SJ901: Evaluation of Mirdametinib in Children, Adolescents, and Young Adults With Low-Grade Glioma

Inclusion Criteria: Screening Phase * Participants with histologically confirmed or suspected low-grade glioma, including neuronal and mixed neuronal-glial tumors * Participant must have adequate tumor tissue from primary and/or relapsed tumor for central pathology review * For Phase 1: Projected to be ≥ 2 years and \< 25 years at the time of study enrollment * Participant's body surface area (BSA) at time of study enrollment must fall within the range outlined in the protocol for the specific dose level under evaluation: * Phase 1: Dose Finding/Dose-escalation * For Phase 1 participant's BSA must fall within the range specified in the protocol for the specific dose level under evaluation. * Phase 2: All Cohorts: * For Phase 2 of the study the upper BSA restrictions will be removed. * Participant and/or guardian can understand and is willing to sign a written informed consent document according to institutional guidelines Exclusion Criteria: Screening Phase * Participants with known current retinal pathology that is consistent with or a precursor for central serous retinopathy, retinal vein occlusion (RVO), or neovascular macular degeneration * Participants with a known malabsorption syndrome or preexisting gastrointestinal conditions that may impair absorption of mirdametinib (e.g., gastric bypass, lap band, or other gastric procedures) * Participant with a known history of liver disease or known hepatic or biliary abnormalities (except for Gilbert's syndrome or asymptomatic gallstones) * Participants with a clinically significant history of chronic interstitial lung disease (such as bronchopulmonary dysplasia, chronic bronchiolitis, obliterative bronchiolitis, chronic aspiration pneumonia, surfactant protein disorder, or other serious chronic pulmonary condition). Participants with a history of asthma, reactive airways disease, or viral pneumonitis are not to be excluded if disease has resolved or is well-controlled. Inclusion Criteria: Phase 1 and Phase 2, All Cohorts * Participant must be ≥ 2 years and \< 25 years of age at the time of enrollment * Participant's BSA at time of study enrollment must fall within the range outlined below for the specific dose level under evaluation: * Phase 1: Dose-finding/Dose-escalation * For Phase 1 participant's BSA must fall within the range specified in the protocol for the specific dose level under evaluation. * Phase 2: All Cohorts * For Phase 2 of the study the upper BSA restrictions will be removed. * Participant must have confirmation of one of the following diagnosis per St. Jude Children's Research Hospital central pathology review of primary and/or relapsed tumor: * Eligible tumors include: * Low-grade glioma/astrocytic tumor/glioneuronal tumor/neuroepithelial tumor, not otherwise specified (NOS) or not elsewhere classified (NEC) * Pilocytic astrocytoma * Pilomyxoid astrocytoma * Pleomorphic xanthroastrocytoma * Ganglioglioma * Gangliocytoma * Diffuse glioma, diffuse astrocytoma, oligodendroglioma, or oligoastrocytoma * Papillary glioneuronal tumor * Rosette-forming glioneuronal tumor * Diffuse leptomeningeal glioneuronal tumor * Central neurocytoma, extraventricular neurocytoma * Angiocentric glioma * Dysembryoplastic neuroepithelial tumor (DNET), septal DNET, myxoid glioneuronal tumor * Tectal glioma * Desmoplastic infantile astrocytoma / ganglioglioma * Polymorphous low-grade neuroepithelial tumor of the young * Multinodular and vacuolating neuronal tumor * In addition, tumor on central review must show evidence supporting MAPK pathway activation as defined by IHC, FISH and/or DNA/RNA sequencing (i.e. BRAF fused or rearranged, FGFR1/2/3 aberration, NF1, NF2, PTPN11, SOS1, RAF1 mutations, MYB or MYBL1 fused or rearranged, etc.) or occur in a participant with known NF1, NF2, SOS1, RAF1, or PTPN11 germline mutation. (Note: tests that show evidence supporting MAPK pathway activation that have been already performed do not need to be repeated as long as deemed acceptable by central review). * Participant must have measurable or evaluable disease (as defined in the protocol) * Note: Participants with metastatic disease or multiple independent primary LGGs are allowed on study. * Participants who are receiving corticosteroids must be on a stable or decreasing dose for at least 1 week prior to enrollment with no plans for escalation. * Participant must have a Lansky (\<16 years) or Karnofsky (≥16 years) performance score of ≥ 50 and, in the opinion of the investigator, a minimum life expectancy of at least 6 weeks. * Note: Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score. * Participant must have adequate bone marrow and organ function as defined as: * ANC ≥ 1.0 x 10\^9/L without growth factor support within 7 days * Platelet count ≥ 75x 10\^9/L without support of a platelet transfusion within 7 days * Hemoglobin ≥8.0 g/dL without support of a blood transfusion within 7 days * Potassium, total calcium (corrected for serum albumin), magnesium, sodium and phosphorus must be ≤ grade 1 or corrected to ≤ grade 1 with supplements before first dose of study medication * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN. For the purposes of this study the ULN of ALT and AST is 45 U/L. * Total bilirubin ≤ ULN; or if \> ULN then direct bilirubin ≤ 1.5 x ULN * Adequate renal function defined as: * Serum creatinine ≤ the maximum serum creatinine based on age/gender: Age: 2 to \< 6 years: maximum serum creatinine (mg/dL) 0.8 (male, female), Age: 6 to \<10 years: maximum serum creatinine (mg/dL) 1 (male, female), Age: 10 to \<13 years: maximum serum creatinine (mg/dL) 1.2 (male, female), Age: 13 to \<16 years: maximum serum creatinine (mg/dL) 1.5 (male); 1.4 (female), Age: ≥ 16 years