Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of GSK2126458 and GSK1120212 Combination Therapy in Subjects With Advanced Solid Tumors.

This is a Phase I, open-label, dose-escalation study to characterize the safety,
tolerability, pharmacokinetic profile, pharmacodynamic profile, and clinical activity of the
oral PI3K inhibitor GSK2126458 and the oral MEK inhibitor GSK1120212 dosed in combination in
subjects with advanced solid tumors. The study will be conducted in 2 parts, a Part 1 dose
escalation phase and a Part 2 tumor specific cohort expansion.

A continuous daily dosing schedule will be utilized initially for both investigational
products. The frequency and schedule of dosing may be adjusted based on emerging safety,
pharmacokinetics, and pharmacodynamics data.

Once a recommended regimen has been characterized in Part 1, it may be further evaluated in
Part 2 . More than one regimen (doses and schedules) may be evaluated in Part 2, based on
findings in Part 1.

Subjects eligible for enrollment in Part 2 will have solid tumors with genetic profiles that
are likely to benefit from a MEK and PI3K pathway inhibition.

Inclusion Criteria:

- Male or female 18 years or older at the time of signing the informed consent.

- Confirmed diagnosis of certain molecular types of colorectal , pancreatic,
endometrial, ovarian, breast or bladder cancers or melanoma for which there is no
approved or curative treatment. Subjects who refuse standard treatment may be
included. Physicians should contact the GSK medical monitor for details about the
types of tumors that may be treated in this study.

- All prior treatment related toxicities must be CTCAE (Version 4.0) ≤ Grade 1 (except
alopecia) at the time of treatment allocation

- Adequate organ system function.

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

- Able to swallow and retain orally administered medication

- Subjects with prior Whipple procedure

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

Exclusion Criteria:

- Primary malignancy of the CNS or malignancies related to HIV or solid organ
transplant. History of known HIV, known Hepatitis B surface antigen or positive
Hepatitis C antibody.

- Chemotherapy, extensive radiotherapy, major surgery, anti-neoplastic antibody or
targeted therapy or immunotherapy within 28 days (or 42 days for prior nitrosoureas
or mitomycin C) prior to the first dose of investigational products.

- Use of an investigational anti-cancer drug within 28 days or five half-lives,
whichever is shorter, prior to the first dose of the investigational products.

- Visible retinal pathology as assessed by ophthalmic exam that is considered a risk
factor for retinal vein occlusion or central serous retinopathy, such as: evidence of
new optic disc cupping, evidence of new visual field defects or intraocular pressure
>21 mm Hg measured by tonography.

- Current use of anticoagulants (e.g., warfarin, heparin) at therapeutic levels within
14 days prior to the first dose of GSK1120212 or GSK2126458. Low dose (prophylactic)
low molecular weight heparin and warfarin are permitted drugs.

- Current use of a prohibited medication

- Previously diagnosed with diabetes mellitus (Type 1 or 2) or steroid-induced
hyperglycemia.

- Evidence of severe or uncontrolled systemic diseases.

- Any serious and/or unstable pre-existing medical (aside from malignancy exception
above), psychiatric disorder, or other conditions that could interfere with subject's
safety, obtaining informed consent or compliance to the study procedures.

- Brain metastases, unless previously treated brain metastases with surgery, whole
brain radiation, or stereotactic radiosurgery and the disease has been confirmed
stable (i.e., no increase in lesion size) for at least 8 weeks with two consecutive
MRI scans using contrast prior to dosing with investigational product.

- History of acute coronary syndromes coronary angioplasty, or stenting within the past
6 months.

- History or evidence of current ≥ Class II congestive heart failure as defined by New
York Heart Association.

- QTcF interval > or = 470 msecs. History or evidence of current clinically significant
uncontrolled arrhythmias. ubjects wtih controlled atrial fibrillation for > 1 month
are eligible.

- Treatment refractory hypertension defined as systolic BP > 140 mmHg and/or diastolic
BP > 90 mmHg

- Subjects with intra-cardiac defibrillators or permanent pacemakers

- Known cardiac metastases

- Hypersensitivity to study drugs

- Pregnant females or lactating females.