A Study of LY3484356 in Participants With Advanced or Metastatic Breast Cancer or Endometrial Cancer (EMBER)

EMBER: A Phase 1a/1b Study of LY3484356 Administered as Monotherapy and in Combination With Anticancer Therapies for Patients With ER+ Locally Advanced or Metastatic Breast Cancer and Other Select Non-Breast Cancers

The reason for this study is to see if the study drug LY3484356 alone or in combination with other anticancer therapies is safe and effective in participants with advanced or metastatic breast cancer or endometrial cancer.

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Cancer; Advanced Breast Cancer; Metastatic Breast Cancer; Endometrial Cancer
• Intervention / Treatment: Drug: Abemaciclib; Drug: LY3484356; Drug: Aromatase Inhibitor (AI); Drug: Everolimus; Drug: Alpelisib; Drug: Trastuzumab; Drug: Pertuzumab

• Study Type: Interventional
• Enrollment (Estimated): 500
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • St Vincent's Hospital Sydney
    • Waratah, New South Wales, Australia, 2298
      • Calvary Mater Newcastle
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Cancer Research SA
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Linear Clinical Research
    • Nedlands, Western Australia, Australia, 6009
      • Breast Cancer Research Centre-WA
• Belgium
  • Antwerpen
    • Edegem, Antwerpen, Belgium, 2650
      • Antwerp University Hospital
  • Bruxelles-Capitale, Région De
    • Anderlecht, Bruxelles-Capitale, Région De, Belgium, 1070
      • Institut Jules Bordet
  • Vlaams-Brabant
    • Leuven, Vlaams-Brabant, Belgium, 3000
      • UZ Leuven
• France
  • Paris, France, 75248
    • Institut Curie
  • Strasbourg, France, 67033
    • Institut de cancérologie Strasbourg Europe (ICANS)
• Japan
  • Hyogo
    • Akashi, Hyogo, Japan, 673-8558
      • Hyogo Cancer Center
  • Tokyo
    • Chuo-ku, Tokyo, Japan, 104-0045
      • National Cancer Center Hospital
• Korea, Republic of
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
  • Korea
    • Seoul, Korea, Korea, Republic of, 03722
      • Severance Hospital, Yonsei University Health System
  • Seoul, Korea
    • Seoul, Seoul, Korea, Korea, Republic of, 03080
      • Seoul National University Hospital
  • Seoul-teukbyeolsi [Seoul]
    • Seoul, Seoul-teukbyeolsi [Seoul], Korea, Republic of, 05505
      • Asan Medical Center
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos
  • Madrid, Spain, 28040
    • Hospital Universitario Fundacion Jimenez Diaz
  • Madrid, Spain, 28009
    • Hospital General Universitario Gregorio Marañón
  • Madrid, Spain, 28050
    • Hospital Universitario HM Sanchinarro
  • Valencia, Spain, 46009
    • Fundación Instituto Valenciano de Oncología
  • Catalunya [Cataluña]
    • Barcelona, Catalunya [Cataluña], Spain, 08036
      • Hospital Clinic De Barcelona
  • Madrid, Comunidad De
    • Madrid, Madrid, Comunidad De, Spain, 28041
      • Hospital Universitario 12 de Octubre
  • Valenciana, Comunitat
    • Valencia, Valenciana, Comunitat, Spain, 46010
      • Hospital Clinico Universitario de Valencia
• Taiwan
  • Kaohsiung, Taiwan, 80756
    • Kaohsiung Medical University Hospital
  • Taichung, Taiwan, 40447
    • China Medical University Hospital
  • Tainan, Taiwan, 704
    • National Cheng-Kung Uni. Hosp.
  • Taipei, Taiwan, 11217
    • Taipei Veterans General Hospital
  • Taipei, Taiwan, 10449
    • Mackay Memorial Hospital
  • Taipei, Taiwan, 10055
    • National Taiwan University Hospital
• United States
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Banner MD Anderson Cancer Center
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic in Arizona - Phoenix
  • Arkansas
    • Springdale, Arkansas, United States, 72762
      • Highlands Oncology Group
  • California
    • Beverly Hills, California, United States, 90211
      • Beverly Hills Cancer Center
    • Orange, California, United States, 92868
      • University of California, Irvine
    • San Francisco, California, United States, 94158
      • UCSF Medical Center at Mission Bay
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic in Florida
    • Orlando, Florida, United States, 32827
      • Lake Nona DDU
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Center Emory University
  • Indiana
    • Indianapolis, Indiana, United States, 46250
      • Community Cancer Center North
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Minnesota Oncology/Hematology PA
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University
  • New Jersey
    • Montvale, New Jersey, United States, 07645
      • Memorial Sloan Kettering - Bergen
  • New York
    • Commack, New York, United States, 11725
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • Rochester, New York, United States, 14642
      • Wilmot Cancer Institute
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center, Stephenson Cancer Center
  • Oregon
    • Medford, Oregon, United States, 97504
      • Asante Rogue Regional Medical Center
  • Pennsylvania
    • Harrisburg, Pennsylvania, United States, 17109
      • UPMC Hillman Cancer Center Harrisburg
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology Nashville
    • Nashville, Tennessee, United States, 37203
      • SCRI Oncology Partners
    • Nashville, Tennessee, United States, 37067
      • Vanderbilt Health One Hundred Oaks
  • Texas
    • Dallas, Texas, United States, 77380
      • Texas Oncology-Baylor Charles A. Sammons Cancer Center
    • Dallas, Texas, United States, 75390-9179
      • UT Southwestern Med Center
    • Houston, Texas, United States, 77030-4009
      • University of Texas MD Anderson Cancer Center
    • San Antonio, Texas, United States, 78229-3307
      • South Texas Accelerated Research Therapeutics (START)
    • The Woodlands, Texas, United States, 77380
      • US Oncology
    • The Woodlands, Texas, United States, 77380
      • Minnesota Oncology/Hematology PA
    • The Woodlands, Texas, United States, 77380
      • Oncology and Hematology Associates of Southwest Virginia Inc
    • The Woodlands, Texas, United States, 77380
      • Texas Oncology - San Antonio Medical Center
    • The Woodlands, Texas, United States, 77380
      • USO-Rocky Mountain Cancer Center
    • Tyler, Texas, United States, 75702
      • Texas Oncology - Tyler
  • Vermont
    • Burlington, Vermont, United States, 05401
      • The University of Vermont Medical Center Inc.
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Inova Schar Cancer Institute
  • Washington
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

All study parts:

• Participants must be willing to provide adequate archival tissue sample
• Participants must be willing to use highly effective birth control
• Participants must have adequate organ function
• Participants must be able to swallow capsules

Dose escalation- Participants must have one of the following:

• Parts A and B: ER+ HER2- breast cancer with evidence of locally advanced unresectable or metastatic disease who have had the following:
• Part A: may have had up to 1 prior regimen of any kind for in the advanced/metastatic setting and no prior cyclin-dependent kinase 4/6 (CDK4/6) inhibitor therapy.
• Part B: may have had up to 2 prior regimens, no more than 1 of which may be endocrine therapy in the advanced/metastatic setting, and must have received a prior CDK4/6 inhibitor
• Cohort E4: No prior everolimus.
• Cohort E5: No prior alpelisib and must have a phosphatidylinositol 3-kinase catalytic α (PIK3Cα) mutation as determined by local testing.
• Part C: ER+, human epidermal growth factor receptor 2 positive (HER2+) breast cancer with evidence of locally advanced unresectable or metastatic disease who have had at least 2 HER2-directed therapies in any setting.
• Part D: ER+, EEC that has progressed after platinum containing chemotherapy and no prior fulvestrant or aromatase inhibitor therapy.
• Part E: ER+ and HER2+ breast cancer with evidence of locally advanced, unresectable, or metastatic disease.
• Part E: Participants must have received induction taxane chemotherapy combined with trastuzumab + pertuzumab as first-line treatment for advanced/metastatic disease and must not have progressed on this regimen.
• Part E: Participants must not have received more than 1 HER2-directed regimen or any endocrine therapy for advanced disease or any prior CDK4/6 inhibitor therapy.

Participants with ER+/HER2- breast cancer enrolled in this study must have had evidence of clinical benefit while on endocrine therapy for at least 24 months in the adjuvant setting or at least 6 months in the advanced/metastatic setting or have untreated de novo metastatic breast cancer

Exclusion Criteria:

• Participants must not have certain infections such as hepatitis or tuberculosis or HIV that are not well controlled
• Participants must not have another serious medical condition
• Participants must not have cancer of the central nervous system that is unstable
• Participants must not be pregnant or breastfeeding

Study Plan

How is the study designed?

Design Details

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

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation LY3484356; LY3484356 given orally.	Drug: LY3484356; Administered orally; Other Names: Imlunestrant
Experimental: Part A: Dose Expansion: LY3484356 + Abemaciclib +/- AI; LY3484356 and abemaciclib given orally in combination with or without Aromatase Inhibitor (AI) of physician's choice (Anastrozole, Exemestane, or Letrozole) administered orally.	Drug: Abemaciclib; Administered orally; Other Names: LY2835219; Drug: LY3484356; Administered orally; Other Names: Imlunestrant; Drug: Aromatase Inhibitor (AI); Anastrozole or Exemestane or Letrozole administered orally (physician choice)
Experimental: Part B: Dose Expansion: Cohort E3: LY3484356; LY3484356 given orally.	Drug: LY3484356; Administered orally; Other Names: Imlunestrant
Experimental: Part B: Dose Expansion: Cohort E4: LY3484356 + Everolimus; LY3484356 and everolimus given orally.	Drug: LY3484356; Administered orally; Other Names: Imlunestrant; Drug: Everolimus; Administered orally
Experimental: Part B: Dose Expansion: Cohort E5: LY3484356 + Alpelisib; LY3484356 and alpelisib given orally.	Drug: LY3484356; Administered orally; Other Names: Imlunestrant; Drug: Alpelisib; Administered orally
Experimental: Part C:Dose Expansion: LY3484356 + Trastuzumab +/- Abemaciclib; LY3484356 administered orally in combination with trastuzumab intravenously with or without Abemaciclib.	Drug: Abemaciclib; Administered orally; Other Names: LY2835219; Drug: LY3484356; Administered orally; Other Names: Imlunestrant; Drug: Trastuzumab; Administered intravenously
Experimental: Part D: Dose Expansion: LY3484356 +/- Abemaciclib; LY3484356 and Abemaciclib given orally with trastuzumab administered intravenously.	Drug: Abemaciclib; Administered orally; Other Names: LY2835219; Drug: LY3484356; Administered orally; Other Names: Imlunestrant
Experimental: Part E: Dose Expansion: LY3484356 + Trastuzumab + Pertuzumab; LY3484356 administered orally in combination with trastuzumab and pertuzumab administered intravenously.	Drug: LY3484356; Administered orally; Other Names: Imlunestrant; Drug: Trastuzumab; Administered intravenously; Drug: Pertuzumab; Administered intravenously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Dose Limiting Toxicities (DLTs) and DLT-Equivalent Toxicities	Number of Participants with DLTs and DLT-Equivalent Toxicities	Baseline through Cycle 1 (21/28 Day Cycle)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of LY3484356	PK: AUC of LY3484356	Predose Cycle 1 Day 1 through Predose Cycle 2 Day 1 (21/28 Day Cycles)
PK: Maximum Concentration (Cmax) of LY3484356	PK: Cmax of LY3484356	Predose Cycle 1 Day 1 through Predose Cycle 2 Day 1 (21/28 Day Cycles)
PK: AUC of LY3484356 in Combination with Other Anticancer Therapies	PK: AUC of LY3484356 in Combination with Other Anticancer Therapies	Predose Cycle 1 Day 1 through Predose Cycle 2 Day 1 (21/28 Day Cycles)
PK: Cmax of LY3484356 in Combination with Other Anticancer Therapies	PK: Cmax of LY3484356 in Combination with Other Anticancer Therapies	Predose Cycle 1 Day 1 through Predose Cycle 2 Day 1 (21/28 Day Cycles)
Overall Response Rate (ORR): Percentage of Participants with Confirmed Complete Response (CR) or Partial Response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1	ORR: Percentage of Participants with Confirmed CR or PR as per RECIST v1.1	Baseline through Disease Progression or Death (Estimated up to 28 Months)
Duration of Response (DoR): Time From the Date of First Evidence of CR, PR (per RESIST v1.1) to the Date of Objective Progression or Death Due to Any Cause, Whichever is Earlier	DoR: Time From the Date of First Evidence of CR, PR (per RESIST v1.1) to the Date of Objective Progression or Death Due to Any Cause, Whichever is Earlier	Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Estimated up to 28 Months)
Disease Control Rate (DCR): Percentage of Participants with a Best Overall Response (BOR) of CR, PR, and Stable Disease (SD) as per RECIST v1.1	DCR: Percentage of Participants with a BOR of CR, PR, and SD as per RECIST v1.1	Baseline through Measured Progressive Disease (Estimated up to 28 Months)
Clinical Benefit Rate (CBR): Percentage of Participants with a BOR of CR or PR, or SD lasting ≥24 weeks as per RECIST v1.1	CBR: Percentage of Participants with a BOR of CR or PR, or SD lasting ≥24 weeks as per RECIST v1.1	Baseline through Measured Progressive Disease (Estimated up to 28 Months)
Progression Free Survival (PFS): Time From Baseline to the Date of Objective Progression or Death Due to Any Cause, Whichever is Earlier	PFS: Time From Baseline to the Date of Objective Progression or Death Due to Any Cause, Whichever is Earlier	Baseline to Objective Progression or Death Due to Any Cause (Estimated up to 28 Months)

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 Participants With Advanced or Metastatic Breast Cancer

Study record dates

Study Major Dates

• Study Start (Actual): December 10, 2019
• Primary Completion (Actual): June 29, 2020
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: November 18, 2019
• First Submitted That Met QC Criteria: December 4, 2019
• First Posted (Actual): December 6, 2019

Study Record Updates

• Last Update Posted (Actual): June 4, 2025
• Last Update Submitted That Met QC Criteria: June 3, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Uterine Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Skin Diseases; Breast Diseases; Uterine Neoplasms; Breast Neoplasms; Endometrial Neoplasms; Antineoplastic Agents, Immunological; MTOR Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hormones, Hormone Substitutes, and Hormone Antagonists; Enzyme Inhibitors; Protein Kinase Inhibitors; Steroid Synthesis Inhibitors; Hormone Antagonists; Estrogen Antagonists; Trastuzumab; Everolimus; Pertuzumab; Aromatase Inhibitors
• Other Study ID Numbers: 17502; J2J-MC-JZLA (Other Identifier: Eli Lilly and Company); 2019-003581-41 (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