A Pharmacokinetics Study of the Effects of GSK2118436 on Warfarin, the Effects of Ketoconazole and Gemfibrozil on GSK2118436, and the Effects of Repeat Doses of GSK2118436 in Subjects With BRAF Mutant Solid Tumors

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 >/= 45 kg and a body mass index >/= 19 kg/m2 and (inclusive);

- Able to swallow and retain oral medication;

- BRAF V600 mutation-positive tumor as determined in a CLIA-approved laboratory or
equivalent (the local BRAF testing may be subject to subsequent verification by
centralized testing);

- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1; NOTE:
Subjects with a performance status of 2 can be enrolled if the patient's confinement
to bed and inability to carry out work activities is due solely to cancer-related
pain, as assessed by the Investigator;

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

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

Absolute neutrophil count (ANC) >/=1.2 x 109/L Hemoglobin >/= 9 g/dL Platelets >/= 100 x
109/L Serum bilirubin >/= 1.5 x Upper Limit of Normal (ULN) AST and ALT >/= 2.5 x ULN; <5
x ULN if liver metastases are present (with approval of GSK medical monitor) Serum
creatinine >/= ULN or calculated creatinine clearance >/= 60 mL/min PT/INR and partial
thromboplastin time (PTT) >/= 1.3 x ULN Left ventricular ejection fraction >/=
institutional lower limit of normal by ECHO

- CYP2C9 genotype of *1/*1 (wildtype), *1/*2 or *1/*3 (Part A only)

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 2 weeks;

- 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: 28 days, 5 half-lives or twice the duration of the biological effect of the
investigational product (whichever is warranted by the data);

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

- Consumption of red wine, Seville oranges, grapefruit or grapefruit juice from 7 days
prior to the first dose of study medication;

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

- Any major surgery within the last 4 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 GI 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;

- 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);

- Presence of invasive malignancy, other than the primary diagnosis;

- Parts B and C: 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. Subjects must also be off of enzyme-inducing anticonvulsants for more than four
weeks; Note: Any brain metastases is exclusionary for Part A (must be excluded by prior
imaging);

- Corrected QT (QTcB) interval >/= 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 ECHO (subjects with minimal abnormalities [i.e., mild regurgitation/stenosis] can
be entered on study - if clarification is needed as to whether an ECHO abnormality is
minimal, please contact the GSK medical monitor); or history of known cardiac
arrhythmias (except sinus arrythmias) 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 FDA);

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

- Pregnant females as determined by positive hCG test at screening or prior to dosing;

- Lactating females who are actively breast feeding;

- Subject is mentally or legally incapacitated;

- Part A only: Use of warfarin or exogenous Vitamin K (other than from dietary sources)
within 30 days prior to treatment with study medication;

- Part A only: Subjects with history of GI bleeding, or GI ulceration;

- Part A only: Subjects with known history of Protein C and/or Protein S deficiency, or
any other type of coagulopathy;

- Part A only: Subjects requiring any type of anticoagulation, or taking Aspirin at
doses greater than 81 mg/day;

- Part A only: Subjects with brain metastases;

- Part A only: Any subject who by history regularly consumes a large quantity of foods
rich in vitamin K will be excluded unless he/she restricts the vitamin K intake for
at least one week prior to the first dose of warfarin. For study purposes, large
quantities of vitamin K-containing food will be defined as 10 or more portions per
week of the following: kale, spinach, turnip greens, cauliflower, chick peas,
brussels sprouts, green tea, liver, soybean oil and soy protein products.