Clinical Trials /

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

NCT04188548

Description:

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.

Related Conditions:
  • Breast Carcinoma
  • Endometrial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: 17502
  • SECONDARY ID: J2J-MC-JZLA
  • SECONDARY ID: 2019-003581-41
  • NCT ID: NCT04188548

Conditions

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

Interventions

DrugSynonymsArms
LY3484356Dose Escalation LY3484356
AbemaciclibLY2835219Part A: Dose Expansion: LY3484356 + Abemaciclib +/- AI
EverolimusPart B: Dose Expansion: Cohort E4: LY3484356 + Everolimus
AlpelisibPart B: Dose Expansion: Cohort E5: LY3484356 + Alpelisib
TrastuzumabPart C:Dose Expansion: LY3484356 + Trastuzumab +/- Abemaciclib
Aromatase Inhibitor (AI)Part A: Dose Expansion: LY3484356 + Abemaciclib +/- AI

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Dose Escalation LY3484356ExperimentalLY3484356 given orally.
  • LY3484356
Part A: Dose Expansion: LY3484356 + Abemaciclib +/- AIExperimentalLY3484356 and abemaciclib given orally in combination with or without Aromatase Inhibitor (AI) of physician's choice (Anastrozole, Exemestane, or Letrozole) administered orally.
  • LY3484356
  • Abemaciclib
  • Aromatase Inhibitor (AI)
Part B: Dose Expansion: Cohort E3: LY3484356ExperimentalLY3484356 given orally.
  • LY3484356
Part B: Dose Expansion: Cohort E4: LY3484356 + EverolimusExperimentalLY3484356 and everolimus given orally.
  • LY3484356
  • Everolimus
Part B: Dose Expansion: Cohort E5: LY3484356 + AlpelisibExperimentalLY3484356 and alpelisib given orally.
  • LY3484356
  • Alpelisib
Part C:Dose Expansion: LY3484356 + Trastuzumab +/- AbemaciclibExperimentalLY3484356 administered orally in combination with trastuzumab intravenously with or without Abemaciclib.
  • LY3484356
  • Abemaciclib
  • Trastuzumab
Part D: Dose Expansion: LY3484356 +/- AbemaciclibExperimentalLY3484356 and Abemaciclib given orally with trastuzumab administered intravenously.
  • LY3484356
  • Abemaciclib

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 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Participants with Dose Limiting Toxicities (DLTs) and DLT-Equivalent Toxicities
Time Frame:Baseline through Cycle 1 (21/28 Day Cycle)
Safety Issue:
Description:Number of Participants with DLTs and DLT-Equivalent Toxicities

Secondary Outcome Measures

Measure: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)
Safety Issue:
Description:PK: AUC of LY3484356
Measure:PK: Maximum Concentration (Cmax) of LY3484356
Time Frame:Predose Cycle 1 Day 1 through Predose Cycle 2 Day 1 (21/28 Day Cycles)
Safety Issue:
Description:PK: Cmax of LY3484356
Measure: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)
Safety Issue:
Description:PK: AUC of LY3484356 in Combination with Other Anticancer Therapies
Measure: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)
Safety Issue:
Description:PK: Cmax of LY3484356 in Combination with Other Anticancer Therapies
Measure: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)
Safety Issue:
Description:ORR: Percentage of Participants with Confirmed CR or PR as per RECIST v1.1
Measure: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)
Safety Issue:
Description: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
Measure: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)
Safety Issue:
Description:DCR: Percentage of Participants with a BOR of CR, PR, and SD as per RECIST v1.1
Measure: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)
Safety Issue:
Description:CBR: Percentage of Participants with a BOR of CR or PR, or SD lasting ≥24 weeks as per RECIST v1.1
Measure: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)
Safety Issue:
Description:PFS: Time From Baseline to the Date of Objective Progression or Death Due to Any Cause, Whichever is Earlier

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Eli Lilly and Company

Last Updated

March 4, 2021