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

• ClinicalTrials.gov Identifier: NCT04188548
• Recruitment Status: Active, not recruiting
• First Posted: December 6, 2019
• Last Update Posted: March 26, 2024
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Tracking Information

• First Submitted Date: November 18, 2019
• First Posted Date: December 6, 2019
• Last Update Posted Date: March 26, 2024
• Actual Study Start Date: December 10, 2019
• Actual Primary Completion Date: June 29, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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 (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

Current Secondary Outcome Measures (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 (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: A Study of LY3484356 in Participants With Advanced or Metastatic Breast Cancer or Endometrial Cancer
• 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
• 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: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Breast Cancer
• Advanced Breast Cancer
• Metastatic Breast Cancer
• Endometrial Cancer

Intervention

• 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

• 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

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: April 28, 2021): 500
• Original Estimated Enrollment (submitted: December 4, 2019): 215
• Estimated Study Completion Date: December 31, 2024
• Actual Primary Completion Date: June 29, 2020 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Belgium, France, Japan, Korea, Republic of, Spain, Taiwan, United States

Administrative Information

• NCT Number: NCT04188548
• Other Study ID Numbers: 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

• Plan to Share IPD: No

• Current Responsible Party: Eli Lilly and Company
• Original Responsible Party: Same as current
• Current Study Sponsor: Eli Lilly and Company
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

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

• PRS Account: Eli Lilly and Company
• Verification Date: March 2024