A Study Evaluating the Efficacy and Safety of Giredestrant Compared With Physician's Choice of Endocrine Monotherapy in Participants With Previously Treated Estrogen Receptor-Positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer (acelERA Breast Cancer)

This Phase II, randomized, open-label, multicenter study will evaluate the efficacy and safety of giredestrant compared with physician's choice of endocrine monotherapy in participants with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer who have received one or two prior lines of systemic therapy in the locally advanced or metastatic setting.

Inclusion Criteria: * Women who are postmenopausal or premenopausal/perimenopausal * For women who are premenopausal or perimenopausal and for men: willing to undergo and maintain treatment with approved LHRH agonist therapy for the duration of study treatment * Locally advanced or metastatic adenocarcinoma of the breast, not amenable to treatment with curative intent * Documented ER-positive tumor and HER2-negative tumor, assessed locally * Disease progression after treatment with one or two lines of systemic therapy (but not more than one prior targeted therapy) in the locally advanced or metastatic setting * Measurable disease as defined per RECIST v.1.1 or bone only disease which must have at least one predominantly lytic bone lesion confirmed by CT or MRI which can be followed * Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 * Adequate organ function Exclusion Criteria: * Prior treatment with a selective estrogen receptor degrader (SERD), with the exception of fulvestrant, if fulvestrant treatment was terminated at least 28 days prior to randomization * Treatment with any investigational therapy within 28 days prior to randomization * Advanced, symptomatic, visceral spread that is at risk of life-threatening complications * Known active uncontrolled or symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease * Active cardiac disease or history of cardiac dysfunction * Pregnant or breastfeeding