Tebentafusp + Radioembolization for Uveal Melanoma

Overseen By Benjamin Spieler, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Miami

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: Large tumors, Cardiac disease, CNS metastases, Active infections, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

30 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on steroids or immunosuppressive drugs, you may need to stop them at least 2 weeks before starting the trial, unless they are for certain conditions like well-controlled asthma or adrenal insufficiency.

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

Tebentafusp 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 clinical trials, it demonstrated a 1-year overall survival rate of 73% and a disease control rate of 46%. ^{1 2 3 4 5}

What makes the drug Tebentafusp unique for treating uveal melanoma?

Tebentafusp is unique because it is the first drug in a new class called ImmTAC, which uses a special mechanism to engage T-cells (a type of immune cell) to target and kill cancer cells in uveal melanoma. It is specifically designed for patients with a certain genetic marker (HLA-A*02:01) and has shown improved survival rates compared to other treatments. ^{1 2 3 4 6}

What is the purpose of this trial?

The purpose of this study is to determine the effects (good and bad) that Tebentafusp in combination with Yttrium-90 (Y-90) radioembolization has on patients with metastatic uveal melanoma that has spread to the liver.

Research Team

Lynn Feun

Principal Investigator

University of Miami

Eligibility Criteria

This trial is for individuals with metastatic uveal melanoma, specifically where the cancer has spread to the liver. Participants should meet certain health standards but specific inclusion and exclusion criteria are not listed.

Inclusion Criteria

Serum bilirubin <2 mg/dl, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 5 x upper limit of normal (ULN)

Ability to provide and understand written informed consent

My cancer can be measured by standard health tests.

Exclusion Criteria

My tumor is larger than 8 cm.

I am unable to make my own medical decisions.

Total bilirubin > 1.5 × ULN, except for patients with Gilbert's syndrome, who are excluded if total bilirubin > 3.0 × ULN or direct bilirubin > 1.5 × ULN

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radioembolization

Participants are administered Yttrium 90 Trans-Arterial Radioembolization (Y90 TARE) therapy, followed by a 14 to 28 day recovery period

2-4 weeks

Treatment

Participants receive Tebentafusp once weekly during every 28-day cycle, for up to 24 months or 24 cycles

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Treatment Details

Interventions

• Tebentafusp
• TheraSphere™ Yttrium-90 Trans-Arterial Radioembolization

Trial Overview The study investigates the combined effect of Tebentafusp (a medication) and TheraSphere™ Yttrium-90 radioembolization (a type of radiation therapy delivered directly into the liver's blood vessels) on patients with liver-spread eye melanoma.

Participant Groups

Group I: Tebentafusp in combination with Radioembolization Group Experimental Treatment 2 Interventions

Participants in this group will first be administered Yttrium 90 Trans-Arterial Radioembolization (Y90 TARE) therapy, followed by a 14 to 28 day recovery period. Participants will then be administered Tebentafusp once weekly during every 28-day cycle. Participants may receive up to 24 months or 24 cycles of Tebentafusp therapy. Total participation is about 3 years.

Tebentafusp is already approved in United States, European Union for the following indications:

Approved in United States as Kimmtrak for:

• Unresectable or metastatic uveal melanoma in HLA-A*02:01-positive adults

Approved in European Union as Kimmtrak for:

• Unresectable or metastatic uveal melanoma in HLA-A*02:01-positive adults

Who Is Running the Clinical Trial?

University of Miami

Lead Sponsor

Trials

976

Recruited

423,000+

Immunocore Ltd

Industry Sponsor

Trials

17

Recruited

4,400+

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, approved by the FDA for treating unresectable or metastatic uveal melanoma, activates T cells to induce tumor cell death, showing a 1-year overall survival rate of 73% in Phase III trials with a disease control rate of 46%.

Common side effects include cytokine release syndrome and rash, but the drug's unique mechanism offers a promising alternative for patients with limited treatment options and poor prognosis in this specific type of melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tebentafusp: a novel drug for the treatment of metastatic uveal melanoma. Wang, Z., Xie, Y., Wang, JQ., et al.[2023]

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]

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 a novel immunotherapy that effectively targets metastatic uveal melanoma by redirecting T cells to attack cancer cells, showing promising early survival data compared to historical outcomes.

The treatment has manageable and usually transient side effects, making it a potentially safer option for patients who do not respond to traditional therapies like kinase inhibitors and immune checkpoint inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tebentafusp: T Cell Redirection for the Treatment of Metastatic Uveal Melanoma. Damato, BE., Dukes, J., Goodall, H., et al.[2023]

Tebentafusp is a groundbreaking immunotherapy that targets a specific protein in uveal melanoma, showing significant efficacy as the first bispecific T-cell engager for advanced solid cancers.

It is the first anti-cancer treatment to demonstrate an overall survival benefit in patients with uveal melanoma, marking a significant advancement in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tebentafusp: a first-in-class treatment for metastatic uveal melanoma. Howlett, S., Carter, TJ., Shaw, HM., et al.[2023]

References

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

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

2. Spain pubmed.ncbi.nlm.nih.gov

Tebentafusp: a novel drug for the treatment of metastatic uveal melanoma. [2023]

3. England pubmed.ncbi.nlm.nih.gov

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

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

Tebentafusp: First Approval. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Tebentafusp: T Cell Redirection for the Treatment of Metastatic Uveal Melanoma. [2023]

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

Tebentafusp: a first-in-class treatment for metastatic uveal melanoma. [2023]