Study to Investigate Safety, Pharmacokinetic (PK), Pharmacodynamic (PD) and Clinical Activity of Trametinib in Subjects With Cancer or Plexiform Neurofibromas and Trametinib in Combination With Dabrafenib in Subjects With Cancers Harboring V600 Mutations

Inclusion Criteria

• General Eligibility Criteria (All Parts)
• Written informed consent - a signed informed consent and/or assent (as age appropriate) for study participation including PK sampling will be obtained according to institutional guidelines.
• Male or female between one month and =50% according to the Karnofsky/Lansky performance status scale.
• Females of child-bearing potential must be willing to practice acceptable methods of birth control. Additionally, females of childbearing potential must have a negative serum pregnancy test within 7 days prior to start of study drugs, throughout treatment period and for 4 months after last dose of study drugs.
• Must have adequate organ function as defined by the following values: renal function - 24 hr creatinine clearance (revised Schwartz formula), or radioisotope glomerular filtration rate (GFR) >=60 milliliter (mL) per minute per 1.73 meter square (mL/min/1.73m^2); or a serum creatinine =lower limit of normal (LLN) by ECHO.
• Able to swallow and retain enterally (per oral [PO] or nasogastric or gastric tube) administered medication and does not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels.
• Adequate Blood Pressure Control defined as: Blood pressure =1000/microliter, hemoglobin >=8.0 gram per deciliter (g/dL) (may receive red blood cell transfusions), platelets >=75,000/ microliter (transfusion independent, defined as not receiving platelet transfusions within a 7 day period prior to enrollment).
• Specific Eligibility Criteria, Part B
• Subjects must meet general eligibility criteria. The specific eligibility criteria listed here will apply to subjects enrolling to different cohorts of Part B.
• Tumor tissue (archived or fresh) is required and must be available to be shipped to GSK or site specific laboratory.
• Solid tumor cohort (B1) specific criteria
• B1: Refractory or relapsed neuroblastoma
• B2: Recurrent or unresectable low grade gliomas with BRAF tandem duplication with fusion
• B3: Neurofibromatosis Type -1 associated plexiform neurofibromas (NF-1 with PN) that are unresectable and medically significant.
• B4: BRAF V600 mutant tumors.
• Specific Eligibility Criteria, Part C - Subjects must meet general eligibility criteria.
• Tumors that have been documented by CLIA or equivalent certified laboratory test to harbor BRAF V600 mutation at diagnosis or relapse
• Measurable or evaluable disease
• Adequate bone marrow function
• Specific Eligibility Criteria, Part D - Subjects must meet general eligibility criteria
• Measurable or evaluable disease
• Recurrent or refractory BRAFV600 mutant LGG or LCH tumors
• Adequate bone marrow function

Exclusion Criteria

• Lactating or pregnant female.
• History of another malignancy including resected non-melanomatous skin cancer.
• Subjects with NF-1 associated optic pathway tumors are excluded if they are actively receiving therapy for the optic pathway tumor or do not meet criteria for PN or malignant solid tumor.
• Subjects with a history of NF-1 related cerebral vascular anomaly (such as Moyamoya).
• Subjects with NF-1 actively receiving therapy for the optic pathway tumor.
• Subjects with NF-1 and only PN lesions that cannot be evaluated by volumetric analysis (only applicable to Part B).
• Any serious and/or unstable pre-existing medical, psychiatric disorder or other conditions that could interfere with subject's safety, obtaining informed consent or compliance to the study procedures.
• Any prohibited medication(s), currently used or expected to be required.
• Any medications for treatment of left ventricular systolic dysfunction.
• Part B, Part C and Part D only: Previous treatment with dabrafenib or any BRAF inhibitor, trametinib or another MEK inhibitor, or and Extracellular signal-regulated kinase inhibitor (exception: prior treatment with sorafenib is permitted). Patients who have received p