Tebentafusp-tebn With LDT in Metastatic UM

Launched by THOMAS JEFFERSON UNIVERSITY · Oct 1, 2024

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment called tebentafusp-tebn for patients with metastatic uveal melanoma, a type of eye cancer that has spread to the liver. The trial aims to find out if this treatment is safe and effective when combined with other therapies that directly target the liver, specifically for patients who have certain genetic markers (HLA-A*0201 positive). The study has two parts: the first part will look at patients with smaller tumors in the liver, while the second part will focus on those with larger tumors.

To participate in the trial, you must be at least 18 years old and have confirmed metastatic uveal melanoma in the liver, with at least one measurable tumor. You should not have received certain prior treatments, and your overall health must meet specific criteria, such as normal liver function. The trial is not yet recruiting participants, but if you qualify, you can expect to receive regular check-ups and monitoring during the study. It’s important to note that participants will need to use effective birth control and will be informed about any potential risks and benefits of the treatment throughout the trial.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. 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.
• • 1. Prior surgery or ablation for oligometastatic disease is allowable.
• • 2. 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.
• 6. 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:
• • 1. Platelet count ≥ 100,000/mm³
• • 2. Hemoglobin \> 8.0g/dL
• • 3. AST and/or ALT \< 3x upper limited of normal (ULN)
• • 4. Total bilirubin ≤ 2.0 mg/ml
• • 5. 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.
• • 6. PT/PTT \< 1.5x ULN
• • 7. Serum creatinine ≤ 2.0 mg/dl or a creatinine clearance \> 60mL/min
• • 8. 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.
• • 12. 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.
• • 13. Ability to understand and the willingness to sign a written informed consent document.
• Exclusion Criteria:
• Parts 1 and 2:
• • 1. Failure to meet any of the criteria set forth in the Inclusion criteria section
• • 2. History of prior tebentafusp-tebn use
• • 3. Prior chemoembolization in Part 2 is not permitted
• • 4. History of severe immediate or delayed hypersensitivity reaction to biologic drugs, monoclonal antibodies, iodinated contrast agent
• • 5. Presence of symptomatic liver failure including ascites and hepatic encephalopathy
• • 6. 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
• • 7. 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.
• • 8. 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)
• • 9. 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
• • 10. 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.
• • 11. 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.
• • 12. 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.
• • 13. Known history of human immunodeficiency virus infection (HIV). Testing for HIV is not necessary unless clinically indicated
• • 14. 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.
• • 15. Patients receiving systemic steroid therapy or any immunosuppressive medication. Local steroid therapies (eg, otic, ophthalmic, intra-articular or inhaled medications) are acceptable.
• • 16. History of bleeding diathesis
• • 17. Pregnant, likely to become pregnant, or breastfeeding women
• • 18. Uncontrolled concurrent illness, evaluated at investigator discretion
• • 19. Biliary obstruction, biliary stent or prior biliary surgery except cholecystectomy, or any anatomic abnormalities that would interfere with immunoembolization or chemoembolization
• • 20. Patients with occlusion of the main portal vein
• • 21. Inadequate collateral flow around an occluded portal vein as determined by angiography
• • 22. Arteriovenous shunt identified on arteriography of the hepatic artery
• • 23. 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:
• • a. History of severe immediate or delayed hypersensitivity reaction to GM-CSF