Tebentafusp-tebn With LDT in Metastatic UM

Inclusion 65

• Minimum age: 18 years
• Study condition: Metastatic Uveal Melanoma
• Age ≥18 years of age 2.
• Histologically or cytologically confirmed metastatic uveal melanoma in the liver.
• Patients must have at least one measurable liver metastasis that is ≥ 10 mm in longest diameter by CT scan or MRI.
• Extra-hepatic disease is allowed. 3.
• Tumor Size Criteria: i.
• Part 1: Total volume of tumor must be \< 50% of the liver involvement by CT or MRI;
• M1a or M1b disease with largest tumor ≤ 5 cm ii.
• Part 2: M1b disease with largest tumor \> 5 cm, M1c disease, or ≥ 50% liver involvement by CT or MRI 4.
• No prior systemic treatment with tebentafusp-tebn 5.
• Prior therapy: i.
• Part 1: Patients must be treatment naïve in the metastatic setting.
• Prior surgery or ablation for oligometastatic disease is allowable.
• Palliative radiation of non-target lesions also allowable. ii.
• Part 2: Patients may have had prior systemic therapy with chemotherapy, immunotherapy, or targeted therapy.
• They can also have had prior liver directed therapy including surgery, ablation, immunoembolization, or radioembolization.
• However cannot have had more than two prior lines of treatment total.
• \. HLA-A\*0201 positive 7. ECOG performance status or 0 or 1 at the time of screening 8. Life expectancy of greater than 3 months as assessed by the investigator 9. Patients must have normal organ and bone marrow function as defined below:
• Platelet count ≥ 100,000/mm³
• Hemoglobin \> 8.0g/dL
• ANC ≥ 1500
• AST and/or ALT \< 3x upper limited of normal (ULN)
• Total bilirubin ≤ 2.0 mg/ml
• Note: Patients with hyperbilirubinemia clinically consistent with an inherited disorder of bilirubin metabolism (e.g., Gilbert syndrome) will be eligible at the discretion of the treating physician and/or the principal investigator.
• PT/PTT \< 1.5x ULN
• Creatinine clearance \> 60mL/min
• Potassium, magnesium, corrected calcium, and phosphate within normal laboratory parameters 10.
• Women must not be pregnant or breast-feeding. 11.
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for the 6 months after the final dose of the study drug.
• Women of child-bearing potential must have a negative serum pregnancy test within 14 days prior to study entry.
• Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
• \. Male patients treated or enrolled on this protocol must be surgically sterile or use double barrier contraception methods from enrollment through treatment, and for 6 months after completion of study therapy.
• \. Ability to understand and the willingness to sign a written informed consent document.
• 1.2 Exclusion Criteria
• Parts 1 and 2:
• Failure to meet any of the criteria set forth in the Inclusion criteria section
• History of prior tebentafusp-tebn use
• Prior chemoembolization in Part 2 is not permitted
• History of severe immediate or delayed hypersensitivity reaction to biologic drugs, monoclonal antibodies, iodinated contrast agent
• Presence of symptomatic liver failure including ascites and hepatic encephalopathy
• Presence of symptomatic or untreated central nervous system (CNS) metastases, or CNS metastases that require corticosteroids within 21 days prior to initiation of study therapy.
• Patients with brain metastases may be eligible if lesions have been treated with local therapy and there is no evidence of CNS disease progression for at least 4 weeks as measured by MRI prior to first dose of study drug
• History of another malignancy except for: 1) those who have been disease-free for 3 years prior to study treatment; 2) patients with a history of completely resected non-melanoma skin cancer; 3) patients with indolent secondary malignancies not requiring active therapy; 4) patients with completely resected carcinoma in situ.
• Consult the study Principal Investigator if unsure whether second malignancies meet the requirements specified above.
• Major surgery within 2 weeks of the first dose of study drug (minimally invasive procedures such as bronchoscopy, tumor biopsy, insertion of a central venous access device, and insertion of a feeding tube are not considered major surgery and are not exclusionary)
• Radiotherapy within 2 weeks of the first dose of study drug, with the exception of palliative radiotherapy to a limited field, such as for the treatment of bone pain or a focally painful tumor mass
• No outstanding toxicities from prior therapies greater than Grade 1. Except for prior immune related side effects such as endocrinopathy that are managed with a stable dose of thyroid or steroid supplement.
• Use of any investigational drugs within 28 days (or five half-lives, whichever is shorter; with a minimum of 14 days from the last dose) preceding the first dose of study therapy and during the study.
• Use of hematopoietic colony-stimulating growth factors (eg.
• G-CSF, GMCSF, M-CSF) within 14 days prior to study treatment initiation.
• An erythroid-stimulating agent is allowed as long as it was initiated at least 2 weeks prior to the first dose of study treatment and the patient is not red blood cell transfusion dependent.
• Known history of human immunodeficiency virus infection (HIV). Testing for HIV is not necessary unless clinically indicated
• Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Testing for HBV or HCV status is not necessary unless clinically indicated or if the patient has a history of HBV or HCV infection.
• Patients receiving systemic steroid therapy or any immunosuppressive medication. Local steroid therapies (eg, otic, ophthalmic, intra-articular or inhaled medications) are acceptable.
• History of bleeding diathesis
• Pregnant, likely to become pregnant, or breastfeeding women
• Uncontrolled concurrent illness, evaluated at investigator discretion
• Biliary obstruction, biliary stent or prior biliary surgery except cholecystectomy, or any anatomic abnormalities that would interfere with immunoembolization or chemoembolization:
• Patients with occlusion of the main portal vein
• Inadequate collateral flow around an occluded portal vein as determined by angiography
• Arteriovenous shunt identified on arteriography of the hepatic artery
• Any medical condition that, in the Investigator's judgement, would prevent patient participation in the clinical study due to safety concerns, compliance with study procedures or interpretation of study results
• Part 1 Only:
• History of severe immediate or delayed hypersensitivity reaction to GM-CSF