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

Required: PIK3CA primary oncogenic mutation

One or more known primary oncogenic PIK3CA mutation(s)

Excluded: AKT1 activating mutation

Known activating AKT mutations

Excluded: PTEN loss-of-function mutation

loss-of-function PTEN mutations

Excluded: PTEN loss

loss of PTEN expression resulting in oncogenic pathway activation downstream of PI3K

Must have received: endocrine therapy — (neo)adjuvant or advanced breast cancer

At least 1 and no more than 2 lines of endocrine therapy (ET) in the (neo)adjuvant setting with recurrence on or within 12 months of completion or in the ABC setting

Must have received: CDK4/6 inhibitor — adjuvant or advanced breast cancer

Only 1 prior line of CDK4/6 inhibitor therapy in one of the following settings: CDK4/6 inhibitor + ET in the ABC setting; CDK4/6 inhibitor therapy in the adjuvant setting if progression occurred during or within 12 months of completion of adjuvant CDK4/6 inhibitor with ET

Cannot have received: CDK2 inhibitor

Exception: other investigational CDK inhibitors could be permitted upon discussion and approval from the Sponsor

Prior treatment with CDK2 inhibitors. Prior treatment with other investigational CDK inhibitors could be permitted upon discussion and approval from the Sponsor

Cannot have received: PIK3 inhibitor

Prior treatment with PIK3 inhibitors

Cannot have received: AKT inhibitor

Prior treatment with AKT inhibitors

Cannot have received: mTOR inhibitor

Prior treatment with mTOR inhibitors

Cannot have received: PIK3/AKT/mTOR pathway inhibitor

Prior treatment with any agent whose mechanism of action is the inhibit the PIK3/AKT/mTOR pathway

Cannot have received: immunotherapy

Prior treatment with immunotherapy

Cannot have received: antibody drug conjugate

Prior treatment with antibody drug conjugates