An Open-Label, Dose-Escalation, Phase I/II Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics and ClinicalActivity of the BRAF Inhibitor GSK2118436 in Combination With the MEK Inhibitor GSK1120212 in Subjects With BRAF Mutant Metastatic Melanoma

Inclusion Criteria:

- Capable of given written informed consent, which includes compliance with the
requirements and restrictions listed in the consent form.

- Male or female age 18 years or greater; able to swallow and retain oral medication.

- BRAF mutation positive melanoma or colorectal cancer; other BRAF mutation positive
tumor types may be considered.

- Measurable disease according to RECIST version 1.1.

- Eastern Cooperative Oncology Group Performance Status of 0 or 1 for Parts A and B.
Subjects with Eastern Cooperative Oncology Group Performance Status of 2 or less may
be entered into Part C with approval of medical monitor.

- Agree to contraception requirements.

- Calcium phosphorus product less than 4.0mmol2/L2.

- Adequate organ system function.

Exclusion Criteria:

- Currently receiving cancer therapy (chemotherapy, radiation therapy, immunotherapy,
or biologic therapy).

- Part A and Part B: Prior exposure to BRAF or MEK inhibitors unless approved by the
GSK Medical Monitor.

- 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).

- Part D: Prior exposure to BRAF inhibitors. A washout period of 6 weeks is required
for ipilimumab.

- Received an investigational anti-cancer drug within 4 weeks or 5 half-lives
(whichever is shorter) of study drug administration--- at least 14 days must have
passed between the last dose of prior investigational anti-cancer drug and the first
dose of study drug.

- Current use of a prohibited medication or requires any of these medications during
treatment with study drug.

- Current use of therapeutic warfarin.

- Any major surgery, radiotherapy, or immunotherapy within the last 4 weeks. Limited
radiotherapy within the last 2 weeks.

- Chemotherapy regimens with delayed toxicity within the last 4 weeks. Chemotherapy
regimens given continuously or on a weekly basis with limited potential for delayed
toxicity within the last 2 weeks.

- Unresolved toxicity greater than National Cancer Institute-Common Terminology
Criteria for Adverse Events version 4 Grade 1 from previous anti-cancer therapy
except alopecia.

- History of retinal vein occlusion, central serous retinopathy or glaucoma.

- Predisposing factors to retinal vein occlusion including uncontrolled hypertension,
uncontrolled diabetes, uncontrolled hyperlipidemia, and coagulopathy.

- Visible retinal pathology as assessed by ophthalmologic exam that is considered a
risk factor for retinal vein occlusion or central serous retinopathy.

- Intraocular pressure greater than 21mm Hg as measured by tonography.

- Glaucoma diagnosed within one month prior to study Day 1.

- Presence of active gastrointestinal disease or other condition that will interfere
significantly with the absorption, distribution, metabolism or excretion of drugs.

- Known human immunodeficiency virus, Hepatitis B or Hepatitis C infection.

- Primary malignancy of the central nervous system.

- Untreated or symptomatic brain metastasis, leptomeningeal disease or spinal cord
compression. Subjects who are on a stable dose of corticosteroids for more than 1
month or off corticosteroids for 2 weeks can be enrolled with approval of medical
monitor. Subjects are not permitted to receive enzyme-inducing anti-epileptic drugs.

- Subjects with brain metastases are excluded, unless

a. All known lesions must be previously treated with surgery or stereotactic
radiosurgery, and- b. 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 consecutive MRI or CT scans using contrast), and c. Asymptomatic
with no corticosteroids requirement for ≥ 30 days prior to first dose on study, and
d. No enzyme-inducing anticonvulsants for ≥ 30 days prior to first dose on study.

- History of alcohol or drug abuse within 6 months prior to screening.

- Psychological, familial, sociological or geographical conditions that do not permit
compliance with the protocol.

- QTc interval greater than or equal to 480msecs.

- History of acute coronary syndromes (including unstable angina), coronary
angioplasty, or stenting within the past 24 weeks.

- Class II, III, or IV heart failure as defined by the New York Heart Association
functional classification system.

- Abnormal cardiac valve morphology (subjects with minimal abnormalities can be entered
on study with approval from the medical monitor.

- 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

- Patients with intra-cardiac defibrillators or permanent pacemakers.

- Cardiac metastases

- Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
chemically related to the study drugs or excipients.

- Pregnant or lactating female.

- Unwillingness or inability to follow the procedures required in the protocol.

- Uncontrolled diabetes, hypertension or other medical conditions that may interfere
with assessment of toxicity.

- Subjects with known glucose 6 phosphate dehydrogenase deficiency.