in tumor volume of 29.9% (5%-59.6%). Tumor volume reduction of up to 20% in 42% (8/19) of patients (29.9%-59.6%). One patient (5%) discontinued treatment due to disease progression, two patients were discharged from the group for other treatment options, and seven patients (36.8%) did not reach 20% shrinkage of the target tumor (5%-18.6%), but all showed a trend toward shrinkage. Mean pain numeric rating scale (lansky) decreased from 2.92 at baseline to 0.58 (p = 0.025). The most common adverse reactions were decreased albumin (11 cases), asymptomatic creatine kinase elevation (8 cases), rash (8 cases), oral ulcers (4 cases), and onychomycosis (5 cases). Except for one Grade 3（CTCAE 5.0 ）adverse event neoplastic tumor, there were no other Grade 3 or higher adverse reactions or serious adverse reactions. Conclusions: In this study, 79% of pediatric NF1-PNs showed a trend toward tumor shrinkage or atrophy within the first 14 months of treatment with FCN-159. Patients had significantly lower mean pain scores, but adverse effects were also common. Subsequent, more substantial studies are still needed to evaluate the effectiveness and long-term adverse effects of FCN-159. Clinical trial information: The retroactive filing operation is underway, with a filing number of MR-11-24-053360 .