IMCgp100 for Uveal Melanoma

Recruiting at 61 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

378 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug IMCgp100 for Uveal Melanoma?

Research shows that immune checkpoint inhibitors, like pembrolizumab and ipilimumab, have improved survival rates in patients with metastatic uveal melanoma, even though response rates are lower compared to other types of melanoma. These drugs have shown some effectiveness in controlling the disease, making them a viable option for treatment. ^{1 2 3 4 5}

Is IMCgp100 safe for treating uveal melanoma?

Ipilimumab, a treatment similar to IMCgp100, has been studied for safety in patients with uveal melanoma. In a study, no severe non-immune side effects were reported, but some patients experienced immune-related side effects like diarrhea and liver enzyme changes, which were managed with steroids. ^{1 5 6 7 8}

How does the drug combination of Dacarbazine, IMCgp100, Ipilimumab, and Pembrolizumab differ from other treatments for uveal melanoma?

This drug combination is unique because it includes IMCgp100, a novel agent specifically designed to target uveal melanoma cells, along with immune checkpoint inhibitors like Ipilimumab and Pembrolizumab, which help the immune system attack cancer cells. This approach is different from traditional chemotherapy, as it combines targeted therapy with immunotherapy to potentially improve outcomes for patients with this rare and aggressive cancer. ^{2 3 5 9 10}

What is the purpose of this trial?

To evaluate the overall survival of HLA-A\*0201 positive adult patients with previously untreated advanced UM receiving IMCgp100 compared to Investigator's Choice of dacarbazine, ipilimumab, or pembrolizumab.

Research Team

Immunocore Medical Information

Principal Investigator

Immunocore Ltd

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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 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]

References

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

Real-World Impact of Immune Checkpoint Inhibitors in Metastatic Uveal Melanoma. [2020]

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

Anti-PD-1 antibodies in metastatic uveal melanoma: a treatment option? [2021]

3. England pubmed.ncbi.nlm.nih.gov

The use of pembrolizumab for the treatment of metastatic uveal melanoma. [2022]

4. Egypt pubmed.ncbi.nlm.nih.gov

Efficacy of Immunotherapy in Patients with Metastatic Mucosal or Uveal Melanoma. [2022]

5. Greece pubmed.ncbi.nlm.nih.gov

New therapeutic agents in uveal melanoma. [2012]

6. Germany pubmed.ncbi.nlm.nih.gov

Ipilimumab in pretreated patients with metastatic uveal melanoma: safety and clinical efficacy. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of ipilimumab monotherapy in patients with pretreated advanced melanoma: a multicenter single-arm phase II study. [2022]

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

Safety, efficacy, and biomarkers of nivolumab with vaccine in ipilimumab-refractory or -naive melanoma. [2022]

9. England pubmed.ncbi.nlm.nih.gov

A phase II study of the insulin-like growth factor type I receptor inhibitor IMC-A12 in patients with metastatic uveal melanoma. [2022]

10. India pubmed.ncbi.nlm.nih.gov

The role of c-kit and imatinib mesylate in uveal melanoma. [2020]