Tests mirdametinib in infants and toddlers with NF1-related plexiform neurofibromas

Who can take part

• Age 1.1. Cohort 1: ≥12 to ≤21 months of age at first dose 1.2. Cohort 2: 0 to ≤9 months of age at first dose For both cohorts, corrected age must be used to determine eligibility for age at first dose. Note: Corrected age is the age of the infant from the expected date of delivery (40 weeks gestation), rather than from the actual date of birth. For example, a 3-month-old infant who was born 2 months early would have a corrected age of 1 month
• Participants must have had the clinical diagnosis of NF1 according to the 2021 International Consensus Guidelines with presence of a PN and at least 1 additional diagnostic criterion for NF1
• Participants must have a target PN, defined as the clinically most relevant PN amenable to volumetric MRI analysis. For the purpose of this study, the target PN must be seen on at least 3 consecutive MRI slices and the field of view must contain the entire tumour of interest. As determined by central radiologic review, a target PN must be analysable by volumetrics using REiNS, at least 3 mL in volume
• Participants must have 1 of the following presentations of PN: 4.1. Asymptomatic: Participant has a target NF1 PN in a high risk location with a high risk of morbidity. A high-risk location with a high risk of morbidity is defined as: • In the head or neck (except for isolated scalp lesions) OR • Within the brachial or lumbosacral plexus OR • Adjacent to high-risk structure(s), defined as: o Major (“named”) blood vessel OR o Major (“named”) airway OR o Hollow viscus OR o Spinal cord and foramina OR o Vital organs (including heart, lungs, liver, spleen, etc) OR 4.2. Symptomatic: Participant has a PN that is causing clinical symptoms at the discretion of the Investigator (e.g., head and neck lesions compromising the airway or great vessels, brachial or lumbar plexus lesions causing nerve compression and loss of function, lesions causing major deformity or significant disfigurement, lesions of the extremity causing limb hypertrophy or loss of function, and painful lesions)

Who cannot take part

• Participant has received NF1 PN-targeted therapy (e.g., farnesyltransferase inhibitors, kinase inhibitors, etc) within 28 days of first dose of study treatment (or 5 half-lives, whichever is longer). All toxicities from prior therapy must resolve to Grade ≤1 or baseline
• Participant is receiving inhibitors or inducers of P-glycoprotein or breast cancer resistance protein
• Participant has family history of sudden cardiac death
• Participant has a history of, or evidence of, retinal pathology on ophthalmologic examination that is considered a risk factor for central serous retinopathy, retinal vein occlusion (RVO), retinal pigment epithelial detachment, or neovascular macular degeneration
• Participant has a history of congenital glaucoma
• Participant is currently enrolled or has past participation in any other clinical study (excluding observational studies) within 28 days of signing of informed consent