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)
Condition: Estrogen Receptor-Positive, HER2-Negative, Locally Advanced or Metastatic Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Giredestrant; Fulvestrant or an Aromatase Inhibitor (Physician Choice); LHRH Agonist
Intervention description: Giredestrant is taken orally once per day on Days 1-28 of each 28-day cycle.; Physician choice of endocrine monotherapy (fulvestrant or an aromatase inhibitor) is taken in accordance with the local prescribing information for the respective product.; Only premenopausal/perimenopausal participants and male participants will receive a luteinizing hormone-releasing hormone (LHRH) agonist on Day 1 of each 28-day treatment cycle. The investigator will determine and supply the appropriate LHRH agonist locally approved for use in breast cancer.
Intervention MeSH terms: Fulvestrant; Aromatase Inhibitors
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 303.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        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