• Be willing and able to provide written informed consent for the trial.

• Have un-resectable (stage III) or advanced (stage IV) melanoma.

• Be 18 years of age or older on day of signing informed consent

• Have measurable disease based on RECIST 1.1. Patients without measurable disease may be included on study after discussion with the Sponsor, given that the primary endpoint of the study is Ki-67 of TIL (flow cytometry)

• Have biopsiable disease. Be willing to provide tissue from a newly obtained biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained up to 30 days prior to initiation of treatment on Day 1.

• Patients may have received prior adjuvant therapy with anti-PD-1, anti-CTLA-4, or BRAF/MEK inhibitors.

• Patients may be immunotherapy treatment naïve in the advanced setting or may be on anti-PD-1 therapy with SD or PR for at least 12 weeks. Patients may have received ipilimumab plus nivolumab in the metastatic setting with SD or PR for at least 12 weeks on maintenance anti-PD1.

• Have a performance status of 0, 1 or 2 on the ECOG Performance Scale.

• Have a baseline HbA1c ≤ 6.4.

• Demonstrate adequate organ function. All screening labs should be performed within 14 days of treatment initiation.

‣ Absolute neutrophil count (ANC) ≥1,500 /mcL

⁃ Platelets ≥100,000 / mcL

⁃ Hemoglobin ≥9 g/dL or ≥5.6 mmol/L without transfusion or EPO dependency (within 7 days of assessment)

⁃ Serum creatinine OR Measured or calculateda creatinine clearance ≤1.5 X upper limit of normal (ULN) (GFR can also be used in place of creatinine or CrCl ≥60 mL/min for subject with creatinine levels \> 1.5 X institutional ULN)

⁃ 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

⁃ Albumin \>2.5 mg/dL

⁃ International Normalized Ratio (INR) or Prothrombin Time (PT) ≤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; 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

• Patients must be free of active brain metastases by contrast-enhanced CT/MRI scans within 2 weeks prior to starting the study drugs. If known to have prior brain metastases, must not have evidence of active (enlarging and/or symptomatic lesions) brain disease on MRI evaluation within 4 weeks from SRS or WBRT treatment.

• Patients who have received radiation may be enrolled if the treating physician determines that they have recovered from radiation and are not experiencing radiation related clinically significant adverse events.

• Female patients of child bearing potential must have a negative urine or serum pregnancy test within 7 days from the time of registration.

• 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.

• Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 1 year.

• Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.