A study to Evaluate Efficacy and Safety of Giredestrant Compared with Fulvestrant (plus a CDK4/6 inhibitor), in Participants with ER+ HER2-Negative Advanced Breast Cancer Resistant to Adjuvant Endocrine Therapy (pionERA Breast Cancer)

Prior treatment

• Prior treatment with a SERD (e.g., fulvestrant, investigational)
• Prior systemic therapy (e.g., prior chemotherapy, immunotherapy, or biologic therapy) for locally advanced unresectable or metastatic breast cancer. Prior therapy for contralateral, local, and/or regional BC treated with curative surgery is allowed

Other illness

• Active cardiac disease or history of cardiac dysfunction
• Clinically significant history of liver disease

Other

• Advanced, symptomatic, visceral spread that is at risk of life-threatening complications

• Confirmed ESR1 mutation status in baseline ctDNA
• Resistance to prior standard adjuvant ET, defined as relapse on-treatment after ≥ 12 months or off-treatment within 12 months of completion. If adjuvant ET included a CDK4/6i, capecitabine, or S-1 relapse should have occurred ≥ 12 months since completion of CDK4/6i such treatment
• Measurable disease as defined per RECIST v.1.1 or non-measurable (including bone-only) disease
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0 - 1
• Locally advanced or metastatic adenocarcinoma of the breast not amenable to treatment with curative intent, with documented ER+ HER2- status assessed locally based on the most recent tumor biopsy (or archived tumor sample if a recent tumor sample is not available for testing)