Study of the Selective PI3K-Beta Inhibitor GSK2636771 in Combination With Pembrolizumab in Patients With Metastatic Melanoma and PTEN Loss

Inclusion Criteria: 1. Be willing and able to provide written informed consent for the trial. 2. Be \>/= 18 years of age on day of signing informed consent. 3. Evidence of PTEN loss in tumors by IHC or molecular analysis. 4. Have measurable disease based on RECIST 1.1. 5. Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale. 6. Patients who have unresectable Stage III through stage IV metastatic cancer who have not achieved complete or partial response after 6 months of therapy or who have progressed on PD-L1 or PD-1 directed therapy including combinations. The Phase II portion eligibility will be restricted to patients with metastatic melanoma. 7. In Phase I, Patients are allowed to have more than three prior systemic therapeutic regimens. Patients enrolled to Phase II, can have no more than three prior systemic therapeutic regimen for unresectable stage III or stage IV metastatic cancer. This includes chemotherapy, biologic therapy, biochemotherapy, or investigational treatment. This does not include any therapies given in the adjuvant setting. 8. Have a life expectancy of at least 12 weeks. 9. Have not received any chemotherapeutic, biological, investigational agent, radiation therapy, or used an investigational device within 28 days of study drug administration. 10. Able to swallow and retain orally administered medication. 11. On the dose expansion and Phase II portions of the study, patients must be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion before and at least one time point while on therapy. Correlative biopsies will be optional in the Phase I portion of the study. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day 1 without intervening systemic therapy. 12. Within 10 days of treatment initiation, the subject must demonstrate adequate organ function defined as follows: Absolute neutrophil count must be \>/= 1500 per microliter (uL). Platelets must be \>/=100,000 per uL. Hemoglobin must be \>/= 9 grams per deciliter or \>/= 5.6 millimoles per liter without transfusion or EPO dependency within 7 days of assessment. Serum creatinine must be \</= 1.0 times the upper limit of normal (ULN) OR measured or calculated creatinine clearance per institutional standard (Glomerular Filtration Rate (GFR) can also be used in place of creatinine or CrCl) must be \>/= 60 milliliters per minute OR proteinuria by urine dipstick must be \</= 1+. Aspartate aminotransferase (AST) AND alanine aminotransferase (ALT) must be \</= 2.5 times the ULN OR each must be \</= 5 times the ULN for subjects with liver metastases. Alkaline phosphatase (ALP) must be \</= 2 times the ULN. Serum 13. Cont#12 total bilirubin must be \</= 2.0 milligrams per deciliter except in patients with Gilbert's disease. Direct bilirubin must be \</= the upper limit of normal for subjects with total bilirubin levels \> 1.5 times the upper limit of normal. Albumin must be \>/= 2.5 grams per deciliter. Left ventricular ejection fraction (LVEF) must be \>/= 50% by echocardiogram (ECHO) or Multigated Acquisition (MUGA) scan. International Normalized Ratio (INR) must be \</= 1.5 times the upper limit of normal unless the subject is receiving anticoagulant therapy as long as prothrombin time(PT) or partial thromboplastin time(PTT) is within therapeutic range of intended use of anticoagulants.Activated partial thromboplastin time(aPTT) must be \</= 1.5 times the upper limit of normal unless the subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants. Serum phosphate must be within normal limit. Serum calcium must be within normal limit 14. Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. 15. Female subjects of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 4 months after the last dose of study medication. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject. 16. Male subjects with a female partner of childbearing potential must agree to use acceptable methods of contraception from the time of Screening until 3 months after the last dose of study treatments. Exclusion Criteria: 1. Patients are excluded if they have a history of or active autoimmune disease, as follows: Patients with a history of inflammatory bowel disease are excluded from this study as are patients with a history of symptomatic disease (e.g., rheumatoid arthritis, systemic progressive sclerosis \[scleroderma\], Systemic Lupus Erythematosus, autoimmune vasculitis \[e.g., Wegener's Granulomatosis\]). Patients with motor neuropathy considered of autoimmune origin (e.g., Guillain-Barre Syndrome and Myasthenia Gravis) are excluded. Patients with a history of autoimmune thyroiditis are eligible if their current thyroid disorder is treated and stable with replacement or other medical therapy. 2. Has active infections or serious general medical conditions (such as active myocardial infarction (MI), cerebrovascular accident (CVA), or respiratory failure). 3. Any unresolved \> Grade 1 toxicity (per CTCAE 4.0) from previous anti-cancer therapy or previously administered agent at the time of enrollment, except for alopecia, Grade 2 anemia (if hemoglobin is \>9 grams per deciliter (g/dL)) Note: If the subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy. 4. Presence of any clinically significant gastrointestinal (GI) abnormality or other condition(s) that may alter absorption such as malabsorption syndrome or major resection of the stomach or substantial portion of the small intestine. 5. Active peptic ulcer disease or history of abdominal fistula, GI perforation, or intra abdominal abscess within 28 days prior to enrollment 6. Previous major surgery within 28 days prior to enrollment. 7. Evidence of severe or uncontrolled systemic diseases (e.g., unstable or uncompensated respiratory, hepatic, renal or cardiac disease). 8. Has a QTc \>450 milliseconds (msec) or QTc \>480 msec for subjects with bundle branch block (BBB) NOTES: The QTc is the QT interval corrected for heart rate by Bazett's formula (QTcB), Fridericia's formula (QTcF), and/or another method, machine-read or manually over-read. The specific formula that will be used to determine eligibility and discontinuation for an individual subject should be determined prior to initiation of the study. In other words, several different formulae cannot be used to calculate the QTc for an individual subject and then the lowest QTc value used to include or discontinue the subject from the trial. For purposes of data analysis QTcF will be used. 9. History or evidence of cardiovascular risk including any of the following: - Clinically significant electrocardiogram (ECG) abnormalities including second degree (Type II) or third degree atrioventricular block - History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, stenting, or bypass grafting within the past 6 months prior to enrollment - Class III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system - Left ventricular ejection fraction (LVEF) below 50% - Known cardiac metastases. 10. Poorly controlled hypertension (defined as systolic blood pressure \[SBP\] of \>/= 150 millimeters of mercury (mmHg) or diastolic blood pressure \[DBP\] of \>100 mmHg based on a mean of three measurements at approximately 2-minute intervals) NOTE: Initiation or adjustment of antihypertensive medication(s) is permitted if done thirty or more days prior to enrollment. 11. History of congenital platelet function defect (e.g., Bernard-Soulier syndrome, Chediak-Higashi syndrome, Glanzmann thrombasthenia, storage pool defect) 12. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. NOTE: Replacement dose steroids (equivalent to 10 mg prednisone) are allowed. 13. Has a known history of active TB (Bacillus Tuberculosis). 14. Hypersensitivity to Pembrolizumab or GSK2636771 or excipients. 15. Has a known prior or additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer. 16. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least two weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability. 17. Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis. 18. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. 19. Has known psychiatric or substance abuse disorders that in the opinion of the registering physician or PI would interfere with cooperation with the requirements of the trial. 20. Has a known history or positive test for Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). Testing at the time of Screening is not required. 21. Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test result at time of Screening or any history of hepatitis. 22. Has received a live vaccine within 30 days of planned start of study therapy. 23. Current use of or anticipated requirement during the study of any prohibited medication(s). Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.