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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04188548
Recruitment Status : Recruiting
First Posted : December 6, 2019
Last Update Posted : September 21, 2022
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Tracking Information
First Submitted Date  ICMJE November 18, 2019
First Posted Date  ICMJE December 6, 2019
Last Update Posted Date September 21, 2022
Actual Study Start Date  ICMJE December 10, 2019
Actual Primary Completion Date June 29, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 22, 2020)
Number of Participants with Dose Limiting Toxicities (DLTs) and DLT-Equivalent Toxicities [ Time Frame: Baseline through Cycle 1 (21/28 Day Cycle) ]
Number of Participants with DLTs and DLT-Equivalent Toxicities
Original Primary Outcome Measures  ICMJE
 (submitted: December 4, 2019)
Number of Participants with Dose Limiting Toxicities (DLTs) [ Time Frame: Baseline through Cycle 1 (28 Day Cycle) ]
Number of Participants with DLTs
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 22, 2020)
  • Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of LY3484356 [ Time Frame: Predose Cycle 1 Day 1 through Predose Cycle 2 Day 1 (21/28 Day Cycles) ]
    PK: AUC of LY3484356
  • PK: Maximum Concentration (Cmax) of LY3484356 [ Time Frame: Predose Cycle 1 Day 1 through Predose Cycle 2 Day 1 (21/28 Day Cycles) ]
    PK: Cmax of LY3484356
  • PK: AUC of LY3484356 in Combination with Other Anticancer Therapies [ Time Frame: 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: Cmax of LY3484356 in Combination with Other Anticancer Therapies [ Time Frame: 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
  • 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 [ Time Frame: 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
  • 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 [ Time Frame: 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
  • 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 [ Time Frame: 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
  • Clinical Benefit Rate (CBR): Percentage of Participants with a BOR of CR or PR, or SD lasting ≥24 weeks as per RECIST v1.1 [ Time Frame: 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
  • Progression Free Survival (PFS): Time From Baseline to the Date of Objective Progression or Death Due to Any Cause, Whichever is Earlier [ Time Frame: 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
Original Secondary Outcome Measures  ICMJE
 (submitted: December 4, 2019)
  • Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of LY3484356 [ Time Frame: Predose Cycle 1 Day 1 through Predose Cycle 2 Day 1 (28 Day Cycles) ]
    PK: AUC of LY3484356
  • PK: Maximum Concentration (Cmax) of LY3484356 [ Time Frame: Predose Cycle 1 Day 1 through Predose Cycle 2 Day 1 (28 Day Cycles) ]
    PK: Cmax of LY3484356
  • PK: AUC of LY3484356 in Combination with Abemaciclib [ Time Frame: Predose Cycle 1 Day 1 through Predose Cycle 2 Day 1 (28 Day Cycles) ]
    PK: AUC of LY3484356 in Combination with Abemaciclib
  • PK: Cmax of LY3484356 in Combination with Abemaciclib [ Time Frame: Predose Cycle 1 Day 1 through Predose Cycle 2 Day 1 (28 Day Cycles) ]
    PK: Cmax of LY3484356 in Combination with Abemaciclib
  • Overall Response Rate (ORR): Percentage of Participants with Complete Response (CR) or Partial Response (PR) [ Time Frame: Baseline through Disease Progression or Death (Estimated up to 42 Months) ]
    ORR: Percentage of Participants with CR or PR
  • Duration of Response (DoR) [ Time Frame: Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Estimated up to 42 Months) ]
    DoR
  • Disease Control Rate (DCR): Percentage of Participants with a Best Overall Response of CR, PR, and Stable Disease [ Time Frame: Baseline through Measured Progressive Disease (Estimated up to 42 Months) ]
    DCR: Percentage of Participants with a Best Overall Response of CR, PR, and Stable Disease
  • Progression Free Survival (PFS) [ Time Frame: Baseline to Objective Progression or Death Due to Any Cause (Estimated up to 42 Months) ]
    PFS
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of LY3484356 in Participants With Advanced or Metastatic Breast Cancer or Endometrial Cancer
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Breast Cancer
  • Advanced Breast Cancer
  • Metastatic Breast Cancer
  • Endometrial Cancer
Intervention  ICMJE
  • Drug: LY3484356
    Administered orally
    Other Name: Imlunestrant
  • Drug: Abemaciclib
    Administered orally
    Other Name: LY2835219
  • Drug: Everolimus
    Administered orally
  • Drug: Alpelisib
    Administered orally
  • Drug: Trastuzumab
    Administered intravenously
  • Drug: Aromatase Inhibitor (AI)
    Anastrozole or Exemestane or Letrozole administered orally (physician choice)
  • Drug: Pertuzumab
    Administered intravenously
Study Arms  ICMJE
  • Experimental: Dose Escalation LY3484356
    LY3484356 given orally.
    Intervention: Drug: LY3484356
  • 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.
    Interventions:
    • Drug: LY3484356
    • Drug: Abemaciclib
    • Drug: Aromatase Inhibitor (AI)
  • Experimental: Part B: Dose Expansion: Cohort E3: LY3484356
    LY3484356 given orally.
    Intervention: Drug: LY3484356
  • Experimental: Part B: Dose Expansion: Cohort E4: LY3484356 + Everolimus
    LY3484356 and everolimus given orally.
    Interventions:
    • Drug: LY3484356
    • Drug: Everolimus
  • Experimental: Part B: Dose Expansion: Cohort E5: LY3484356 + Alpelisib
    LY3484356 and alpelisib given orally.
    Interventions:
    • Drug: LY3484356
    • Drug: Alpelisib
  • Experimental: Part C:Dose Expansion: LY3484356 + Trastuzumab +/- Abemaciclib
    LY3484356 administered orally in combination with trastuzumab intravenously with or without Abemaciclib.
    Interventions:
    • Drug: LY3484356
    • Drug: Abemaciclib
    • Drug: Trastuzumab
  • Experimental: Part D: Dose Expansion: LY3484356 +/- Abemaciclib
    LY3484356 and Abemaciclib given orally with trastuzumab administered intravenously.
    Interventions:
    • Drug: LY3484356
    • Drug: Abemaciclib
  • Experimental: Part E: Dose Expansion: LY3484356 + Trastuzumab + Pertuzumab
    LY3484356 administered orally in combination with trastuzumab and pertuzumab administered intravenously.
    Interventions:
    • Drug: LY3484356
    • Drug: Trastuzumab
    • Drug: Pertuzumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 28, 2021)
500
Original Estimated Enrollment  ICMJE
 (submitted: December 4, 2019)
215
Estimated Study Completion Date  ICMJE December 31, 2023
Actual Primary Completion Date June 29, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
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  ICMJE Australia,   Belgium,   France,   Japan,   Korea, Republic of,   Spain,   Taiwan,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04188548
Other Study ID Numbers  ICMJE 17502
J2J-MC-JZLA ( Other Identifier: Eli Lilly and Company )
2019-003581-41 ( EudraCT Number )
Has Data Monitoring Committee No
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  ICMJE
Plan to Share IPD: No
Current Responsible Party Eli Lilly and Company
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Eli Lilly and Company
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
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 September 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP