Phase 3 Trial of Elacestrant vs. Standard of Care for the Treatment of Patients With ER+/HER2- Advanced Breast Cancer

This Phase 3 clinical study compares the efficacy and safety of elacestrant to the standard of care (SoC) options of fulvestrant or an aromatase inhibitor (AI) in women and men with breast cancer whose disease has advanced on at least one endocrine therapy including a CDK4/6 inhibitor in combination with fulvestrant or an aromatase inhibitor (AI) .

This is an international, multicenter, randomized, open-label, active-controlled, event-driven, Phase 3 clinical study comparing the efficacy and safety of elacestrant to the SoC options of fulvestrant or an aromatase inhibitor (AI) in postmenopausal women and in men with advanced or metastatic ER+/HER2- breast cancer, either in subjects with tumors that harbor mutations in the ligand binding domain (LBD) of the estrogen receptor 1 (ESR1) gene (ESR1-mut subjects) or in all subjects regardless of ESR1 status (ESR1-mut and ESR1 wild type \[ESR1-WT\]) and whose disease has relapsed or progressed on at least one and no more than two prior lines of endocrine therapy (with documented progression), which must have included prior CDK4/6 inhibitor therapy in combination with fulvestrant or an aromatase inhibitor (AI) and for whom hormonal monotherapy with one of the SoC drugs (fulvestrant, anastrozole, letrozole, exemestane) is an appropriate treatment option.

Eligibility Criteria:
Critical Inclusion Criteria:

1. Subjects with proven diagnosis of adenocarcinoma of the breast with evidence of either locally advanced disease not amenable to resection or radiation therapy with curative intent or metastatic disease not amenable to curative therapy.
2. Subjects must be appropriate candidates for endocrine monotherapy
3. Subjects must have measurable disease or bone only disease
4. Female or male subjects age ≥ 18 years; female subjects must be postmenopausal women and male subjects must not allow pregnancy with their sperm (abstain, do not donate sperm, etc).
5. Subjects must have ER+ and HER2- tumor status
6. Subjects must have previously received at least one and no more than two lines of endocrine therapy for advanced/metastatic breast cancer and meet additional previous treatment criteria.
7. Subjects must have received prior treatment with a CDK4/6 inhibitor in combination with either fulvestrant or an aromatase inhibitor (AI) for advanced/metastatic breast cancer (mBC).
8. Subjects may have received no more than one line of chemotherapy in the advanced/metastatic setting.

Critical Exclusion Criteria:

1. Prior treatment with elacestrant or other investigational selective estrogen receptor degrader (SERD) or ER antagonist (D-0502, GDC-0810, GDC- 0927, GDC-9545, G1T-48, LSZ102, AZD9496, SAR439859, ZN-c5, H3B-6545, bazedoxifene, lasofoxifene).
2. Prior anticancer or investigational drug treatment within the following windows:

   1. Fulvestrant treatment \< 42 days before first dose of study drug
   2. Any endocrine therapy \< 14 days before first dose of study drug
   3. Chemotherapy \< 21 days before first dose of study drug
   4. Any investigational anti-cancer drug therapy \< 28 days or five half-lives (whichever is shorter) before the first dose of study drug. Enrollment of subjects whose most recent therapy was an investigational agent should be discussed with the Sponsor
   5. Bisphosphonates or RANKL inhibitors initiated or dose changed \< 3 months prior to first dose of study drug
3. Presence of symptomatic visceral disease as defined in protocol.