Optimal Neo-adjuvant Combination Scheme of Ipilimumab and Nivolumab

Inclusion Criteria

• •Adults at least 18 years of age
• •World Health Organization (WHO) Performance Status 0 or 1
• •Cytologically or histologically confirmed resectable stage III melanoma with one or more macroscopic lymph node metastases (measurable according to RECIST 1.1), that can be biopsied, and no history of in-transit metastases within the last 6 months
• •No other malignancies, except adequately treated and a cancer-related life-expectancy of more than 5 years
• •Patient willing to undergo triple tumor biopsies and extra blood withdrawal during screening and in case of relapse
• •No prior immunotherapy targeting CTLA-4, PD-1 or PD-L1
• •No immunosuppressive medications within 6 months prior study inclusion
• •Screening laboratory values must meet the following criteria: WBC ≥ 2.0x109/L, Neutrophils ≥1.5x109/L, Platelets ≥100 x109/L, Hemoglobin ≥5.5 mmol/L, Creatinine ≤1.5x ULN, AST ≤ 1.5 x ULN, ALT ≤ 1.5 x ULN, Bilirubin ≤1.5 X ULN
• •Normal LDH
• •Women of childbearing potential (WOCBP) must use appropriate method(s) of contra-ception. WOCBP should use an adequate method to avoid pregnancy for 23 weeks (30 days plus the time required for nivolumab to undergo five half-lives) after the last dose of investigational drug
• •Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of ipilimumab + nivolumab
• •Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year. Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 31 weeks after the last dose of investigational product
• •Women who are not of childbearing potential (i.e., who are postmenopausal), or surgically sterile as well as azoospermic men do not require contraception
• •Patient is capable of understanding and complying with the protocol requirements and has signed the Informed Consent document.