• Age greater than or equal to 18 years

• Participants must have histologically confirmed Stage III unresectable or Stage IV metastatic melanoma

• Patients should be treatment naïve and eligible for treatment with anti-PD-1 or anti-PD-1/LAG3 as a first line therapy (as selected by their treating physician)

• Patients previously treated for melanoma with surgical resection alone who present with recurrent Stage III unresectable or Stage IV metastatic melanoma are eligible for enrollment

• Patients who were previously treated with systemic neo-adjuvant or adjuvant anti-PD-1 therapy more than 6 months prior to study enrollment will be eligible. There are no restrictions to the use of prior BRAF targeted therapy.

• Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \> 20 mm with conventional techniques or as \> 10 mm with spiral CT scan

• Diagnostic imaging studies such as MRIs and CT scans must be performed within 30 days of the date of registration

• Participants must have normal organ and marrow function as defined below:

‣ Leukocytes (WBC) \> 3,000/uL

⁃ Absolute neutrophil count \> 1,500uL

⁃ Platelets \> 100,000/uL

⁃ Total bilirubin \< 1.5 X institutional upper limits of normal; total bilirubin \> 1.5X above institutional upper limits of normal will be allowed if direct bilirubin is within normal limits or if patients has a documented history of Gilbert's disease

⁃ AST (SGOT)/ALT (SGPT) \< 2.5 X institutional upper limit of normal and ≤5 ULN for patients with liver metastases

• Baseline laboratory measurements must be documented from tests within 14 days of the date of registration

• ECOG performance status ≤ 1 (see Appendix A)

• Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial

• Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification which can be performed by the study investigators. To be eligible for this trial, participants should be class 2B or better

• Ability to understand and willingness to sign a written informed consent document

• Baseline tumor biopsies are required for all patients who have tumors that are deemed by the study investigators to be safely accessible