Tebentafusp for Advanced Melanoma

Recruiting at 75 trial locations

Overseen By Immunocore Medical Information EU

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Immunocore Ltd

Must not be taking: Steroids, Immunosuppressives, Chemotherapy, others

Disqualifiers: Pregnancy, Ocular melanoma, CNS metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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: 9 weeks

540 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the efficacy and safety of tebentafusp-based regimens, including tebentafusp monotherapy and in combination with anti-PD1 vs investigator choice (including clinical trials of investigational agents, salvage therapy per local standard of care \[SoC\], best supportive care \[BSC\] on protocol survivor follow up) in patients with advanced non-ocular melanoma.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it mentions that you should not have received certain cancer therapies or immunosuppressive drugs within specific time frames before starting the trial. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug tebentafusp for advanced melanoma?

Tebentafusp has shown an overall survival benefit in patients with metastatic uveal melanoma, with a 1-year overall survival rate of 73% in clinical trials. It works by targeting a specific protein on melanoma cells, activating the immune system to attack these cells. ^{1 2 3 4 5}

What safety information is available for tebentafusp in humans?

Tebentafusp has been shown to be generally safe in humans, with common side effects including cytokine release syndrome (a condition where the immune system releases too many proteins into the blood too quickly), skin rashes, fever, itching, fatigue, nausea, chills, abdominal pain, swelling, low blood pressure, dry skin, headache, and vomiting. Monitoring for liver issues and managing side effects like low blood pressure with intravenous fluids are important for safety. ^{1 3 5 6 7}

How is the drug Tebentafusp different from other treatments for advanced melanoma?

Tebentafusp is unique because it is a first-in-class drug that specifically targets a protein called gp100 on melanoma cells, using a special mechanism to engage the body's T cells (a type of immune cell) to attack the cancer. This approach is different from traditional treatments and has shown promise, especially for a type of melanoma called uveal melanoma, which doesn't respond well to other therapies. ^{1 2 3 4 5}

Research Team

Mohammed Dar, MD

Principal Investigator

Immunocore Ltd

Eligibility Criteria

This trial is for adults with advanced non-ocular melanoma who are HLA-A*02:01-positive, have a good performance status (able to carry out daily activities), and can provide a tumor tissue sample. They must not be pregnant or breastfeeding, have no history of other cancers or severe psychiatric disorders, and cannot currently be in another clinical study.

Inclusion Criteria

My melanoma cannot be removed with surgery and is advanced.

Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the Informed Consent (ICF) and protocol

I have provided a sample of my tumor, either from stored tissue or a new biopsy.

Exclusion Criteria

You had a serious allergic reaction to a different kind of antibody treatment before.

I cannot receive pembrolizumab again due to a past side effect.

Known psychiatric or substance abuse disorders

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive tebentafusp as monotherapy or in combination with pembrolizumab, or investigator's choice of therapy

9 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 4 years

Long-term follow-up

Participants are monitored for overall survival and adverse events

Up to 4 years

Treatment Details

Interventions

• Investigators Choice
• Pembrolizumab
• Tebentafusp

Trial Overview The trial tests Tebentafusp alone or combined with Pembrolizumab against treatments chosen by the investigator, which could include standard care or supportive measures. It aims to see how well these tebentafusp-based regimens work and their safety compared to current options.

Participant Groups

Group I: Arm C: Investigator's Choice Experimental Treatment 1 Intervention

Participants receive investigator's choice of therapy.

Group II: Arm B: Tebentafusp + Pembrolizumab Experimental Treatment 1 Intervention

Participants receive tebentafusp in combination with pembrolizumab.

Group III: Arm A: Tebentafusp Monotherapy Experimental Treatment 1 Intervention

Participants receive tebentafusp as single agent.

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?

Immunocore Ltd

Lead Sponsor

Trials

17

Recruited

4,400+

Findings from Research

Tebentafusp, approved by the FDA for treating unresectable or metastatic uveal melanoma, activates T cells to induce tumor cell death, showing a 1-year overall survival rate of 73% in Phase III trials with a disease control rate of 46%.

Common side effects include cytokine release syndrome and rash, but the drug's unique mechanism offers a promising alternative for patients with limited treatment options and poor prognosis in this specific type of melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tebentafusp: a novel drug for the treatment of metastatic uveal melanoma. Wang, Z., Xie, Y., Wang, JQ., et al.[2023]

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]

In a phase 1b trial involving 85 heavily pretreated patients with metastatic cutaneous melanoma, tebentafusp combined with durvalumab and/or tremelimumab showed a promising overall survival rate of 76% at one year, indicating potential efficacy for patients who had previously progressed on checkpoint inhibitors.

The combination therapy was well-tolerated, with no new safety concerns or treatment-related deaths reported, suggesting that tebentafusp can be safely administered alongside existing checkpoint inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tebentafusp in combination with durvalumab and/or tremelimumab in patients with metastatic cutaneous melanoma: a phase 1 study. Hamid, O., Hassel, JC., Shoushtari, AN., et al.[2023]

In a multicenter phase I/II trial involving 84 patients with advanced melanoma, tebentafusp demonstrated a 1-year overall survival rate of 65%, indicating its efficacy in treating both metastatic uveal and cutaneous melanoma.

Tebentafusp was well-tolerated and showed a mechanism of action that includes the induction of T-cell activity and changes in cytokine levels, suggesting it effectively redirects T cells to target tumor cells expressing the gp100 antigen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tebentafusp, A TCR/Anti-CD3 Bispecific Fusion Protein Targeting gp100, Potently Activated Antitumor Immune Responses in Patients with Metastatic Melanoma. Middleton, MR., McAlpine, C., Woodcock, VK., et al.[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]

Tebentafusp is the first approved treatment for HLA-A*02:01 metastatic uveal melanoma, showing improved overall survival compared to standard treatment options, making it a significant advancement in cancer therapy.

The treatment has a manageable safety profile, with key adverse events including cytokine release syndrome and skin-related issues, necessitating careful monitoring and pre-treatment hydration to mitigate risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Practical guidelines for the management of adverse events of the T cell engager bispecific tebentafusp. Hassel, JC., Berking, C., Forschner, A., et al.[2023]

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]

References

1. Spain pubmed.ncbi.nlm.nih.gov

Tebentafusp: a novel drug for the treatment of metastatic uveal melanoma. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

Tebentafusp in combination with durvalumab and/or tremelimumab in patients with metastatic cutaneous melanoma: a phase 1 study. [2023]

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

Tebentafusp, A TCR/Anti-CD3 Bispecific Fusion Protein Targeting gp100, Potently Activated Antitumor Immune Responses in Patients with Metastatic Melanoma. [2022]

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

Tebentafusp: First Approval. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Practical guidelines for the management of adverse events of the T cell engager bispecific tebentafusp. [2023]

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

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