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 of expression resulting in oncogenic pathway activation downstream of PI3K

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

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

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

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

Prior treatment with...CDK2 or selective CDK4 inhibitors or any investigational therapies targeting cyclin dependent kinases

Cannot have received: PIK3 inhibitor

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

Cannot have received: AKT inhibitor

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

Cannot have received: mTOR inhibitor

Prior treatment with...PIK3, AKT, or mTOR inhibitors or 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