A Study of Imlunestrant, Investigator's Choice of Endocrine Therapy, and Imlunestrant Plus Abemaciclib in Participants With ER+, HER2- Advanced Breast Cancer (EMBER-3)

• ClinicalTrials.gov Identifier: NCT04975308
• Recruitment Status: Recruiting
• First Posted: July 23, 2021
• Last Update Posted: March 9, 2023
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Tracking Information

• First Submitted Date: July 22, 2021
• First Posted Date: July 23, 2021
• Last Update Posted Date: March 9, 2023
• Actual Study Start Date: October 4, 2021
• Estimated Primary Completion Date: April 30, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 13, 2022)

• Progression Free Survival (PFS) in the Intent-to-Treat (IIT) Population [ Time Frame: Randomization to the date of first documented progression of disease or death from any cause (estimated as up to 3 years) ]
  PFS by investigator assessment in the IIT population
• PFS in the Estrogen Receptor 1 (ESR1)-mutation Detected Population [ Time Frame: Randomization to the date of first documented progression of disease or death from any cause (estimated as up to 3 years) ]
  PFS by investigator assessment in ESR1-mutation detected population

Original Primary Outcome Measures (submitted: July 22, 2021)

Progression Free Survival (PFS) [ Time Frame: Randomization to the date of first documented progression of disease or death from any cause (estimated as up to 3 years) ]

PFS by investigator assessment

Current Secondary Outcome Measures (submitted: September 13, 2022)

• Overall Survival (OS) in the IIT Population [ Time Frame: Randomization until death from any cause (estimated as up to 5 years) ]
  OS in the IIT population
• OS in the ESR1-mutation Detected Population [ Time Frame: Randomization until death from any cause (estimated as up to 5 years) ]
  OS in the ESR1-mutation detected population
• Objective Response Rate (ORR): Percentage of Participants Who Achieve a Confirmed Best Overall Response of Complete Response (CR) or Partial Response (PR) [ Time Frame: Randomization until measured progressive disease (estimated as up to 1 year) ]
  ORR
• Duration of Response (DoR) [ Time Frame: Date of CR or PR to date of disease progression or death due to any cause (estimated up to 3 years) ]
  DoR
• Clinical Benefit Rate (CBR): Percentage of Participants Who Achieve a Best Overall Response of CR, PR or Stable Disease for Greater than or Equal to (≥) 24 Weeks [ Time Frame: Randomization until measured progressive disease (estimated as up to 1 year) ]
  CBR
• Progression Free Survival (PFS) [ Time Frame: Randomization to the date of first documented progression of disease or death from any cause(estimated as up to 3 years) ]
  PFS by blinded independent review
• Patient Reported Outcomes (PRO): Time to Worsening of "Worst Pain" [ Time Frame: Screening through follow-up (estimated as up to 3 years) ]
  Measured by the Worst Pain Numeric Rating Scale (NRS). NRS is a single item, participant-administered, 11-point horizontal scale anchored at 0 and 10, with 0 representing "no pain" and 10 representing "pain as bad as you can imagine."
• Pharmacokinetics (PK): Steady State Plasma Concentrations of Imlunestrant [ Time Frame: Cycle 2 to Cycle 4 (cycle = 28 days) ]
  PK: steady state plasma concentrations of imlunestrant
• PK: Steady State Plasma Concentrations of Imlunestrant and Abemaciclib [ Time Frame: Cycle 2 to Cycle 4 (cycle = 28 days) ]
  PK: steady state plasma concentrations of imlunestrant and abemaciclib

Original Secondary Outcome Measures (submitted: July 22, 2021)

• Overall Survival (OS) [ Time Frame: Randomization until death from any cause (estimated as up to 5 years) ]
  OS
• Objective Response Rate (ORR): Percentage of Participants Who Achieve a Confirmed Best Overall Response of Complete Response (CR) or Partial Response (PR) [ Time Frame: Randomization until measured progressive disease (estimated as up to 1 year) ]
  ORR
• Duration of Response (DoR) [ Time Frame: Date of CR or PR to date of disease progression or death due to any cause (estimated up to 3 years) ]
  DoR
• Clinical Benefit Rate (CBR): Percentage of Participants Who Achieve a Best Overall Response of CR, PR or Stable Disease for Greater than or Equal to (≥) 24 Weeks [ Time Frame: Randomization until measured progressive disease (estimated as up to 1 year) ]
  CBR
• PFS by Estrogen Receptor 1 Gene (ESR1) Mutation Status in Plasma [ Time Frame: Randomization to the date of first documented progression of disease or death from any cause (estimated as up to 3 years) ]
  Investigator-assessed PFS by ESR1 mutation status in plasma
• Progression Free Survival (PFS) [ Time Frame: Randomization to the date of first documented progression of disease or death from any cause(estimated as up to 3 years) ]
  PFS by blinded independent review
• Patient Reported Outcomes (PRO): Time to Worsening of "Worst Pain" [ Time Frame: Screening through follow-up (estimated as up to 3 years) ]
  Measured by the Worst Pain Numeric Rating Scale (NRS). NRS is a single item, participant-administered, 11-point horizontal scale anchored at 0 and 10, with 0 representing "no pain" and 10 representing "pain as bad as you can imagine."
• Pharmacokinetics (PK): Steady State Plasma Concentrations of LY3484356 [ Time Frame: Cycle 2 to Cycle 4 (cycle = 28 days) ]
  PK: steady state plasma concentrations of LY3484356

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

Descriptive Information

• Brief Title: A Study of Imlunestrant, Investigator's Choice of Endocrine Therapy, and Imlunestrant Plus Abemaciclib in Participants With ER+, HER2- Advanced Breast Cancer
• Official Title: EMBER-3: A Phase 3, Randomized, Open-Label Study of Imlunestrant, Investigator's Choice of Endocrine Therapy, and Imlunestrant Plus Abemaciclib in Patients With Estrogen Receptor Positive, HER2 Negative Locally Advanced or Metastatic Breast Cancer Previously Treated With Endocrine Therapy
• Brief Summary: The main purpose of this study is to measure how well imlunestrant works compared to standard hormone therapy, and how well imlunestrant with abemaciclib work compared to imlunestrant in participants with breast cancer that is estrogen receptor positive (ER+) and human epidermal receptor 2 negative (HER2-). Participants must have breast cancer that is advanced or has spread to another part of the body. Study participation could last up to 5 years.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Breast Neoplasms
• Neoplasm Metastasis

Intervention

• Drug: Imlunestrant
  Administered orally.
  Other Name: LY3484356
• Drug: Exemestane
  Administered orally.
• Drug: Fulvestrant
  Administered IM.
• Drug: Abemaciclib
  Administered orally.
  Other Name: LY2835219

Study Arms

• Experimental: Imlunestrant
  Imlunestrant administered orally.
  Intervention: Drug: Imlunestrant
• Active Comparator: Investigator's Choice of Endocrine Therapy
  Investigator's choice of exemestane administered orally or fulvestrant administered intramuscularly (IM). See local approved label for additional instructions.
  Interventions:

  • Drug: Exemestane
  • Drug: Fulvestrant
• Experimental: Imlunestrant plus Abemaciclib
  Imlunestrant plus abemaciclib administered orally.
  Interventions:

  • Drug: Imlunestrant
  • Drug: Abemaciclib

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 30, 2022): 860
• Original Estimated Enrollment (submitted: July 22, 2021): 500
• Estimated Study Completion Date: August 31, 2027
• Estimated Primary Completion Date: April 30, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Have a diagnosis of ER+, HER2- locally advanced or metastatic breast cancer

• Have disease that has demonstrated progression on or after an aromatase inhibitor alone or in combination with a cyclin-dependent kinase (CDK)4/6 inhibitor

  -- Participants are expected to have received prior treatment with a CDK4/6 inhibitor, if this treatment is approved and can be reimbursed

• Must be deemed appropriate for treatment with endocrine therapy
• If female, have a postmenopausal status by natural or surgical means or by ovarian function suppression
• Have RECIST evaluable disease (measurable disease and/or nonmeasurable bone-only disease)
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group scale (Oken et al. 1982)
• Have adequate renal, hematologic, and hepatic organ function
• Must be able to swallow capsules/tablets

Exclusion Criteria:

• Have received prior treatment with chemotherapy (except for neoadjuvant/ adjuvant chemotherapy), fulvestrant, or any investigational-ER-directed therapy (including SERDs and non-SERDs), any PI3K-, mTOR- or AKT- inhibitor
• Have visceral crisis, lymphangitic spread within the lung, or any evidence of leptomeningeal disease.
• Have symptomatic or untreated brain metastasis.
• Have serious preexisting medical conditions that, in the judgment of the investigator, would preclude participation in this study
• Known allergic reaction against any of the components of the study treatment

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or; 1-317-615-4559; ClinicalTrials.gov@lilly.com

• Listed Location Countries: Argentina, Australia, Austria, Belgium, Brazil, China, Czechia, France, Germany, Greece, India, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Russian Federation, Spain, Taiwan, Turkey, Ukraine, United States

Administrative Information

• NCT Number: NCT04975308
• Other Study ID Numbers: 18175; J2J-OX-JZLC ( Other Identifier: Eli Lilly and Company ); 2021-000079-35 ( EudraCT Number )
• Has Data Monitoring Committee: No

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
• Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and European Union (EU), whichever is later. Data will be indefinitely available for requesting.
• Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• URL: https://vivli.org/

• Current Responsible Party: Eli Lilly and Company
• Original Responsible Party: Same as current
• Current Study Sponsor: Eli Lilly and Company
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST); Eli Lilly and Company

• PRS Account: Eli Lilly and Company
• Verification Date: March 2023