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.
Principal investigator
Eligibility criteria
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 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
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
* 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
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
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