Breast Cancer Clinical Trials

• Locally advanced or metastatic adenocarcinoma of the breast, not amenable to treatment with curative intent

• Documented estrogen receptor-positive (ER+), HER2-negative (HER2-) tumor assessed locally on the most recent tumor biopsy (or an archived tumor sample if a recent tumor sample is not available for testing)

• Confirmed ESR1 mutation status (ESR1m versus ESR1nmd) in baseline circulating tumor DNA (ctDNA) through central laboratory testing

• Resistance to prior adjuvant endocrine therapy (ET), which is defined as having relapsed with prior standard adjuvant ET, on-treatment after \>/=12 months or off-treatment within 12 months of completion. Prior use of adjuvant CDK4/6i is allowed (if relapse occurred \>/=12 months since completion).

• No prior systemic anti-cancer therapy for advanced disease

• Measurable disease as defined per RECIST v.1.1 or non-measurable (including bone-only) disease

• Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-1

• For pre/perimenopausal women and for men: willing to undergo and maintain treatment with approved LHRH agonist therapy (as per local guidelines) for the duration of study treatment