Neoadjuvant Ipilimumab/Nivolumab for Patients With Recurrent, High Risk, Resectable Melanoma

Inclusion Criteria: * Subjects aged ≥ 18 years. * Histologically confirmed Stage IIIB-D or Stage IV recurrent metastatic melanoma that is resectable or borderline resectable as determined by a Surgical Oncologist. * Recurrent disease at eligibility must have been confirmed with biopsy after receiving prior anti-PD1 based systemic therapy (either adjuvant, neoadjuvant, or definitive therapy). * ECOG Performance Status ≤ 1. * Adequate organ function as defined as: * Hematologic: * Absolute neutrophil count (ANC) ≥ 1500/mm3 * Platelet count ≥ 100,000/mm3 * Hemoglobin ≥ 10 g/dL * Hepatic: * Total Bilirubin ≤ 1.5x institutional upper limit of normal (ULN) * AST(SGOT)/ALT(SGPT) ≤ 3 × institutional ULN * Subjects with liver metastases will be allowed to enroll with AST and ALT levels ≤ 5 x ULN. * Renal: * Estimated creatinine clearance ≥ 50 mL/min by Cockcroft-Gault formula: * For subjects of childbearing potential: Negative pregnancy test or evidence of post-menopausal status or evidence of permanent surgical sterilization. The post-menopausal status will be defined as having been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply: * Subjects \< 50 years of age: * Amenorrheic for ≥ 12 months following cessation of exogenous hormonal treatments; and * Luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution * Subjects ≥ 50 years of age: * Amenorrheic for ≥ 12 months following cessation of all exogenous hormonal treatments; or * Had radiation-induced menopause with last menses \>1 year ago; or * Had chemotherapy-induced menopause with last menses \>1 year ago * Subjects of childbearing potential and subjects with a sexual partner of childbearing potential must agree to use a highly effective method of contraception. * Recovery to baseline or ≤ Grade 1 CTCAE v5 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy per the treating investigator. * Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines. Exclusion Criteria: * Prior exposure to anti-CTLA4 therapy. * Receiving other investigational agents currently or within 28 days of study treatment. * Prior systemic anti-cancer therapy ≤ 14 days or within five half-lives prior to starting study treatment, whichever is shorter. * Prior radiotherapy 45 days prior to the first dose of study treatment. * Major surgery 4 weeks prior to starting study drug or who have not fully recovered from major surgery. * Active infection requiring the use of systemic antibiotics. * Systemic steroid therapy greater than physiologic equivalent (10mg prednisone/day) or any other form of systemic immunosuppressive therapy within 7 days prior to registration. * Active secondary malignancy, unless the malignancy is not expected to interfere with the evaluation of safety * Known brain metastases or cranial epidural disease. * Current evidence of uncontrolled, significant intercurrent illness including, but not limited to, the following conditions: * Cardiovascular disorders: * Congestive heart failure New York Heart Association Class III or IV, unstable angina pectoris, serious cardiac arrhythmias. * Stroke (including transient ischemic attack \[TIA\]), myocardial infarction (MI), or other ischemic events, or thromboembolic event (eg, deep venous thrombosis, pulmonary embolism) within 3 months before the first dose. * QTc prolongation defined as a QTcF \> 500 ms. * Known congenital long QT. * Left ventricular ejection fraction \< 55%. * Uncontrolled hypertension defined as ≥ 140/90 as assessed from the mean of three consecutive blood pressure measurements taken over 10 minutes. * Any other condition that would, in the Investigator's judgment, contraindicate the subject's participation in the clinical study due to safety concerns or compliance with clinical study procedures (e.g., infection/inflammation, intestinal obstruction, unable to swallow medication, \[subjects may not receive the drug through a feeding tube\], social/psychological issues, etc.) * HIV infection with a detectable viral load within 6 months of the anticipated start of treatment. --Note: Subjects on effective antiretroviral therapy with an undetectable viral load within 6 months of the anticipated start of treatment are eligible for this trial. * Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination, radiographic findings, and TB testing in line with local practice), hepatitis B (positive HBV surface antigen (HBsAg) result), or hepatitis C. --Note: Subjects with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \[anti-HBc\] and absence of HBsAg) are eligible. Subjects positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA. * Medical, psychiatric, cognitive, or other conditions that may compromise the subject's ability to understand the subject information, give informed consent, comply with the study protocol or complete the study. * Known prior severe hypersensitivity to investigational product (IP) or any component in its formulations (NCI CTCAE v5.0 Grade ≥ 3). * Subjects taking prohibited medications as described in Section 6.7.2. A washout period of prohibited medications for a period of at least five half-lives or as clinically indicated should occur before the start of treatment.