Pembrolizumab TX-naive Distant Mets Melanoma and Use of (C11-AMT) PET at Baseline as Imaging Biomarker

Inclusion Criteria

• Sign written informed consent and HIPAA authorization for release of personal health information. Note: HIPAA authorization may be included in the informed consent or obtained separately.
• Subject must be 18 years of age or more on the day of signing informed consent.
• Have histologic or cytologic biopsy-proven diagnosis of unresectable stage III or distant metastatic melanoma, irrespective of histologic type (i.e. cutaneous, unknown primary, mucosal, or ocular). Patients with resectable bulky stage IIIB or stage IIIC melanoma (for example at least 2.5-cm in shortest diameter for lymph nodes infiltrated by tumor and at least 2-cm in longest diameter for non-lymph nodes infiltrated by tumor) can also be entered into the study at the discretion of the Principal Investigator.
• Have measurable disease based on RECIST v1.1. for solid tumors
• Be willing to undergo fresh tumor tissue biopsy of an accessible tumor lesion prior to pembrolizumab. A mandatory fresh biopsy will be collected following C11-AMT PET imaging. Subjects for whom fresh samples cannot be provided (e.g. inaccessible or subject safety concern) or do not agree to this fresh tumor research biopsy of accessible tumor will be deemed ineligible for study participation. Exception to the mandatory tumor tissue collection are patients with metastatic lung lesions as the only site of metastatic disease. Fresh biopsy collection from these subjects will be optional, due to high risk of pneumothorax.
• Be willing to allow for investigators to collect archival tumor tissues from surgical procedures that may have been performed before or after enrollment into this trial for research purposes (in-house cases and/or outside cases). These samples will be obtained by study staff as long as subject continues on follow-up. Blocks of tissue will be requested, and if blocks are not able to be obtained, 5micron slides (10-15) will be sufficient.
• Be willing to be injected with 11C-methyl-L-tryptophan (C11-AMT)
• Have a performance status of 0 - 2 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
• Has not received prior therapy with cytotoxic T lymphocyte antigen (CTLA)-4, PD-1/PD-L1 inhibitors, other co-stimulatory or co-inhibitory immune checkpoint antibody therapies (e.g. LAG3, TIM3, cluster of differentiation (CD) 137, Killer immunoglobulin-like receptor (KIR3DL), cluster of differentiation (CD) 70, and CD27) for distant metastatic melanoma. Patients who have received mitogen-activated protein kinase (MAPK) inhibitors are allowed on condition that they have recovered from adverse events to at most Grade 1 by CTCAE v4.03 and at least 15 days have elapsed between last dose of MAPK inhibitors and C11-AMT imaging. Patients who have previously received CTLA-4 inhibitors in the adjuvant setting are allowed to participate as long as they discontinued CTLA-4 treatment at least 30 days ago and meet criteria outlined in inclusion #14. Patients who have previously received adjuvant PD-1 inhibitors are excluded.
• Demonstrate adequate organ function as defined in below; all screening labs to be obtained within 14 days prior to C11-AMT PET scan:

Hematological:

Hemoglobin (Hgb) - ≥ 9 g/dL or ≥ 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of Hgb) Absolute Neutrophil Count (ANC) - ≥ 1,500/mm3 Platelets - ≥ 100,000/mm3

Renal:

Serum Creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) - ≤1.5 x ULN OR ≥ 60 mL/min using the Cockcroft-Gault formula for subject with creatinine levels > 1.5 X institutional upper limits of normal (ULN)

Hepatic:

Serum Total Bilirubin - ≤ 1.5 X ULN Aspartate aminotransferase (AST) - ≤ 2.5 X ULN OR 1 year.

Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.

Male subjects should agree to use an adequate method of contraception as outlined - Contraception starting with