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

• ClinicalTrials.gov Identifier: NCT03778931
• Recruitment Status: Active, not recruiting
• First Posted: December 19, 2018
• Results First Posted: December 5, 2023
• Last Update Posted: March 29, 2024
• Sponsor: Stemline Therapeutics, Inc.
• Information provided by (Responsible Party): Stemline Therapeutics, Inc.

Tracking Information

• First Submitted Date: December 3, 2018
• First Posted Date: December 19, 2018
• Results First Submitted Date: March 20, 2023
• Results First Posted Date: December 5, 2023
• Last Update Posted Date: March 29, 2024
• Actual Study Start Date: May 10, 2019
• Actual Primary Completion Date: August 24, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 9, 2023)

• Progression-free Survival in ESR1-mut Subjects [ Time Frame: From Date of Randomization until Disease Progression or Death Due to Any Cause (up to 12 Months) ]
  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.
• Progression-free Survival in All Subjects [ Time Frame: From Date of Randomization until Disease Progression or Death Due to Any Cause (up to 12 Months) ]
  Progression-free Survival based on blinded Imaging Review Committee (IRC) assessment in all (ESR1-mut and ESR1-WT) subjects

Original Primary Outcome Measures (submitted: December 14, 2018)

• Progression Free Survival (PFS) in the ESR1-mut subjects [ Time Frame: From Date of Randomization until Disease Progression or Death Due to Any Cause (up to 12 Months) ]
  Progression Free Survival (PFS) based on blinded IRC assessment in the ESR1-mut subjects
• PFS in all (ESR1-mut and ESR1-WT) subjects [ Time Frame: From Date of Randomization until Disease Progression or Death Due to Any Cause (up to 12 Months) ]
  PFS based on blinded Imaging Review Committee (IRC) assessment in all (ESR1-mut and ESR1-WT) subjects

Current Secondary Outcome Measures (submitted: March 20, 2023)

• Overall Survival in ESR1-mut Subjects [ Time Frame: From Date of Randomization until Death Due to Any Cause (Estimated up to 24 Months) ]
  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
• Overall Survival in All Subjects [ Time Frame: From Date of Randomization until Death Due to Any Cause (Estimated up to 24 Months) ]
  Overall Survival in All (ESR1-mut and ESR1-WT) Subjects

Original Secondary Outcome Measures (submitted: December 14, 2018)

• Objective Survival (OS) in ESR1-mut subjects [ Time Frame: From Date of Randomization until Death Due to Any Cause (Estimated up to 24 Months) ]
  OS in ESR1-mut subjects, where OS is defined as the length of time from randomization until the date of death from any cause
• OS in all (ESR1-mut and ESR1-WT) subjects [ Time Frame: From Date of Randomization until Death Due to Any Cause (Estimated up to 24 Months) ]
  OS in all (ESR1-mut and ESR1-WT) subjects

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Phase 3 Trial of Elacestrant vs. Standard of Care for the Treatment of Patients With ER+/HER2- Advanced Breast Cancer
• Official Title: 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
• Brief Summary: 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: 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.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Breast Cancer

Intervention

• Drug: Elacestrant
  400 mg/day once daily oral dosing
  Other Name: RAD1901
• Drug: Standard of Care
  • 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
  Other Name: Faslodex, Arimidex, Femara, Aromasin

Study Arms

• Experimental: Elacestrant
  Subjects in Arm 1 will receive elacestrant
  Intervention: Drug: Elacestrant
• Active Comparator: Standard of Care (SoC)
  Subjects in Arm 2 will receive Investigator's choice of one of the Standard of Care drugs (fulvestrant, anastrozole, letrozole, or exemestane)
  Intervention: Drug: Standard of Care

Publications *

• Bidard FC, Kaklamani VG, Neven P, Streich G, Montero AJ, Forget F, Mouret-Reynier MA, Sohn JH, Taylor D, Harnden KK, Khong H, Kocsis J, Dalenc F, Dillon PM, Babu S, Waters S, Deleu I, Garcia Saenz JA, Bria E, Cazzaniga M, Lu J, Aftimos P, Cortes J, Liu S, Tonini G, Laurent D, Habboubi N, Conlan MG, Bardia A. Elacestrant (oral selective estrogen receptor degrader) Versus Standard Endocrine Therapy for Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Results From the Randomized Phase III EMERALD Trial. J Clin Oncol. 2022 Oct 1;40(28):3246-3256. doi: 10.1200/JCO.22.00338. Epub 2022 May 18. Erratum In: J Clin Oncol. 2023 Aug 10;41(23):3962.
• Bardia A, Aftimos P, Bihani T, Anderson-Villaluz AT, Jung J, Conlan MG, Kaklamani VG. EMERALD: Phase III trial of elacestrant (RAD1901) vs endocrine therapy for previously treated ER+ advanced breast cancer. Future Oncol. 2019 Oct;15(28):3209-3218. doi: 10.2217/fon-2019-0370. Epub 2019 Aug 20.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: March 20, 2023): 478
• Original Estimated Enrollment (submitted: December 14, 2018): 466
• Estimated Study Completion Date: August 2024
• Actual Primary Completion Date: August 24, 2021 (Final data collection date for primary outcome measure)

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 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 with Guardant360CDx® 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Austria, Belgium, Canada, Denmark, France, Greece, Hungary, Ireland, Israel, Italy, Korea, Republic of, Portugal, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT03778931
• Other Study ID Numbers: RAD1901-308
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes

• Current Responsible Party: Stemline Therapeutics, Inc.
• Original Responsible Party: Radius Pharmaceuticals, Inc.
• Current Study Sponsor: Stemline Therapeutics, Inc.
• Original Study Sponsor: Radius Pharmaceuticals, Inc.
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Stemline Therapeutics, Inc.
• Verification Date: March 2024