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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04188548




Registration number
NCT04188548
Ethics application status
Date submitted
18/11/2019
Date registered
6/12/2019

Titles & IDs
Public title
A Study of LY3484356 in Participants With Advanced or Metastatic Breast Cancer or Endometrial Cancer
Scientific 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
Secondary ID [1] 0 0
J2J-MC-JZLA
Secondary ID [2] 0 0
17502
Universal Trial Number (UTN)
Trial acronym
EMBER
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Cancer 0 0
Advanced Breast Cancer 0 0
Metastatic Breast Cancer 0 0
Endometrial Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast
Cancer 0 0 0 0
Womb (Uterine or endometrial cancer)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - LY3484356
Treatment: Drugs - Abemaciclib
Treatment: Drugs - Everolimus
Treatment: Drugs - Alpelisib
Treatment: Drugs - Trastuzumab
Treatment: Drugs - Aromatase Inhibitor (AI)
Treatment: Drugs - Pertuzumab

Experimental: Dose Escalation LY3484356 - LY3484356 given 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.

Experimental: Part B: Dose Expansion: Cohort E3: LY3484356 - LY3484356 given orally.

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

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

Experimental: Part C:Dose Expansion: LY3484356 + Trastuzumab +/- Abemaciclib - LY3484356 administered orally in combination with trastuzumab intravenously with or without Abemaciclib.

Experimental: Part D: Dose Expansion: LY3484356 +/- Abemaciclib - LY3484356 and Abemaciclib given orally with trastuzumab administered intravenously.

Experimental: Part E: Dose Expansion: LY3484356 + Trastuzumab + Pertuzumab - LY3484356 administered orally in combination with trastuzumab and pertuzumab administered intravenously.


Treatment: Drugs: LY3484356
Administered orally

Treatment: Drugs: Abemaciclib
Administered orally

Treatment: Drugs: Everolimus
Administered orally

Treatment: Drugs: Alpelisib
Administered orally

Treatment: Drugs: Trastuzumab
Administered intravenously

Treatment: Drugs: Aromatase Inhibitor (AI)
Anastrozole or Exemestane or Letrozole administered orally (physician choice)

Treatment: Drugs: Pertuzumab
Administered intravenously
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants with Dose Limiting Toxicities (DLTs) and DLT-Equivalent Toxicities
Timepoint [1] 0 0
Baseline through Cycle 1 (21/28 Day Cycle)
Secondary outcome [1] 0 0
Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of LY3484356
Timepoint [1] 0 0
Predose Cycle 1 Day 1 through Predose Cycle 2 Day 1 (21/28 Day Cycles)
Secondary outcome [2] 0 0
PK: Maximum Concentration (Cmax) of LY3484356
Timepoint [2] 0 0
Predose Cycle 1 Day 1 through Predose Cycle 2 Day 1 (21/28 Day Cycles)
Secondary outcome [3] 0 0
PK: AUC of LY3484356 in Combination with Other Anticancer Therapies
Timepoint [3] 0 0
Predose Cycle 1 Day 1 through Predose Cycle 2 Day 1 (21/28 Day Cycles)
Secondary outcome [4] 0 0
PK: Cmax of LY3484356 in Combination with Other Anticancer Therapies
Timepoint [4] 0 0
Predose Cycle 1 Day 1 through Predose Cycle 2 Day 1 (21/28 Day Cycles)
Secondary outcome [5] 0 0
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
Timepoint [5] 0 0
Baseline through Disease Progression or Death (Estimated up to 28 Months)
Secondary outcome [6] 0 0
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
Timepoint [6] 0 0
Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Estimated up to 28 Months)
Secondary outcome [7] 0 0
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
Timepoint [7] 0 0
Baseline through Measured Progressive Disease (Estimated up to 28 Months)
Secondary outcome [8] 0 0
Clinical Benefit Rate (CBR): Percentage of Participants with a BOR of CR or PR, or SD lasting =24 weeks as per RECIST v1.1
Timepoint [8] 0 0
Baseline through Measured Progressive Disease (Estimated up to 28 Months)
Secondary outcome [9] 0 0
Progression Free Survival (PFS): Time From Baseline to the Date of Objective Progression or Death Due to Any Cause, Whichever is Earlier
Timepoint [9] 0 0
Baseline to Objective Progression or Death Due to Any Cause (Estimated up to 28 Months)

Eligibility
Key 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 a (PIK3Ca) 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
10/12/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2027
Actual
Sample size
Target
500
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,WA
Recruitment hospital [1] 0 0
St Vincent's Hospital Sydney - Darlinghurst
Recruitment hospital [2] 0 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [3] 0 0
Cancer Research SA - Adelaide
Recruitment hospital [4] 0 0
Breast Cancer Research Centre-WA - Nedlands
Recruitment hospital [5] 0 0
Linear Clinical Research - Nedlands
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
2298 - Waratah
Recruitment postcode(s) [3] 0 0
5000 - Adelaide
Recruitment postcode(s) [4] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Indiana
Country [7] 0 0
United States of America
State/province [7] 0 0
Maryland
Country [8] 0 0
United States of America
State/province [8] 0 0
Massachusetts
Country [9] 0 0
United States of America
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Minnesota
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United States of America
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Missouri
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New Jersey
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New York
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North Carolina
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United States of America
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Ohio
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United States of America
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Oklahoma
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United States of America
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Oregon
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United States of America
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Pennsylvania
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Rhode Island
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Tennessee
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Texas
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United States of America
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Vermont
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United States of America
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Virginia
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United States of America
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Washington
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Belgium
State/province [24] 0 0
Antwerpen
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Belgium
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Bruxelles-Capitale, Région De
Country [26] 0 0
Belgium
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Vlaams-Brabant
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France
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Paris
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France
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Strasbourg
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Japan
State/province [29] 0 0
Hyogo
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Japan
State/province [30] 0 0
Tokyo
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Korea, Republic of
State/province [31] 0 0
Korea
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Korea, Republic of
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Seoul, Korea
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Korea, Republic of
State/province [33] 0 0
Seoul-teukbyeolsi [Seoul]
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Korea, Republic of
State/province [34] 0 0
Seoul
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Spain
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Catalunya [Cataluña]
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Spain
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Madrid, Comunidad De
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Spain
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Valenciana, Comunitat
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Spain
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Barcelona
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Spain
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Madrid
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Spain
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Valencia
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Taiwan
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Kaohsiung
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Taiwan
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Taichung
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Taiwan
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Tainan
Country [44] 0 0
Taiwan
State/province [44] 0 0
Taipei

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Eli Lilly and Company
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
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)
Address 0 0
Eli Lilly and Company
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04188548