An Open Label Study to Examine the Effects of a High-Fat Meal and Particle Size on the Pharmacokinetics of Orally Administered GSK2118436 in Subjects With BRAF Mutation Positive Tumor

GSK2118436 is an orally administered, potent and selective small molecule BRAF inhibitor that
is currently being developed for the treatment of BRAF mutation-positive tumors. This study
is designed to evaluate the effects of particle size on the relative bioavailability of
GSK2118436 (Cohort 1) and to evaluate the effects of a high-fat meal on the pharmacokinetics
of GSK2118436 (Cohort 2). Subjects will randomly receive two of four possible regimens over
two periods. Subjects enrolled in Cohort 1 will receive a single 150 mg dose of GSK2118436 as
micronized particles fasted (gelatin capsule formulation) and a single 150 mg dose of
GSK2118436 as non-micronized particles fasted (larger particle size). Subjects enrolled in
Cohort 2 will receive a single 150 mg dose of GSK2118436 (HydroxyPropyl Methyl Cellulose
(HPMC) capsule formulation) fasted and with a high-fat breakfast. GSK2118436 will be
administered as the mesylate salt (equivalent to 150 mg free base). Safety and tolerability
will also be evaluated. The study will be conducted at a sufficient number of centers to
complete approximately 28 adult subjects (14 subjects per cohort) with BRAF mutation-positive
tumors. Following completion of this study, subjects may continue dosing with GSK2118436 in
the roll-over study, Protocol BRF114144.

Inclusion Criteria:

- Male or female at least 18 years of age at the time of signing the informed consent
form;

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

- Body weight >/= to 45 kg and a Body Mass Index (BMI) >/= to 19 kg/m2 and less than or
equal to 35 kg/m2 (inclusive);

- Able to swallow and retain oral medication;

- BRAF mutation-positive tumor as determined via relevant genetic testing;

- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 at the time of
transition to this study. NOTE: Subjects with an ECOG performance status of may be eligible with the approval of the GlaxoSmithKline (GSK) Medical Monitor.

- Women of child-bearing potential and men with reproductive potential must be willing
to practice acceptable methods of birth control. Additionally, women of child-bearing
potential must have a negative serum pregnancy test within 14 days prior to the first
dose of study treatment;

- Must have adequate organ function as defined by the following values:

- Absolute neutrophil count (ANC) >/= to 1.2 x 10^9/L

- Hemoglobin >/= to 9 g/dL

- Platelets >/= to 100 x 10^9/L

- Serum bilirubin
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <5 x ULN if liver metastases are present (with approval of GSK medical monitor)

- Serum creatinine /= 60 mL/min

- Prothrombin time (PT)/International normalized ratio (INR) and partial thromboplastin
time (PTT) < /= to 1.3 x ULN

- Left ventricular ejection fraction (LVEF) >/= to institutional lower limit of normal
by Echocardiogram

Exclusion Criteria:

- Currently receiving cancer therapy (e.g., chemotherapy with delayed toxicity,
extensive radiation therapy, immunotherapy, biologic therapy) within the last three
weeks; chemotherapy regimens without delayed toxicity within the last two weeks; or
use of an investigational anti-cancer drug within 28 days preceding the first dose of
GSK2118436;

- Current use of a prohibited medication or requires any of these medications during the
study;

- Consumption of red wine, Seville oranges, grapefruit or grapefruit juice from seven
days prior to the first dose of study medication;

- Current use of therapeutic warfarin (note: low molecular weight heparin and
prophylactic low-dose warfarin are permitted);

- History of sensitivity to heparin or heparin-induced thrombocytopenia;

- Any major surgery within the last four weeks;

- Unresolved toxicity greater than National Cancer Institute Common Terminology Criteria
for Adverse Events, version 4.0 (NCI CTCAE v4.0) [NCI, 2009] Grade 2 from previous
anti-cancer therapy except alopecia;

- Presence of active gastrointestinal disease or other condition (e.g., small bowel or
large bowel resection) that will interfere significantly with the absorption of drugs.
If clarification is needed as to whether a condition will significantly affect
absorption of drugs, contact the GSK medical monitor for permission to enroll the
subject;

- A history of known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or
Hepatitis C Virus (HCV) infection (subjects with laboratory evidence of HBV clearance
may be enrolled with permission of the GSK medical monitor);

- Presence of invasive malignancy other than one of the malignancies covered under
Inclusion Criterion #5; patients with a history of malignancy that have been
definitively treated can be enrolled with approval of the GSK medical monitor;

- Subjects with brain metastases are excluded if their brain metastases are either:

Symptomatic Treated (surgery, radiation therapy) but not clinically and radiographically
stable one month after local therapy, or Asymptomatic and untreated but > 1 cm in the
longest dimension Patients with small (≤ 1 cm in the longest dimension), asymptomatic brain
metastases that do not need immediate local therapy can be enrolled with the approval of
the GSK medical monitor. Subjects on a stable dose of corticosteroids for more than one
month, or those who have been off corticosteroids for at least two weeks can be enrolled
with approval of the GSK medical monitor. Subjects must also be off of enzyme-inducing
anticonvulsants for more than four weeks;

- Presence of rheumatoid arthritis;

- History of alcohol or drug abuse within six months prior to screening;

- Corrected QT (QTc) interval >/= to 480 msecs;

- 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 (NYHA)
functional classification system; abnormal cardiac valve morphology documented by
echocardiogram (subjects with minimal abnormalities [ie, mild regurgitation/stenosis]
can be entered on study with approval from the GSK medical monitor); or history of
known cardiac arrhythmias (except sinus arrhythmias) within the past 24 weeks;

- Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
chemically related to the study drugs, or excipients (note: to date there are no known
drugs chemically related to GSK2118436 which are approved by the Food and Drug
Administration);

- Uncontrolled medical conditions (e.g., diabetes mellitus, hypertension),
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;

- Subjects with known glucose 6 phosphate dehydrogenase (G6PD) deficiency;

- The subject has participated in a clinical trial and has received an investigational
product within the following time period prior to the first dosing day in the current
study: 30 days, five half-lives or twice the duration of the biological effect of the
investigational product (whichever is longer);

- Where participation in the study would result in donation of blood or blood products
in excess of 500 mL within a 56 day period;

- Pregnant females as determined by positive human chorionic gonadotrophin (hCG) test at
screening or prior to dosing;

- Lactating females who are actively breast feeding;

- Subject is mentally or legally incapacitated;