Dose Escalation Study of GSK2820151 in Subjects With Advanced or Recurrent Solid Tumors

Inclusion Criteria:

* Written informed consent provided
* Males and females 18 years old and greater
* Diagnosis of advanced or recurrent, histologically or cytologically confirmed, solid malignancy that is either metastatic or unresectable. At time of enrollment, subjects either refuse standard curative or palliative therapy, are not candidates for standard curative or palliative therapy, have a disease for which no non-investigational therapy exists, OR have progressed on prior therapy (up to three lines of prior cytotoxic agents are permitted).
* Subjects with solid tumors, with the exception of castration-resistant prostate cancer (CRPC), must demonstrate measurable disease, per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
* All prior treatment- related toxicities must be National Cancer Institute- Common Terminology Criteria for Adverse Events (NCI-CTCAE) v4.03 \<=Grade 1 (except alopecia \[permissible at any Grade\] and peripheral neuropathy \[which must be \<= Grade 2\]) at the time of treatment allocation.
* Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 to 1.
* Adequate organ function defined as follows: System and Laboratory Values: Hematologic - Absolute neutrophil count (ANC) \>=1.5 X 10\^9/liter (L), Hemoglobin \>=9 grams (g)/deciliter (dL) (subjects that required transfusion or growth factor need to demonstrate stable hemoglobin for 7 days of 9 g/dL), Platelets \>=100 X 10\^9/L, prothrombin time (PT)/ international normalized ratio (INR) and partial thromboplastin time (PTT) - \<=1.5 X upper limit of normal (ULN); Hepatic - Albumin \>=2.5 g/dL, Total bilirubin \<=1.5 X ULN (isolated bilirubin \>1.5 X ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35% or subject has a diagnosis of Gilbert's syndrome), Alanine aminotransferase (ALT) \<=2.5 x ULN OR \<5 x ULN is acceptable for subjects with documented liver metastases/tumor infiltration; Renal - Creatinine \<=1.5 X ULN OR Creatinine clearance \[either directly measured or calculated by Cockcroft-Gault formula\] \>=40 milliliter (mL)/minute (min); Cardiac - Ejection fraction \>=50% by echocardiogram or multigated acquisition scan (MUGA), Troponin (T) \<=ULN, Potassium \>=Lower limit of normal (LLN) and \<=ULN, Magnesium \>=LLN
* Able to swallow and retain orally administered medication.
* A female subject is eligible to participate if she is of: Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation, hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion, hysterectomy, or documented bilateral tubal oophorectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea \[in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) \>40 units (U)/mL and estradiol \<40 picograms (pg)/mL (\<140 picomoles (pmol)/L) is confirmatory\]. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least 2 to 4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method. Child-bearing potential and agrees to use one of the contraception methods for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception until 7 months after the last dose of study medication. Negative serum pregnancy test \<=7 days prior to first study drug dose. Female subjects who are lactating must discontinue nursing prior to the first dose of study treatment and must refrain from nursing throughout the treatment period and for 5 half-lives of GSK2820151 or at least 28 days (whichever is longer) following the last dose of study treatment.
* Male subjects with female partners of child bearing potential must agree to use one of the methods of contraception specified. This method must be used from the time of the first dose of study medication until 16 weeks after the last dose of study medication. In addition, male subjects whose partners are or become pregnant on study medication must continue to use condoms for 7 days after stopping study medication

Exclusion Criteria:

* Primary malignancy of the central nervous system or malignancies related to human immunodeficiency virus (HIV) or solid organ transplant.
* More than three prior lines of cytotoxic therapy.
* Recent prior therapy, defined as follows: 1) Any investigational or Food and Drug Administration (FDA)-approved anti-cancer drug within 14 days or 5 half-lives, whichever is longer, prior to the first dose of GSK2820151. Any nitrosoureas or mitomycin C within 42 days prior to the first dose of GSK2820151. Prior therapy with monoclonal antibodies is permitted so long as 14 days have elapsed since therapy and all therapy-related toxicity has resolved to Grade 1 or less. Note that an investigational drug is defined as a drug without an approved oncologic indication.

  2\) Any radiotherapy within 14 days or major surgery within 28 days prior to the first dose of GSK2820151.

  3\) Anti-androgen therapies for prostate cancer, such as bicalutamide, must be stopped 4 weeks prior to enrollment. Second-line hormone therapies such as enzalutamide, abiraterone, or orteronel should be stopped 2 weeks prior to enrolment. Subjects with prostate cancer should remain on luteinizing hormone releasing hormone (LHRH) agonists or antagonists. Subjects with prostate cancer may also remain on low-dose prednisone or prednisolone (up to 10 milligrams \[mg\]/day) and still be eligible for this study.

  4\) In addition, any therapy-related toxicity must have resolved to Grade 1 or less, with the exception of alopecia (acceptable at any Grade) and peripheral neuropathy (which must be Grade 2 or less prior to enrollment).
* Therapeutic anticoagulation (e.g., warfarin, heparin) must be discontinued and coagulation parameters must be normalized prior to the first dose of GSK2820151. Low dose (prophylactic) low molecular weight heparin (LMWH) is permitted. In addition, INR must be monitored in accordance with local institutional practices.
* Current use of a prohibited medication or planned use of any forbidden medications during treatment with GSK2820151.
* Evidence of severe or uncontrolled systemic diseases (e.g., unstable or uncompensated respiratory, hepatic, renal, cardiac disease, or clinically significant bleeding episodes). Any serious and/or unstable pre-existing medical (aside from malignancy), psychiatric disorder, or other conditions that could interfere with subject's safety, obtaining informed consent or compliance to the study procedures, in the opinion of the Investigator.
* Symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression. NOTE: Subjects previously treated for these conditions that have had stable central nervous system (CNS) disease (verified with consecutive imaging studies) for \>1 months, are asymptomatic and off corticosteroids, or are on stable dose of corticosteroids for at least 1 month prior to study Day 1 are permitted. Stability of brain metastases must be confirmed with imaging. Subject treated with gamma knife therapy can be enrolled 2 weeks post-procedure as long as there are no post-procedure complications/stable. In addition, subjects treated or currently taking enzyme-inducing anticonvulsant (EIAC) are allowed on study.
* Cardiac abnormalities as evidenced by any of the following: History of or current "untreated" clinically significant uncontrolled arrhythmias, Clinically significant conduction abnormalities or arrhythmias, Presence of cardiac pacemaker, History or evidence of current \>=Class II congestive heart failure as defined by New York Heart Association (NYHA), History of acute coronary syndromes (including unstable angina and myocardial infarction), coronary angioplasty, or stenting within the past 3 months. Subjects with a history of stent placement requiring ongoing antithrombotic therapy (e.g., clopidogrel, prasugrel) will not be permitted to enroll.
* Any of the following electrocardiogram (ECG) findings: Baseline QTcF \>=450 millisecond (msec). NOTE: Any clinically significant ECG assessments should be reviewed by the site cardiologist prior to study entry.
* Any of the following liver findings: ALT \>2.5xULN, ALT \> 5xULN with liver metastases/tumor infiltration, Bilirubin \>1.5xULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%), Current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones, liver metastases or otherwise stable chronic liver disease per investigator assessment). NOTE: Stable chronic liver disease should generally be defined by the absence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, esophageal or gastric varices, persistent jaundice or cirrhosis
* Presence of hepatitis B surface antigen (HBsAg) or positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment. History of known HIV infection. NOTE: Subjects with positive Hepatitis C antibody due to prior resolved disease can be enrolled only if a confirmatory negative Hepatitis C ribonucleic acid (RNA) polymerase chain reaction (PCR) is obtained.
* Any serious known immediate or delayed hypersensitivity reaction(s) to GSK2820151 or idiosyncrasy to drugs chemically related to the investigational drug.
* Hemoptysis \>1 teaspoon in 24 hours within the last 28 days.
* History of major gastrointestinal bleeding within the last 6 months.
* Any clinically significant gastrointestinal (GI) abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach and/or bowels.