An Intermediate Access Protocol for Selumetinib for Treatment of Neurofibromatosis Type 1

Inclusion Criteria:

1. Diagnosis of neurofibromatosis type 1 (NF1) and have inoperable,progressive/symptomatic plexiform neurofibromas (PN)

2. Presence of inoperable PN , defined as a PN that cannot be surgically completelyremoved without risk for substantial morbidity

3. Patients aged ≥2 with onset of disease before they were 18 years and a BSA ≥ 0.55 m2who are able to swallow whole capsules. (approx. length 15.4 mm, diameter 5.4 mm). Aswallow test must be performed before requesting drug

4. Normal cardiac function defined as normal ejection fraction (ECHO, MUGA or cardiacMRI) as per institutional normal and absence of prior heart disease

5. Adequate blood pressure as defined in line with local practice.

6. The patient has exhausted all available approved therapies as appropriate for NF1 withinoperable progressive/symptomatic PN

7. Provision of a signed informed consent prior to any protocol specific procedures.Patients already receiving selumetinib through single patient access who enroll inthis protocol must be reconsented and sign the consent form for this intermediateaccess protocol.

8. For female patients of childbearing potential, have evidence of a post-menopausalstatus, or a negative urinary or serum pregnancy test.

Exclusion Criteria:

1. Unresolved chronic toxicity ≥ CTCAE Grade 2 from previous therapy

2. Patients eligible for any ongoing clinical trials with selumetinib in the indicationin question

3. Ophthalmological conditions: Current or past history of retinal pigment epithelialdetachment (RPED)/central serous retinopathy (CSR) or retinal vein occlusionIntraocular pressure (IOP) should not be > 21 mmHg for adults or outside the range ofnormal for children or uncontrolled glaucoma (irrespective of IOP)

4. Male or female patients of reproductive potential and, as judged by the investigator,are not employing an effective method of birth control.

5. Female patients who are breast-feeding.

6. Have evidence of any other significant clinical disorder or laboratory finding that,as judged by the treating physician, makes it undesirable for the patient toparticipate in the study.

7. Have any evidence of a severe or uncontrolled systemic disease (e.g. unstable oruncompensated respiratory, cardiac, hepatic, or renal disease, active infection (including hepatitis B, hepatitis C, HIV), active bleeding diatheses or renaltransplant

8. Have refractory nausea and vomiting, chronic gastrointestinal diseases (e.g.,inflammatory bowel disease), or significant bowel resection that would adverselyaffect the absorption / bioavailability of the orally administered study medication