Open-Label Umbrella Study To Evaluate Safety And Efficacy Of Elacestrant In Various Combination In Participants With Metastatic Breast Cancer

Required: ESR1 overexpression (ER+; ≥10% nuclear staining by IHC) (≥10% nuclear staining by IHC)

ER status will be considered positive if ≥10% of tumor cells demonstrate positive nuclear staining by immunohistochemistry

Required: HER2 (ERBB2) negative

HER2-

Required: PIK3CA mutation

PIK3CA mutation by local laboratory assessment (Alpelisib Combination)

Required: PIK3CA alteration

PIK3CA/AKT1/PTEN-alteration as detected by an FDA and/or locally approved test (Capivasertib Combination)

Required: AKT1 alteration

PIK3CA/AKT1/PTEN-alteration as detected by an FDA and/or locally approved test (Capivasertib Combination)

Required: PTEN alteration

PIK3CA/AKT1/PTEN-alteration as detected by an FDA and/or locally approved test (Capivasertib Combination)

Allowed: BRCA1 germline mutation

Participants with known germline BRCA mutation without prior treatment with a PARP inhibitor before study entry [excluded]

Allowed: BRCA2 germline mutation

Participants with known germline BRCA mutation without prior treatment with a PARP inhibitor before study entry [excluded]

Must have received: hormonal therapy — advanced or metastatic

Documented radiological disease progression during or after the most recent therapy

Cannot have received: chemotherapy

Exception: adjuvant/neoadjuvant allowed; advanced/metastatic setting excluded

Prior chemotherapy or elacestrant in the advanced/metastatic setting

Cannot have received: elacestrant

Prior chemotherapy or elacestrant in the advanced/metastatic setting

Cannot have received: selective estrogen receptor degrader

Exception: fulvestrant not exclusionary except for Arm E

Prior therapy with elacestrant or other investigational selective estrogen receptor degraders, or investigational alike agents such as selective estrogen receptor modulators, selective estrogen receptor covalent antagonists, complete estrogen receptor antagonists, and proteolysis-targeting chimeras, in the metastatic setting. Prior treatment with fulvestrant is not exclusionary, except for Arm E, as it is an approved medication.