TriangleNCT04975308 · CITED IN SOURCE DOCUMENTS
A Study of Imlunestrant, Investigator's Choice of Endocrine Therapy, and Imlunestrant Plus Abemaciclib in Participants With ER+, HER2- Advanced Breast Cancer
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE3
- Status at capture
- ACTIVE NOT RECRUITING
- Registry last update
- 2026-07-22
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.
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
Investigator-assessed Progression Free Survival (PFS) (Between Arm A and Arm B)
Investigator-assessed PFS (Between Arm C and Arm A)
Investigator-assessed PFS in the Estrogen Receptor 1 (ESR1)-Mutation Detected Population (Between Arm A and Arm B)
Blinded Independent Review Committee (BIRC) Assessed PFS (Between Arm A and Arm B)
Blinded Independent Review Committee (BIRC) Assessed PFS (Between Arm C and Arm A)
Percentage of Participants With Investigator-assessed Objective Response Rate (ORR) (Between Arm A and Arm B)
Investigator-assessed Duration of Response (DoR) (Between Arm A and Arm B)
Percentage of Participants With Investigator-assessed Clinical Benefit Rate (CBR) (Between Arm A and Arm B)
Percentage of Participants With Investigator-assessed Objective Response Rate (ORR) (Between Arm C and Arm A)
Investigator-assessed Duration of Response (DoR) (Between Arm C and Arm A)
Percentage of Participants With Investigator-assessed Clinical Benefit Rate (CBR) (Between Arm C and Arm A)
Time to Sustained Worsening of the "Worst Pain" as Measured by Worst Pain NRS (Between Arm A and Arm B)
Time to Sustained Worsening of the "Worst Pain" as Measured by Worst Pain NRS (Between Arm C and Arm A)
Pharmacokinetics (PK): Plasma Concentration of Imlunestrant
Pharmacokinetics (PK): Plasma Concentration of Total Abemaciclib
Overall Survival (OS) in the ITT Population
OS in the ESR1-mutation Detected Population
Blinded Independent Review Committee (BIRC) Assessed PFS in the ESR1-Mutation Detected Population (Between Arm A and Arm B)
Percentage of Participants With Investigator-assessed Objective Response Rate (ORR) in the ESR1-Mutation Detected Population (Between Arm A and Arm B)
Investigator-assessed Duration of Response (DoR) in the ESR1-Mutation Detected Population (Between Arm A and Arm B)
Percentage of Participants With Investigator-assessed Clinical Benefit Rate (CBR) in the ESR1-Mutation Detected Population (Between Arm A and Arm B)
Adverse events
Limitations, agreements, and source contact
Who could take part
- 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
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- Participants received Imlunestrant 400 milligrams (mg) orally once daily on days 1 to 28 of a 28-day cycle, until disease progression or a criterion for discontinuation were met.
- intervention Names
- Drug: Imlunestrant
- label
- Arm A: Imlunestrant
- type
- EXPERIMENTAL
- description
- Participants received the investigator's choice of endocrine therapy, either exemestane 25 mg administered orally once daily on days 1 to 28 of a 28-day cycle, or Fulvestrant 500 mg intramuscularly on days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond, until disease progression or a criterion for discontinuation was met.
- intervention Names
- Drug: Exemestane
- Drug: Fulvestrant
- label
- Arm B: Investigator's Choice of Endocrine Therapy
- type
- EXPERIMENTAL
- description
- Participants received Imlunestrant 400 mg orally once daily on Days 1 to 28 of a 28-day cycle, plus Abemaciclib 150 mg orally twice daily on Days 1 to 28 of a 28-day cycle, until disease progression or a criterion for discontinuation was met.
- intervention Names
- Drug: Imlunestrant
- Drug: Abemaciclib
- label
- Arm C: Imlunestrant + Abemaciclib
- type
- EXPERIMENTAL
- interventions
- arm Group Labels
- Arm A: Imlunestrant
- Arm C: Imlunestrant + Abemaciclib
- description
- Administered orally.
- name
- Imlunestrant
- other Names
- LY3484356
- type
- DRUG
- arm Group Labels
- Arm B: Investigator's Choice of Endocrine Therapy
- description
- Administered orally.
- name
- Exemestane
- type
- DRUG
- arm Group Labels
- Arm B: Investigator's Choice of Endocrine Therapy
- description
- Administered IM.
- name
- Fulvestrant
- type
- DRUG
- arm Group Labels
- Arm C: Imlunestrant + Abemaciclib
- description
- Administered orally.
- name
- Abemaciclib
- other Names
- LY2835219
- type
- DRUG
Study design
- allocation
- RANDOMIZED
- intervention Model
- PARALLEL
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 874
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- 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).
- measure
- 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)
- description
- 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).
- measure
- 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)
- description
- 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).
- measure
- 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)
- secondary Outcomes
- description
- 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).
- measure
- 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)
- description
- 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).
- measure
- 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)
- description
- 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.
- measure
- 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)
- description
- 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).
- measure
- 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)
- description
- 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.
- measure
- 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)
- description
- 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.
- measure
- 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)
- description
- 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).
- measure
- 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)
- description
- 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.
- measure
- 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)
- description
- 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.
- measure
- 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)
- description
- 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.
- measure
- 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)
- description
- * 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.
- measure
- 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)
- description
- * 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.
- measure
- 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)
Full study description
- 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.
Source references
- references
- citation
- Jhaveri KL, Neven P, Casalnuovo ML, Kim SB, Tokunaga E, Aftimos P, Saura C, O'Shaughnessy J, Harbeck N, Carey LA, Curigliano G, Llombart-Cussac A, Lim E, Garcia Tinoco ML, Sohn J, Mattar A, Zhang Q, Huang CS, Hung CC, Martinez Rodriguez JL, Ruiz Borrego M, Nakamura R, Pradhan KR, Cramer von Laue C, Barrett E, Cao S, Wang XA, Smyth LM, Bidard FC; EMBER-3 Study Group. Imlunestrant with or without Abemaciclib in Advanced Breast Cancer. N Engl J Med. 2025 Mar 27;392(12):1189-1202. doi: 10.1056/NEJMoa2410858. Epub 2024 Dec 11.
- pmid
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- type
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- see Also Links
- label
- Study of LY3484356 Versus Hormone Therapy, in Participants With Estrogen Receptor Positive (ER+), Human Epidermal Growth Factor Receptor 2 Negative (HER2-) Breast Cancer (EMBER-3)
Source notices and limitations
Discovery and provenance
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Preserved source evidence · Not medical advice