Tebentafusp-tebn for Uveal Melanoma

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Waitlist Available

Sponsor: Thomas Jefferson University

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

We will conduct 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, we 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, we will investigate the efficacy of tebentafusp-tebn in combination with TACE in patients with bulky hepatic disease.

Research Team

Eligibility Criteria

This trial is for HLA-A*0201 positive patients with metastatic uveal melanoma, specifically those with a low to moderate liver disease burden in Part 1, and those with more significant liver disease in Part 2. Participants must be able to receive liver-directed therapies.

Inclusion Criteria

I am fully active or restricted in physically strenuous activity but can do light work.

Life expectancy of greater than 3 months as assessed by the investigator

Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

Any medical condition that, in the Investigator's judgement, would prevent patient participation in the clinical study

Use of any investigational drugs within 28 days preceding the first dose of study therapy and during the study

I have been diagnosed with HIV.

Treatment Details

Interventions

• Tebentafusp-Tebn (Cancer Vaccine)

Trial Overview The study tests the safety and effectiveness of tebentafusp-tebn combined with two types of liver treatments: hepatic intra-arterial infusion (IE) for less severe cases, and transarterial chemoembolization (TACE) for more advanced cases.

Participant Groups

Group I: Part 1A: Safety Lead-in Experimental Treatment 2 Interventions

Phase I safety lead-in followed by a phase II trial with 6-month PFS rate as the preliminary efficacy endpoint. We will conduct a single-arm 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. 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. 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.

Group II: Part 1B: Tebentafusp-tebn alone Active Control 1 Intervention

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.

Group III: Part 1B: Combination Active Control 2 Interventions

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.

Group IV: Part 2: Efficacy of Combo Active Control 2 Interventions

To assess the efficacy of tebentafusp-tebn in sequence with TACE in HLA-A\*0201-positive patients with metastatic uveal melanoma to the liver

Who Is Running the Clinical Trial?

Thomas Jefferson University

Lead Sponsor

Trials

475

Recruited

189,000+

Dr. Eugene Kennedy

Thomas Jefferson University

Chief Medical Officer since 2020

MD

Dr. Joseph G. Cacchione

Thomas Jefferson University

Chief Executive Officer since 2022

MD, MBA

Sidney Kimmel Cancer Center at Thomas Jefferson University

Collaborator

Trials

164

Recruited

10,900+

Dr. Andrew Chapman

Sidney Kimmel Cancer Center at Thomas Jefferson University

Chief Executive Officer since 2022

Bachelor's degree from the University of Pennsylvania; D.O. from the University of Health Sciences College of Osteopathic Medicine in Kansas City, Missouri

Dr. Baligh R. Yehia

Sidney Kimmel Cancer Center at Thomas Jefferson University

Chief Medical Officer

MD, institution not specified