A Study of LY3484356 in Participants With Advanced or Metastatic Breast Cancer or Endometrial Cancer (EMBER)
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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. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT04188548 |
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Recruitment Status :
Active, not recruiting
First Posted : December 6, 2019
Last Update Posted : March 26, 2024
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Sponsor:
Eli Lilly and Company
Information provided by (Responsible Party):
Eli Lilly and Company
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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) Drug: Pertuzumab | Phase 1 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated 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 : | December 10, 2019 |
| Actual Primary Completion Date : | June 29, 2020 |
| Estimated Study Completion Date : | December 31, 2024 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Breast cancer
MedlinePlus related topics:
Breast Cancer
| Arm | Intervention/treatment |
|---|---|
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Experimental: Dose Escalation LY3484356
LY3484356 given orally.
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Drug: LY3484356
Administered orally
Other Name: Imlunestrant |
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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.
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Drug: LY3484356
Administered orally
Other Name: Imlunestrant Drug: Abemaciclib Administered orally
Other Name: LY2835219 Drug: Aromatase Inhibitor (AI) Anastrozole or Exemestane or Letrozole administered orally (physician choice) |
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Experimental: Part B: Dose Expansion: Cohort E3: LY3484356
LY3484356 given orally.
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Drug: LY3484356
Administered orally
Other Name: Imlunestrant |
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Experimental: Part B: Dose Expansion: Cohort E4: LY3484356 + Everolimus
LY3484356 and everolimus given orally.
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Drug: LY3484356
Administered orally
Other Name: Imlunestrant Drug: Everolimus Administered orally |
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Experimental: Part B: Dose Expansion: Cohort E5: LY3484356 + Alpelisib
LY3484356 and alpelisib given orally.
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Drug: LY3484356
Administered orally
Other Name: Imlunestrant Drug: Alpelisib Administered orally |
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Experimental: Part C:Dose Expansion: LY3484356 + Trastuzumab +/- Abemaciclib
LY3484356 administered orally in combination with trastuzumab intravenously with or without Abemaciclib.
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Drug: LY3484356
Administered orally
Other Name: Imlunestrant Drug: Abemaciclib Administered orally
Other Name: LY2835219 Drug: Trastuzumab Administered intravenously |
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Experimental: Part D: Dose Expansion: LY3484356 +/- Abemaciclib
LY3484356 and Abemaciclib given orally with trastuzumab administered intravenously.
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Drug: LY3484356
Administered orally
Other Name: Imlunestrant Drug: Abemaciclib Administered orally
Other Name: LY2835219 |
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Experimental: Part E: Dose Expansion: LY3484356 + Trastuzumab + Pertuzumab
LY3484356 administered orally in combination with trastuzumab and pertuzumab administered intravenously.
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Drug: LY3484356
Administered orally
Other Name: Imlunestrant Drug: Trastuzumab Administered intravenously Drug: Pertuzumab Administered intravenously |
Primary Outcome Measures :
- 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 :
- 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
Information from the National Library of Medicine
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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 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
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
Locations
Show 76 study locations
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 |
Additional Information:
| 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: | March 26, 2024 |
| Last Verified: | March 2024 |
| Individual Participant Data (IPD) Sharing Statement: | |
| 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:
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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 Genital Diseases, Female Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Urogenital Diseases Genital Diseases |
Trastuzumab Pertuzumab Everolimus Aromatase Inhibitors Antineoplastic Agents, Immunological Antineoplastic Agents MTOR Inhibitors Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Steroid Synthesis Inhibitors Estrogen Antagonists |