Tebentafusp for Uveal Melanoma

Overseen By Danielle L Bednarz, RN, BSN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Diwakar Davar

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: Cardiac disease, CNS metastases, 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: 12 weeks

44 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called tebentafusp (also known as Kimmtrak or IMCgp100) for individuals with metastatic uveal melanoma, a type of eye cancer that has spread beyond the eye. Researchers aim to evaluate the effectiveness of this treatment in patients who have not received prior treatment for their advanced cancer. Participants must have a specific genetic marker (HLA-A*0201) and should not have previously tried certain cancer therapies. The trial seeks to determine if tebentafusp can improve outcomes for these patients. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot be on systemic steroid therapy or any other immunosuppressive medication, as these may interfere with the study treatment. Local steroid therapies are acceptable.

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

Research has shown that tebentafusp, the treatment under study, has undergone testing in several previous studies. A combined analysis of 410 patients from three different studies provided important safety information. Most patients tolerated the treatment well, though some experienced common side effects, including skin reactions and flu-like symptoms, such as fever and chills.

Additionally, long-term safety data from other studies have indicated that these side effects can be managed. The treatment has been used in various trials, and its use in metastatic uveal melanoma (a type of eye cancer) has been linked to a survival benefit. This suggests that while some side effects exist, tebentafusp is considered safe enough for further study in clinical trials. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Tebentafusp is unique because it targets a specific protein called gp100 that's present on uveal melanoma cells. Unlike traditional treatments for uveal melanoma, which often include surgery, radiation, or chemotherapy, Tebentafusp is a bispecific T-cell engager. This means it helps the body's immune system recognize and attack the cancer cells directly. Researchers are excited about Tebentafusp because it represents a new way to harness the immune system, offering hope for improved outcomes in this challenging type of eye cancer.

What evidence suggests that tebentafusp might be an effective treatment for uveal melanoma?

Research has shown that tebentafusp yields promising results for treating metastatic uveal melanoma, a type of eye cancer that has spread. Studies have found that it extends patients' lives. Tebentafusp boosts the immune system to find and attack cancer cells. In past studies, patients who received tebentafusp lived longer than those who received other treatments. This treatment offers hope by enhancing the body's natural ability to fight cancer. ^{1 2 5 6 7}

Who Is on the Research Team?

Diwakar Davar, MD

Principal Investigator

UPMC Hillman Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with untreated metastatic uveal melanoma who are HLA-A*0201 positive and have not had systemic therapy for advanced cancer. They must be willing to undergo a ctDNA test, have a life expectancy over 6 months, and an ECOG status of 0 or 1. Excluded are those with severe allergies to biologics, certain heart conditions, active brain metastases, uncontrolled HIV/HBV/HCV infections, recent major surgery or radiotherapy.

Inclusion Criteria

My blood test shows I am HLA-A*0201 positive.

I haven't had chemotherapy or targeted therapy for my advanced cancer.

My eye melanoma has spread and hasn't been treated yet.

Exclusion Criteria

Pregnant, likely to become pregnant, or lactating women

I do not have uncontrolled HIV, HBV, or HCV.

I have not had radiotherapy in the last 2 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive tebentafusp with an intra-patient escalation regimen starting at 20 mcg, followed by 30 mcg, and then 68 mcg weekly on Day 1 of 12-week cycles

12 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Long-term follow-up

Participants are monitored for overall survival and progression-free survival

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Tebentafusp

Trial Overview The study tests Tebentafusp in patients with specific genetic makeup (HLA-A*0201) who haven't been treated before for their advanced eye melanoma. It's an open-label phase II trial where all participants receive the drug while also having their tumor DNA monitored.

How Is the Trial Designed?

Group I: Tebentafusp (IMCgp100) Experimental Treatment 1 Intervention

Dose: 20mcg W1D; 30mcg W2D1; 68mcg W3D1and subsequent doses Frequency: Weekly on D1 of 12-week cycles

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?

Diwakar Davar

Lead Sponsor

Trials

12

Recruited

420+

Immunocore Ltd

Industry Sponsor

Trials

17

Recruited

4,400+

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

Efficacy and safety of tebentafusp in patients with metastatic ... Although local treatment of primary uveal melanoma can achieve 5-y survival in up to 85% of cases, more than 50% patients will ultimately ...

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

Pooled Safety Analysis of 410 patients Purpose: We conducted an integrated safety analysis from three clinical studies of tebentafusp, a first-in-class ImmTAC bispecific T cell ...

7. 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 ...