Inclusion Criteria:  Male and female participants aged ≥ 12 to < 18 years at the time of signing the informed consent. All study participants must be diagnosed with (i) NF1 per NIH Consensus Development Conference Statement and (ii) inoperable PN. In addition to PN, participants must have at least 1 other diagnostic criterion for NF1 as defined in protocol. Participants must require treatment for NF1 and inoperable PN due to actual symptoms or because of the potential to develop significant clinical complications, as judged by the Investigator, as defined in the protocol. Participants who have had prior treatment with any MEKi (including selumetinib) may be considered for inclusion in this study. Participants must have a BSA ≥ 1.3 and ≤ 2.5 m2  Exclusion Criteria:  Evidence or suspicion of optic glioma, malignant glioma, MPNST, or other cancer requiring treatment with chemotherapy or radiation therapy Prior malignancy requiring active treatment (except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the participant had been disease free for ≥ 2 years or which would not have limited survival to < 2 years). A life-threatening illness, medical condition, organ system dysfunction of laboratory finding which, in the Investigator's opinion, could compromise the participant's safety, interfere with the absorption or metabolism of selumetinib, or put the study outcomes at undue risk. Participants with clinically significant cardiovascular disease as listed in the protocol. Liver function tests: bilirubin > 1.5 × the ULN for age (with the exception of those with Gilbert syndrome) or AST/ALT > 2 × upper limit of normal. Renal Function: Creatinine clearance or radioisotope glomerular filtration rate < 30 mL/min/1.73 m2 or a serum creatinine > 1.2 mg/dL (for participants aged between 12 and 15 years) or > 1.5 mg/dL for participants aged > 15 years). Participants with abnormal ophthalmological findings/conditions as listed in the protocol. Have any unresolved chronic toxicity, associated with previous therapy for NF1-PN: Gastrointestinal toxicity of CTCAE Grade 1 or higher; Have any other unresolved chronic toxicity with CTCAE Grade ≥ 2, except hair changes (such as alopecia or hair lightening). Participants who have previously been treated with a MEKi (including selumetinib) and either discontinued treatment or required a dose reduction due to toxicity Have had recent major surgery within a minimum of 4 weeks prior to starting study intervention, with the exception of surgical placement for vascular access. Have planned major surgery during the treatment period. Any multivitamin containing vitamin E must be stopped at least 7 days prior to initiation of selumetinib.