A Study Evaluating the Efficacy and Safety of Giredestrant Plus Everolimus Compared With the Physician's Choice of Endocrine Therapy Plus Everolimus in Participants With Estrogen Receptor-Positive, HER2-Negative, Locally Advanced or Metastatic Breast Cancer (evERA Breast Cancer)

To join this study, your breast cancer must be advanced (can't be removed by surgery) or has spread to other parts of your body. Your cancer cells must also be 'ER-positive' (meaning they respond to oestrogen) and 'HER2-negative'. You'll need to provide a blood sample to check for a specific gene change in your cancer.

You must have already received certain hormone treatments along with a CDK4/6 inhibitor drug. This previous treatment could have been for advanced cancer, where your cancer grew after at least 6 months on the treatment. Or, if it was for earlier-stage cancer, your cancer must have come back within a year of stopping the treatment, having taken it for at least 12 months (with 6 months including the CDK4/6 inhibitor).

The study also needs to be able to measure your cancer, either through scans of areas like lymph nodes or organs, or through specific bone scans if the cancer is mainly in the bones. Your general health and ability to carry out daily activities should be good. If you are a woman who hasn't gone through menopause or a man, you'll need to be on specific hormone-blocking medication throughout the study. You cannot have been treated with certain other new types of hormone drugs or everolimus before, though previous treatment with fulvestrant (another hormone drug) is allowed if it was stopped at least 28 days before starting this study.

If you join this study, you will be randomly assigned to one of two treatment groups, meaning you won't choose which group you're in. One group will receive the new drug giredestrant along with everolimus. The other group will receive a standard hormone therapy (chosen by your doctor from options like exemestane, fulvestrant, or tamoxifen) plus everolimus. All drugs are taken orally, except for fulvestrant which is an injection.

You will have regular hospital visits for doctor check-ups, blood tests, and scans (like CT or MRI) to monitor your health and how your cancer is responding. For men and pre/peri-menopausal women, you will also receive monthly injections of an LHRH agonist (a hormone-blocking drug). If you experience mouth sores, you might also receive a special mouth rinse containing dexamethasone. The exact number of visits and tests will be detailed by the study team, and participation will continue as long as the treatment is helping and side effects are manageable.