PHP in Combination With IPI1/NIVO3 Compared to IPI3/NIVO1 Only in Patients With Uveal Melanoma Liver Metastases

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.