Tebentafusp-tebn for Uveal Melanoma

Overseen By Carolyn Palumbo

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Thomas Jefferson University

Must not be taking: Systemic steroids, Immunosuppressives

Disqualifiers: CNS metastases, HIV, Hepatitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

109 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of a new treatment, tebentafusp-tebn, for individuals with uveal melanoma that has spread to the liver. The study consists of two parts: one examines the treatment combined with liver-directed therapies for smaller liver tumors, while the other tests the treatment with a different liver therapy for larger tumors. Suitable candidates are those with metastatic uveal melanoma in the liver who are HLA-A*0201 positive, a specific genetic marker. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking cancer research.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, you cannot participate if you are on systemic steroid therapy or any immunosuppressive medication, and you must not have used investigational drugs within 28 days before starting the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that tebentafusp-tebn yields promising results for treating metastatic uveal melanoma, though it often comes with some common side effects. In earlier studies, patients taking tebentafusp-tebn lived longer overall. Importantly, these studies did not identify any new safety issues, which is reassuring.

Tebentafusp-tebn has been tested in various situations, including in patients who had already tried other treatments and those who had not. The safety in real-life use mirrored what was observed in clinical trials. While side effects are common, they are usually manageable and expected with this kind of treatment.

Overall, evidence suggests that tebentafusp-tebn is safe for use in people, though participants may experience some side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for uveal melanoma, which may include surgery, radiation therapy, or systemic chemotherapy, tebentafusp-tebn offers a unique approach by using a bispecific protein that targets gp100, a melanoma-associated antigen, and redirects T cells to attack the tumor cells. Researchers are excited about tebentafusp-tebn because it harnesses the body's immune system to specifically target melanoma cells, potentially offering a more precise and effective treatment. Additionally, tebentafusp-tebn is designed to work in combination with hepatic immunoembolization (IE), potentially enhancing its effectiveness against liver metastases in uveal melanoma, which is a common and challenging complication in this condition.

What evidence suggests that this trial's treatments could be effective for uveal melanoma?

Studies have shown that tebentafusp-tebn yields promising results for treating metastatic uveal melanoma, a type of eye cancer that has spread. It significantly improved survival rates in patients with this cancer, particularly those with the genetic marker HLA-A*02:01. In this trial, participants will receive either tebentafusp-tebn alone or in combination with hepatic IE. Research indicates that tebentafusp-tebn is now a standard treatment for this condition due to its effectiveness. Additionally, it is the first approved treatment to clearly extend patients' lives. These findings suggest that tebentafusp-tebn could effectively treat metastatic uveal melanoma. ^{1 2 4 5 6}

Who Is on the Research Team?

Rino Seedor, MD

Principal Investigator

Thomas Jefferson University

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment - Part 1A

Phase I safety lead-in with tebentafusp-tebn and hepatic IE for patients with low to moderate hepatic disease burden

4 weeks (Cycle 1) + subsequent cycles

Weekly visits for treatment

Treatment - Part 1B

Randomized phase II trial with tebentafusp-tebn in combination with hepatic IE or tebentafusp-tebn alone

6 months

Weekly visits for treatment

Treatment - Part 2

Efficacy assessment of tebentafusp-tebn in combination with TACE for patients with bulky hepatic disease

6 months

Weekly visits for treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2.5 years

What Are the Treatments Tested in This Trial?

Interventions

• Tebentafusp-Tebn

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.

How Is the Trial Designed?

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. 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

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+

Sidney Kimmel Cancer Center at Thomas Jefferson University

Collaborator

Trials

164

Recruited

10,900+

Published Research Related to This Trial

Tebentafusp-tebn is the first drug in the ImmTAC class of T cell-directed therapies and has shown improved overall survival and progression-free survival in patients with metastatic uveal melanoma compared to standard treatments like pembrolizumab and ipilimumab.

The drug has been approved by the US Food and Drug Administration as a first-line therapy specifically for HLA-A*02:01-positive patients, highlighting its targeted approach in treating this aggressive form of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tebentafusp-tebn: A Novel Bispecific T-Cell Engager for Metastatic Uveal Melanoma. Hua, G., Carlson, D., Starr, JR.[2022]

Tebentafusp is the first drug approved by the FDA that has been shown to extend overall survival in patients with inoperable or metastatic uveal melanoma, a type of aggressive eye cancer.

It is also notable for being the first T-cell receptor therapy to be made available on the market, representing a significant advancement in cancer treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First Drug Approved for Rare Eye Cancer. [2022]

Tebentafusp is a groundbreaking bispecific T cell engager that targets HLA-A*02:01-positive uveal melanoma cells, activating T cells to attack and destroy tumor cells, demonstrating its mechanism of action in cancer treatment.

In January 2022, tebentafusp became the first approved treatment for adults with unresectable or metastatic uveal melanoma in the USA, with ongoing regulatory reviews in other countries, highlighting its significance in melanoma therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tebentafusp: First Approval. Dhillon, S.[2023]

In a phase 3 trial involving 378 patients with metastatic uveal melanoma, treatment with tebentafusp led to a significant increase in overall survival at 1 year (73%) compared to the control group (59%), demonstrating its efficacy as a new treatment option.

Tebentafusp was associated with manageable treatment-related adverse events, primarily cytokine-mediated and skin-related, which decreased in severity after initial doses, indicating a favorable safety profile with no treatment-related deaths reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overall Survival Benefit with Tebentafusp in Metastatic Uveal Melanoma. Nathan, P., Hassel, JC., Rutkowski, P., et al.[2022]

Tebentafusp is the first approved treatment for HLA-A*02:01 metastatic uveal melanoma, showing improved overall survival compared to standard treatment options, making it a significant advancement in cancer therapy.

The treatment has a manageable safety profile, with key adverse events including cytokine release syndrome and skin-related issues, necessitating careful monitoring and pre-treatment hydration to mitigate risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Practical guidelines for the management of adverse events of the T cell engager bispecific tebentafusp. Hassel, JC., Berking, C., Forschner, A., et al.[2023]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2304753

Three-Year Overall Survival with Tebentafusp in Metastatic ... Tebentafusp has shown promising results with respect to survival in phase 1–2 studies of previously treated metastatic uveal melanoma, with ...

2. jitc.bmj.com jitc.bmj.com/content/12/6/e009028

Long-term survival follow-up for tebentafusp in previously ... Tebentafusp, a bispecific (gp100×CD3) ImmTAC, significantly improved overall survival (OS) outcomes for HLA-A*02:01+ adult patients with untreated metastatic ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11249029/

Efficacy and safety of tebentafusp in patients with metastatic ... Although local treatment of primary uveal melanoma can achieve 5-y survival in up to 85% of cases, more than 50% patients will ultimately ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e21533

Tebentafusp in metastatic uveal melanoma patients Tebentafusp has become a standard of care for metastatic uveal melanoma patients positive for HLA-A*02:01 after the results of the phase III trial.

5. sciencedirect.com sciencedirect.com/science/article/pii/S0959804925004162

Real-life data on tebentafusp in metastatic uveal ... Tebentafusp is the first approved systemic therapy with overall survival (OS) benefit in HLA-A*02:01-positive patients with metastatic uveal melanoma (mUM). We ...

6. esmoopen.com esmoopen.com/article/S2059-7029(25)00365-5/fulltext

How we treat patients with metastatic uveal melanoma In a post hoc OS analysis, patients who received tebentafusp treatment beyond progression presented longer OS without new safety signals.