A Phase III Randomized Trial of Physician/Patient Choice of Either High Dose Interferon or Ipilimumab to MK-3475 (Pembrolizumab) in Patients with High-Risk Resected Melanoma -

STEP 1 REGISTRATION: Pts must have completely resected melanoma of cutaneous origin or of unknown primary and must be classified as Stage IIIA (N2a), IIIB, IIIC, or Stage IV melanoma. Pts w/melanoma of mucosal or other non-cutaneous origin are eligible. Pts must not have melanoma of ocular origin or a history of brain metastases; Pts at eligible at initial presentation of melanoma or at the time of first detected nodal, satellite/in-transit, distant metastases, or recurrent disease in prior lymphadenectomy basin or distant site. Nodal, satellite/in-transit metastasis, distant metastases or disease in prior complete lymphadenectomy basin must have been confirmed histologically by H&E stained slides; Pts w/multiple regional nodal basin involvement are eligible. Gross or microscopic extracapsular nodal extension is permitted; Pts at initial presentation of melanoma must undergo an adequate wide excision of primary lesion, if present. Pts w/previously diagnosed melanoma must have had all current disease resected with pathologically negative margins and have no evidence of disease at primary site, or must undergo re-resection of the primary site. Full lymphadenectomy is required for all node-positive pts including those with positive sentinel nodes. All pts must have all disease resected with negative pathological margins and no clinical, radiologic, or pathological evidence of any incompletely resected melanoma. PTS MUST BE REGISTERED W/IN 98 DAUS OF THE LAST SURGERY PERFORMED TO RENDER PT FREE OF DISEASE; Must be able/willing to submit min of 5 unstained slides to determine PDL1 expression; must be offered the opportunity to participate in specimen banking.; must be willing to have blood draws for PK/ADA analysis; prior radiation therapy is allowed; must not have had prior neoadjuvant trt for melanoma and must not have had prior immunotherapy and must not be planning to receive any prohibited therapies listed in Section 7.2 during screening or treatment; must not be planning to receive concomitant or other biologic therapy, radiation therapy, hormonal therapy, other chemotherapy, surgery, or other therapy after Step 2 registration; must be 18 years of age or older; must have disease-free status documented by complete physical and imaging studies w/in 42 days prior to reg. Imaging studies must include total body PET-CT (of diagnostic quality) or CT of chest, abdomen, and pelvis; Pts w/melanoma arising from head and neck must have dedicated neck imaging; if pt has had unknown primary with disease in axilla, neck imagining is req�d. All pts must have CT or MRI of brain within 90 days prior to reg. Must have the following lab values within 42 days prior to reg: ANC >/= 1,500 mcL, platelets >/= 100,000mcl, hemoglobin >/= 10 g/dL, total bilirubin </= 1.5 x IULN, SGOT (AST) and SGPT (ALT) and alkaline phosphatase </= 2 x IULN, serum creatinine </= IULN OR measured or calculated creatinine clearance >/= 60 mL/min, and LDH must be performed; Zubrod PS </= 1; ECG w/in 42 days prior to reg that is considered normal or not clinical significant by site investigator; no evidence of active, non-infectious pneumonitis; no active infection requiring systemic therapy; no active autoimmune disease that has required systemic treatment in the past 2 years; must not have received live vaccines w/in 42 days prior to reg; if HIV positive, must have stable and adequate CD4 counts (>/= 350 mm3) and serum HIV viral load of < 25,000 UI/ml w/in 30 days prior to reg; no known active HBV or HCV infection prior to reg; no history or current evidence of any condition, therapy, or lab abnormality that might confound trial results, interfere in pts participation in full duration of trial, or indication that participation is not in the patient�s best interests, in the opinion of treating investigator; no prior malignancy except for: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, lobular carcinoma of the breast in situ, atypical melanocytic hyperplasia or melanoma in situ, adequately treated Stage I or II cancer from which the patient is current in complete remission or any other cancer from which the pt has been disease free for three years; serum pregnancy test for women of childbearing potential w/in 28 days prior to reg; pts that can respond to questionnaires in English must participate in QOL assessments.

STEP 2 REGISTRATION: Pts must not be registered until receiving confirmation the tissue is adequate for PD-L1 testing; must verify there is no known change in Step 1 eligibility since initial registration; women of childbearing potential must have pregnancy test within 72hrs prior to receiving first dose of study medication. No tests/exams must be repeated for Step 2 reg, but pts known to have change in eligibility status after Step 1 reg are not eligible for Step 2 reg.