Pharmacokinetics, Safety and Efficacy of the Selumetinib Granule Formulation in Children Aged ≥1 to <7 Years With NF1-related Symptomatic, Inoperable PN

Inclusion Criteria:

1. Male and female participants aged ≥ 1 to < 7 years of age at the time their legallyauthorised representative (parent or guardian) signs the informed consent.

2. All study participants must be diagnosed with NF1 with symptomatic inoperable PN asdefined in protocol.

3. Participants must have at least one measurable PN, defined as a PN of at least 3 cmmeasured in one dimension, which can be seen on at least 3 imaging slices and have areasonably well-defined contour. Participants who have undergone surgery forresection of a PN are eligible provided the PN was incompletely resected and ismeasurable. The target PN will be defined as the clinically most relevant PN, whichis symptomatic, inoperable and measurable by volumetric MRI analysis.

4. Performance status: Participants must have a Lansky performance of ≥ 70 except inparticipants who are wheelchair bound or have limited mobility secondary to a needfor mechanical breathing support (such as an airway PN requiring tracheostomy orcontinuous positive airway pressure) who must have a Lansky performance of ≥ 40.

5. Participants must have a BSA ≥ 0.4 and ≤ 1.09 m2 at study entry (date of ICFsignature).

6. Mandatory provision of consent for the study signed and dated by a participant'slegally authorised representative (parent or guardian) along with the paediatricassent form, if applicable.

Exclusion Criteria:

1. Participants with confirmed or suspected malignant glioma or MPNST. Participantswith low grade glioma (including optic glioma) not requiring systemic therapy arepermitted.

2. History of malignancy except for malignancy treatment with curative intent with noknown active disease ≥ 2 years before the first dose of study intervention and oflow potential risk of recurrence.

3. Refractory nausea and vomiting, chronic gastrointestinal disease, inability toswallow the formulated product, or previous significant bowel resection that wouldpreclude adequate absorption, distribution, metabolism, or excretion of selumetinib.

4. A life-threatening illness, medical condition, organ system dysfunction orlaboratory finding which, in the Investigator's opinion, could compromise theparticipant's safety, interfere with the absorption or metabolism of selumetinib, orput the study outcomes at undue risk.

5. Participants with clinically significant cardiovascular disease as defined in theprotocol.

6. Liver function tests: Bilirubin > 1.5 × the ULN for age with the exception of thosewith Gilbert syndrome (≥ 3 × ULN) or AST/ALT > 2 × ULN.

7. Renal Function: Creatinine clearance or radioisotope glomerular filtration rate < 60mL/min/1.73 m2 or Serum creatinine > 0.8 mg/dL (for participants aged ≥ 1 to < 4years) or > 1.0 mg/dL (for participants aged ≥ 4 years).

8. Participants with ophthalmological findings/condition as listed in the protocol.

9. Have any unresolved chronic toxicity with CTCAE Grade ≥ 2 which are associated withprevious therapy for NF1-PN (except hair changes such as alopecia or hairlightening)

10. Participants who have previously been treated with a MEKi (including selumetinib)and have had disease progression, or due to toxicity have either discontinuedtreatment and/or required a dose reduction.

11. Have inadequate haematological function defined as: An absolute neutrophil count < 1500/μL or Haemoglobin < 9g/dL or Platelets <100,000/μL or Have had a transfusion (of red cells or other blood derived products) within the 28 days prior to studyentry (date of ICF signature).

12. Have received or are receiving an IMP or other systemic NF1-PN target treatment (including MEKi) within 4 weeks prior to the first dose of study intervention, orwithin a period during which the IMP or systemic PN target treatment has not beencleared from the body (eg, a period of 5 'half-lives'), whichever is longer.

13. Has received radiotherapy in the 6 weeks prior to start of study intervention or anyprior radiotherapy directed at the target or non-target PN.

14. Receiving herbal supplements or medications known to be strong or moderateinhibitors of the CYP3A4 and CYP2C19 enzymes or inducers of the CYP3A4 enzyme unlesssuch products can be safely discontinued at least 14 days or 5 half-lives (whicheveris longer) before the first dose of study medication.

15. Inability to undergo MRI and/or contraindication for MRI examinations. Prosthesis ororthopaedic or dental braces that would interfere with volumetric analysis of targetPN on MRI.