Tebentafusp-tebn for Uveal Melanoma

Overseen By Tina Savio

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

Trial Summary

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.

What data supports the effectiveness of the drug Tebentafusp-tebn for uveal melanoma?

Tebentafusp-tebn has been shown to improve overall survival and progression-free survival in patients with metastatic uveal melanoma compared to other treatments like pembrolizumab, ipilimumab, or dacarbazine. In a study, the 1-year overall survival rate was 62% with a median overall survival of 16.8 months, indicating a significant benefit for patients. ^{1 2 3 4 5}

Is Tebentafusp-tebn safe for humans?

Tebentafusp-tebn can cause side effects like cytokine release syndrome (a condition where the immune system releases too many proteins into the blood too quickly) and skin-related issues, but these are manageable with proper care. It may also lead to tumor lysis syndrome (a potentially serious condition where cancer cells break down rapidly), but patients can recover fully with treatment. ^{1 5 6 7 8}

What makes the drug Tebentafusp-tebn unique for treating uveal melanoma?

Tebentafusp-tebn is unique because it is the first drug specifically approved for metastatic uveal melanoma, using a novel approach called ImmTAC, which engages T-cells to target and destroy cancer cells. It has shown improved survival rates compared to other treatments and is the first T-cell receptor therapy available for this condition. ^{1 2 4 5 9}

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.

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.

Timeline

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

Treatment Details

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.

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+

Sidney Kimmel Cancer Center at Thomas Jefferson University

Collaborator

Trials

164

Recruited

10,900+

Findings from Research

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 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]

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 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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Tebentafusp-tebn: A Novel Bispecific T-Cell Engager for Metastatic Uveal Melanoma. [2022]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Tebentafusp: First Approval. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Clinical and molecular response to tebentafusp in previously treated patients with metastatic uveal melanoma: a phase 2 trial. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

First Drug Approved for Rare Eye Cancer. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Tebentafusp in advanced uveal melanoma: proof of principle for the efficacy of T-cell receptor therapeutics and bispecifics in solid tumors. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Tumor lysis syndrome induced by tebentafusp. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Tebentafusp in Patients with Metastatic Uveal Melanoma: A Real-Life Retrospective Multicenter Study. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Practical guidelines for the management of adverse events of the T cell engager bispecific tebentafusp. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Overall Survival Benefit with Tebentafusp in Metastatic Uveal Melanoma. [2022]