The Study to Determine Safety, Tolerability and Pharmacokinetics of Oral Dabrafenib In Pediatric Subjects

Inclusion Criteria:

• Written informed consent - a signed informed consent and/or assent (as age appropriate) will be obtained according to institutional guidelines
• Male or female between one month and <18 years of age (inclusive) at the time of signing the informed consent form
• Recurrent disease or progressive disease after having received at least one standard therapy for their disease
• At least one evaluable lesion
• BRAF V600 mutation-positive tumor as confirmed in a Clinical Laboratory Improvement Amendments (CLIA)-approved laboratory or equivalent
• Performance score of >=50% according to the Karnofsky/Lansky performance status scale (subjects with a performance status of <=50% can be enrolled if the subject's confinement to bed and inability to carry out activities is due solely to cancer-related pain, as assessed by the investigator)
• Females of child-bearing potential (with negative serum pregnancy test within 7 days prior to the first dose of study medication) and males with reproductive potential must be willing to practice acceptable methods of birth control.
• Must have adequate organ function as defined by the following values: Adequate bone marrow function defined as-absolute neutrophil count (ANC) >=1000/ microliter (µL), hemoglobin >=8.0 grams (g)/ deciliter (dL) (may receive red blood cell transfusions), platelets >=75,000/µL (transfusion independent, defined as not receiving platelet transfusions within a 7 day period prior to enrollment; adequate renal and metabolic function defined as: calculated creatinine clearance (Cockcroft-Gault), calculated glomerular filtration rate (GFR) (revised Schwartz formula), or radioisotope GFR >=60 milliliters/minutes (mL/min)/1.73 meter square (m^2); or a serum creatinine within the institutional reference range upper limit of normal (for age/gender, if available); adequate liver function defined as: bilirubin (sum of conjugated + unconjugated) <=1.5 x upper limit of normal (ULN) for age, aspartate aminotransaminase (AST) and alanine transaminase (ALT) <=2.5 x ULN; AST/ALT may be <5 x ULN at baseline if liver metastases are present (requires radiographic confirmation of liver metastases) and adequate cardiac function defined as: left ventricular ejection fraction (LVEF) of either >=50% by ECHO or greater than institutional lower limit of normal (LLN) by echocardiogram (ECHO) (while not receiving medications for cardiac function), corrected QT using Bazett's (QTcB) interval <450 milliseconds (msecs).

Exclusion Criteria:

• Part 2 ONLY: Previous treatment with dabrafenib, another RAF inhibitor, or a mitogen-activated protein kinase (MEK) inhibitor (exception: prior treatment with sorafenib is permitted)
• Malignancy OTHER than the BRAF mutant malignancy under study
• Had chemotherapy or radiotherapy within 3 weeks (or 6 weeks for nitrosoureas or mitomycin C) prior to administration of the first dose of study treatment
• The subject has received an investigational product within the following time period prior to the first dosing day in the current study: 28 days or 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is warranted by the data)
• History of another malignancy
• Exception: (a) Subjects who have been successfully treated and are disease-free for 3 years, (b) a history of completely resected non-melanoma skin cancer, (c) successfully treated in situ carcinoma, (d) CLL in stable remission, or (e) indolent prostate cancer (definition: clinical stage T1 or T2a, Gleason score <=6, and prostate specific antigen [PSA] <10 nanograms (ng)/mL) requiring no or only anti-hormonal therapy with histologically confirmed tumour lesions that can be clearly differentiated from lung cancer target and non-target lesions are eligible
• Current use of a prohibited medication or herbal preparation or requires any of these medications during the study
• Unresolved toxicity greater than National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0 Grade 2 or higher from previous anti-cancer therapy except those that in the opinion of the investigator are not clinically relevant given the known safety/toxicity profile of dabrafenib (e.g., alopecia and/or peripheral neuropathy related to platinum or vinca alkaloid based chemotherapy)
• Has leukaemia
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to dabrafenib and its excipients.
• Autologous or allogeneic stem cell transplant within 3 months prior to enrolment
• History of myocardial infarction, severe or unstable angina, peripheral vascular disease or familial QTc prolongation
• Subjects with abnormal cardiac valve morphology (>=grade 2) documented by echocardiogram, moderate valvular thickening.
• Subjects with known glucose-6-phosphate dehydrogenase (G6PD) deficiency
• Known, uncontrolled cardiac arrhythmias (except sinus arrhythmia) within the past 24 weeks
• Uncontrolled medical conditions (e.g., diabetes mellitus, hypertension, liver disease or uncontrolled infection), psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol; or unwillingness or inability to follow the procedures required in the protocol
• Presence of active GI disease or other condition (e.g., small bowel or large bowel resection) that will interfere significantly with the absorption of drugs.
• A history of known Human Immunodeficiency Virus (HIV), Hepatitis B Virus, or Hepatitis C Virus infection (subjects with laboratory evidence of Hepatitis B Virus clearance may be enrolled)
• Pregnant females as determined by positive human chorionic gonadotropin (hCG) test at screening or prior to dosing and lactating females who are actively breast feeding.