SUPRAME-ACTengine® IMA203 vs. Investigator's Choice of Treatment in Previously Treated, Unresectable or Metastatic Cutaneous Melanoma

For this study, we are looking for adults aged 18 and over who have advanced skin melanoma that has either spread or cannot be removed through surgery. You must have already received at least one course of treatment with a type of drug called a PD-1 inhibitor (a common cancer immunotherapy) and your cancer must have continued to grow or spread during or after this treatment.

Your doctors will also check if you have a specific genetic marker called HLA-A*02:01, as the new treatment, IMA203, is designed to work with this marker. You should also be generally well enough to take part and have good organ function, as assessed by the researchers. If you have a specific change in your cancer called a BRAF mutation, you should have also tried a BRAF-targeted treatment before, unless your doctor felt it wasn't suitable for you.

There are also some reasons why you might not be able to join. For example, if you have melanoma that started in the eye or in internal linings (mucosal melanoma), or if you’ve had certain other cancers recently. Also, if you have a serious autoimmune disease, you might not be suitable, unless your doctor says it's very well controlled without strong immune-suppressing medicines.

If you decide to take part in this study, the first step is a screening process to confirm if you're eligible. This includes blood tests, like checking for the HLA-A*02:01 marker, and other assessments. If you are eligible and have the correct marker, some of your white blood cells will be collected through a procedure called 'leukapheresis'. This is similar to giving blood but takes a bit longer as your blood is separated, and then the remaining parts are returned to you. These cells will then be sent away to create your personalised IMA203 treatment.

If you are in the group receiving IMA203, you will need to be admitted to the hospital. Before the IMA203 is given, you'll receive some medicine (cyclophosphamide and fludarabine) to help prepare your body for the treatment. The IMA203 will then be given directly into your bloodstream. After this, you'll receive a low dose of another medication (IL-2) for up to 10 days, given as injections under the skin. If you are in the standard treatment group, you will receive the chosen treatment as prescribed by your doctor, which could involve infusions, tablets, or injections.

Throughout the study, regardless of which treatment you receive, you'll have regular hospital visits for check-ups, blood tests, and scans to monitor your health and how the treatment is affecting your cancer. Researchers will also keep track of any side effects you might experience. Women who are able to become pregnant and men will need to use effective contraception during the study and for a period after their last treatment to prevent pregnancy. The total duration of your participation will depend on how you respond to treatment and will involve ongoing follow-up.