Observational Study to evaluate the effect and safety of Selumetinib in Pediatric Patients with NF1-PNs - PEDIA

This is a prospective, multicenter, observational study of Chinese pediatric NF1-PN patients treated with selumetinib. The study will be conducted at approximately 12 centers in China and will include approximately 80-100 patients. Treatment centers that have PN diagnosis and/or selumetinib treatment experience will be targeted for recruitment. Patients/caregivers who are eligible and willing to participate will be enrolled into the study. Patients will start selumetinib treatment after enrollment. The study will have a 16-month enrollment period. Patients will be followed up until the end of a 24-month observation period after first dose of selumetinib, or patient death, lost to follow-up, withdrawal of consent, whichever occurs first. Patients will be followed within a 24-month period (starting after first dose received) in the study even if selumetinib is discontinued. The aims of this study are to expand understanding of disease characteristics and treatment pattern of NF1-PN in China in a real-world setting and to evaluate real-world effectiveness and safety of selumetinib for Chinese pediatric patients with NF1-PN.

Neurofibromatosis type 1 (NF1) is a rare and incurable autosomal dominant genetic disorder that is characterized by manifestations in multiple organ systems including tumors of the nervous system. Although NF1 is inherited via autosomal dominance, 50% of detected mutations are de novo. The population prevalence of NF1 estimates ranging from approximately 1/2000 to 1/4000 , and there are estimated 460,000 patients in China. The condition is usually recognized in early childhood, when pigmentary manifestations emerge. NF1 patients have decreased life expectancy of 15 years compared to the general population. High-grade glioma (HGG) and malignant peripheral nerve sheath tumor (MPNST) were noteworthy causes of death among patients with NF1. Plexiform neurofibromas (PN) are tumors arise from Schwann cells of peripheral, visceral, or subcutaneous nerves, affecting 30%-50% of patients with NF1. PN can cause substantial complications including pain, functional impairment, disfigurement and have a risk of malignant transformation. The lifetime incidence of MPNST in patients with NF1 is 8%-13% , and the presence of a PN elevates the risk of MPNST formation by 20-fold among NF1 patients. Most PN are diagnosed in early childhood and grow most rapidly during this period. Surgical resection is the mainstay treatment for PN, yet surgical treatment does not have satisfactory effect. Complete surgical resection of these tumors is often infeasible due to the extensive growth of the tumor and invasion of surrounding tissues, and partial removal often comes with a high recurrence rate. Conventional chemotherapy and radiotherapy have shown limited efficacy for NF1-associated PN. As a result, medical therapies targeting PN have been evaluated in clinical trials. The therapeutic revolution came in 2020 with the approval of selumetinib for pediatric patients with NF1-associated PN. Selumetinib is an oral selective inhibitor of MEK 1 and 2 and has been confirmed effective for NF1-associated PN in SPRINT Phase II Stratum 1. The overall response rate was 68% (34/50), and 82% (28/34) of these patients had a durable response (lasting ≥12 months) (Gross AM et al, 2020). Selumetinib was approved by the United States Food and Drug Administration (US-FDA) on April 10, 2020, becoming the first approved targeted therapy for pediatric patients with NF1-associated PN. On April 28, 2023, the China National Medical Products Administration (NMPA) approved selumetinib for pediatric patients aged 3 years and older diagnosed with NF1 who have symptomatic, inoperable PN. To date, evidence on real-world data of clinical benefit of selumetinib for NF1-associated PN patients among Chinese population is lacking. Moreover, due to the relatively rare affected population, disease knowledge of NF1 and PN is limited among healthcare professionals (HCPs) and throughout the society. An observational study of pediatric patients with NF1-associated PN treated with selumetinib in China will fulfill the data gap of effectiveness and safety of selumetinib for Chinese NF1-PN patients and will facilitate the understanding of disease characteristics and treatment in this population in a real-world setting. Observational Study of the Effectiveness and Safety of the MEK 1/2 Inhibitor (MEKi) Koselugo (Selumetinib) in Pediatric Patients with Symptomatic, Inoperable, Neurofibromatosis Type 1 (NF1)-Associated Plexiform Neurofibromas (PN) . The aims of this study are to expand understanding of disease characteristics and treatment pattern of NF1-PN in China in a real-world setting and to evaluate real-world effectiveness and safety of selumetinib for Chinese pediatric patients with NF1-PN. This is a prospective, multicenter, observational study of Chinese pediatric NF1-PN patients treated with selumetinib. The study will be conducted at approximately 12 centers in China and will include approximately 80-100 patients (ie, at least 80 patients will be enrolled into the study, but should not enrol more than 100 patients within 16 months). Treatment centers that have PN diagnosis and/or selumetinib treatment experience will be targeted for recruitment. Patients/caregivers who are eligible and willing to participate will be enrolled into the study. Patients will start selumetinib treatment after enrollment. The study will have a 16-month enrollment period. Patients will be followed up until the end of a 24-month observation period after first dose of selumetinib, or patient death, lost to follow-up, withdrawal of consent, whichever occurs first. Patients will be followed within a 24-month period (starting after first dose received) in the study even if selumetinib is discontinued. Pediatric patients with neurofibromatosis type 1 (NF1) aged 3-16 years (3 and 16 years are inclusive) who have symptomatic, inoperable plexiform neurofibromas (PN) and intend to use selumetinib after enrollment. Approximately 80-100 eligible patients will be enrolled in the study. Exposure to selumetinib is of interest for this study. Based on prescribing information, the recommended dosage of selumetinib is 25 mg/m2 orally twice daily (approximately every 12 hours) until disease progression, unacceptable toxicity, risk or no longer benefit from selumetinib treatment in the judgement of physicians, or the end of 24-month follow-up period, whichever occurs first. After 24-month follow-up period, whether the patients continue exposure to selumetinib will not be collected. Based on the study purpose, the following outcomes will be collected or measured: Patient demographics and disease characteristics at baseline and during selumetinib treatment Treatment profile with selumetinib Effectiveness outcomes of selumetinib Safety outcomes of selumetinib Time to tumor regrowth after selumetinib discontinuation Disease and treatment course after selumetinib discontinuation Caregiver- or patient-reported selumetinib treatment adherence Patient-reported pain intensity.