IMCgp100 for Uveal Melanoma

Not currently recruiting at 72 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Immunocore Ltd

Must not be taking: Systemic steroids, Immunosuppressives

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

Compensation: Varies

Number of Visits: 1

Duration: up to 36 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness of a new treatment, IMCgp100, for individuals with advanced uveal melanoma (a type of eye cancer) who have not received prior treatment. It compares IMCgp100 to standard treatments like dacarbazine (a chemotherapy drug), ipilimumab, and pembrolizumab to determine which is more effective in extending patient survival. Suitable candidates are adults with metastatic uveal melanoma who have not yet begun treatment for their advanced condition. Participants must have a specific genetic marker (HLA-A*0201) to enroll. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

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

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

Research has shown that IMCgp100, also known as tebentafusp or Kimmtrak, has been studied for safety. A study of 410 patients found that this treatment is generally well-tolerated. The most common side effects were skin reactions and fever, mostly mild to moderate. Serious side effects occurred in some cases but were less common.

Ipilimumab and pembrolizumab have been used for other cancers and have well-known safety records. They can cause side effects when the immune system attacks normal organs, but these are often manageable with prompt treatment.

Dacarbazine is another option that has been used for a long time. It can cause side effects like nausea and tiredness, but these are generally known and manageable.

Each of these treatments has its own safety profile. Participants should discuss potential risks with their healthcare provider to understand what might be best for them. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

IMCgp100, also known as tebentafusp or Kimmtrak, is unique because it uses a novel mechanism that combines a T cell receptor with an anti-CD3 single-chain variable fragment (scFV). This allows it to specifically target cancer cells in uveal melanoma patients, a feature not seen in traditional treatments like dacarbazine, ipilimumab, or pembrolizumab. Researchers are excited because IMCgp100 directly engages and redirects T cells to attack the melanoma cells, potentially offering a more targeted and effective approach compared to existing systemic therapies.

What evidence suggests that this trial's treatments could be effective for uveal melanoma?

Research has shown that IMCgp100, also known as tebentafusp, holds promise for treating advanced uveal melanoma. Studies found it significantly improved survival rates in patients with untreated metastatic uveal melanoma who have the specific genetic marker HLA-A*02:01. Long-term data confirms that this treatment helps patients live longer. Additionally, most side effects, such as rashes, improved or resolved over time.

In this trial, participants will receive either IMCgp100 or one of the investigator's choice treatments, which include dacarbazine, ipilimumab, or pembrolizumab. While these other treatments are standard for melanoma, IMCgp100 has shown specific benefits for uveal melanoma, making it a strong option for combating advanced uveal melanoma. ^{4 6 7 8 9}

Who Is on the Research Team?

Immunocore Medical Information

Principal Investigator

Immunocore Ltd

Are You a Good Fit for This Trial?

Adults with advanced Uveal Melanoma (UM) who haven't had systemic or regional liver-directed therapy for metastatic UM can join. They must be HLA-A*0201 positive, have measurable disease, and a good performance status. Excluded are those on steroids/immunosuppressants, with certain medical histories like severe allergies to biologics or active infections requiring antibiotics.

Inclusion Criteria

Ability to provide and understand written informed consent prior to any study procedures

I've had initial treatment for my cancer when it was localized, aiming for a cure.

I haven't had any liver-targeted treatments like chemo, radiation, or embolization.

Exclusion Criteria

I do not have brain metastases needing steroids in the last 3 weeks.

I have not had major surgery within the last 2 weeks.

I have a history of adrenal insufficiency.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either IMCgp100 or Investigator's Choice treatment (dacarbazine, ipilimumab, or pembrolizumab) in cycles of 21 days

up to 36 months

Visits on Day 1 of every cycle, every other cycle to Cycle 5, every fourth cycle thereafter

Follow-up

Participants are monitored for safety and effectiveness after treatment

90 days after end of treatment

Long-term Follow-up

Participants are assessed for overall survival and progression-free survival

up to 5.5 years

What Are the Treatments Tested in This Trial?

Interventions

• Dacarbazine
• IMCgp100
• Ipilimumab
• Pembrolizumab

Trial Overview The trial is testing the effectiveness of IMCgp100 compared to other treatments (dacarbazine, ipilimumab, pembrolizumab) in improving survival rates for patients with advanced UM. Participants will be assigned to receive either IMCgp100 or one of the investigator's choice drugs.

How Is the Trial Designed?

Group I: IMCgp100 (tebentafusp, Kimmtrak) Experimental Treatment 1 Intervention

Biologic:IMCgp100 (Soluble gp 100-specific T cell receptor with anti - CD3 scFV: IMCgp100)

Group II: Investigator's Choice Active Control 3 Interventions

1 of 3 Investigator's Choice options: Systemic Dacarbazine 1 of 3 Investigator's Choice options: Systemic Ipilimumab 1 of 3 Investigator's Choice options: Systemic Pembrolizumab

Dacarbazine is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Dacarbazine for:

• Hodgkin lymphoma
• Melanoma
• Soft tissue sarcoma

Approved in European Union as Dacarbazine for:

• Hodgkin lymphoma
• Melanoma
• Soft tissue sarcoma

Approved in Canada as Dacarbazine for:

• Hodgkin lymphoma
• Melanoma
• Soft tissue sarcoma

Who Is Running the Clinical Trial?

Immunocore Ltd

Lead Sponsor

Trials

17

Recruited

4,400+

Published Research Related to This Trial

In a study involving 13 patients with metastatic uveal melanoma treated with ipilimumab, no objective tumor responses were observed, but some patients achieved stable disease, suggesting potential for further investigation.

The treatment was generally well-tolerated, with no severe non-immune adverse events reported, although 23% of patients experienced grade 3 immune-related adverse events that were manageable with steroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipilimumab in pretreated patients with metastatic uveal melanoma: safety and clinical efficacy. Danielli, R., Ridolfi, R., Chiarion-Sileni, V., et al.[2022]

In a study of 55 uveal melanoma specimens, 78.2% showed positive expression of the c-kit protein, indicating its potential role in this type of cancer.

Imatinib mesylate significantly reduced the proliferation and invasion of five human uveal melanoma cell lines in vitro, suggesting it could be an effective treatment option and warranting further clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of c-kit and imatinib mesylate in uveal melanoma. Pereira, PR., Odashiro, AN., Marshall, JC., et al.[2020]

Uveal melanoma, the most common eye cancer in adults, has a significant risk of metastasis, with up to 50% of patients developing metastases within 15 years after treatment of the primary tumor.

Current systemic therapies for uveal melanoma have limited efficacy, but ongoing research is exploring new candidate drugs, including bortezomib and MEK inhibitors, to improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New therapeutic agents in uveal melanoma. Velho, TR., Kapiteijn, E., Jager, MJ.[2012]

In a retrospective review of 15 patients with metastatic uveal melanoma treated with anti-PD-1 antibodies (pembrolizumab or nivolumab), the best response observed was stable disease in four patients, indicating limited efficacy as no objective responses were recorded.

The treatment was generally well tolerated, with manageable toxicity, and the median progression-free survival was 3 months, while the overall survival was 5 months, suggesting that while the therapy may not be highly effective, it can be safely administered.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-PD-1 antibodies in metastatic uveal melanoma: a treatment option? Bender, C., Enk, A., Gutzmer, R., et al.[2021]

Ipilimumab showed a best overall response rate (BORR) of 5.8% and a disease control rate (DCR) of 27% in patients with advanced melanoma, indicating some level of efficacy in this challenging population.

The treatment resulted in promising long-term survival rates, with 1- and 2-year survival rates of 47.2% and 32.8%, respectively, and a median overall survival of 10.2 months, while adverse events were primarily immune-related but manageable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of ipilimumab monotherapy in patients with pretreated advanced melanoma: a multicenter single-arm phase II study. O'Day, SJ., Maio, M., Chiarion-Sileni, V., et al.[2022]

Nivolumab, administered at 3 mg/kg with or without a peptide vaccine, was well tolerated and demonstrated a 25% response rate in patients with advanced melanoma, regardless of prior ipilimumab treatment.

The study suggests that nivolumab can induce long-lasting responses, with some patients responding for up to 140 weeks, and highlights the potential for combining or sequencing nivolumab with ipilimumab for better treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, efficacy, and biomarkers of nivolumab with vaccine in ipilimumab-refractory or -naive melanoma. Weber, JS., Kudchadkar, RR., Yu, B., et al.[2022]

In a nationwide study of patients with metastatic uveal melanoma (UM), the introduction of immune checkpoint inhibitors (ICI) as first-line treatment significantly improved overall survival rates, increasing from 25.0% to 41.9% one year after treatment.

Despite relatively low response rates (7% for anti-PD-1 monotherapy and 21% for combined therapy), median overall survival improved from 7.8 months to 10.0 months, indicating that ICI therapy offers a meaningful benefit for patients with metastatic UM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Impact of Immune Checkpoint Inhibitors in Metastatic Uveal Melanoma. Bol, KF., Ellebaek, E., Hoejberg, L., et al.[2020]

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11163599/

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. 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. 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 ...

6. kimmtrakhcp.com kimmtrakhcp.com/safety/

KIMMTRAK Safety Information for HCPs - Learn More Uncertain about KIMMTRAK efficacy and safety? Review our comprehensive data designed for HCPs and explore adverse reactions and discontinuation rates.

7. 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 ...

8. 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 ...

9. 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.