A Study of Imlunestrant Versus Standard Endocrine Therapy in Participants With Early Breast Cancer (EMBER-4)

• ClinicalTrials.gov Identifier: NCT05514054
• Recruitment Status: Recruiting
• First Posted: August 24, 2022
• Last Update Posted: April 19, 2024
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Tracking Information

• First Submitted Date: August 23, 2022
• First Posted Date: August 24, 2022
• Last Update Posted Date: April 19, 2024
• Actual Study Start Date: October 4, 2022
• Estimated Primary Completion Date: October 15, 2027 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 23, 2022)

Invasive Disease-Free Survival (IDFS) [ Time Frame: Randomization to recurrence or death from any cause (up to 10 years) ]

IDFS excluding second non-breast primary invasive cancers

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 31, 2023)

• Distant Recurrence-Free Survival (DRFS) [ Time Frame: Randomization to Distant Recurrence or Death from Any Cause (up to 10 Years) ]
  DRFS
• Overall Survival (OS) [ Time Frame: Randomization to Death from Any Cause (up to 10 Years) ]
  OS
• Pharmacokinetics (PK): Steady State Plasma Concentrations of Imlunestrant [ Time Frame: Year 1, Month 2 to Month 4 ]
  PK: steady state plasma concentrations of imlunestrant
• Change from Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire (EORTC QLQ-C30) Physical Functioning [ Time Frame: Visit 1 Day 1 up to end of Year 5 ]
  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).
• Change from Baseline in the EORTC QLQ-C30 Role Functioning [ Time Frame: Visit 1 Day 1 up to end of Year 5 ]
  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).
• Change from Baseline in the EORTC QLQ-C30 Global QOL [ Time Frame: Visit 1 Day 1 up to end of Year 5 ]
  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).
• Proportion of Time on Study Treatment with High Overall Adverse Event Burden [ Time Frame: Visit 1 Day 1 up to end of Year 5 ]
  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.

Original Secondary Outcome Measures (submitted: August 23, 2022)

• Distant Recurrence-Free Survival (DRFS) [ Time Frame: Randomization to Distant Recurrence or Death from Any Cause (up to 10 Years) ]
  DRFS
• Overall Survival (OS) [ Time Frame: Randomization to Death from Any Cause (up to 10 Years) ]
  OS
• Pharmacokinetics (PK): Steady State Plasma Concentrations of Imlunestrant [ Time Frame: Cycle 2 to Cycle 4 (cycle = 28 days) ]
  PK: steady state plasma concentrations of imlunestrant
• Change from Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire (EORTC QLQ-C30) Physical Functioning [ Time Frame: Cycle 1 (cycle = 28 days) up to end of Year 5 ]
  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).
• Change from Baseline in the EORTC QLQ-C30 Role Functioning [ Time Frame: Cycle 1 (cycle = 28 days) up to end of Year 5 ]
  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).
• Change from Baseline in the EORTC QLQ-C30 Global QOL [ Time Frame: Cycle 1 (cycle = 28 days) up to end of Year 5 ]
  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).
• Proportion of Time on Study Treatment with High Overall Adverse Event Burden [ Time Frame: Cycle 1 (cycle = 28 days) up to end of Year 5 ]
  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.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Imlunestrant Versus Standard Endocrine Therapy in Participants With Early Breast Cancer
• Official Title: 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
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Breast Neoplasms

Intervention

• Drug: Imlunestrant
  Administered orally.
  Other Name: LY3484356
• Drug: Tamoxifen
  Administered per local approved label.
• Drug: Anastrozole
  Administered per local approved label.
• Drug: Letrozole
  Administered per local approved label.
• Drug: Exemestane
  Administered per local approved label.

Study Arms

• Experimental: Imlunestrant
  Imlunestrant administered orally.
  Intervention: Drug: Imlunestrant
• Active Comparator: Investigator's Choice of Endocrine Therapy
  Investigator's choice of tamoxifen, anastrozole, letrozole, or exemestane administered per local approved label.
  Interventions:

  • Drug: Tamoxifen
  • Drug: Anastrozole
  • Drug: Letrozole
  • Drug: Exemestane

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 23, 2022): 6000
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 15, 2032
• Estimated Primary Completion Date: October 15, 2027 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or; 1-317-615-4559; ClinicalTrials.gov@lilly.com

• Listed Location Countries: Argentina, Australia, Austria, Belgium, Brazil, Canada, China, Czechia, Finland, France, Germany, Greece, Hong Kong, Hungary, India, Ireland, Israel, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Poland, Portugal, Romania, Singapore, Slovakia, Spain, Taiwan, Turkey, United Kingdom, United States

Administrative Information

• NCT Number: NCT05514054
• Other Study ID Numbers: 18459; J2J-MC-JZLH ( Other Identifier: Eli Lilly and Company ); 2022-501007-28 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and European Union (EU), whichever is later. Data will be indefinitely available for requesting.
• Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• URL: https://vivli.org/

• Current Responsible Party: Eli Lilly and Company
• Original Responsible Party: Same as current
• Current Study Sponsor: Eli Lilly and Company
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST); Eli Lilly and Company

• PRS Account: Eli Lilly and Company
• Verification Date: April 2024