Tebentafusp for Eye Cancer

Overseen By Rino Seedor, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Thomas Jefferson University

Must not be taking: Antibiotics

Disqualifiers: Metastatic disease, Cardiac disease, HIV, 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: 6

Duration: 8 weeks

19 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that all other medical conditions must be well-managed and stable for at least 28 days before starting the study drug, so it's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Tebentafusp for eye cancer?

Tebentafusp has been shown to improve overall survival and progression-free survival in patients with metastatic uveal melanoma, a type of eye cancer, compared to other treatments like pembrolizumab, ipilimumab, or dacarbazine. It is the first drug approved by the FDA for this condition, demonstrating significant survival benefits in clinical trials. ^{1 2 3 4 5}

How is the drug tebentafusp unique for treating eye cancer?

Tebentafusp is unique because it is the first drug in a new class called ImmTACs, which specifically targets a protein called Gp-100 on uveal melanoma cells and activates the immune system to attack these cancer cells. Unlike other treatments, it has shown improved survival rates in patients with metastatic uveal melanoma, a condition with limited effective treatment options. ^{1 2 4 6 7}

What is the purpose of this trial?

This phase II trial tests how well tebentafusp works to shrink tumors prior to primary treatment with surgery or radiation in patients with uveal (eye) melanoma that has spread to nearby tissue or lymph nodes (locally advanced) or that cannot be removed by surgery (unresectable). Tebentafusp is a drug that binds to melanoma tumor cells as well as immune cells called T-cells. This binding causes an immune response against the melanoma cells, which leads to tumor cell death. Tebentafusp has been approved for the treatment of locally advanced and unresectable uveal melanoma. Giving tebentafusp before primary treatment with surgery or radiation may help shrink the tumor, prevent the disease from spreading, or reduce the likelihood that patients will require total eye removal (called enucleation).

Eligibility Criteria

This trial is for patients with uveal melanoma, a type of eye cancer that has spread locally or can't be removed surgically. Participants should have tumors suitable for shrinkage before surgery or radiation.

Inclusion Criteria

Predicted life expectancy of at least 12 weeks as estimated by investigator

Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule

All other relevant medical conditions must be well-managed and stable, in the opinion of the investigator, for at least 28 days prior to first administration of study drug

Exclusion Criteria

I need urgent eye surgery due to my melanoma.

I am currently on antibiotics for an infection.

Patients with any out-of-range laboratory values

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive tebentafusp intravenously over 15-20 minutes on days 1, 8, 15, and 22 of each cycle, repeating every 28 days for up to 2 cycles

8 weeks

4 visits per cycle (in-person)

Primary Eye Treatment

Within 28 days of the last dose of tebentafusp, patients undergo standard of care primary eye treatment (plaque radiotherapy or eye enucleation)

4 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after primary eye treatment, with follow-up at 3 months and then every 3 months for up to 5 years

5 years

Quarterly visits (in-person)

Treatment Details

Interventions

• Tebentafusp

Trial Overview The trial tests tebentafusp's effectiveness in shrinking uveal melanoma tumors before the main treatment. Tebentafusp stimulates an immune response to kill tumor cells and may reduce disease spread or the need for total eye removal.

Participant Groups

Group I: Neoadjuvant Tebentafusp in Patients Locally Advanced, Unresectable Primary Uveal Melanoma Experimental Treatment 1 Intervention

Tebentafusp administration: 20mcg on Day 1, 30mcg on Day 8, 68 mcg on Day 15, and weekly doses of 68 mcg thereafter. Eye evaluations including clinical examination, ophthalmic ultrasound, optical coherence tomography, and wide-angle fundus imaging will be performed at baseline, Cycle 1 day 1, Cycle 1 day 8, Cycle 2 day 1, prior to definitive treatment for primary uveal melanoma (post-Tebentafusp), and at post-eye treatment evaluation at 3 months. Additionally optical coherence tomography angiography, autofluorescence, fluorescein angiography and MRI orbit will be performed at baseline, post-tebentafusp, and at post-eye treatment evaluation. Blood circulating tumor-derived DNA will be performed at baseline, Cycle 2 day 1, post-Tebentafusp, and at post-eye treatment evaluation at 3 months. Primary eye tumor biopsy (collected by fine-needle aspiration) and aqueous circulating tumor-derived DNA will be performed at baseline and post-Tebentafusp.

Who Is Running the Clinical Trial?

Thomas Jefferson University

Lead Sponsor

Trials

475

Recruited

189,000+

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, a novel bispecific protein targeting the Gp-100 protein in uveal melanoma, has shown an overall survival benefit in a recent phase III trial for patients with untreated metastatic uveal melanoma.

Unlike traditional treatments for cutaneous melanoma, tebentafusp effectively creates an immune response against tumor cells by targeting a specific peptide presented by HLA*A0201, highlighting its unique mechanism of action in this rare cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gp-100 as a Novel Therapeutic Target in Uveal Melanoma. Martinez-Perez, D., Viñal, D., Solares, I., et al.[2021]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

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

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

Phase I Study of Safety, Tolerability, and Efficacy of Tebentafusp Using a Step-Up Dosing Regimen and Expansion in Patients With Metastatic Uveal Melanoma. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Gp-100 as a Novel Therapeutic Target in Uveal Melanoma. [2021]

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

First Drug Approved for Rare Eye Cancer. [2022]

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

Tebentafusp: First Approval. [2023]

7. 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]