Skip to main content
OpenTrials
Active, Not Recruiting

NCT Number: NCT04975308

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

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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Notify Me

Key information

Conditions

Breast Neoplasms Breast Diseases Neoplasm Metastasis Neoplasms Neoplasms by Site Neoplastic Processes Pathologic Processes Pathological Conditions, Signs and Symptoms Skin Diseases Skin and Connective Tissue Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Instituto de Investigaciones Clínicas Mar del Plata, Mar del Plata, Buenos Aires, Argentina

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Imlunestrant

Drug

Administered orally.

Other names: LY3484356

Exemestane

Drug

Administered orally.

Fulvestrant

Drug

Administered IM.

Abemaciclib

Drug

Administered orally.

Other names: LY2835219

Primary outcomes

  1. Investigator-assessed Progression Free Survival (PFS) (Between Arm A and Arm B)

    Time frame: Randomization to the date of first documented progression of disease or death from any cause (up to 28 months)

    PFS was defined as the time from randomization to the date of first documented progression of disease or death from any cause in the absence of disease progression using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria, as assessed by investigator. Progressive disease (PD) was defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. Participants known to be alive and without disease progression were censored at the date of their last adequate tumor assessment per RECIST 1.1 criteria, or date of randomization (whichever is later).

  2. Investigator-assessed PFS (Between Arm C and Arm A)

    Time frame: Randomization to the date of first documented progression of disease or death from any cause (up to 26 months)

    PFS was defined as the time from randomization to the date of first documented progression of disease or death from any cause in the absence of disease progression using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria, as assessed by investigator. Progressive disease (PD) was defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. Participants known to be alive and without disease progression were censored at the date of their last adequate tumor assessment per RECIST 1.1 criteria, or date of randomization (whichever is later).

  3. Investigator-assessed PFS in the Estrogen Receptor 1 (ESR1)-Mutation Detected Population (Between Arm A and Arm B)

    Time frame: Randomization to the date of first documented progression of disease or death from any cause (up to 28 months)

    PFS was defined as the time from randomization to the date of first documented progression of disease or death from any cause in the absence of disease progression using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria, as assessed by investigator. Progressive disease (PD) was defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. Participants known to be alive and without disease progression were censored at the date of their last adequate tumor assessment per RECIST 1.1 criteria, or date of randomization (whichever is later).

Secondary outcomes

  1. Blinded Independent Review Committee (BIRC) Assessed PFS (Between Arm A and Arm B)

    Time frame: Randomization to the date of first documented progression of disease or death from any cause (up to 28 months)

    PFS was defined as the time from randomization to the date of first documented progression of disease or death from any cause in the absence of disease progression using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria, as assessed by investigator. Progressive disease (PD) was defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. Participants known to be alive and without disease progression were censored at the date of their last adequate tumor assessment per RECIST 1.1 criteria, or date of randomization (whichever is later).

  2. Blinded Independent Review Committee (BIRC) Assessed PFS (Between Arm C and Arm A)

    Time frame: Randomization to the date of first documented progression of disease or death from any cause (up to 25 months)

    PFS was defined as the time from randomization to the date of first documented progression of disease or death from any cause in the absence of disease progression using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria, as assessed by investigator. Progressive disease (PD) was defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. Participants known to be alive and without disease progression were censored at the date of their last adequate tumor assessment per RECIST 1.1 criteria, or date of randomization (whichever is later).

  3. Percentage of Participants With Investigator-assessed Objective Response Rate (ORR) (Between Arm A and Arm B)

    Time frame: Randomization until measured progressive disease (up to 28 months)

    ORR was the best confirmed overall tumor response of complete response (CR) or partial response (PR) as classified by the investigator according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1). CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions.

  4. Investigator-assessed Duration of Response (DoR) (Between Arm A and Arm B)

    Time frame: From Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Up To 26 Months)

    DoR is defined as the time from the date measurement criteria for CR or PR (whichever is first recorded) are first met until the first date that disease is recurrent or objective progression is observed, per RECIST 1.1 criteria, or the date of death from any cause in the absence of objectively determined disease progression or recurrence. Participants known to be alive and without disease progression were censored at the date of their last adequate tumor assessment per RECIST 1.1 criteria, or date of randomization (whichever is later).

  5. Percentage of Participants With Investigator-assessed Clinical Benefit Rate (CBR) (Between Arm A and Arm B)

    Time frame: Randomization until measured progressive disease (up to 28 months)

    CBR was the best confirmed overall tumor response of stable disease (SD) for greater than or equal to (≥) 24 weeks, CR or PR as defined by RECIST v1.1. CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD) for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.

  6. Percentage of Participants With Investigator-assessed Objective Response Rate (ORR) (Between Arm C and Arm A)

    Time frame: Randomization until measured progressive disease (up to 26 months)

    ORR was the best confirmed overall tumor response of complete response (CR) or partial response (PR) as classified by the investigator according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1). CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions.

  7. Investigator-assessed Duration of Response (DoR) (Between Arm C and Arm A)

    Time frame: From Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Up To 19 Months)

    DoR is defined as the time from the date measurement criteria for CR or PR (whichever is first recorded) are first met until the first date that disease is recurrent or objective progression is observed, per RECIST 1.1 criteria, or the date of death from any cause in the absence of objectively determined disease progression or recurrence. Participants known to be alive and without disease progression were censored at the date of their last adequate tumor assessment per RECIST 1.1 criteria, or date of randomization (whichever is later).

  8. Percentage of Participants With Investigator-assessed Clinical Benefit Rate (CBR) (Between Arm C and Arm A)

    Time frame: Randomization until measured progressive disease (up to 26 months)

    CBR was the best confirmed overall tumor response of stable disease (SD) for greater than or equal to (≥) 24 weeks, CR or PR as defined by RECIST v1.1. CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD) for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.

  9. Time to Sustained Worsening of the "Worst Pain" as Measured by Worst Pain NRS (Between Arm A and Arm B)

    Time frame: Randomization through follow-up (up to 24 months)

    Time to sustained worsening of worst pain is defined as the time from randomization to the first increase (≥2 points) in the weekly average of the worst pain score, with confirmation in the next consecutive week. It was measured by the Worst Pain Numeric Rating Scale (NRS). NRS is a single-item, participant-administered, 11-point horizontal scale ranging from 0 to 10, with 0 representing "no pain" and 10 representing "pain as bad as you can imagine." Participants not known to have sustained worsening will be censored at the last documented assessment.

  10. Time to Sustained Worsening of the "Worst Pain" as Measured by Worst Pain NRS (Between Arm C and Arm A)

    Time frame: Randomization through follow-up (up to 20 months)

    Time to sustained worsening of worst pain is defined as the time from randomization to the first increase (≥2 points) in the weekly average of the worst pain score, with confirmation in the next consecutive week. It was measured by the Worst Pain Numeric Rating Scale (NRS). NRS is a single-item, participant-administered, 11-point horizontal scale ranging from 0 to 10, with 0 representing "no pain" and 10 representing "pain as bad as you can imagine." Participants not known to have sustained worsening will be censored at the last documented assessment.

  11. Pharmacokinetics (PK): Plasma Concentration of Imlunestrant

    Time frame: Cycle 1 Day 1 (within 2 to 4 hours post-dose), Cycle 2 Day 1 (Predose), Cycle 3 Day 1 (3 hours post-dose, 5 hours post-dose), Cycle 4 Day 1 (Predose)

    • Sampling timepoints for PK outcome analysis were relative to Imlunestrant dosing.
    • For Cycle 1 Day 1, sampling occurred at a "single" timepoint within the 2- to 4-hour window after Imlunestrant dosing, with the timepoint varying across analyzed participants.

  12. Pharmacokinetics (PK): Plasma Concentration of Total Abemaciclib

    Time frame: Cycle 1 Day 1 (within 2 to 4 hours post-dose), Cycle 2 Day 1 (Predose), Cycle 3 Day 1 (3 hours post-dose, 5 hours post-dose), Cycle 4 Day 1 (Predose)

    • Plasma concentration of total abemaciclib is the concentration of the parent abemaciclib and its metabolites in the plasma.
    • Sampling timepoints for PK outcome analysis were relative to Imlunestrant dosing.
    • For Cycle 1 Day 1, sampling occurred at a "single" timepoint within the 2- to 4-hour window after Imlunestrant dosing, with the timepoint varying across analyzed participants.

  13. Overall Survival (OS) in the ITT Population

    Time frame: Randomization until death from any cause (estimated as up to 5 years)

    OS in the ITT population

  14. 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

  15. Blinded Independent Review Committee (BIRC) Assessed PFS in the ESR1-Mutation Detected Population (Between Arm A and Arm B)

    Time frame: Randomization to the date of first documented progression of disease or death from any cause (up to 28 months)

    PFS was defined as the time from randomization to the date of first documented progression of disease or death from any cause in the absence of disease progression using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria, as assessed by investigator. Progressive disease (PD) was defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. Participants known to be alive and without disease progression were censored at the date of their last adequate tumor assessment per RECIST 1.1 criteria, or date of randomization (whichever is later).

  16. Percentage of Participants With Investigator-assessed Objective Response Rate (ORR) in the ESR1-Mutation Detected Population (Between Arm A and Arm B)

    Time frame: Randomization until measured progressive disease (up to 28 months)

    ORR was the best confirmed overall tumor response of complete response (CR) or partial response (PR) as classified by the investigator according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1). CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions.

  17. Investigator-assessed Duration of Response (DoR) in the ESR1-Mutation Detected Population (Between Arm A and Arm B)

    Time frame: From Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Up To 24 Months)

    DoR is defined as the time from the date measurement criteria for CR or PR (whichever is first recorded) are first met until the first date that disease is recurrent or objective progression is observed, per RECIST 1.1 criteria, or the date of death from any cause in the absence of objectively determined disease progression or recurrence. Participants known to be alive and without disease progression were censored at the date of their last adequate tumor assessment per RECIST 1.1 criteria, or date of randomization (whichever is later).

  18. Percentage of Participants With Investigator-assessed Clinical Benefit Rate (CBR) in the ESR1-Mutation Detected Population (Between Arm A and Arm B)

    Time frame: Randomization until measured progressive disease (up to 28 months)

    CBR was the best confirmed overall tumor response of stable disease (SD) for greater than or equal to (≥) 24 weeks, CR or PR as defined by RECIST v1.1. CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD) for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.

Sponsors and collaborators

Lead sponsor

Eli Lilly and Company

Industry

Registry information

Official study 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

Acronym: EMBER-3

Important dates

Study start
2021
Primary completion
2024
Study completion
2027
First posted
Jul 23, 2021
Registry last updated
Jul 22, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.