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
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 874
- 试验地点
- 402
- 主要终点
- Investigator-assessed Progression Free Survival (PFS) (Between Arm A and Arm B)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Arm A: Imlunestrant
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.
干预措施: Imlunestrant (Drug)
Arm B: Investigator's Choice of Endocrine Therapy
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.
干预措施: Exemestane (Drug)
Arm B: Investigator's Choice of Endocrine Therapy
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.
干预措施: Fulvestrant (Drug)
Arm C: Imlunestrant + Abemaciclib
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.
干预措施: Imlunestrant (Drug)
Arm C: Imlunestrant + Abemaciclib
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.
干预措施: Abemaciclib (Drug)
结局指标
主要结局
Investigator-assessed Progression Free Survival (PFS) (Between Arm A and Arm B)
时间窗: 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).
Investigator-assessed PFS (Between Arm C and Arm A)
时间窗: 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).
Investigator-assessed PFS in the Estrogen Receptor 1 (ESR1)-Mutation Detected Population (Between Arm A and Arm B)
时间窗: 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).
次要结局
- Blinded Independent Review Committee (BIRC) Assessed PFS (Between Arm A and Arm B)(Randomization to the date of first documented progression of disease or death from any cause (up to 28 months))
- Blinded Independent Review Committee (BIRC) Assessed PFS (Between Arm C and Arm A)(Randomization to the date of first documented progression of disease or death from any cause (up to 25 months))
- Percentage of Participants With Investigator-assessed Objective Response Rate (ORR) (Between Arm A and Arm B)(Randomization until measured progressive disease (up to 28 months))
- Investigator-assessed Duration of Response (DoR) (Between Arm A and Arm B)(From Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Up To 26 Months))
- Percentage of Participants With Investigator-assessed Clinical Benefit Rate (CBR) (Between Arm A and Arm B)(Randomization until measured progressive disease (up to 28 months))
- Percentage of Participants With Investigator-assessed Objective Response Rate (ORR) (Between Arm C and Arm A)(Randomization until measured progressive disease (up to 26 months))
- Investigator-assessed Duration of Response (DoR) (Between Arm C and Arm A)(From Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Up To 19 Months))
- Percentage of Participants With Investigator-assessed Clinical Benefit Rate (CBR) (Between Arm C and Arm A)(Randomization until measured progressive disease (up to 26 months))
- Time to Sustained Worsening of the "Worst Pain" as Measured by Worst Pain NRS (Between Arm A and Arm B)(Randomization through follow-up (up to 24 months))
- Time to Sustained Worsening of the "Worst Pain" as Measured by Worst Pain NRS (Between Arm C and Arm A)(Randomization through follow-up (up to 20 months))
- Pharmacokinetics (PK): Plasma Concentration of Imlunestrant(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))
- Pharmacokinetics (PK): Plasma Concentration of Total Abemaciclib(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))
- Overall Survival (OS) in the ITT Population(Randomization until death from any cause (estimated as up to 5 years))
- OS in the ESR1-mutation Detected Population(Randomization until death from any cause (estimated as up to 5 years))
- Blinded Independent Review Committee (BIRC) Assessed PFS in the ESR1-Mutation Detected Population (Between Arm A and Arm B)(Randomization to the date of first documented progression of disease or death from any cause (up to 28 months))
- Percentage of Participants With Investigator-assessed Objective Response Rate (ORR) in the ESR1-Mutation Detected Population (Between Arm A and Arm B)(Randomization until measured progressive disease (up to 28 months))
- Investigator-assessed Duration of Response (DoR) in the ESR1-Mutation Detected Population (Between Arm A and Arm B)(From Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Up To 24 Months))
- Percentage of Participants With Investigator-assessed Clinical Benefit Rate (CBR) in the ESR1-Mutation Detected Population (Between Arm A and Arm B)(Randomization until measured progressive disease (up to 28 months))
- OS in the ESR1-mutation Detected Population(Randomization until death from any cause (estimated as up to 5 years))