Neoadjuvant and Adjuvant Checkpoint Blockade

Inclusion Criteria

• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form
• Patients must have histologically or cytologically confirmed stage IIIB/C or stage IV oligometastatic melanoma; oligometastatic melanoma is defined as three or fewer areas of resectable disease excluding central nervous system and bone involvement; patients with cutaneous, mucosal, acral, ocular or unknown primary melanomas are eligible for enrollment; for patients with stage IV disease with distant lymph nodes (stage M1a), a maximum of three separate lymph node sites fit the definition of oligometastatic disease; resectable tumors are defined as having no significant vascular, neural or bony involvement; only cases where a complete surgical resection with tumor-free margins can safely be achieved are defined as resectable
• Patients will have at least one melanoma deposit that can undergo serial biopsy (at least 2 time points) during the neoadjuvant phase of the protocol; patients must be willing to provide tumor samples at the time points specified in the Study Procedure Tables
• All patients must undergo a baseline tumor biopsy; in Arms A and B, tumor biopsy for PD-L1 testing (PD-L1 positivity is determined by greater than or equal to 1% of cells staining in the membrane by immunohistochemistry) is required for stratification; PD-L1 status is not required for enrollment on Arm C; the 28-8 clone for PD-L1 testing is required for assessment of PD-L1 status; for patients with stage IV disease, site of tumor biopsy will preferably be from non-lymph node disease site; for PD-L1 testing, the biopsy should contain sufficient tumor content (> 100 tumor cells/4-micron tissue section); if a sample contains insufficient tumor content, a re-biopsy will be required to obtain a sample with sufficient tumor content prior to treatment
• Patients must be medically fit enough to undergo surgery as determined by the treating medical and surgical oncology team
• Patients who have been previously treated in the adjuvant setting for melanoma will be eligible for treatment after a 28 day wash-out period
• Patients must have measurable disease, defined by RECIST 1.1
• Age >/= 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Absolute neutrophil count (ANC) >= 1.5 X 10^9/L (within 28 days of first study treatment)
• Hemoglobin >= 8.5 g/dL (within 28 days of first study treatment)
• Platelets >= 100 X 10^9/L (>= 60 for hepatocellular carcinoma [HCC]) (within 28 days of first study treatment)
• Prothrombin time (PT)/international normalized ratio (INR) and partial thromboplastin time (PTT) = = 2.0 X 10^9/L (within 28 days of first study treatment)
• Total bilirubin = = 2.5 g/dL (within 28 days of first study treatment)
• Creatinine = = 40 mL/min OR 24-hour urine creatinine clearance >= 50 mL/min (within 28 days of first study treatment)
• Lipase = 50% by transthoracic echocardiography (TTE) (preferred) or multigated acquisition (MUGA) within 6 months from first study drug administration
• Women are eligible to participate if: non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous follicle stimulating hormone [FSH] > 40 MlU/mL and estradiol 24 hours; contraception should be continued for a period of 30 days plus the time required for the study drug to undergo 5 half-lives; WOCBP should use an adequate method to avoid pregnancy for 24 weeks (30 days plus the time required for study drug to undergo 5 half-lives) after the last dose of study drug; WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 24 hours prior to the start of investigational product
• Women must not be breastfeeding
• Men who a