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

Sponsor
Eli Lilly and Company (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04188548
Collaborator
(none)
500
Enrollment
78
Locations
8
Arms
48.7
Anticipated Duration (Months)
6.4
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Anticipated Enrollment :
500 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
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
Actual Study Start Date :
Dec 10, 2019
Actual Primary Completion Date :
Jun 29, 2020
Anticipated Study Completion Date :
Dec 31, 2023

Arms and Interventions

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: LY3484356
    Administered orally
    Other Names:
  • Imlunestrant

    • Drug: Abemaciclib
    Administered orally
    Other Names:
  • LY2835219

    • 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: LY3484356
    Administered orally
    Other Names:
  • Imlunestrant

    • Drug: Abemaciclib
    Administered orally
    Other Names:
  • LY2835219

    • Drug: Trastuzumab
    Administered intravenously
    Experimental: Part D: Dose Expansion: LY3484356 +/- Abemaciclib

    LY3484356 and Abemaciclib given orally with trastuzumab administered intravenously.

    Drug: LY3484356
    Administered orally
    Other Names:
  • Imlunestrant

    • Drug: Abemaciclib
    Administered orally
    Other Names:
  • LY2835219

    		•
    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

    Outcome Measures

    Primary Outcome Measures

    1. Number of Participants with Dose Limiting Toxicities (DLTs) and DLT-Equivalent Toxicities [Baseline through Cycle 1 (21/28 Day Cycle)]

      Number of Participants with DLTs and DLT-Equivalent Toxicities

    Secondary Outcome Measures

    1. Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of LY3484356 [Predose Cycle 1 Day 1 through Predose Cycle 2 Day 1 (21/28 Day Cycles)]

      PK: AUC of LY3484356

    2. PK: Maximum Concentration (Cmax) of LY3484356 [Predose Cycle 1 Day 1 through Predose Cycle 2 Day 1 (21/28 Day Cycles)]

      PK: Cmax of LY3484356

    3. 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: AUC of LY3484356 in Combination with Other Anticancer Therapies

    4. 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)]

      PK: Cmax of LY3484356 in Combination with Other Anticancer Therapies

    5. 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 [Baseline through Disease Progression or Death (Estimated up to 28 Months)]

      ORR: Percentage of Participants with Confirmed CR or PR as per RECIST v1.1

    6. 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 [Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Estimated up to 28 Months)]

      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

    7. 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 [Baseline through Measured Progressive Disease (Estimated up to 28 Months)]

      DCR: Percentage of Participants with a BOR of CR, PR, and SD as per RECIST v1.1

    8. Clinical Benefit Rate (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)]

      CBR: Percentage of Participants with a BOR of CR or PR, or SD lasting ≥24 weeks as per RECIST v1.1

    9. Progression Free Survival (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)]

      PFS: Time From Baseline to the Date of Objective Progression or Death Due to Any Cause, Whichever is Earlier

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Banner MD Anderson Cancer Center Gilbert Arizona United States 85234
    2 Mayo Clinic Hospital Phoenix Arizona United States 85054
    3 Highlands Oncology Group Fayetteville Arkansas United States 72703
    4 Beverly Hills Cancer Center Beverly Hills California United States 90211
    5 Cedars Sinai Medical Center Los Angeles California United States 90048
    6 Univ of California Irvine College of Medicine Orange California United States 92868
    7 UCSF Medical Center at Mission Bay San Francisco California United States 94158
    8 Rocky Mountain Cancer Center Aurora Colorado United States 80012
    9 Mayo Clinic in Florida Jacksonville Florida United States 32224
    10 Lake Nona DDU Orlando Florida United States 32827
    11 Winship Cancer Center Emory University Atlanta Georgia United States 30322
    12 Northwestern University Chicago Illinois United States 60611
    13 Community Health Network Indianapolis Indiana United States 46250
    14 Johns Hopkins University Baltimore Maryland United States 21287
    15 Massachusetts General Hospital Boston Massachusetts United States 02114
    16 Dana-Farber Cancer Institute Boston Massachusetts United States 02215
    17 Minnesota Oncology/Hematology PA Minneapolis Minnesota United States 55404
    18 Mayo Clinic Rochester Minnesota United States 55905
    19 Washington University Medical School Saint Louis Missouri United States 63110
    20 Memorial Sloan Kettering Cancer Center Commack New York United States 11725
    21 Memorial Sloan Kettering Cancer Center New York New York United States 10065
    22 Memorial Sloan Kettering Cancer Center New York New York United States 10065
    23 University of Rochester School of Medicine Rochester New York United States 14642
    24 University of North Carolina Chapel Hill North Carolina United States 27599
    25 Duke University Medical Center Durham North Carolina United States 27710
    26 Ohio State University Medical Center Columbus Ohio United States 43210
    27 Peggy and Charles Stephenson Oklahoma Cancer Center Oklahoma City Oklahoma United States 73104
    28 Asante Rogue Regional Medical Center Medford Oregon United States 97504
    29 University of Pittsburgh Medical Center Pittsburgh Pennsylvania United States 15213
    30 Rhode Island Hospital Providence Rhode Island United States 02903
    31 Sarah Cannon Research Institute SCRI Nashville Tennessee United States 37203
    32 Tennessee Oncology PLLC Nashville Tennessee United States 37203
    33 Henry-Joyce Cancer Clinic Nashville Tennessee United States 37232
    34 Texas Oncology-Baylor Charles A. Sammons Cancer Center Dallas Texas United States 75246
    35 UT Southwestern Med Center Dallas Texas United States 75390
    36 University of Texas MD Anderson Cancer Center Houston Texas United States 77030-4009
    37 South Texas Accelerated Research Therapeutics, LLC San Antonio Texas United States 78229-3307
    38 Texas Oncology - San Antonio Medical Center San Antonio Texas United States 78240
    39 US Oncology The Woodlands Texas United States 77380
    40 Texas Oncology - Tyler Tyler Texas United States 75702
    41 University of Vermont Medical Center Burlington Vermont United States 05401
    42 Inova Schar Cancer Institute Fairfax Virginia United States 22031
    43 Oncology and Hematology Associates of Southwest Virginia Inc Roanoke Virginia United States 24014
    44 Seattle Cancer Care Alliance Seattle Washington United States 98109
    45 St Vincent's Hospital Sydney Darlinghurst New South Wales Australia 2010
    46 Calvary Mater Newcastle Waratah New South Wales Australia 2298
    47 Ashford Cancer Centre Research Kurralta Park South Australia Australia 5037
    48 Breast Cancer Research Centre-WA Nedlands Western Australia Australia 6009
    49 Linear Clinical Research Nedlands Western Australia Australia 6009
    50 Institut Jules Bordet Brussel - Capital Belgium 1070
    51 Universitair Ziekenhuis Antwerpen Edegem Belgium 2650
    52 Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg Leuven Belgium 3000
    53 Institut Curie Paris France 75248
    54 Institut de Cancérologie de l'Ouest Centre René Gauducheau Saint Herblain Cedex France 44805
    55 ICANS_Institut de Cancerologie Strasbourg Europe Strasbourg France 67033
    56 Gustave Roussy Villejuif Cedex France 94805
    57 Hyogo Cancer Center Akashi Hyogo Japan 673-8558
    58 National Cancer Center Hospital Chuo-ku Tokyo Japan 104-0045
    59 Severance Hospital, Yonsei University Health System Seoul Korea Korea, Republic of 03722
    60 Seoul National University Hospital Seoul Seoul, Korea Korea, Republic of 03080
    61 Asan Medical Center Seoul Seoul-teukbyeolsi [Seoul] Korea, Republic of 05505
    62 Samsung Medical Center Seoul Korea, Republic of 06351
    63 Hospital Universitari Vall d'Hebron Barcelona Spain 08035
    64 Hospital Clinic I Provincial Barcelona Spain 08036
    65 Hospital General Universitario Gregorio Marañon Madrid Spain 28007
    66 Hospital Universitario Ramón y Cajal Madrid Spain 28034
    67 Hospital Clinico San Carlos Madrid Spain 28040
    68 Hospital Universitario 12 de Octubre Madrid Spain 28041
    69 Fundación Jiménez Díaz-Oncology Madrid Spain 28050
    70 Hospital Madrid Norte Sanchinarro Madrid Spain 28050
    71 Fundación Instituto Valenciano de Oncología Valencia Spain 46009
    72 Hospital Clínico Universitario de Valencia Valencia Spain 46010
    73 Kaohsiung Medical University Chung-Ho Memorial Hospital Kaohsiung Taiwan 807
    74 China Medical University Hospital Taichung Taiwan 40447
    75 National Cheng-Kung Uni. Hosp. Tainan Taiwan 704
    76 National Taiwan University Hospital Taipei Taiwan 10002
    77 Mackay Memorial Hospital Taipei Taiwan 10449
    78 Taipei Veterans General Hospital Taipei Taiwan 11217

    Sponsors and Collaborators

    • 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

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Eli Lilly and Company
    ClinicalTrials.gov Identifier:
    NCT04188548
    Other Study ID Numbers:
    • 17502
    • J2J-MC-JZLA
    • 2019-003581-41
    First Posted:
    Dec 6, 2019
    Last Update Posted:
    Aug 18, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Breast Neoplasms
    Endometrial Neoplasms
    Trastuzumab
    Pertuzumab
    Everolimus
    Aromatase Inhibitors

    Study Results

    No Results Posted as of Aug 18, 2022