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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 : November 25, 2020
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

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
Breast Cancer Advanced Breast Cancer Metastatic Breast Cancer Endometrial Cancer Drug: LY3484356 Drug: Abemaciclib Drug: Everolimus Drug: Alpelisib Drug: Trastuzumab Drug: Aromatase Inhibitor (AI) Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 460 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 : December 10, 2019
Estimated Primary Completion Date : February 28, 2021
Estimated Study Completion Date : April 26, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Dose Escalation LY3484356
LY3484356 given orally.
Drug: LY3484356
Administered orally

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

Drug: Abemaciclib
Administered orally
Other Name: 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

Experimental: Part B: Dose Expansion: Cohort E4: LY3484356 + Everolimus
LY3484356 and everolimus given orally.
Drug: LY3484356
Administered orally

Drug: Everolimus
Administered orally

Experimental: Part B: Dose Expansion: Cohort E5: LY3484356 + Alpelisib
LY3484356 and alpelisib given orally.
Drug: LY3484356
Administered orally

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

Drug: Abemaciclib
Administered orally
Other Name: 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

Drug: Abemaciclib
Administered orally
Other Name: LY2835219




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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

  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 [ 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

  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 [ 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

  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 [ 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

  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 [ 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

  9. 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 for advanced disease and prior trastuzumab, pertuzumab, and TDM-1 required in any setting.
  • Part D: ER+, EEC that has progressed after platinum containing chemotherapy and no prior fulvestrant or aromatase 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04188548


Contacts
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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

Locations
Show Show 65 study locations
Sponsors and Collaborators
Eli Lilly and Company
Investigators
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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
Additional Information:
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Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT04188548    
Other Study ID Numbers: 17502
J2J-MC-JZLA ( Other Identifier: Eli Lilly and Company )
2019-003581-41 ( EudraCT Number )
First Posted: December 6, 2019    Key Record Dates
Last Update Posted: November 25, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Breast Neoplasms
Endometrial Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Uterine Diseases
Trastuzumab
Everolimus
Aromatase Inhibitors
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists