A Study to Evaluate Efficacy and Safety of Giredestrant Compared With Fulvestrant (Plus a CDK4/6 Inhibitor), in Participants With ER-Positive, HER2-Negative Advanced Breast Cancer Resistant to Adjuvant Endocrine Therapy (pionERA Breast Cancer)

To join this study, people generally need to have advanced breast cancer that is definitely Estrogen Receptor-Positive and HER2-Negative. This means the cancer has spread from where it started or cannot be cured with surgery, and it's confirmed to be the specific type that responds to hormones but not HER2-targeted treatments. Your doctors would check your tumour samples to confirm this. Importantly, your cancer must have shown resistance to previous hormone therapy given after your initial diagnosis, meaning it came back or progressed either during or shortly after finishing that treatment. Doctors will also check a blood sample for a specific gene change called 'ESR1 mutation'.

You cannot have had other treatments for advanced breast cancer, such as chemotherapy or other targeted drugs, before joining this study. Your general health should be good enough to take part, and doctors will assess this with an ‘ECOG PS’ score of 0 or 1. This means you are fully active, or able to carry out light work. If you are a pre-menopausal or peri-menopausal woman, or a man, you will need to be willing to take standard hormone-blocking injections (LHRH agonists) during the study.

There are also some reasons why you might not be able to join. For example, if you have severe or rapidly worsening symptoms from your cancer, or have ever had certain heart conditions or significant liver disease. Also, if you've already received a similar type of drug to giredestrant (called a SERD, like fulvestrant) or other specific hormone-targeting drugs for advanced cancer, you wouldn't be eligible.

Taking part in this study means you would receive one of the study treatments (either giredestrant or fulvestrant, plus a CDK4/6 inhibitor). The specific treatment you receive would be decided randomly, like flipping a coin. You would also have regular appointments at the hospital for blood tests, physical examinations, and scans to check how your body is responding to the treatment and how the cancer is behaving. This would also involve regular checks of your heart health. You might also need to take LHRH agonist injections if you are pre-menopausal, peri-menopausal, or a man. The total length of your participation would vary depending on how well the treatment works for you, and you would continue treatment as long as it is benefiting you and you are not experiencing severe side effects. Once you stop the study treatment, there might be follow-up visits or calls to monitor your long-term health.