This is an expanded access program (EAP) for patient with Melanoma and Glioblastoma who have progressed after prior Protocol therapy including Bevacizumab, Temozolomide ( TMZ ), Ipilimumab, BRAF and MEK inhibitors. The patients whose tumors are EGFR, MET or ALK positive should first receive an EFGR or ALK inhibitor, respectively, prior to treatment with pembrolizumab.

Pembrolizumab has been approved by the U.S. Food and Drug Administration for the treatment of patients with Glioblastoma and Melanoma The Expanded Access Program (EAP) for this medicine in the U.S. is closed. The EAP will continue outside the U.S.

Inclusion Criteria:

• Patient's willing to sign Informed Consent.
• Unresectable metastatic Melanoma / Glioblastoma / Glioma.
• Failed or progressed on standard of care systemic therapy including bevacizumab, ipilimumab, radiotherapy, regardless of prior treatment with a BRAF/ MEK/ EGFR/ MET/ ALK inhibitors, as long as all other eligibility criteria for this study are met.
• Female participants of childbearing potential must be willing to use adequate contraception or be surgically sterile, or abstain from heterosexual activity starting with the first dose of treatment through at least 120 days after the last dose of pembrolizumab.
• Male participants must agree to use an adequate method of contraception starting with the first dose of treatment through 120 days after the last dose of pembrolizumab.
• Results of partial genomic or full-genomic sequencing or genetic studies to determine the status of the patient's mutation load.
• ECOG performance status greater than or equal to 2
• Adequate kidney function: serum creatinine less than or equal to 2.0 mg/dL or creatinine clearance greater than or equal to 40 mL/min
• Adequate bone marrow function: absolute neutrophil count greater than or equal to 1.5 x 10^9/L, hemoglobin greater than or equal to 10 g/dL (can be corrected by growth factor or transfusion), and platelet count greater than or equal to 100 x 10^9/L
• Adequate liver function: total bilirubin less than or equal to 1.5 x upper limit of normal (ULN), alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase less than or equal to 3 x ULN (or less than or equal to 5 x ULN in case of liver metastases). If alkaline phosphatase is greater than 3 x ULN (in absence of liver metastases) or greater than 5 x ULN (in presence of liver metastases) AND patient also is known to have bone metastases, the liver specific alkaline phosphatase must be used to assess liver function instead of total alkaline phosphatase
• Willing and able to comply with all aspects of the treatment protocol

Exclusion Criteria:

• Eligibility for any other pembrolizumab study open in the same region.
• Existing anti-cancer therapy-related toxicities of grade 2 or more, except that alopecia and grade 2 neuropathy are acceptable.
• History of congestive heart failure with New York Heart Association Classification greater than grade II, unstable angina, myocardial infarction within the past 6 months or serious cardiac arrhythmia.
• Electrocardiogram with QTc interval of greater than or equal to 500 msec based upon Bazett's formula (QTcB).
• The Investigator believes the patient to be medically unfit to receive pembrolizumab or unsuitable for any other reason.
• Pregnancy (positive B-hCG test) or breastfeeding.
• Hypersensitivity to pembrolizumab.
• Use of corticosteroids for this indication has been discontinued for at least 4 weeks before starting treatment in this protocol.
• History of or concomitant medical condition that, in the opinion of the Investigator, would compromise the patient's ability to safely complete the treatment protocol.
• Meningeal carcinomatosis.
• Pulmonary lymphangitic involvement resulting in pulmonary dysfunction requiring active treatment, including use of oxygen.
• Not recovered from minor or major surgery and less than 4 weeks from major surgery
• History of life-threatening or severe immune-related adverse events on treatment with another immunotherapy.
• Expected to require any other form of systemic antineoplastic therapy while receiving pembrolizumab.
• History of clinically severe autoimmune disease (e.g., requires chronic immunosuppressive therapy).
• History of pneumonitis, organ transplant, human immunodeficiency virus (HIV), active hepatitis B or hepatitis C.