This is a Phase I/II, single arm, open-label study in children aged ≥ 1 to < 7 years at study entry (date of ICF signature) with a clinical diagnosis of NF1 related symptomatic, inoperable PN. The study is designed to evaluate the PK, safety and tolerability of selumetinib given as a granule formulation.~Participants will receive selumetinib for 25 cycles (or until they meet discontinuation criteria). Enrolment into the initial dose-finding phase will be stratified by age group:~Cohort 1: participants aged between ≥ 4 and < 7 years~Cohort 2: participants aged between ≥ 1 to < 4 years~In addition to the Global Cohorts, 6 Japanese participants in Japan aged between ≥ 1 to < 7 years with NF1 related symptomatic, inoperable PN will be enrolled into the Japan Cohort.~After completion of at least one cycle (28 days) of dosing in the first 3 participants in Cohort 1, Safety Review Committee(SRC) will review the emerging safety and PK data. Providing the single dose PK exposure is within the acceptable range and there are no safety concerns as determined by SRC then recruitment into Cohort 2 will be initiated and further participants will be recruited into Cohort 1. If the PK exposure is not within the acceptable range, the dose schema may be adjusted to ensure that selumetinib exposure is within the range observed in the SPRINT study; and a further 3 participants will be enrolled in Cohort 1 at the adjusted dose and the PK will be assessed against acceptance criteria as before. Cohort 2 will be initiated once the selumetinib granule formulation dose schema is identified for Cohort 1. The physiologically-based PK model will be updated, if required, based on emerging PK data.~Additional SRC reviews will be held for each of the cohorts following at least one cycle of dosing in approximately 6 evaluable participants and again in approximately 10 evaluable participants. The SRC will evaluate the PK, safety and tolerability of the granule formulation for that dose schema. The Japan Cohort will not participate in the dose-finding phase.~Participants who are aged ≥ 5 years at the end of 25 cycles of selumetinib will be considered to have completed the study for data analysis purposes. Participants who terminate treatment prior to Cycle 25 will be followed up to collect MRIs performed as standard of care and details of NF1-PN treatment information until the time when they would have completed 25 cycles of treatment, or they commence an alternative systemic NF1-PN treatment, whichever is the earliest. Any participant who is aged < 5 years after 25 cycles of selumetinib (or when they terminate treatment with selumetinib) will enter a safety follow-up phase. Participation in the safety follow-up will continue until they reach the age of 5 years or commence an alternative systemic NF1-PN treatment, whichever is the earlier. Participants can continue to receive selumetinib (capsule or sprinkle capsule) during the safety follow-up as long as they are considered to be receiving benefit in the opinion of their Investigator.
This study is designed to define a dosing regimen and assess the pharmacokinetics(PK) and safety of the granule formulation; the study will also include descriptive analyses of exploratory efficacy endpoints. The study will inform the benefit risk profile of the granule formulation in children aged ≥ 1 to < 7 years with NF1 related symptomatic, inoperable PN.