Tebentafusp for Advanced Melanoma

Recruiting at 87 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called tebentafusp for individuals with advanced non-ocular melanoma, a serious type of skin cancer. The study aims to evaluate the effectiveness of tebentafusp both alone and in combination with pembrolizumab (an immunotherapy drug), compared to other doctor-selected treatments. It seeks participants with non-ocular melanoma that cannot be surgically removed and who have tested positive for a specific cell marker, HLA-A*02:01. As a Phase 3 trial, this study represents the final step before FDA approval, providing participants an opportunity to access potentially groundbreaking treatment.

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.

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

Research has shown that tebentafusp holds promise for treating melanoma, a type of skin cancer. In previous studies, patients who received tebentafusp lived longer. The treatment is usually well-tolerated, though some patients developed rashes, which often improved or resolved over time.

When combined with pembrolizumab, another medication, similar safety results have been observed. Both treatments are being tested to ensure they are safe and effective. As this study is in a later stage, researchers have gathered more information about the treatment's safety, providing more evidence that it is generally safe for people. However, like any treatment, side effects may occur, so discussing any concerns with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Tebentafusp is unique because it targets melanoma cells in a novel way, using a mechanism called a T-cell receptor (TCR) fusion protein. This approach is different from the standard treatments like immune checkpoint inhibitors or targeted therapies, as tebentafusp specifically binds to a protein present on the surface of melanoma cells and activates T-cells to attack them. Researchers are excited about this treatment because it offers a new strategy to stimulate the immune system against melanoma, potentially improving outcomes for patients with advanced stages of the disease. Additionally, one of the treatment arms combines tebentafusp with pembrolizumab, which could enhance the immune response even further.

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

Research has shown that tebentafusp yields promising results for treating advanced melanoma. In studies with patients who have metastatic uveal melanoma, tebentafusp significantly improved survival rates compared to standard treatments. This drug is a bispecific ImmTAC, targeting certain proteins to help the immune system identify and destroy cancer cells. Participants in this trial may receive tebentafusp alone or combined with pembrolizumab, a drug that enhances the immune system's ability to fight cancer. Earlier research suggests that both approaches may offer a survival benefit for treating advanced melanoma. Additionally, some participants will receive the investigator's choice of therapy, providing a comprehensive evaluation of treatment options. ^{1 6 7 8 9}

Who Is on the Research Team?

Mohammed Dar, MD

Principal Investigator

Immunocore Ltd

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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, 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]

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. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK612651/

Tebentafusp for treating advanced uveal melanoma - NCBI - NIH Clinical evidence results. Overall-survival data from the IMCgp100-202 trial suggests tebentafusp improves overall survival compared with usual ...

4. 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 ...

5. curemelanoma.org curemelanoma.org/patient-eng/melanoma-treatment/options/kimmtrak-tebentafusp

Kimmtrak (Tebentafusp) for Uveal Melanoma Treatment Tebentafusp (KIMMTRAK®) helps shrink tumors and helps patients with advanced uveal melanoma live longer.

6. 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)

7. 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 ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.21.01805

Phase I Study of Safety, Tolerability, and Efficacy ... Tebentafusp showed promising activity in patients with metastatic uveal melanoma (mUM) in a first-in-human study, with greater responses ...

9. 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 ...