A Study of LY3484356 in Women With Breast Cancer Before Having Surgery (EMBER-2)

EMBER-2: A Phase 1, Open-Label, Preoperative Window Study Evaluating the Biological Effects of LY3484356 in Post-menopausal Women With Stage I-III Estrogen Receptor-Positive, HER2-Negative Breast Cancer

The purpose for this study is to see if the study drug, LY3484356, is safe and to determine what effects it has on breast cancer in participants with Estrogen Receptor Positive (ER+), HER2 Negative (HER2-) early stage (stage I-III) breast cancer, when given prior to surgery. Participation in this study could last up to 2.5 months.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: LY3484356

• Study Type: Interventional
• Enrollment (Actual): 87
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Brussel - Capital, Belgium, 1070
    • Institut Jules Bordet
  • Leuven, Belgium, 3000
    • Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
• France
  • Hauts-de-Seine
    • Saint-Cloud, Hauts-de-Seine, France, 92210
      • Hopital René Huguenin
• Germany
  • München, Germany, 80336
    • Klinikum der Universitaet Muenchen
  • Bavaria
    • Erlangen, Bavaria, Germany, 91054
      • Universitätsklinikum Erlangen
  • Mecklenburg-Vorpommern
    • Schwerin, Mecklenburg-Vorpommern, Germany, 19049
      • Helios Kliniken Schwerin
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic i Provincial
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañon
  • Madrid, Spain, 28050
    • Hospital Madrid Norte Sanchinarro
• United Kingdom
  • Cornwall
    • Truro, Cornwall, United Kingdom, TR1 3LJ
      • The Royal Cornwall Hospital
  • London City
    • London, London City, United Kingdom, EC1A 7BE
      • Barts Cancer Institute
• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Center Emory University
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Memorial Hosptial
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute SCRI
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center
  • Vermont
    • Burlington, Vermont, United States, 05401
      • University of Vermont Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Have histologically confirmed invasive ER+, HER2- breast carcinoma
• Be willing and able to provide pre- and on-treatment tumor samples
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group scale
• Have adequate organ function
• Be able to swallow capsules
• Be a postmenopausal woman

Exclusion Criteria:

• Have bilateral invasive breast cancer
• Have metastatic breast cancer
• Plan to receive concurrent neoadjuvant therapy with any other non-protocol anti-cancer therapy
• Have had prior therapy (of any kind) for an invasive or non-invasive breast cancer
• Have had prior radiotherapy to the ipsilateral chest wall for any malignancy
• Have had prior anti-estrogen therapy with raloxifene, tamoxifen, aromatase inhibitor, or other selective estrogen receptor modulator (SERM), either for osteoporosis or prevention of breast cancer
• Have had prior hormone-replacement therapy within 4 weeks of the start of study treatment
• Have had major surgery within 28 days prior to randomization to allow for post-operative healing of the surgical wound and site(s)
• Have certain infections such as hepatitis or tuberculosis or HIV that are not well controlled
• Have another serious medical condition
• Have a history of any other cancer (except nonmelanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission with no therapy for a minimum of 3 years

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 200 milligrams (mg) LY3484356; Participants received 200 mg LY3484356 administered orally once daily for 15 days	Drug: LY3484356; Administered orally.; Other Names: Imlunestrant
Experimental: 400 mg LY3484356; Participants received 400 mg LY3484356 administered orally once daily for 15 days	Drug: LY3484356; Administered orally.; Other Names: Imlunestrant
Experimental: 800 mg LY3484356; Participants received 800 mg LY3484356 administered orally once daily for 15 days	Drug: LY3484356; Administered orally.; Other Names: Imlunestrant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Estrogen Receptor (ER) Expression	Tumor tissue collected by biopsy is used to determine ER expression. ER expression is measured by immunohistochemistry (IHC) and quantified by H-score. The H-score was calculated as the sum of multiplying the tumor cell ER staining intensity level 0 to 3 (0=none, 1=low, 2=moderate, 3=high) by the percentage (0 to 100) of cells at each intensity. Total ER H-score ranged from 0 to 300, where a higher score indicated stronger ER expression. Percent change in ER expression was defined as 100*(ER expression on-treatment - ER expression pre-treatment)/(ER expression pre-treatment). Geometric mean percent change and 90 percent (%) confidence interval for percent change were obtained from a t-test of the log ratio i.e. log(ER expression on-treatment/ER expression pre-treatment).	Baseline, Day 15

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Ki-67	Tumor tissue collected by biopsy is used to determine Ki-67 expression. It is measured by IHC and the Ki-67 index is defined as the percent of cells staining positive by validated central assay. Percent change in Ki-67 index was defined as 100*(Ki-67 index on-treatment - Ki-67 index pre-treatment)/(Ki-67 index pre-treatment). Geometric mean percent change and 90 percent (%) confidence interval for percent change were obtained from a t-test of the log ratio i.e. log(Ki-67 index on-treatment/Ki-67 index pre-treatment).	Baseline, Day 15
Percent Change From Baseline in Progesterone Receptor (PR) Expression	Tumor tissue collected by biopsy is used to determine PR expression. PR expression is measured by IHC and quantified by H-score. The H-score was calculated as the sum of multiplying the tumor cell ER staining intensity level 0 to 3 (0=none, 1=low, 2=moderate, 3=high) by the percentage (0 to 100) of cells at each intensity. Total PR H-score ranged from 0 to 300, where a higher score indicated stronger PR expression. Percent change in PR expression was defined as 100*(PR expression on-treatment - PR expression pre-treatment)/(PR expression pre-treatment). Geometric mean percent change and 90 percent (%) confidence interval for percent change were obtained from a t-test of the log ratio i.e. log(PR expression on-treatment/PR expression pre-treatment).	Baseline, Day 15
Pharmacokinetics (PK): Plasma Concentration of LY3484356	Plasma Concentration of LY3484356 evaluated using sparse sampling methodology	Day 1: 3.5 hours (h) postdose; Day 8: Predose; Day 8: 3.5 h postdose

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• 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

Publications and helpful links

Helpful Links

• A Study of LY3484356 in Women With Breast Cancer Before Having Surgery (EMBER-2)

Study record dates

Study Major Dates

• Study Start (Actual): April 21, 2021
• Primary Completion (Actual): November 11, 2022
• Study Completion (Actual): November 11, 2022

Study Registration Dates

• First Submitted: November 30, 2020
• First Submitted That Met QC Criteria: November 30, 2020
• First Posted (Actual): December 1, 2020

Study Record Updates

• Last Update Posted (Actual): November 12, 2025
• Last Update Submitted That Met QC Criteria: October 22, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: SERD
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Imlunestrant
• Other Study ID Numbers: 17575; J2J-MC-JZLB (Other Identifier: Eli Lilly and Company); 2020-002810-42 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No