Clinical Trials for Ocular Melanoma

This Phase 1 clinical trial is investigating a new type of immunotherapy called RP2 for people with advanced solid tumours, including metastatic uveal melanoma. RP2 is an engineered herpes simplex virus (HSV-1) designed to infect and destroy cancer cells while also stimulating the body’s immune system to recognise and attack the tumour. The treatment has also been modified to deliver immune-activating proteins directly into the tumour environment. 

The study is testing RP2 both on its own and in combination with nivolumab, an immunotherapy drug already used to treat several cancers. RP2 is given by direct injection into accessible tumours, while nivolumab is administered through an intravenous drip (IV infusion). Researchers are assessing the safety and tolerability of the treatment, as well as how well it helps shrink or control tumours in patients with advanced cancers that have continued to progress despite previous treatment. 

Researchers are particularly interested in whether RP2 can help “turn on” the immune system in cancers that do not normally respond well to immunotherapy alone. Early results from related RP1 and RP2 studies in melanoma and other cancers have shown encouraging anti-tumour activity in some patients. 

At the present time, active study locations for this trial are listed in the United Kingdom and Spain. The trial has included UK recruitment sites, making it one of the few investigational immunotherapy studies for metastatic uveal melanoma with UK involvement. 

This Phase 1 clinical trial is investigating a personalised T-cell therapy called IMA203 (also known as anzutresgene autoleucel) for people with advanced solid tumours, including metastatic uveal melanoma. IMA203 is a type of immunotherapy designed to genetically modify a patient’s own immune cells (T cells) so they can better recognise and attack cancer cells carrying a protein called PRAME, which is commonly found in uveal melanoma. To take part, patients must also have a specific tissue type called HLA-A*02:01. 

The study is assessing the safety, tolerability, and effectiveness of IMA203 both on its own and in combination with nivolumab, an immunotherapy drug already used to treat several cancers. Participants undergo a process called leukapheresis, where white blood cells are collected and modified in a laboratory before being infused back into the body. Prior to receiving the treatment, patients also receive chemotherapy to prepare the immune system. Researchers are monitoring side effects, tumour response, and how long the treatment can control the cancer. 

Early results presented from the uveal melanoma cohort have shown encouraging anti-tumour activity in some heavily pre-treated patients, including tumour shrinkage and durable responses. Researchers are continuing to expand the study to better understand the long-term benefits and safety of this treatment approach. 

At the present time, there are no active UK locations listed for this trial (NCT03686124). Current recruitment appears to be focused on sites in the United States and Germany, and we are not currently aware of any plans for the study to open at UK sites.

This Phase 1/2 clinical trial is investigating a new targeted treatment called NBM-BMX for people with metastatic uveal melanoma, a type of eye cancer that has spread to other parts of the body. NBM-BMX is designed to target a pathway involved in tumour growth and cancer cell survival, with researchers hoping it may help slow down or shrink tumours in patients with advanced disease. 

The study aims to determine the safest and most effective dose of NBM-BMX, while also assessing how the drug is processed by the body (pharmacokinetics, or PK), its side effects, and its potential anti-tumour activity. Participants will take NBM-BMX as an oral capsule twice daily in repeated 28-day treatment cycles and will undergo regular scans, blood tests, and safety monitoring throughout the trial. 

NBM-BMX is a selective HDAC8 inhibitor, a type of treatment targeting epigenetic changes linked to the development and progression of uveal melanoma. Early research and previous Phase 1 studies in advanced solid tumours have suggested the drug is generally well tolerated and may show activity in metastatic uveal melanoma. The treatment has also received FDA Fast Track and Orphan Drug designations in the United States, highlighting its potential as a promising therapy for this rare cancer. 

At the present time, there are no active UK locations listed for this trial (NCT07136181), and we are not currently aware of any plans for the study to open at UK sites.

This Phase 1/2 clinical trial is investigating the safety and effectiveness of darovasertib (also known as IDE196) in people with advanced solid tumours, including metastatic uveal melanoma. Darovasertib is a targeted treatment designed to block a protein called PKC, which is abnormally activated in around 90% of uveal melanoma cases due to GNAQ or GNA11 genetic mutations. Researchers hope this may help slow tumour growth and improve outcomes for patients with metastatic disease.

The study is testing darovasertib both on its own and in combination with other targeted treatments, including crizotinib and binimetinib. Researchers are assessing the safest and most effective dose of these treatments, while also monitoring how well they control or shrink tumours. Participants receive regular scans, blood tests, and safety monitoring throughout the trial. Early results from the darovasertib and crizotinib combination have shown encouraging tumour response rates and progression-free survival in some patients with metastatic uveal melanoma.

Although this study has included sites in Europe and North America, there are currently no active UK locations listed for this specific trial (NCT03947385), and we are not currently aware of any plans for the study to open at UK sites.

This Phase 3 clinical trial, known as PRISM-MEL-301, is investigating whether a new immunotherapy treatment called brenetafusp (IMC-F106C), given in combination with nivolumab, works better than standard nivolumab-based treatment for people with advanced melanoma that cannot be removed surgically or has spread to other parts of the body. The study is specifically for patients who are HLA-A*02:01 positive, a genetic tissue type found in around half of people. Brenetafusp is designed to help the immune system recognise and attack cancer cells by targeting a protein called PRAME, which is commonly found in melanoma cells. 

This is a Phase 3 randomised study, meaning participants are placed into different treatment groups by chance. Patients will receive either brenetafusp plus nivolumab, or standard nivolumab-based treatment. Researchers are assessing whether the combination treatment can better control tumour growth, improve survival, and provide longer-lasting responses compared to current standard treatments. The trial will also compare different dose levels of brenetafusp to identify the safest and most effective dose. 

The study will include around 680 participants worldwide and will closely monitor side effects, tumour response, quality of life, and overall survival. Treatment continues until the cancer progresses, side effects become unacceptable, or the participant chooses to stop treatment. UK sites are involved in this study.

This Phase 1/2 clinical trial is investigating the safety and effectiveness of a targeted treatment combination using darovasertib (IDE196) and crizotinib in people with metastatic uveal melanoma. Darovasertib is a protein kinase C (PKC) inhibitor designed to target genetic pathways commonly involved in uveal melanoma, while crizotinib targets another pathway linked to tumour growth. Researchers hope the combination may help slow tumour growth and improve outcomes for patients with metastatic disease.

The study includes patients with metastatic uveal melanoma who have specific genetic mutations linked to the disease. Researchers are assessing the safest and most effective dose of the treatment combination, while also monitoring how well the drugs work together to shrink or control tumours. Participants receive the treatments orally and undergo regular scans, blood tests, and safety monitoring throughout the study.

Early results from the trial have shown encouraging tumour response and survival outcomes in some patients with metastatic uveal melanoma. However, this remains an investigational treatment and further research is needed to confirm its long-term benefits and safety.

At the present time, there are no active UK locations listed for this specific trial, and we are not currently aware of any plans for the study to open at UK sites

This Phase 3 clinical trial, known as the ATOM study, is investigating whether a drug called tebentafusp can help prevent or delay the return of uveal melanoma in patients who are considered at high risk of their cancer spreading after treatment of the primary tumour.

Tebentafusp is an immunotherapy drug that has already shown benefits in patients with advanced or metastatic uveal melanoma.The study will assess whether giving tebentafusp after primary treatment can improve long-term outcomes and help patients live longer.

Researchers will also use blood tests to look for signs of molecular residual disease (MRD), which may indicate that microscopic cancer cells remain in the body even when scans appear clear.

This is a Phase 3 trial, meaning the treatment has already been through earlier safety testing and is now being studied in a larger group of patients to better understand its effectiveness.

Participants will receive regular monitoring throughout the study, including blood tests, scans, and follow-up assessments to track for any signs of recurrence and to monitor the safety and tolerability of the treatment.

This study will evaluate the safety, efficacy, optimal dose, and pharmacokinetics (PK) of BNT326 as monotherapy (Part 1) and as combination treatment with immunotherapeutic agents (Part 2) in participants with histologically or cytologically confirmed solid tumors that are advanced (i.e., either metastatic or recurrent tumors with no further definitive treatment possible) and/or have relapsed/progressed after prior therapy.

This early-phase clinical trial is testing a new treatment called brenetafusp (IMC-F106C) for adults with advanced cancers that test positive for a specific protein called PRAME. Brenetafusp is a type of immunotherapy known as an ImmTAC®, which is designed to help the immune system find and destroy cancer cells.

To take part in the trial, patients must also have a particular tissue marker called HLA-A2, which is found through routine testing.

The trial will be carried out in two parts:

• Phase 1 will focus on finding the safest dose of brenetafusp, either on its own or in combination with other treatments such as chemotherapy, targeted therapy, or other immunotherapies.
• Phase 2 will explore how well brenetafusp works in shrinking or controlling selected types of advanced cancers.

This is the first time brenetafusp is being tested in humans, so the study will carefully monitor safety and side effects, as well as how the drug behaves in the body and its impact on the cancer.

This is an early-phase clinical trial testing a new drug called BI-1607 for people with melanoma that has spread or cannot be removed by surgery. The aim is to see whether combining BI-1607 with two existing treatments, ipilimumab and pembrolizumab, is safe and more effective than current options. BI-1607 is designed to help the body’s immune system work better by enhancing the effects of ipilimumab and pembrolizumab, two immunotherapies already used to treat melanoma.

Around 35 people are expected to take part in the study, all of whom have melanoma that hasn’t responded to standard treatments.The trial has two parts:

Phase 1: At least 15 participants will be given BI-1607 alongside ipilimumab every three weeks over a 12-week period. Pembrolizumab will be added during the later part of this phase. After the initial 12 weeks, participants who continue in the trial will receive pembrolizumab alone for up to two years. Different groups will receive different dose levels to help researchers find the safest and most effective combination.

Phase 2: Around 20 more participants will receive the dose combination found to be safest in Phase 1. They will follow a similar treatment schedule, beginning with BI-1607, ipilimumab, and pembrolizumab for 12 weeks, followed by pembrolizumab alone.

All treatments are given through a drip into a vein (IV infusion). Participants will be closely monitored throughout the trial, with regular blood tests, scans, and health checks. The lowest dose of BI-1607 will be 350 mg, and the highest will be 700 mg. Ipilimumab will be given at 1 or 3 mg per kilogram of body weight, and pembrolizumab at 200 mg.

The trial will also look at how the treatment affects the immune system and how well it controls the cancer. Researchers will monitor any side effects, including serious ones that could stop treatment.

While participants may not benefit personally, their involvement could help improve treatment for future melanoma patients.

The study began in late 2024 and is expected to run until 2028.