Study on Tebentafusp and Liver Radiotherapy for Patients with Metastatic Uveal Melanoma HLA A*02:01 Positive

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What is this study about?

This study examines the effectiveness of adding hepatic radiotherapy (radiation therapy directed at the liver) to the standard treatment with tebentafusp for patients with metastatic uveal melanoma that is HLA A*02:01 positive. Metastatic uveal melanoma is a rare form of eye cancer that has spread to other parts of the body, particularly the liver. The HLA A*02:01 refers to a specific genetic marker present in these patients that makes them eligible for this treatment approach.

The purpose of this study is to investigate whether adding liver-directed radiation therapy to standard treatment can prolong the time before the cancer progresses. Patients will receive the established treatment with tebentafusp (a medication that helps the immune system recognize and attack cancer cells) along with radiation therapy specifically targeting the liver metastases (cancer that has spread to the liver).

Throughout the study, patients will undergo regular assessments to monitor how their cancer responds to treatment, how long the treatment remains effective, and what side effects may occur. The study will also collect blood samples to analyze circulating tumor DNA and immune markers to better understand how the treatment affects the cancer at a molecular level.

1 Screening and Eligibility Confirmation

You will undergo testing to confirm your HLA-A*02:01 positive metastatic uveal melanoma (a type of eye cancer that has spread) with liver metastases.

The medical team will verify that you meet all requirements, including having at least one measurable liver lesion no larger than 8 cm, and adequate bone marrow, kidney, and liver function.

You must be 18 years or older with an ECOG performance status of 0 or 1 (able to perform most daily activities).

2 Treatment with Tebentafusp and Liver-Directed Therapy

You will receive tebentafusp, which is the standard treatment for this type of cancer.

In addition to the standard treatment, you will receive hepatic radiotherapy (radiation therapy directed at the liver).

The purpose of adding liver-directed therapy to the standard treatment is to potentially prolong the time before the disease progresses.

3 Regular Monitoring and Assessments

Throughout the trial, you will have regular medical assessments to monitor your response to treatment.

These assessments will include imaging scans to measure tumor size and blood tests to check your overall health status.

The first tumor assessment will evaluate whether the treatment is controlling your disease.

4 Continuation of Treatment

You will continue receiving the treatment until your disease progresses, you experience unacceptable side effects, or you decide to withdraw from the study.

During this time, ongoing assessments will track how your cancer responds to treatment.

5 Follow-up Period

After completing treatment, you will enter a follow-up period where your health will continue to be monitored.

The medical team will track your progression-free survival (time from treatment start until the disease progresses) with special interest in the 6-month mark.

Other measurements include overall survival, response to treatment, and time until you might need another type of treatment.

6 Additional Research

Blood samples will be collected to analyze your circulating immune profile and inflammatory markers.

The study will also analyze ctDNA (circulating tumor DNA, which is genetic material from tumor cells found in your bloodstream) to correlate with your outcomes.

Who Can Join the Study?

You must have metastatic uveal melanoma (a type of eye cancer that has spread to other parts of the body) that is HLA-A*02:01 positive (a specific genetic marker)
You must have liver metastases (cancer that has spread to the liver), with at least one measurable tumor according to specific criteria
Your largest liver tumor must be 8 cm or smaller
You must be 18 years or older
You can be female or male
You must have good overall physical function (ECOG score of 0 or 1)
You must have adequate bone marrow function (healthy blood cell production)
You must have adequate kidney function (based on specific blood test values)
You must have adequate liver function (based on specific blood test values)
You must be willing and able to follow the study protocol
You must provide written informed consent
If you are a woman who can become pregnant, you must have a negative pregnancy test within 24 hours before starting the study
If you are a woman who can become pregnant or a man with a female partner who can become pregnant, you must use effective birth control during the study and for at least 1 week after the last treatment

Who Cannot Join the Study?

Previous treatment with immunotherapies targeting the MAGE A3, MAGE A4, MAGE A10, NYESO-1, or gp100 proteins (these are specific types of proteins targeted in certain cancer treatments)
Prior treatment with certain liver-directed therapies, including hepatic artery infusion (a way to deliver medicine directly to the liver) or radioembolization (a procedure that delivers radiation directly to liver tumors)
Active autoimmune disease requiring systemic treatment in the past 2 years (conditions where your immune system attacks your own body’s tissues)
History of severe immune-related side effects from previous immunotherapy treatments
Uncontrolled brain metastases (cancer that has spread to the brain and is not under control)
Significant heart disease including heart failure, heart attack within 6 months, or uncontrolled high blood pressure
Serious infections requiring treatment
Pregnant or breastfeeding women
Known HIV, hepatitis B, or hepatitis C infection (specific viral infections)
Unable to understand or comply with study procedures

Where you can join this trial?

Verified and Recommended Sites

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Verified Sites

Site Name	City	Country	Status
Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Rome	Italy

Other Sites

No sites found in this category

Trial status

Country	Status	Recruitment Start
Italy	Recruiting	01.07.2025

Trial locations

Investigated drugs:

Tebentafusp

Tebentafusp is a medication that helps the immune system recognize and attack cancer cells. It is specifically designed for patients with uveal melanoma (a type of eye cancer) that has spread to other parts of the body. Tebentafusp works by connecting T cells (a type of immune cell) to cancer cells, which helps the immune system find and destroy the cancer.

Hepatic radiotherapy is a treatment that uses radiation to target cancer in the liver. This approach directs radiation specifically to liver tumors while trying to minimize damage to healthy liver tissue. For patients with uveal melanoma that has spread to the liver, this targeted radiation therapy aims to control or reduce the liver tumors.

Investigated diseases:

Uveal melanoma

Metastatic Uveal Melanoma – A condition that occurs when uveal melanoma, a rare cancer that originates in the eye’s uveal tract (iris, ciliary body, and choroid), spreads beyond the eye to other parts of the body, most commonly the liver. The disease typically begins as a primary tumor in the eye, which can grow and eventually shed cancer cells that travel through the bloodstream. These cells can then establish new tumors in distant organs, marking the metastatic stage of the disease. Metastatic uveal melanoma progresses when these secondary tumors grow and multiply in the affected organs. The disease often develops silently, with metastases sometimes appearing years after treatment of the primary eye tumor.

Trial ID:

2024-519760-40-00

Protocol code:

TEBE-RT

Trial Phase:

Therapeutic exploratory (Phase II)

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Study on Tebentafusp and Liver Radiotherapy for Patients with Metastatic Uveal Melanoma HLA A*02:01 Positive

What is this study about?

Who Can Join the Study?

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