A Tissue Collection Study of Pembrolizumab (MK-3475) in Subjects With Resectable Advanced Melanoma

Inclusion Criteria

• The subject must have clinical stage III or resectable stage IV MEL. Subject's may not have a diagnosis of uveal or mucosal melanoma.
• The subject must be expected to have an adequate amount of tumor burden to yield 2-4 pre-operative research core biopsy (14-gauge needle) specimens or the equivalent amount of tissue (4-6 mm punch biopsy), in addition, to the tissue required for diagnostic purposes.
• The subject must be expected to have an adequate amount of residual tumor after their pre-operative research tumor tissue collection, such that their operative research tumor collection will also yield at least 4-6 research core biopsy specimens or the equivalent amount of tissue
• The subject must be willing to undergo the two paired tumor tissue biopsy procedures to obtain samples for biomarker analysis. Tissue obtained must not be previously irradiated.
• Either the subject or the subject's legal representative must be willing and able to provide written informed consent for the trial.
• The subject must be ≥ 18 years of age on day of signing informed consent.
• The subject must have a performance status of 0 or 1 on the ECOG Performance Scale.
• The subject must demonstrate adequate organ function as defined in Table 1, all screening labs must be performed within 10 days of treatment initiation.

Table 1 Adequate Organ Function Laboratory Values System Laboratory Value Hematological Absolute neutrophil count (ANC)

• 1500/mcL Platelets
• 100,000/ mcL Hemoglobin
• 9 g/dL or ≥5.6 mmol/L Renal Serum creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl)

≤1.5 X upper limit of normal (ULN) OR

• 50 mL/min for subject with creatinine levels > 1.5 X institutional ULN UPCC# 01615: Tissue Collection Study of Pembrolizumab in Advanced Melanoma Version Date: 12/30/2014 Page 10 Hepatic Serum total bilirubin
• 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN AST (SGOT) and ALT (SGPT)
• 2.5 X ULN OR
• 5 X ULN for subjects with liver metastases Coagulation International Normalized Ratio (INR) or Prothrombin Time (PT) Activated Partial Thromboplastin Time (aPTT)
• 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
• 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants aCreatinine clearance should be calculated per institutional standard.
• Female subject's of childbearing potential must have a negative serum pregnancy test within 72 hours prior to receiving the first dose of study medication.
• The subject must be willing to use protocol defined method(s) of contraception:

Female subjects of childbearing potential must be willing to use 2 methods of contraception, or abstain from heterosexual sexual intercourse for two weeks before the time of the first dose of study medication, while on study, through 120 days after the last dose of study medication.

Female subject's of childbearing potential are defined as those women who have not been surgically sterilized or have not been free from menses for > 1 year.

Male subjects must agree to use an adequate method of contraception starting with the first dose of study medication, while on study, through 120 days after the last dose of study medication.

Acceptable forms of birth control include condoms, diaphragms, cervical cap, an intra-uterine device (IUD), surgical sterility (tubal ligation or a partner that has undergone a vasectomy), or oral contraceptives, OR the subject must agree to completely abstain from heterosexual intercourse. Abstinence at certain times of the cycle only, such as during the days of ovulation, after ovulation and withdrawal are not acceptable methods of birth control

Exclusion Criteria

• Subject has unresectable disease; i.e. in the opinion of the surgical o