Clinical Trials for Ocular Melanoma

Quisinostat for High-Risk Uveal Melanoma

Phase: Phase 2
Trial ID: NCT06932757
Treatment: Quisinostat
Stage: High-risk uveal melanoma following treatment of the primary eye tumour, with no evidence that the cancer has spread
Location: United States – University of Miami, Florida

What is this trial looking at?

This Phase 2 study is investigating whether a drug called quisinostat can reduce or delay the risk of uveal melanoma spreading to other parts of the body in people considered to have a high risk of developing metastatic disease.

The trial is for people who have already completed treatment for the melanoma in their eye, such as radiotherapy or surgery, and currently have no evidence that the cancer has spread elsewhere in the body.

Treatment given after the primary cancer has been treated, with the aim of reducing the risk of the cancer returning or spreading, is known as adjuvant treatment.

At present, there is no established adjuvant drug treatment proven to prevent uveal melanoma from spreading. This study is therefore investigating whether quisinostat could have a role in this setting.

What is quisinostat?

Quisinostat is an experimental drug known as an HDAC inhibitor.

HDACs are proteins involved in controlling how genes are switched on and off within cells. Blocking these proteins may interfere with the ability of some cancer cells to survive and grow.

Researchers want to find out whether giving quisinostat after treatment of a high-risk primary uveal melanoma can help prevent or delay metastatic disease developing.

Quisinostat is taken by mouth rather than being given through an infusion.

Who may be able to take part?

The study is specifically looking for adults with high-risk uveal melanoma who have already completed treatment of their primary eye tumour and currently have no evidence of metastatic disease.

Participants generally need to:

• be aged over 18;
• have had a primary uveal melanoma measuring at least 12 mm across its largest basal diameter before treatment;
• have a tumour classified as Class 2 using the DecisionDx-UM gene expression profiling test;
• have completed their primary uveal melanoma treatment within approximately six months (183 days) before starting the trial treatment;
• have no evidence that the melanoma has spread elsewhere in the body;
• be well enough to take part in the study; and
• be able to swallow and absorb oral medication.

Previous adjuvant drug treatment for uveal melanoma is generally not permitted.

There are additional medical eligibility requirements, including checks relating to heart function, other medications and general health.

Meeting these general criteria does not necessarily mean somebody will be eligible. Eligibility would need to be confirmed by the clinical trial team.

What does taking part involve?

Everyone taking part in this study receives quisinostat. There is no placebo or comparison treatment group.

Quisinostat is taken by mouth three times each week – on Monday, Wednesday and Friday.

Treatment is organised into three-week cycles and can continue for up to 17 cycles, which is approximately 51 weeks, provided the cancer has not spread and the treatment remains suitable and tolerable.

Participants also have regular monitoring during the study. This includes:

• blood tests;
• MRI and CT scans;
• monitoring for possible side effects; and
• checks of heart function where required.

After completing treatment, participants continue to be followed by the study team. Follow-up takes place approximately 30 days after treatment finishes and then every three months for two years.

What is the study hoping to find out?

The main aim is to determine whether quisinostat can reduce or delay the development of metastatic uveal melanoma in people considered at high risk following treatment of their primary tumour.

Researchers will look at:

• how many participants remain free from metastatic disease;
• how long people remain free from progression of their cancer;
• overall survival;
• where the cancer first returns if metastatic disease does develop;
• the safety and side effects of quisinostat; and
• biological changes that may help researchers better understand how the treatment works.

Why does Class 2 matter for this study?

This trial is specifically selecting people whose tumour has been classified as Class 2 by the DecisionDx-UM gene expression profiling test.

A Class 2 result is associated with a higher risk of uveal melanoma spreading compared with lower-risk gene expression profiles.

This requirement is specific to this particular clinical trial. Other methods of assessing metastatic risk are used within UK clinical practice, and having been described as having “high-risk” uveal melanoma by a UK clinical team does not automatically mean somebody would meet this trial’s Class 2 eligibility requirement.

Trial location

The study is being led by the University of Miami Miller School of Medicine / Sylvester Comprehensive Cancer Center in Florida, USA.

There are currently no UK trial centres listed for this study.

Anyone interested in the trial should first discuss it with their ocular oncology or oncology team. Their treating team can help establish whether the study may be relevant and whether contacting the trial centre would be appropriate.

Quisinostat is an investigational treatment and is not an approved standard adjuvant treatment for uveal melanoma. Eligibility and any decisions about treatment should always be discussed with the treating clinical team.

REVEAL – RP2 + Nivolumab for Metastatic Uveal Melanoma

Phase: Phase 2/3
Trial ID: NCT06581406 / RP2-202
Treatment: RP2 + nivolumab compared with ipilimumab + nivolumab
Stage: Metastatic uveal melanoma
UK locations: The Royal Marsden, London and The Clatterbridge Cancer Centre, Liverpool
Status: Recruiting

What is this trial looking at?

The REVEAL study is investigating a new type of immunotherapy called RP2, given together with nivolumab, for people with uveal melanoma that has spread to other parts of the body.

Researchers want to find out whether RP2 combined with nivolumab can control metastatic uveal melanoma more effectively than treatment with the immunotherapy combination ipilimumab and nivolumab.

RP2 is a specially modified version of the herpes simplex virus. It has been designed to enter and destroy cancer cells while also helping stimulate the immune system to recognise and attack the cancer.

Unlike most drug treatments, RP2 is injected directly into a tumour. Nivolumab is then given through an intravenous infusion.

The study is particularly interested in whether injecting RP2 into one or more tumours can stimulate an immune response that also attacks cancer elsewhere in the body, including tumours that have not themselves been injected.

Who may be able to take part?

The trial is for adults with metastatic uveal melanoma that cannot be removed completely with surgery.

Participants generally need to:

• be aged 18 or over;
• have confirmed metastatic uveal melanoma;
• have at least one tumour measuring approximately 1 cm or more that can safely be reached and repeatedly injected with RP2;
• not previously have received immune checkpoint inhibitor treatment, such as nivolumab, pembrolizumab or ipilimumab, for their metastatic uveal melanoma;
• be well enough to take part in the study; and
• be willing to provide tumour biopsy samples.

The study may allow some people who have already received one previous treatment for metastatic uveal melanoma, provided that treatment was not an immune checkpoint inhibitor and the other eligibility requirements are met.

There are also restrictions relating to factors such as the amount of cancer within the liver, previous liver-directed treatments and certain medical conditions.

Meeting these general criteria does not necessarily mean somebody will be eligible. A full assessment by the clinical trial team is required.

What does taking part involve?

Participants are randomly assigned to one of two treatment groups:

Group 1 – RP2 + nivolumab

Participants receive RP2 by injection directly into an accessible tumour.

RP2 is initially given every two weeks for up to eight treatments. Nivolumab is also given intravenously and can continue for up to approximately two years.

Depending on how the cancer responds, some participants may be able to receive an additional course of RP2 injections.

Group 2 – Ipilimumab + nivolumab

Participants receive the established immunotherapy combination ipilimumab and nivolumab.

The two medicines are initially given together for four treatments. Nivolumab can then continue on its own for up to approximately two years.

Participants in both groups have regular scans and assessments so researchers can monitor the cancer, treatment response and any side effects.

What is the study hoping to find out?

The main aim is to determine whether RP2 + nivolumab can improve outcomes compared with ipilimumab + nivolumab for people with metastatic uveal melanoma who have not previously received checkpoint immunotherapy.

Researchers will look particularly at:

• how long participants live;
• how long the cancer remains controlled before getting worse;
• how many participants experience tumour shrinkage;
• how many achieve either tumour shrinkage or stable disease;
• how long responses to treatment last; and
• the safety and side effects of the treatments.

Does HLA type matter?

Unlike tebentafusp, patients do not need to be HLA-A*02:01 positive to be considered for this trial.

This means the study may potentially be relevant to people who are HLA-A02:01 negative as well as those who are HLA-A02:01 positive, although previous treatments and the other trial eligibility requirements remain important.

UK trial locations

The study currently lists two UK centres:

• The Royal Marsden NHS Foundation Trust, London
• The Clatterbridge Cancer Centre NHS Foundation Trust, Liverpool

Not every listed site will necessarily be open to recruitment at all times.

Anyone interested in the study should speak to their oncology team. Their treating team can review their previous treatments and medical history and, where appropriate, discuss referral to a participating trial centre.

RP2 is an investigational treatment and has not yet been approved as a standard treatment for metastatic uveal melanoma. Eligibility for a clinical trial and decisions about treatment must be discussed with the patient’s treating clinical team.

OptimUM-10 – Darovasertib before treatment for primary uveal melanoma

Phase: Phase 3
Trial ID: NCT07015190
Treatment: Darovasertib
Stage: Primary uveal melanoma – the cancer must not have spread to other parts of the body
UK locations: University College London Hospital and The Clatterbridge Cancer Centre, Liverpool

What is this trial looking at?

OptimUM-10 is investigating whether giving a drug called darovasertib before the usual treatment for uveal melanoma can shrink the tumour and help protect the eye and vision.

This type of treatment is known as neoadjuvant treatment, which simply means treatment given before the main treatment.

Darovasertib is a tablet that blocks a protein called PKC, which is involved in the growth of many uveal melanomas.

The study is particularly interested in whether shrinking the tumour before treatment could:

• reduce the risk of significant sight loss for people who need plaque brachytherapy; or
• allow some people who would normally need their eye removed (enucleation) to receive an eye-preserving treatment instead.

Who may be able to take part?

This trial is for adults with a new diagnosis of primary uveal melanoma that has not spread elsewhere in the body.

There are two groups within the study:

Group 1 – Plaque brachytherapy

This group is for people whose tumour would normally be treated with plaque brachytherapy and who are considered at higher risk of losing vision as a result of their tumour or treatment.

Group 2 – Enucleation

This group is for people whose tumour would normally be treated by removing the eye (enucleation).

Participants generally need to:

• be aged 18 or over;
• have primary uveal melanoma with no evidence that it has spread;
• not have previously received treatment for their uveal melanoma;
• be well enough to take part in the study; and
• meet the trial’s other medical and eye-related eligibility requirements.

There are additional eligibility criteria, and meeting the points above does not necessarily mean someone will be able to join the trial. Eligibility must be assessed by the clinical trial team.

What does taking part involve?

Participants are randomly assigned to receive either darovasertib before their normal treatment or to receive their normal treatment without darovasertib.

For people receiving darovasertib, the medication is taken by mouth twice a day for up to approximately six months before their main eye treatment.

For people in the plaque brachytherapy group, the study compares:

• darovasertib followed by plaque brachytherapy; with
• plaque brachytherapy without darovasertib beforehand.

For people in the enucleation group, the study compares:

• darovasertib followed by the most appropriate treatment depending on how the tumour responds, which may include plaque brachytherapy, another form of radiotherapy or enucleation; with
• immediate enucleation without darovasertib beforehand.

Participants will continue to be followed after their treatment so researchers can look at longer-term outcomes, including vision and whether the tumour returns.

What is the study hoping to find out?

For people who would normally receive plaque brachytherapy, researchers primarily want to find out whether giving darovasertib beforehand can help reduce significant loss of vision.

For people who would normally require enucleation, researchers want to determine whether treatment with darovasertib can shrink the tumour enough to allow more people to keep their eye.

The study will also collect information about how well the treatment works, its side effects and longer-term outcomes.

UK trial locations

The trial currently lists two UK centres:

• University College London Hospital (UCLH), London
• The Clatterbridge Cancer Centre, Liverpool

Anyone interested in the trial should speak to their ocular oncology or oncology team. They can discuss whether the study may be appropriate and arrange a referral to a participating trial centre if necessary.

Darovasertib is an investigational treatment and is not currently an approved standard treatment for primary uveal melanoma. Participation in a clinical trial and treatment decisions should always be discussed with the treating clinical team.

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 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.

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