A Study of Imlunestrant Versus Standard Endocrine Therapy in Participants With Early 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 in participants with early breast cancer that is estrogen receptor positive (ER+) and human epidermal receptor 2 negative (HER2-). Participants must have already taken endocrine therapy for two to five years and must have a higher-than-average risk for their cancer to return. Study participation could last up to 10 years.

Official Title
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EMBER-4: A Randomized, Open-Label, Phase 3 Study of Adjuvant Imlunestrant vs Standard Adjuvant Endocrine Therapy in Patients Who Have Previously Received 2 to 5 Years of Adjuvant Endocrine Therapy for ER+, HER2- Early Breast Cancer With an Increased Risk of Recurrence

Conditions
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Breast Neoplasms

Intervention / Treatment
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* Drug: Imlunestrant
* Drug: Tamoxifen
* Drug: Anastrozole
* Drug: Letrozole
* Drug: Exemestane


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a diagnosis of ER+, HER2- early-stage, resected, invasive breast cancer without evidence of distant metastasis. Participants must have received at least 24 months but not more than 60 months of any adjuvant ET, from time of adjuvant ET initiation. Participants may have received (neo) adjuvant chemotherapy and/or targeted therapy with a CDK4/6- or PARP- inhibitor. Must have an increased risk of disease recurrence based on clinical-pathological risk features. Have a Performance Status of 0 or 1 on the Eastern Cooperative Oncology Group scale. Have adequate organ function. Exclusion Criteria: Have any evidence of metastatic disease (including contralateral ALN) or inflammatory breast cancer at primary breast cancer diagnosis. Participants with more than a 6-month consecutive gap in therapy during the course of prior adjuvant ET. Participants who have completed or discontinued prior adjuvant ET >6 months prior to screening. Participants with a history of previous breast cancer are excluded, with the exception of ipsilateral DCIS treated by locoregional therapy alone ≥5 years ago. Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 180 days after the last dose of study intervention. Participant has previously received ET of any duration for breast cancer prevention (tamoxifen or AIs) or raloxifene. Participants with a history of any other cancer. Have serious preexisting medical conditions that, in the judgment of the investigator, would preclude participation in this study.

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 tamoxifen, anastrozole, letrozole, or exemestane administered per local approved label. | Drug: Tamoxifen<br>* Administered per local approved label.<br>Drug: Anastrozole<br>* Administered per local approved label.<br>Drug: Letrozole<br>* Administered per local approved label.<br>Drug: Exemestane<br>* Administered per local approved label.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Invasive Disease-Free Survival (IDFS) | IDFS excluding second non-breast primary invasive cancers | Randomization to recurrence or death from any cause (up to 10 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Distant Recurrence-Free Survival (DRFS) | DRFS | Randomization to Distant Recurrence or Death from Any Cause (up to 10 Years) | 
| Overall Survival (OS) | OS | Randomization to Death from Any Cause (up to 10 Years) | 
| Pharmacokinetics (PK): Steady State Plasma Concentrations of Imlunestrant | PK: steady state plasma concentrations of imlunestrant | Year 1, Month 2 to Month 4 | 
| Change from Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire (EORTC QLQ-C30) Physical Functioning | The EORTC QLQ-C30 is a 30-question patient reported instrument used to assess multidimensional quality of life (QOL) in cancer patients. It consists of 15 domains: 1 global QOL scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). Physical functioning was measured by items 1 to 5. The sum score was linearly transformed to the range 0 - 100 as recommended by the EORTC (higher score is better). | Visit 1 Day 1 up to end of Year 5 | 
| Change from Baseline in the EORTC QLQ-C30 Role Functioning | The EORTC QLQ-C30 is a 30-question patient reported instrument used to assess the multidimensional QOL in cancer patients. It consists of 15 domains: 1 global QOL scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). Role functioning was measured by items 6 and 7. The sum score was linearly transformed to the range 0 - 100 as recommended by the EORTC (higher score is better). | Visit 1 Day 1 up to end of Year 5 | 
| Change from Baseline in the EORTC QLQ-C30 Global QOL | The EORTC QLQ-C30 is a 30-question patient reported instrument used to assess the multidimensional QOL in cancer patients. It consists of 15 domains: 1 global QOL scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). Global QOL was measured by items 29 and 30. The sum score was linearly transformed to the range 0 - 100 as recommended by the EORTC (higher score is better). | Visit 1 Day 1 up to end of Year 5 | 
| Proportion of Time on Study Treatment with High Overall Adverse Event Burden | FACT GP5 = Functional Assessment of Cancer Therapy - General Physical Well-being Item 5 (FACT GP5). High overall adverse event burden is defined as a score of 3 or 4 on a 5-point Likert scale. Higher scores represent higher symptom burden. | Visit 1 Day 1 up to end of Year 5 |