|Exclusion Criteria:||1) Currently receiving cancer therapy (chemotherapy, radiation therapy, immunotherapy, or biologic therapy).|
2) Part A and Part B: Prior exposure to BRAF or MEK inhibitors unless approved by the GSK medical monitor.
3) Part C: Prior exposure to BRAF or MEK inhibitors. Prior anti-cancer therapy in the metastatic setting, with the exception of up to one regimen of chemotherapy and/or interleukin-2 (IL-2).
4) Part D: Prior exposure to BRAF inhibitors. A washout period of 6 weeks is required for ipilimumab.
5) Received an investigational anti-cancer drug within four weeks or five half-lives (whichever is shorter) of the first dose of study drug administration. At least 14 days must have passed between the last dose of the prior investigational agent and the first dose of study drug. This washout period is not required for prior GSK2118436 or prior GSK1120212 administration. One week of washout is required for PLX4032.
6) Current use of a prohibited medication or requires any of these medications during treatment with study drug.
7) Known HIV, Hepatitis B or Hepatitis C infection. Subjects who have evidence of clearance of Hepatitis B infection can be enrolled with approval of the GSK medical monitor.
8) Current use of therapeutic warfarin. Low molecular weight heparin (LMWH) is permitted provided that subject's PT and PTT meet entry criteria. Subjects requiring therapeutic levels of LMWH must receive approval from GSK Medical Monitor and must be monitored appropriately as clinically indicated.
9) Any major surgery, radiotherapy, or immunotherapy within the last 4 weeks. Limited radiotherapy within the last 2 weeks.
10) Chemotherapy regimens with delayed toxicity within the last 3 weeks. Chemotherapy regimens given continuously or on a weekly basis with limited potential for delayed toxicity within the last 2 weeks.
11) Unresolved toxicity greater than NCI-CTCAE v4 Grade 1 from previous anti-cancer therapy except alopecia.
12) History of retinal vein occlusion (RVO) or central serous retinopathy (CSR), or predisposing factors to RVO or CSR (e.g. uncontrolled glaucoma or ocular hypertension, uncontrolled systemic disease such as hypertension, diabetes mellitus, or history of hyperviscosity or hypercoagulability syndromes).
13) Visible retinal pathology as assessed by ophthalmologic exam that is considered a risk factor for RVO or CSR such as: evidence of new optic disc cupping, evidence of new visiaul field defects, intraocular pressure >21 mm Hg as measured by tonography.
14) Presence of active gastrointestinal disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of drugs.
15) Subjects with brain metastases are excluded, unless all known lesions must be previously treated with surgery or stereotactic radiosurgery, and brain lesion(s), if still present, must be confirmed stable (i.e. no increase in lesion size) for >/= 90 days prior to first dose on study (must be documented with two consecurive MRI or CT scans using contrast), and asymptomatic with no corticosteroids requirement for >/= 30 days prior to first dose on study, and no enzyme-inducing anticonfulsants for >/= 30 days prior to first dose on study.
16) Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.
17) Patients with a history of pneumonitis or interstitial lung disease.
18) History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within the past 6 months.
19) QTc interval >/= 480 msec (>/= 500 msec for subjects with Bundle Branch Block). Uncontrolled arrhythmias. Subjects with controlled atrial fibrillation for >1 month prior to study Day 1 were eligible.
20) Class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system. a. Abnormal cardiac valve morphology (subjects with minimal abnormalities, could be entered on study with approval from the GSK Medical Monitor).
21) Treatment refractory hypertension defined as a blood pressure of systolic> 140 mmHg and/or diastolic > 90 mm Hg which cannot be controlled by anti-hypertensive therapy
22) Patients with intra-cardiac defibrillators or permanent pacemakers
23) Cardiac metastases
24) Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study drugs, or excipients.
25) Pregnant or lactating female.
26) Unwillingness or inability to follow the procedures required in the protocol.
27) Uncontrolled diabetes, hypertension or other medical conditions that may interfere with assessment of toxicity
28) Subjects with known glucose 6 phosphate dehydrogenase (G6PD) deficiency