Immune Response to Percutaneous Hepatic Perfusion With Melphalan for Ocular Melanoma Metastatic to the Liver

Inclusion criteria

• Patient has histologically or cytologically confirmed diagnosis of uveal melanoma metastatic to the liver and is determined to be a candidate for percutaneous hepatic perfusion with melphalan
• The subject has read, signed and dated the Informed Consent Form (ICF), having been advised of the risks and benefits of the trial in a language understood by the subject.
• Age \> 18 years at date of informed consent signature having the ability to comply with the protocol.
• Contrast-enhanced cross-sectional imaging of the abdomen (either CT or MRI) obtained within two months prior to study enrollment
• Measurable metastatic disease. Subject must have at least one site of metastatic disease ≥ 1 cm in size and amenable to percutaneous image-guided biopsy
• Life expectancy \> 12 weeks.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Laboratory requirements:
• Absolute neutrophil count (ANC) \> 1 x 109/L
• Platelets \> 75 x 109/L
• Alanine aminotransferase (ALT) / Aspartate aminotransferase (AST) \< 5 x ULN
• Total bilirubin \<3 mg/dL
• International normalized ratio (INR) \<1.7
• Glomerular filtration rate (GFR) \>30 ml/min

Exclusion criteria

• Lesion to undergo biopsy cannot have undergone prior radiation therapy or other locoregional therapy
• Continued adverse events from a previously administered chemotherapeutic agents. Grade 1 adverse events and ongoing toxicities such as alopecia are exempt
• Treatment with systemic corticosteroids exceeding the equivalent of 10 mg/day of prednisone or other systemic immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, and anti-tumor necrosis factor \[anti-tumor necrosis factor (TNF)\] agents) within 2 weeks prior to Day 1, or anticipated requirement for systemic immunosuppressive medications exceeding the equivalent of 10 mg/day of prednisone during the trial
• Patients who receive acute, low-dose, systemic corticosteroid medications (e.g., a one-time dose of dexamethasone for nausea) or for prevention of hypersensitivity reactions to contrast agents may be enrolled in the trial.
• Anticoagulant or anti-platelet medication that cannot be interrupted prior to biopsy
• Pregnant or lactating
• Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicated the use of an investigational drug or that could affect the interpretation of the results or render the patient at high risk from treatment complications.
• Treatment with systemic immunostimulatory agents (including but not limited to interferon(IFN)s, interleukin \[IL\]-2) within 6 weeks or five half- lives of the drug, whichever was shorter, prior to Day 1.
• Treatment with immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies, anti-LAG-3 antibodies, within the past three months. Prior treatment with tebentafusp is allowed with no washout period required.
• Treatment with any investigational systemic medication within at least one month prior to biopsy. If an investigational agent is an immune checkpoint inhibitor, a three-month washout is required. Prior treatment with Darovasertib and Crizotinib is allowed with no washout period required.
• Signs or symptoms clinically significant of infection within 2 weeks prior to Day 1.