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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Breast Neoplasms, Neoplasm Metastasis

Intervention / Treatment
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* Drug: Imlunestrant
* Drug: Exemestane
* Drug: Fulvestrant
* Drug: Abemaciclib


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Imlunestrant<br>Imlunestrant administered orally. | Drug: Imlunestrant<br>* Administered orally.<br>* Other names: LY3484356;|
| Active Comparator: Investigator's Choice of Endocrine Therapy<br>Investigator's choice of exemestane administered orally or fulvestrant administered intramuscularly (IM). See local approved label for additional instructions. | Drug: Exemestane<br>* Administered orally.<br>Drug: Fulvestrant<br>* Administered IM.<br>|
| Experimental: Imlunestrant plus Abemaciclib<br>Imlunestrant plus abemaciclib administered orally. | Drug: Imlunestrant<br>* Administered orally.<br>* Other names: LY3484356;Drug: Abemaciclib<br>* Administered orally.<br>* Other names: LY2835219;|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) in the IIT Population | OS in the IIT population | Randomization until death from any cause (estimated as up to 5 years) | 
| OS in the ESR1-mutation Detected Population | OS in the ESR1-mutation detected population | Randomization until death from any cause (estimated as up to 5 years) | 
| Objective Response Rate (ORR): Percentage of Participants Who Achieve a Confirmed Best Overall Response of Complete Response (CR) or Partial Response (PR) | ORR | Randomization until measured progressive disease (estimated as up to 1 year) | 
| Duration of Response (DoR) | DoR | Date of CR or PR to date of disease progression or death due to any cause (estimated up to 3 years) | 
| 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 | CBR | Randomization until measured progressive disease (estimated as up to 1 year) | 
| Progression Free Survival (PFS) | PFS by blinded independent review | Randomization to the date of first documented progression of disease or death from any cause(estimated as up to 3 years) | 
| Patient Reported Outcomes (PRO): Time to Worsening of Worst Pain | 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. | Screening through follow-up (estimated as up to 3 years) | 
| Pharmacokinetics (PK): Steady State Plasma Concentrations of Imlunestrant | PK: steady state plasma concentrations of imlunestrant | Cycle 2 to Cycle 4 (cycle = 28 days) | 
| PK: Steady State Plasma Concentrations of Imlunestrant and Abemaciclib | PK: steady state plasma concentrations of imlunestrant and abemaciclib | Cycle 2 to Cycle 4 (cycle = 28 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SERD