Evaluating the Effect of Nivolumab for Patients With In-transit Metastases Treated With Isolated Limb Perfusion

Inclusion criteria

• Male or female aged above 18 years.
• Signed and dated written informed consent before the start of specific protocol procedures.
• Histologically or cytologically proven in-transit metastases of malignant melanoma with or without regional lymph node metastases (AJCC v8 stage N1c, N2c and N3c).
• Measurable disease with at least 1 metastasis measuring at least 5mm
• ECOG performance status of 0-2

Exclusion criteria

• 1. Life expectancy of less than 6 months
• Inability to understand given information or undergo study procedures according to protocol.
• Pregnant or breast-feeding. Women of childbearing potential must have a negative pregnancy test performed within 24 hours before the administration of study drug.
• Patients must agree to follow instructions for method of contraception for 5 months (women) and 7 months (males) after treatment.
• Active cardiac conditions, including unstable coronary syndromes (unstable or severe angina, recent myocardial infarction), significant arrhythmias and severe valvular disease that precludes general anaesthesia.
• History or evidence of clinically significant pulmonary disease e.g., severe COPD that precludes general anesthesia.
• Reduced renal function defined as S-Creatinine >=1.5xULN
• Reduced hepatic function (defined as ASAT, ALAT, bilirubin >1.5 ULN and PK-INR >1.5) or a medical history of liver cirrhosis or portal hypertension.
• Reduced blood leukocytes or platelets defined as a leucocyte count < 2.0x109/L and thrombocyte count <100x109/L.
• Active, autoimmune disease. Subjects are permitted to enrolment if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger.
• Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
• A condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 30 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses >10 mg daily prednisone equivalents are permitted.
• Has an active infection requiring systemic therapy.
• Has received a live vaccine within 30 days prior to the first dose of trial treatment and 3 months after treatment.
• Concomitant therapy with any of the following: IL 2 or other non-study immunotherapy regimens; cytotoxic chemotherapy except melphalan (ILP); other investigational therapies within 30 days before trial treatment and 3 months after trial treatment.