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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial evaluates the effectiveness and safety of combining Tebentafusp (also known as Kimmtrak or IMCgp100) with Yttrium-90 (Y-90) radioembolization for treating uveal melanoma that has spread to the liver. Uveal melanoma is a type of eye cancer that often metastasizes to the liver. Participants will first receive Y-90 radioembolization, followed by weekly Tebentafusp therapy for up to two years. Suitable candidates have uveal melanoma primarily in the liver and can provide consent. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant advancements in cancer treatment.

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.

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

Research has shown that Tebentafusp has been studied in people with advanced uveal melanoma. Safety data from 410 patients highlight some risks. The main side effects include cytokine release syndrome (a reaction where the immune system releases too many proteins into the blood), skin reactions, and changes in liver function tests.

Yttrium-90 (Y-90) radioembolization, when combined with other treatments, has proven to be safe and effective. Studies suggest it works well with immunotherapy and does not cause major safety concerns.

Overall, these treatments have been tested in people and have a known safety profile. Participants in previous studies demonstrated that these treatments can be well-tolerated, though they do come with some risks. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for uveal melanoma, which typically include surgery, radiation, and chemotherapy, Tebentafusp offers a novel approach. Tebentafusp works by engaging the immune system to specifically target and attack melanoma cells, using a mechanism that combines a T-cell receptor with an anti-CD3 effector. This targeted approach is what sets Tebentafusp apart, potentially leading to more effective and precise treatment. Researchers are excited because this unique mechanism could improve outcomes for patients who have limited options with current therapies.

What evidence suggests that Tebentafusp combined with radioembolization could be effective for uveal melanoma?

Research has shown that Tebentafusp can extend the lives of patients with metastatic uveal melanoma. It proves effective for both new patients and those previously treated, making it a promising option. Studies suggest that Yttrium-90 (Y-90) radioembolization is a safe and effective treatment for cancer that has spread to the liver. In this trial, participants will receive a combination of Tebentafusp and Y-90 radioembolization, aiming to improve treatment outcomes, potentially extending survival and better controlling the disease. Overall, these treatments offer hope for managing metastatic uveal melanoma. ^{1 4 5 6 7}

Who Is on the Research Team?

Lynn Feun

Principal Investigator

University of Miami

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

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 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 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]

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, 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]

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. clinicaltrials.gov clinicaltrials.gov/study/NCT03070392

NCT03070392 | Safety and Efficacy of IMCgp100 Versus ... This Phase II study is designed to evaluate the safety and efficacy of IMCgp100 compared with Investigator's Choice (dacarbazine, ipilimumab or pembrolizumab)

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40680464/

Real-life data on tebentafusp in metastatic uveal ... Tebentafusp is safe for pre-treated and treatment-naive patients with mUM in real-life. Treatment effect was observed in patients treated ...

5. kimmtrak.com kimmtrak.com/why-kimmtrak/

KIMMTRAK clinical trial results (primary) In the clinical trial, most rashes got better or went away with time. Metastatic uveal melanoma cells are similar to your skin cells. In an effort to fight your ...

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

Real-life data on tebentafusp in metastatic uveal ... The recently published 3-year efficacy and safety results of the IMCgp100–202 randomized trial showed a long-term confirmed OS benefit of tebentafusp in ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40938927/

Pooled Safety Analysis of 410 patients AEs of special interest (AESIs) included cytokine release syndrome (CRS), acute skin reactions (ASR), and liver function test (LFT) elevations.