Clinical Trial Finder

Inclusion Criteria:

1. Patient is ≥18 years. 2. Signed informed consent. 3. ECOG performance status of 0 or 1. 4. Histologically or cytologically confirmed liver metastasis of uveal melanoma. 5. Measurable disease by computed tomography (CT) per RECIST 1.1 criteria with at least one target lesion identified in the liver. 6. No previous treatment for uveal melanoma metastases, except patients that have confirmed progression on tebentafusp, or after surgical resection or ablative treatments (e.g., radiofrequency ablation or stereotactic body radiation therapy). 7. Patient deemed suitable for percutaneous hepatic perfusion. 8. Female patient of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. 9. Female patients of childbearing potential must be willing to use an adequate method of contraception, for the course of the study through 150 days after the last dose of study medication. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject. 10. Male patients of childbearing potential must agree to use an adequate method of contraception, starting with the first dose of study therapy through 150 days after the last dose of study therapy. Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.

Exclusion Criteria:

1. Life expectancy of less than 6 months. 2. More than 50% of the liver volume replaced by tumor as measured by CT. 3. Extrahepatic disease as measured by CT of thorax and abdomen. 4. History of congestive heart failure, active cardiac conditions, including unstable coronary syndromes (unstable or severe angina, recent myocardial infarction), significant arrhythmias and severe valvular disease that precludes the use of general anesthesia. 5. History or evidence of clinically significant pulmonary disease e.g. severe COPD that precludes the use of general anesthesia. 6. Patients who are unable to undergo general anesthesia for any reason. 7. Reduced renal function defined as S-Creatinine >=1.5xULN or Creatinine Clearance < 40 mL/min, calculated using the Cockroft and Gault formula. 8. Reduced hepatic function (defined as AST, ALT, bilirubin>2.5*ULN and PK-INR>1.5) or medical history of liver cirrhosis (Child-Pugh Class B or C) or evidence of portal hypertension by history, endoscopy or radiology. 9. Hemoglobin <90 g/L or platelets <100x109/L or neutrophils <1.5x109/L. 10. Use of live vaccines four weeks before or after the last study treatment. 11. History of severe reactions to monoclonal antibodies, melphalan, heparin or iodine contrast. 12. Known human immunodeficiency virus (HIV) infection, acquired immunodeficiency syndrome (AIDS), hepatitis B or hepatitis C. 13. Active autoimmune disease or a documented history of autoimmune disease requiring systemic immunomodulatory treatment. Diabetes, rheumatoid arthritis, psoriasis, atopic dermatitis and hypothyroidism are excepted. 14. A condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses >10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. 15. Concomitant therapy with any other anti-cancer therapy, concurrent medical conditions requiring use of immunosuppressive medications or use of other investigational drugs. 16. Has a known additional malignancy that is progressing or requires active treatment. 17. Pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 150 days after the last dose of study drug. 18. A history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate in the opinion of the treating investigator.

Arms

Active Comparator: IPI3/NIVO1

Patients will be treated with 4 cycles of intravenous (i.v.) infusion with ipilimumab 3mg/kg and nivolumab 1mg/kg q3w followed by continued i.v. nivolumab 480mg q4w up to 1 year

Experimental: PHP + IPI1/NIVO3

Patients will be treated with two cycles of PHP (CHEMOSAT® Hepatic Delivery System for Melphalan) six weeks apart, followed by two cycles of i.v. ipilimumab 1mg/kg and nivolumab 3mg/kg q3w, followed by continued i.v. nivolumab 480mg q4w up to 1 year

Interventions

Device: - PHP

Patients will be treated with 2 cycles of PHP (CHEMOSAT® Hepatic Delivery System for Melphalan) six weeks apart

Drug: - IPI1/NIVO3

Patients will be treated with 2 cycles of i.v. ipilimumab 1mg/kg and nivolumab 3mg/kg q3w, followed by continued i.v. nivolumab 480mg q4w up to 1 year.

Drug: - IPI3/NIVO1

Patients will be treated with 4 cycles of intravenous (i.v.) infusion with ipilimumab 3mg/kg and nivolumab 1mg/kg q3w followed by continued i.v. nivolumab 480mg q4w up to 1 year.