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

Study Overview
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Brief Summary
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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) .

Detailed Description
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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.

Official Title
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Elacestrant Monotherapy vs. Standard of Care for the Treatment of Patients With ER+/HER2- Advanced Breast Cancer Following CDK4/6 Inhibitor Therapy: A Phase 3 Randomized, Open-label, Active-controlled, Multicenter Trial

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Elacestrant
* Drug: Standard of Care


Participation Criteria
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Eligibility Criteria
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Critical Inclusion Criteria: 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. Subjects must be appropriate candidates for endocrine monotherapy Subjects must have measurable disease or nonmeasurable (evaluable) bone-only disease 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). Subjects must have ER+/HER2- tumor status 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. Subjects must have received prior treatment with a CDK4/6 inhibitor in combination with either fulvestrant or an aromatase inhibitor (AI). Subjects may have received no more than one line of chemotherapy in the advanced/metastatic setting. Subjects must have ctDNA ESR1-mut or ESR1-WT status as determined by central testing with Guardant360CDx® before subject is randomized. Critical Exclusion Criteria: Prior treatment with elacestrant, GDC-0810, GDC-0927, GDC-9545, LSZ102, AZD9496, bazedoxifene, or other investigational SERD or investigational ER antagonist. Prior anticancer or investigational drug treatment within the following windows: Fulvestrant treatment < 28 days before first dose of study drug Any endocrine therapy < 14 days before first dose of study drug (with the exception of GnRH agonist therapy in male subjects) Chemotherapy < 21 days before first dose of study drug 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 Presence of symptomatic visceral disease as defined in protocol.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Elacestrant<br>Subjects in Arm 1 will receive elacestrant | Drug: Elacestrant<br>* 400 mg/day once daily oral dosing<br>* Other names: RAD1901;|
| Active Comparator: Standard of Care (SoC)<br>Subjects in Arm 2 will receive Investigator's choice of one of the Standard of Care drugs (fulvestrant, anastrozole, letrozole, or exemestane) | Drug: Standard of Care<br>* Fulvestrant: 500 mg administered intramuscularly (IM) into the buttocks as two 5 mL injections on C1D1, C1D15 and C2D1 and Day 1 of every subsequent 28-day cycle Anastrozole 1 mg/day on a continuous dosing schedule Letrozole: 2.5 mg/day on a continuous dosing schedule Exemestane: 25 mg/day on a continuous dosing schedule<br>* Other names: Faslodex, Arimidex, Femara, Aromasin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival in ESR1-mut Subjects | Progression-free Survival based on blinded IRC assessment in ESR1-mut subjects defined as the length of time from randomization until the date of objective disease progression per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) as assessed by the blinded IRC or death from any cause. Progression is defined per RECIST v1.1 as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. | From Date of Randomization until Disease Progression or Death Due to Any Cause (up to 12 Months) | 
| Progression-free Survival in All Subjects | Progression-free Survival based on blinded Imaging Review Committee (IRC) assessment in all (ESR1-mut and ESR1-WT) subjects | From Date of Randomization until Disease Progression or Death Due to Any Cause (up to 12 Months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival in ESR1-mut Subjects | Overall Survival in ESR1-mut subjects, where Overall Survival is defined as the length of time from randomization until the date of death from any cause | From Date of Randomization until Death Due to Any Cause (Estimated up to 24 Months) | 
| Overall Survival in All Subjects | Overall Survival in All (ESR1-mut and ESR1-WT) Subjects | From Date of Randomization until Death Due to Any Cause (Estimated up to 24 Months) |