ReDiscover-2 / RLY-2608-102

The purpose of this study is to learn about the effectiveness and safety of the investigational drug called RLY-2608 in combination with fulvestrant compared to capivasertib in combination with fulvestrant when given to individuals who have been diagnosed with locally advanced or metastatic hormone receptor-positive, human epidermal growth factor 2-negative (HR+/HER2-) breast cancer and have at least one mutation in a gene called PIK3CA. “Investigational” means that the U.S. Food and Drug Administration (FDA) has not approved this treatment as a prescription medicine and it must be tested to see if it is a safe and effective treatment method for the disease or condition being studied.

RLY-2608 in combination with fulvestrant was tested in a previous study (ReDiscover) and has shown encouraging results. This new study aims to confirm the evidence of benefit seen in the ReDiscover study in a larger group of participants compared to standard therapy with capivasertib in combination with fulvestrant to find out which is better for treating your type of breast cancer.

Capivasertib and fulvestrant are approved for your type of cancer by the FDA and are available for sale as marketed products.

If you agree to participate in this study, your participation may last up to 6 months to a year, or longer and you will be asked to complete 12 study visits.

In order to participate you must meet the following criteria:

• Have an ECOG performance status of 0-1.
• Have one or more known primary oncogenic PIK3CA mutation(s).
• Are an adult female, pre- and/or post-menopausal, or an adult male.
• Have radiological evidence of disease progression on or after previous treatment for HR+/HER2- breast cancer.

You will be excluded from the study if any of the following criteria apply to you:

• Have had prior treatment with certain drugs (the study team can provide more info).
• Have clinically significant, uncontrolled cardiovascular disease.
• Have any factors that increase the risk of QTc prolongation or risk of arrhythmic events.
• Have past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease.

This is a partial list of eligibility requirements. To inquire about your eligibility, please call the contact number provided. If you wish to inquire via email, please include the title of the study in your message.