Phase 3 Study of RLY-2608 + Fulvestrant vs Capivasertib + Fulvestrant as Treatment for Locally Advanced or Metastatic PIK3CA-mutant HR+/HER2- Breast Cancer

To be able to take part in this study, there are certain things doctors need to check. You must be an adult, either male or female. If you are a woman who hasn't gone through menopause, you'll need to be taking special medication (a GnRH agonist) to temporarily stop your ovaries from making hormones, and you'd need to continue this during the study. Your cancer must be HR+ and HER2-, and have a specific gene change called PIK3CA mutation. Your cancer needs to be locally advanced (spread nearby) or metastatic (spread further) and have shown signs of growing or coming back after previous treatment.

You would have received previous treatment for your breast cancer with a CDK4/6 inhibitor. This means you would have taken a CDK4/6 inhibitor either for advanced breast cancer or after surgery. You generally can't have had more than two lines of hormone therapy before the study. Also, doctors will check your general health and how well you can do daily activities; you should be in reasonably good health.

Some things would prevent you from joining. For example, if you've already had certain other types of cancer treatment, such as other drugs that target the PIK3/AKT/mTOR pathway or specific types of CDK inhibitors, you wouldn't be able to participate. You also can't have certain other conditions, like Type 1 diabetes, or have received immunotherapy or antibody drug conjugates recently.

If you decide to take part in this study, you'll be assigned to one of two treatment groups by chance (like flipping a coin). You'll receive either RLY-2608 with fulvestrant, or capivasertib with fulvestrant. Both drugs are given alongside fulvestrant. The study is 'open-label,' meaning both you and your study doctors will know which treatment you are receiving.

Taking part will involve regular visits to the hospital for check-ups, blood tests, and scans to see how you're responding to the treatment. These visits will be needed to monitor your health, how the drugs are working, and to check for any side effects. You will receive your medication during these visits or as prescribed. The duration of your participation will vary depending on how your cancer responds to the treatment, but you will continue treatment for as long as it is benefiting you and any side effects are manageable. After treatment stops, there will likely be follow-up appointments to track your long-term health. The full length of the study for all patients could be several years.