Overview
This is a Phase III, randomized, open-label multicenter study that will evaluate the efficacy and safety of giredestrant compared with fulvestrant, both in combination with the investigator's choice of a CDK4/6 inhibitor (palbociclib, ribociclib or abemaciclib), in participants with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer who have developed resistance to adjuvant endocrine therapy.
Eligibility
Inclusion Criteria:
- 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 archived tumor sample)
- Confirmed ESR1 mutation status (ESR1m vs. ESR1nmd) in baseline circulating tumor DNA (ctDNA) through central laboratory testing
- Resistance to prior adjuvant endocrine therapy (ET). Prior use of neo/adjuvant CDK4/6i is allowed.
- No prior systemic anti-cancer therapy for advanced disease
- Measurable disease as defined per RECIST v.1.1 or non-measurable bone-only disease
- Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-1
- For pre/perimenopausal women and for men: treatment with LHRH agonist therapy (as per local guidelines) for the duration of study treatment is required
Exclusion Criteria:
- Prior systemic therapy (e.g., prior chemotherapy, immunotherapy, or biologic therapy) for locally advanced unresectable or metastatic breast cancer
- Prior treatment with another SERD (e.g., fulvestrant, oral SERDs) or novel ER-targeting agents
- Advanced, symptomatic, visceral spread that is at risk of life-threatening complications in the short term
- Active cardiac disease or history of cardiac dysfunction
- Clinically significant history of liver disease