Metastatic Uveal MelanomaPhase 1/2NCT06626516

Tebentafusp-tebn With LDT in Metastatic UM

A Phase 1/2 study testing Tebentafusp-Tebn, GM-CSF (Sargramostim) and BCNU in people with Metastatic Uveal Melanoma, run by Thomas Jefferson University at 1 site in United States.

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Sites and contacts

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Metastatic Uveal Melanoma
What is being tested?: Tebentafusp-Tebn, GM-CSF (Sargramostim) and BCNU
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 109 participants
Where: 1 siteUnited States
Study dates: 15 Oct 2025to Aug 2032
Phase: Phase 1/2
Are there results?: Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.
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.
6. HLA-A0201 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

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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.
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.
4.1.2 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

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Site Public Contact contact

215-600-9151

ONCTrialNow@jefferson.edu

United States1 site, 1 recruiting

Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
Rino Seedor, MD, 215-600-9151, ONCTrialNow@jefferson.edu
Rino Seedor, MD
Recruiting

Other trials in United States

About this study

Official title: A Phase I/II Study of Tebentafusp-tebn in Combination With Liver-Directed Therapies for the Treatment of Metastatic Uveal Melanoma

This study is a multicenter, open label phase I/ II trial to assess the safety and clinical efficacy of tebentafusp-tebn in combination with liver-directed therapies in HLA-A*0201 positive patients with metastatic uveal melanoma. In Part 1 of the study, the Prinicipal Investigator will investigate the safety and efficacy of tebentafusp-tebn in combination with hepatic IE in patients with a low to moderate hepatic disease burden. In Part 2, the study will investigate the efficacy of tebentafusp-tebn in combination with TACE in patients with bulky hepatic disease.

Read the detailed description

PART 1: TEBENTAFUSP AND IE Part 1A, Phase I/II: This is a single-arm study of 18 patients treated with combination therapy (tebentafusp-tebn with hepatic IE with GM-CSF), with the first cohort of six patients being enrolled in a safety lead in. The SKCC DSMC will monitor and approve the cohort expansion. The preliminary clinical efficacy endpoint is defined as a target 6-month liver-specific PFS rate of 60%. All patients will receive a 4-week induction course of tebentafusp-tebn alone (Cycle 1) using the approved step-up dosing regimen. Should the 4th dose be tolerated well as an outpatient, patients will receive their first IE treatment on Cycle 2 week 1 followed by continued weekly tebentafusp-tebn on weeks 2, 3, and 4 of Cycle 2. Patients will not receive tebentafusp-tebn concurrently with their first IE treatment during Week 1 of Cycle 2. Should Cycle 2 be well tolerated, patients may receive both tebentafusp-tebn and IE on Week 1 of subsequent cycles, with tebentafusp administered alone on weeks 2-4 of subsequent cycles. Patients may skip 1 week of tebentafusp in order to travel to TJU for IE without this being a protocol deviation.

Part 1B, Phase II: If the safety and preliminary efficacy in Part 1A are met, the study will then proceed with a randomized phase II trial. 52 patients will be randomized in a 2:1 ratio to receive tebentafusp-tebn in combination with hepatic IE or tebentafusp-tebn alone, with PFS as the primary endpoint. Secondary endpoints will include ORR, duration of response, systemic PFS, and OS. Patients randomized to tebentafusp-tebn + IE arm will be treated as above (See Figure 1). Patients randomized to tebentafusp-tebn alone will receive weekly treatment using the approved step-up dosing regimen. Tumor biopsies will be optional for all patients on this portion of the study; however, peripheral blood and ctDNA will be collected as above.

PART 2: TEBENTAFUSP AND TACE The trial will conduct a single-arm, two-stage phase II trial of sequential TACE with BCNU followed by tebentafusp-tebn in 39 patients with higher liver tumor burden (greatest tumor size >5 cm and/or ≥50% liver involvement on imaging). Patients with unilobar disease will first receive at least two treatments of TACE with 300mg BCNU; patients with bilobar disease will receive at least 4 treatments. Following completion of the TACE course, patients will receive tebentafusp-tebn on a weekly basis at the standard-care step-up dosing regimen.

Patients will undergo imaging studies at baseline, after completion of every two TACE treatments, and every 8 weeks thereafter while on tebentafusp-tebn alone. Tumor biopsies will be performed at baseline, following TACE, and after 4 weeks of treatment with tebentafusp-tebn. Peripheral blood will be collected for serum cytokine and PBMC analysis after completion of each TACE treatment and every 4 weeks thereafter. ctDNA will be collected at the time of each interval scan. Correlative studies will be performed as above in Part 1. Following the initial TACE treatments and subsequent tebentafusp induction, patients may receive additional TACE treatments at the discretion of the investigator. These will only be offered once a patient is through tebentafusp induction and has transitioned outpatient. Patients who proceed with additional TACE will hold tebentafusp the week of treatment and be followed with weekly labs to ensure return to baseline before proceeding with next scheduled tebentafusp at the discretion of the investigator.

Participants will continue treatment until confirmed disease progression, or for as long as the patient is deriving clinical benefit in the opinion of the treating investigator with approval of the study PI. The treating investigator may provide rationale and request approval for treatment beyond progression via email to the Study PI.

Conditions: Metastatic Uveal Melanoma
Being tested: Tebentafusp-Tebn, GM-CSF (Sargramostim), BCNU
Keywords: Uveal, uveal melanoma, metastatic uveal melanoma, melanoma, Liver-directed therapy, Liver-directed, Liver, liver-directed therapies, MUM, LDT
Medical subject headings: Uveal Melanoma, Melanoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Tebentafusp-TebnDrug
Also called kimmtrak, IMCgp100
Dosing: All patients enrolled in this study will receive treatment with tebentafusp-tebn based on the approved step-up dosing regimen of 20 mcg on C1D1, 30 mcg on C1D8, then 68 mcg weekly beginning on C1D15 and thereafter. This escalated dose administered at C1D15 will be the dose used for the remainder of the treatment period unless dose reduction is implemented for toxicity. Beginning with C1D8, tebentafusp-tebn will be administered on the scheduled day (± 2 days), and consecutive infusions of tebentafusp-tebn must be administered at least 5 days apart.
GM-CSF (Sargramostim)Drug
Also called yeast-derived recombinant human GM-CSF, Leukine, Hepatic Immunoembolization, GM-CSF
Recombinant human GM-CSF (Sargramostim, Leukine®, Sanofi US) 1,500mg will be mixed with ethiodized oil (Ethiodol®). The GM-CSF/ethiodized oil mixture will be injected selectively into one of the hepatic lobes, followed by infusion of gelatin sponge particles to achieve the stasis of blood flow. This will repeat every 4 weeks.
BCNUDrug
Also called Carmustine, BiCNU, bis-chloroethylnitrosourea, Hepatic Chemoembolization
Patients will be treated with hepatic artery infusion of 300mg BCNU (1,3-bis [2-chloroethyl]-1-nitrosourea, Carmustine) dissolved in ethiodized oil followed by embolization with gelatin sponge particles [TACE with BCNU 300mg]; every 4 weeks +/- 7 days in the case of either bilobar or unilobar metastasis

Study groups in NCT06626516
Study group	Role	What they receive
Part 1A: Safety Lead-in	Experimental	Phase I safety lead-in followed by a phase II trial with 6-month PFS rate as the preliminary efficacy endpoint. All patients will receive a 4-week induction course of tebentafusp-tebn alone (Cycle 1) using the approved step-up dosing regimen. Should the 4th dose be tolerated well as an outpatient, patients will receive their first IE treatment on Cycle 2 week 1 followed by continued weekly tebentafusp-tebn on weeks 2, 3, and 4 of Cycle 2 (See Figure 1). Patients will not receive tebentafusp-tebn concurrently with their first IE treatment during Week 1 of Cycle 2. Should Cycle 2 be well tolerated, patients may receive both tebentafusp-tebn and IE on Week 1 of subsequent Receives: Drug: Tebentafusp-Tebn; Drug: GM-CSF (Sargramostim)
Part 1B: Combination	Active comparator	If the safety and preliminary efficacy in Part 1A are met, we will then proceed with a randomized phase II trial. 52 patients will be randomized in a 2:1 ratio to receive tebentafusp-tebn in combination with hepatic IE or tebentafusp-tebn alone, with PFS as the primary endpoint. Patients randomized to tebentafusp-tebn + IE arm will be treated as Part 1A. Receives: Drug: Tebentafusp-Tebn; Drug: GM-CSF (Sargramostim)
Part 1B: Tebentafusp-tebn alone	Active comparator	If the safety and preliminary efficacy in Part 1A are met, we will then proceed with a randomized phase II trial. 52 patients will be randomized in a 2:1 ratio to receive tebentafusp-tebn in combination with hepatic IE or tebentafusp-tebn alone, with PFS as the primary endpoint. Patients randomized to tebentafusp-tebn alone will receive weekly treatment using the approved step-up dosing regimen. Receives: Drug: Tebentafusp-Tebn
Part 2: Efficacy of Combo	Active comparator	To assess the efficacy of tebentafusp-tebn in sequence with TACE in HLA-A*0201-positive patients with metastatic uveal melanoma to the liver Receives: Drug: Tebentafusp-Tebn; Drug: BCNU

What is being measured

The primary outcome is the main question the study is designed to answer.

Part 1A: Safety lead-in
Adverse events (AEs) according to NCI CTCAE Version 5.0. Safety and tolerability data will be presented by treatment arm using the safety population. Safety data will be summarized descriptively and will not be formally analyzed. AE presentation will include incidence, severity, and relationship to study drug.
Measured: From when the patient receives the first study treatment to 7 days (for non-serious AEs) or 30 days (for SAEs) after completion of study treatment or withdrawal from the study.
Part 1A: Efficacy
6-month progression-free survival rate as determined by response criteria (RECIST 1.1). Will be summarized by count and percentage along with the two-sided 90% exact confidence interval (CI).
Measured: From when the patient receives the first study treatment to 6 months after first treatment
Part 1B: Progression-free Survival
Defined as the time from the date of randomization until the date of objective disease progression or death by any cause. The primary Progression-free Survival (PSF) analysis will use a one-sided log-rank test, with a type I error of 0.05. In addition, PFS will be analyzed using Cox proportional hazards model and the estimated HR with 90% Confidence Interval (CI) will be reported. Kaplan-Meier curves of PFS will be presented by treatment arm along with estimated medians PFS (CIs).
Measured: From when patient joins study until disease progression or death, up to 2.5 years after last patient's last treatment.
Part 2: 6-month progression-free survival rate
As determined by response criteria (RECIST 1.1). Defined as the proportion of patients alive and progression-free at 6 months after treatment initiation. Will be summarized by count and percentage. In addition, a two-sided 90% Confidence Interval (CI) based on the method of Koyama and Chen will be provided. This method is appropriate because it is proposed for Simon's 2-stage design, accounting for the inherent futility analysis.
Measured: From when the patient receives the first study treatment to 6 months after first treatment.

Secondary outcomes (4)

All toxicities using the NCI CTCAE Version 5.0
Safety and tolerability data will be presented by treatment arm using the safety population. Safety data will be summarized descriptively and will not be formally analyzed. AE presentation will include incidence, severity, and relationship to study drug.
Measured: From when the patient receives the first study treatment to 7 days (for non-serious AEs) or 30 days (for SAEs) after completion of study treatment or withdrawal from the study.
Overall response rate (ORR)
Count and percentage of patients with a tumor response (Complete Response/Partial Response)
Measured: From when the patient receives the first study treatment to at least one year (and up to 2.5 years) after discontinuing treatment
Liver-specific progression-free survival
As determined by response criteria (RECIST 1.1). Defined as the proportion of patients alive and progression-free at 6 months after treatment initiation. Will be summarized by count and percentage.
Measured: From when patient joins study until disease progression or death, up to 2.5 years after last patient's last treatment.
Overall survival
Measured from the start of the treatment to death due to any cause. Date and cause of death will be recorded. Any patient not known to have died at the time of analysis will be censored based on the last recorded date on which the patient was known to be alive. The cause of death will be categorized as either cancer-related or cancer-unrelated.
Measured: From the start of the treatment to death due to any cause (assessed up to 2.5 years after last patient's last treatment)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

15 Oct 2025Aug 2032

First posted4 Oct 2024
Study start15 Oct 2025
Primary completionOct 2030 (estimated)
Study completionAug 2032 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Metastatic Uveal MelanomaStudies of the same condition, open and under way.
More trials run by Thomas Jefferson UniversityThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Sequential
Model description: Part 1A: Single-arm combination therapy (tebentafusp-tebn with hepatic IE with GM-CSF), with the first cohort of six patients being enrolled in a safety lead in. Part 1B: If the safety and preliminary efficacy in Part 1A are met, we will then proceed with a randomized phase II trial. 52 patients will be randomized in a 2:1 ratio to receive tebentafusp-tebn in combination with hepatic IE or tebentafusp-tebn alone Part 2: Single-arm, two-stage phase II trial of sequential TACE with BCNU followed by tebentafusp-tebn in 39 patients with higher liver tumor burden
Masking: None (open label)
Enrolment: 109 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT06626516
Sponsor's protocol ID: 2024-3117
Other IDs: JT 31444
Status last verified: Jul 2026
First submitted: 19 Sep 2024
Last updated: 21 Jul 2026
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Interested in taking part?

Site Public Contact

215-600-9151

ONCTrialNow@jefferson.edu

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See sites and contacts

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A Phase 1 and 2 Study of VMD-102 in Hepatocellular Carcinoma and Other Solid Tumors
Hepatocellular Carcinoma (HCC), Metastatic Uveal Melanoma
Recruiting
Immune Response to Percutaneous Hepatic Perfusion With Melphalan for Ocular Melanoma Metastatic to the Liver
Uveal Melanoma
Active, not recruitingPhase 2
Sunitinib Malate or Valproic Acid in Preventing Metastasis in Patients With High-Risk Uveal Melanoma
Ciliary Body and Choroid Melanoma, Medium/Large Size, Ciliary Body and Choroid Melanoma, Small Size
Not yet recruitingPhase 1/2
Safety and Efficacy Study in Adults With Advanced Solid Tumors Receiving REGN13089-M404-M2980, an Antibody-drug Conjugate That Targets MET Protein on Tumors
Advanced Solid Tumors
Active, not recruitingPhase 1/2
Different Doses of BI-1607 in Combination With Pembrolizumab and Ipilimumab, in Participants With Unresectable or Metastatic Melanoma
Melanoma Metastatic, Melanoma of Skin

All Metastatic Uveal Melanoma trials

Study at a glance

From the registry record, last updated by the sponsor on 21 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase I/II Study of Tebentafusp-tebn in Combination With Liver-Directed Therapies for the Treatment of Metastatic Uveal Melanoma
ClinicalTrials.gov ID: NCT06626516
Acronym / sponsor ID: 2024-3117
Conditions: Metastatic Uveal Melanoma
Keywords: Uveal, uveal melanoma, metastatic uveal melanoma, melanoma, Liver-directed therapy, Liver-directed, Liver, liver-directed therapies
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Recruiting
Enrolment: 109 participants (estimated)
Lead sponsor: Thomas Jefferson UniversityUniversity, hospital or other
Collaborators: Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University, Wills Eye
Study start: 15 Oct 2025 (actual)
Primary completion: Oct 2030 (estimated)
Study completion: Aug 2032 (estimated)
First posted: 4 Oct 2024 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Sequential
Masking: None (open label)
Number of arms: 4
Model description: Part 1A: Single-arm combination therapy (tebentafusp-tebn with hepatic IE with GM-CSF), with the first cohort of six patients being enrolled in a safety lead in. Part 1B: If the safety and preliminary efficacy in Part 1A are met, we will then proceed with a randomized phase II trial. 52 patients will be randomized in a 2:1 ratio to receive tebentafusp-tebn in combination with hepatic IE or tebentafusp-tebn alone Part 2: Single-arm, two-stage phase II trial of sequential TACE with BCNU followed by tebentafusp-tebn in 39 patients with higher liver tumor burden

Arm	Type	Receives
Part 1A: Safety Lead-in	Experimental	Drug: Tebentafusp-Tebn, Drug: GM-CSF (Sargramostim)Phase I safety lead-in followed by a phase II trial with 6-month PFS rate as the preliminary efficacy endpoint. All patients will receive a 4-week induction course of tebentafusp-tebn alone (Cycle 1) using the approved step-up dosing regimen. Should the 4th dose be tolerated well as an outpatient, patients will receive their first IE treatment on Cycle 2 week 1 followed by continued weekly tebentafusp-tebn on weeks 2, 3, and 4 of Cycle 2 (See Figure 1). Patients will not receive tebentafusp-tebn concurrently with their first IE treatment during Week 1 of Cycle 2. Should Cycle 2 be well tolerated, patients may receive both tebentafusp-tebn and IE on Week 1 of subsequent
Part 1B: Combination	Active comparator	Drug: Tebentafusp-Tebn, Drug: GM-CSF (Sargramostim)If the safety and preliminary efficacy in Part 1A are met, we will then proceed with a randomized phase II trial. 52 patients will be randomized in a 2:1 ratio to receive tebentafusp-tebn in combination with hepatic IE or tebentafusp-tebn alone, with PFS as the primary endpoint. Patients randomized to tebentafusp-tebn + IE arm will be treated as Part 1A.
Part 1B: Tebentafusp-tebn alone	Active comparator	Drug: Tebentafusp-TebnIf the safety and preliminary efficacy in Part 1A are met, we will then proceed with a randomized phase II trial. 52 patients will be randomized in a 2:1 ratio to receive tebentafusp-tebn in combination with hepatic IE or tebentafusp-tebn alone, with PFS as the primary endpoint. Patients randomized to tebentafusp-tebn alone will receive weekly treatment using the approved step-up dosing regimen.
Part 2: Efficacy of Combo	Active comparator	Drug: Tebentafusp-Tebn, Drug: BCNUTo assess the efficacy of tebentafusp-tebn in sequence with TACE in HLA-A*0201-positive patients with metastatic uveal melanoma to the liver

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (42 listed)

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.
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.
6. HLA-A0201 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

Key exclusion criteria (0 listed)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Tebentafusp-TebnAlso: kimmtrak, IMCgp100Dosing: All patients enrolled in this study will receive treatment with tebentafusp-tebn based on the approved step-up dosing regimen of 20 mcg on C1D1, 30 mcg on C1D8, then 68 mcg weekly beginning on C1D15 and thereafter. This escalated dose administered at C1D15 will be the dose used for the remainder of the treatment period unless dose reduction is implemented for toxicity. Beginning with C1D8, tebentafusp-tebn will be administered on the scheduled day (± 2 days), and consecutive infusions of tebentafusp-tebn must be administered at least 5 days apart.	Drug	Part 1A: Safety Lead-in, Part 1B: Combination, Part 1B: Tebentafusp-tebn alone, Part 2: Efficacy of Combo
GM-CSF (Sargramostim)Also: yeast-derived recombinant human GM-CSF, Leukine, Hepatic Immunoembolization, GM-CSFRecombinant human GM-CSF (Sargramostim, Leukine®, Sanofi US) 1,500mg will be mixed with ethiodized oil (Ethiodol®). The GM-CSF/ethiodized oil mixture will be injected selectively into one of the hepatic lobes, followed by infusion of gelatin sponge particles to achieve the stasis of blood flow. This will repeat every 4 weeks.	Drug	Part 1A: Safety Lead-in, Part 1B: Combination
BCNUAlso: Carmustine, BiCNU, bis-chloroethylnitrosourea, Hepatic ChemoembolizationPatients will be treated with hepatic artery infusion of 300mg BCNU (1,3-bis [2-chloroethyl]-1-nitrosourea, Carmustine) dissolved in ethiodized oil followed by embolization with gelatin sponge particles [TACE with BCNU 300mg]; every 4 weeks +/- 7 days in the case of either bilobar or unilobar metastasis	Drug	Part 2: Efficacy of Combo

Primary outcome

Part 1A: Safety lead-in
Time frame: From when the patient receives the first study treatment to 7 days (for non-serious AEs) or 30 days (for SAEs) after completion of study treatment or withdrawal from the study.
Adverse events (AEs) according to NCI CTCAE Version 5.0. Safety and tolerability data will be presented by treatment arm using the safety population. Safety data will be summarized descriptively and will not be formally analyzed. AE presentation will include incidence, severity, and relationship to study drug.
Part 1A: Efficacy
Time frame: From when the patient receives the first study treatment to 6 months after first treatment
6-month progression-free survival rate as determined by response criteria (RECIST 1.1). Will be summarized by count and percentage along with the two-sided 90% exact confidence interval (CI).
Part 1B: Progression-free Survival
Time frame: From when patient joins study until disease progression or death, up to 2.5 years after last patient's last treatment.
Defined as the time from the date of randomization until the date of objective disease progression or death by any cause. The primary Progression-free Survival (PSF) analysis will use a one-sided log-rank test, with a type I error of 0.05. In addition, PFS will be analyzed using Cox proportional hazards model and the estimated HR with 90% Confidence Interval (CI) will be reported. Kaplan-Meier curves of PFS will be presented by treatment arm along with estimated medians PFS (CIs).
Part 2: 6-month progression-free survival rate
Time frame: From when the patient receives the first study treatment to 6 months after first treatment.
As determined by response criteria (RECIST 1.1). Defined as the proportion of patients alive and progression-free at 6 months after treatment initiation. Will be summarized by count and percentage. In addition, a two-sided 90% Confidence Interval (CI) based on the method of Koyama and Chen will be provided. This method is appropriate because it is proposed for Simon's 2-stage design, accounting for the inherent futility analysis.

4 secondary outcomes

All toxicities using the NCI CTCAE Version 5.0
Time frame: From when the patient receives the first study treatment to 7 days (for non-serious AEs) or 30 days (for SAEs) after completion of study treatment or withdrawal from the study.
Overall response rate (ORR)
Time frame: From when the patient receives the first study treatment to at least one year (and up to 2.5 years) after discontinuing treatment
Liver-specific progression-free survival
Time frame: From when patient joins study until disease progression or death, up to 2.5 years after last patient's last treatment.
Overall survival
Time frame: From the start of the treatment to death due to any cause (assessed up to 2.5 years after last patient's last treatment)

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 21 Jul 2026.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.

Site Public Contact contact

215-600-9151

ONCTrialNow@jefferson.edu

Rino Seedor, MD principal investigator

Thomas Jefferson University

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Tebentafusp-Tebn, GM-CSF (Sargramostim) and BCNU in people with Metastatic Uveal Melanoma, run by Thomas Jefferson University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 42 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 21 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Site Public Contact (215-600-9151, ONCTrialNow@jefferson.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part 1A: Safety lead-in (time frame: From when the patient receives the first study treatment to 7 days (for non-serious AEs) or 30 days (for SAEs) after completion of study treatment or withdrawal from the study.). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06626516.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jul 2026.