A Study to Learn How Safe the Study Treatment Actinium-225-macropa-pelgifatamab (BAY3546828) is, How it Affects the Body, How it Moves Into, Through and Out of the Body, and About Its Anticancer Activity in Participants With Advanced Metastatic Castration-resistant Prostate Cancer (mCRPC)

To be considered for this study, you must be a man with prostate cancer that has spread (metastatic) and is no longer responding to hormone therapy (castration-resistant). Your doctors must have confirmed that your cancer is a specific type called adenocarcinoma.

You must have already tried at least one 'novel androgen axis drug' (a type of hormone therapy like enzalutamide or abiraterone). You also need to have had an operation to remove your testicles or be receiving ongoing hormone treatment, with your testosterone levels kept low. Depending on which part of the study you might join, you may also need to have received previous chemotherapy with taxane drugs, or have been advised against them by your doctor. For one specific group, you would need to have had a previous treatment called 177Lu-PSMA therapy.

If you join this study, it could last for nearly six years in total. It starts with a screening phase, lasting up to 30 days, to make sure the study is right for you. During this time, you'll have two visits for tests. If you're eligible, you'll then receive the study treatment, BAY3546828, as an infusion into your vein once every six weeks for up to four cycles, provided it's helping you.

During your first treatment cycle, you'll have eight visits, and seven visits during any following cycles. Around 6 to 12 weeks after your last dose, you'll have a follow-up visit. For the first year after treatment, you'll have visits every six weeks, and for the next four years, you'll either have clinic visits or phone calls approximately every 12 weeks. Throughout the study, the medical team will carry out physical exams, check your blood pressure, heart rate, and temperature, take blood and urine samples, and monitor your heart health with ECGs and echocardiograms. They'll also take tumour samples, use imaging scans like PET, CT, MRI, and bone scans to check your cancer, and track BAY3546828 in your body. You'll also be asked about how you're feeling and how the disease affects your daily life.