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

Eligibility 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 while receiving or within 3 months of completion of adjuvant anti-PD1 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 as described in Section 5.3.1.
• * Subject has adequate archival tissue or agrees to undergo a fresh tissue biopsy if sufficient archival tissue is unavailable.
• * 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.
• * 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:
• * 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.
• * 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.
• * 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.