Dose-Escalation Study of GSK2126458

This study is a Phase I, first-time-in-human dose escalation study in subjects with
refractory solid tumors or lymphoma. The primary objective of this study is to determine the
recommended Phase II dose of GSK2126458 based on safety and tolerability, pharmacokinetics,
pharmacodynamics and preliminary evidence of clinical activity. Secondary objectives are to
characterize the pharmacokinetics of GSK2126458; and to explore relationships between
GSK2126458 pharmacokinetics, pharmacodynamics, response prediction biomarkers and clinical
endpoints.

Subjects with solid tumors or lymphoma will initially receive oral GSK2126458 daily for 28
consecutive days in each 28 day cycle. Subjects may be dosed once or twice a day or may be
dosed on an intermittent schedule depending on the safety, pharmacokinetic and
pharmacodynamic results that become available as the study progresses. The starting dose
will be 0.1 mg once a day. Expansion of some cohorts will be conducted to test tumor
pharmacodynamics, further explore the toxicity profile and to look for preliminary evidence
of activity in subjects with tumors with PIK3CA mutations. The recommended Phase II dose
will be the lowest dose explored (at or below MTD) that maintains biologic activity with an
acceptable tolerability profile.

Inclusion Criteria:

- Histologically- or cytologically- confirmed diagnosis of solid tumor malignancy, or
lymphoma

- Performance Status score of 0 or 1 according to the Eastern Cooperative Oncology
Group (ECOG) scale.

- Female or male that is willing to take measures to avoid pregnancy in self or a
partner, including abstinence, or double barrier method.

- Adequate organ system function

Exclusion Criteria:

- Use of an investigational anti-cancer medication within 28 days or 5 half-lives
preceding the first dose of GSK2126458.

- Chemotherapy within the last 3 weeks (6 weeks for prior nitrosourea or mitomycin C

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

- Prior use of any PI3K inhibitor.

- Current use of a prohibited medication or requires any of these medications during
treatment with GSK2126458.

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

- Unresolved toxicity greater than Grade 1 from previous anti-cancer therapy except
alopecia.

- QTc interval ≥ 480 msecs.

- History of acute coronary syndromes; Class II, III, or IV heart failure; stroke or
subarachnoid hemorrhage.

- Systolic blood pressure (SBP) of ≥140 mmHg or diastolic blood pressure (DBP) of ≥
90mmHg.

- Previously diagnosed Type 1 diabetes mellitus. Subjects with Type 2 diabetes are
prohibited in the dose escalation part of the study.

- Symptomatic or untreated leptomeningeal or brain metastases.

- Primary malignancy of the central nervous system.