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

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 leastone target lesion identified in the liver.

6. No previous treatment for uveal melanoma metastases, except patients that haveconfirmed progression on tebentafusp, or after surgical resection or ablativetreatments (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 serumpregnancy test within 72 hours prior to receiving the first treatment. If the urinetest is positive or cannot be confirmed as negative, a serum pregnancy test will berequired.

9. Female patients of childbearing potential must be willing to use an adequate methodof contraception, for the course of the study through 150 days after the last doseof study medication. Note: Abstinence is acceptable if this is the usual lifestyleand preferred contraception for the subject.

10. Male patients of childbearing potential must agree to use an adequate method ofcontraception, starting with the first dose of study therapy through 150 days afterthe last dose of study therapy. Abstinence is acceptable if this is the usuallifestyle 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 unstablecoronary syndromes (unstable or severe angina, recent myocardial infarction),significant arrhythmias and severe valvular disease that precludes the use ofgeneral anesthesia.

5. History or evidence of clinically significant pulmonary disease e.g. severe COPDthat 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) ormedical history of liver cirrhosis (Child-Pugh Class B or C) or evidence of portalhypertension 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 iodinecontrast.

12. Known human immunodeficiency virus (HIV) infection, acquired immunodeficiencysyndrome (AIDS), hepatitis B or hepatitis C.

13. Active autoimmune disease or a documented history of autoimmune disease requiringsystemic immunomodulatory treatment. Diabetes, rheumatoid arthritis, psoriasis,atopic dermatitis and hypothyroidism are excepted.

14. A condition requiring systemic treatment with either corticosteroids (>10 mg dailyprednisone equivalents) or other immunosuppressive medications within 14 days ofstudy drug administration. Inhaled or topical steroids and adrenal replacement doses >10 mg daily prednisone equivalents are permitted in the absence of activeautoimmune disease.

15. Concomitant therapy with any other anti-cancer therapy, concurrent medicalconditions requiring use of immunosuppressive medications or use of otherinvestigational 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 theprojected duration of the study, starting with the screening visit through 150 daysafter the last dose of study drug.

18. A history or current evidence of any condition, therapy, or laboratory abnormalitythat might confound the results of the study, interfere with the patient'sparticipation for the full duration of the study, or is not in the best interest ofthe patient to participate in the opinion of the treating investigator.