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.