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

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.

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, nonmeasurable (evaluable) 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+/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).

8. Subjects may have received no more than one line of chemotherapy in the
advanced/metastatic setting.

9. Subjects must have ctDNA ESR1-mut or ESR1-WT status as determined by central testing
before subject is randomized.

Critical Exclusion Criteria:

1. Prior treatment with elacestrant, GDC-0810, GDC-0927, GDC-9545, LSZ102, AZD9496,
bazedoxifene, or other investigational SERD or investigational ER antagonist.

2. Prior anticancer or investigational drug treatment within the following windows:

1. Fulvestrant treatment < 28 days before first dose of study drug

2. Any endocrine therapy < 14 days before first dose of study drug (with the
exception of GnRH agonist therapy in male subjects)

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

3. Presence of symptomatic visceral disease as defined in protocol.