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

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;