Phase 1/2 Study of Mirdametinib + Vinblastine for Newly Diagnosed/Previously Untreated PLGG + Activation of MAPK

Inclusion Criteria: * Signed written informed consent prior to study participation. * Study activities compliance: must be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other requirements of the study, including disease assessment by contrast enhanced MRI. * Aged ≥ 2 years to ≤ 25 years when starting mirdametinib. * BSA ≥ 0,40m2 * Diagnosis: Participants must have PLGG with NF1 gene mutation (based on clinical NIH criteria, germline NF1 mutation or molecular analysis of the tumor) or PLGG with KIAA1549-BRAF fusion (based on molecular analysis of the tumor) or PLGG with evidence of MAPK pathway alteration with the exception of patients with BRAF V600E mutation (based on molecular analysis of the tumor). * Tumor tissue is required (at minimum, paraffin-embedded tissue block and additionally fresh frozen tissue \[if available\]). Patients with NF1 and Low Grade Glioma (LGG) can still be enrolled without tissue if no surgery or biopsy was conducted. * Baseline MRI. * Life expectancy greater than 6 months. * Lansky/Karnofsky score ≥ 50. * Normal organ and marrow function (see study protocol for specifics). * Female and male patients of fertile age must agree to use highly effective contraceptive measures. * Must be able to ingest by mouth and retain entirely the administered medication. Mirdametinib can not be administered via nasogastric tube or gastrostomy tube. Exclusion Criteria: * Patients who are receiving other investigational agents. * Cardiac: QTcB ≥ 480 msec or an absolute resting left ventricular ejection fraction (LVEF) of ≤ 49%. * Patients who have any other malignancy, except if the other primary malignancy is neither currently clinically significant nor requiring active intervention. * Tumor with BRAF V600E mutation. * Patients who received previous systemic or radiotherapy treatment. * Other severe and uncontrollable medical disease * Blood pressure higher than 95th percentile for patient's age, height and gender. * Increased risk of serious retinopathy and retinal vein occlusion. * Known diagnosis of human immunodeficiency virus infection, hepatitis B or C. * Previous major surgery within 2 weeks. * History of allergic reactions to compounds of similar chemical or biological composition to mirdametinib. * Pregnant or breastfeeding.