Tebentafusp for Eye Cancer

Recruiting at 1 trial location

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how well the drug tebentafusp can shrink tumors in patients with uveal melanoma before surgery or radiation. The drug helps the body's immune system attack cancer cells. The goal is to reduce tumor size, prevent cancer from spreading, and possibly avoid removing the entire eye. Suitable candidates for this trial have uveal melanoma that cannot be completely removed without taking out the eye and have not received previous treatments for this condition. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that tebentafusp is likely to be safe for humans?

Research has shown that tebentafusp is generally safe for patients. In a study of 410 people with uveal melanoma, common side effects included skin rash and fever. Most side effects were mild and easily managed. Tebentafusp is approved for use in cases of uveal melanoma that cannot be surgically removed or have spread, indicating its safety. While some side effects are common, they are usually not serious and can often be treated. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for eye cancer?

Unlike the standard treatments for uveal melanoma, which often involve surgery or radiation, Tebentafusp offers a different approach by using a novel mechanism of action. Tebentafusp is a bispecific fusion protein that targets a specific protein on melanoma cells, directing the body's own immune system to attack the cancer. Researchers are excited because this targeted action could lead to more effective treatment outcomes with potentially fewer side effects compared to traditional therapies. Additionally, Tebentafusp's ability to be administered as a systemic therapy means it might also help treat microscopic disease that surgery can't reach.

What is the effectiveness track record for tebentafusp in treating uveal melanoma?

Studies have shown that tebentafusp effectively treats uveal melanoma, a type of eye cancer. Research indicates that it can extend patients' lives by destroying cancer cells. Tebentafusp links melanoma cells with immune cells called T-cells, which then kill the cancer cells. In previous research, patients with uveal melanoma who received tebentafusp lived longer than those who received other standard treatments. In this trial, participants with locally advanced, unresectable primary uveal melanoma will receive neoadjuvant tebentafusp. This treatment is already approved for uveal melanoma that cannot be surgically removed, demonstrating its effectiveness in fighting this cancer. ^{3 4 6 7 8}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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-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]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2304753

Three-Year Overall Survival with Tebentafusp in Metastatic ... The 1-year overall survival percentages of 52% and 56% in two single-group phase 2 studies of ipilimumab plus nivolumab as first-line treatment ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37870955/

Three-Year Overall Survival with Tebentafusp in Metastatic ... This 3-year analysis supported a continued long-term benefit of tebentafusp for overall survival among adult HLA-A*02:01-positive patients.

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 ...

4. 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 ...

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa2103485

Overall Survival Benefit with Tebentafusp in Metastatic ... Treatment with tebentafusp resulted in longer overall survival than the control therapy among previously untreated patients with metastatic uveal melanoma.

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

Pooled Safety Analysis of 410 patients Incidence and Management of Adverse Events Associated with Tebentafusp Treatment in Metastatic Uveal Melanoma: Pooled Safety Analysis of 410 patients. Clin ...

7. kimmtrak.com kimmtrak.com/

KIMMTRAK® (tebentafusp-tebn) - Official Website KIMMTRAK is a prescription medicine used to treat HLA-A*02:01–positive adults with uveal melanoma that cannot be removed by surgery or has spread.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11249029/

Efficacy and safety of tebentafusp in patients with metastatic ... Tebentafusp exhibits promising treatment outcomes for mUM patients. Although accompanied with a common occurrence of adverse events, which can typically be ...