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

Breast Cancer Clinical Trial

— EMBER  

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 Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04188548
• Other study ID #: 17502
• Secondary ID: J2J-MC-JZLA2019-
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: December 10, 2019
• Est. completion date: December 2027

Study information

• Verified date: May 2024
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 500
• Est. completion date: December 2027
• Est. primary completion date: June 29, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• LY3484356
Administered orally
• Abemaciclib
Administered orally
• Everolimus
Administered orally
• Alpelisib
Administered orally
• Trastuzumab
Administered intravenously
• Aromatase Inhibitor (AI)
Anastrozole or Exemestane or Letrozole administered orally (physician choice)
• Pertuzumab
Administered intravenously

Locations

Country	Name	City	State
Australia	Cancer Research SA	Adelaide	South Australia
Australia	St Vincent's Hospital Sydney	Darlinghurst	New South Wales
Australia	Breast Cancer Research Centre-WA	Nedlands	Western Australia
Australia	Linear Clinical Research	Nedlands	Western Australia
Australia	Calvary Mater Newcastle	Waratah	New South Wales
Belgium	Institut Jules Bordet	Anderlecht	Bruxelles-Capitale, Région De
Belgium	Antwerp University Hospital	Edegem	Antwerpen
Belgium	UZ Leuven	Leuven
France	Institut Curie	Paris
France	Institut de cancérologie Strasbourg Europe (ICANS)	Strasbourg
Japan	Hyogo Cancer Center	Akashi	Hyogo
Japan	National Cancer Center Hospital	Chuo-ku	Tokyo
Korea, Republic of	Asan Medical Center	Seoul	Seoul-teukbyeolsi [Seoul]
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul	Seoul, Korea
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul	Korea
Spain	Hospital Clínic de Barcelona	Barcelona	Catalunya [Cataluña]
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital Clinico San Carlos	Madrid
Spain	Hospital General Universitario Gregorio Marañon	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid	Madrid, Comunidad De
Spain	Hospital Universitario Fundación Jiménez Díaz	Madrid
Spain	Hospital Universitario HM Sanchinarro	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid
Spain	Fundación Instituto Valenciano de Oncología	Valencia
Spain	Hospital Clínico Universitario de Valencia	Valencia	Valenciana, Comunitat
Taiwan	Kaohsiung Medical University Hospital	Kaohsiung
Taiwan	China Medical University Hospital	Taichung
Taiwan	National Cheng-Kung Uni. Hosp.	Tainan
Taiwan	Mackay Memorial Hospital	Taipei
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei
United States	Winship Cancer Center Emory University	Atlanta	Georgia
United States	Johns Hopkins University	Baltimore	Maryland
United States	Beverly Hills Cancer Center	Beverly Hills	California
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	The University of Vermont Medical Center Inc.	Burlington	Vermont
United States	University of North Carolina School of Medicine	Chapel Hill	North Carolina
United States	Northwestern University	Chicago	Illinois
United States	Ohio State University Medical Center	Columbus	Ohio
United States	Memorial Sloan Kettering Cancer Center	Commack	New York
United States	Texas Oncology-Baylor Charles A. Sammons Cancer Center	Dallas	Texas
United States	UT Southwestern Med Center	Dallas	Texas
United States	Duke University	Durham	North Carolina
United States	Inova Schar Cancer Institute	Fairfax	Virginia
United States	Banner MD Anderson Cancer Center	Gilbert	Arizona
United States	UPMC Hillman Cancer Center Harrisburg	Harrisburg	Pennsylvania
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Community Cancer Center North	Indianapolis	Indiana
United States	Mayo Clinic in Florida	Jacksonville	Florida
United States	Asante Rogue Regional Medical Center	Medford	Oregon
United States	Minnesota Oncology/Hematology PA	Minneapolis	Minnesota
United States	Memorial Sloan Kettering - Bergen	Montvale	New Jersey
United States	SCRI Oncology Partners	Nashville	Tennessee
United States	Tennessee Oncology Nashville	Nashville	Tennessee
United States	Vanderbilt Health One Hundred Oaks	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	University of Oklahoma Health Sciences Center, Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	University of California, Irvine	Orange	California
United States	Lake Nona DDU	Orlando	Florida
United States	Mayo Clinic in Arizona - Phoenix	Phoenix	Arizona
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Mayo Clinic	Rochester	Minnesota
United States	Wilmot Cancer Institute	Rochester	New York
United States	Washington University	Saint Louis	Missouri
United States	South Texas Accelerated Research Therapeutics (START)	San Antonio	Texas
United States	UCSF Medical Center at Mission Bay	San Francisco	California
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	Highlands Oncology Group	Springdale	Arkansas
United States	Minnesota Oncology/Hematology PA	The Woodlands	Texas
United States	Oncology and Hematology Associates of Southwest Virginia Inc	The Woodlands	Texas
United States	Texas Oncology - San Antonio Medical Center	The Woodlands	Texas
United States	US Oncology	The Woodlands	Texas
United States	USO-Rocky Mountain Cancer Center	The Woodlands	Texas
United States	Texas Oncology - Tyler	Tyler	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  France,  Japan,  Korea, Republic of,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants with Dose Limiting Toxicities (DLTs) and DLT-Equivalent Toxicities	Number of Participants with DLTs and DLT-Equivalent Toxicities	Baseline through Cycle 1 (21/28 Day Cycle)
Secondary	Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of LY3484356	PK: AUC of LY3484356	Predose Cycle 1 Day 1 through Predose Cycle 2 Day 1 (21/28 Day Cycles)
Secondary	PK: Maximum Concentration (Cmax) of LY3484356	PK: Cmax of LY3484356	Predose Cycle 1 Day 1 through Predose Cycle 2 Day 1 (21/28 Day Cycles)
Secondary	PK: AUC of LY3484356 in Combination with Other Anticancer Therapies	PK: AUC of LY3484356 in Combination with Other Anticancer Therapies	Predose Cycle 1 Day 1 through Predose Cycle 2 Day 1 (21/28 Day Cycles)
Secondary	PK: Cmax of LY3484356 in Combination with Other Anticancer Therapies	PK: Cmax of LY3484356 in Combination with Other Anticancer Therapies	Predose Cycle 1 Day 1 through Predose Cycle 2 Day 1 (21/28 Day Cycles)
Secondary	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	ORR: Percentage of Participants with Confirmed CR or PR as per RECIST v1.1	Baseline through Disease Progression or Death (Estimated up to 28 Months)
Secondary	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	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	Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Estimated up to 28 Months)
Secondary	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	DCR: Percentage of Participants with a BOR of CR, PR, and SD as per RECIST v1.1	Baseline through Measured Progressive Disease (Estimated up to 28 Months)
Secondary	Clinical Benefit Rate (CBR): Percentage of Participants with a BOR of CR or PR, or SD lasting =24 weeks as per RECIST v1.1	CBR: Percentage of Participants with a BOR of CR or PR, or SD lasting =24 weeks as per RECIST v1.1	Baseline through Measured Progressive Disease (Estimated up to 28 Months)
Secondary	Progression Free Survival (PFS): Time From Baseline to the Date of Objective Progression or Death Due to Any Cause, Whichever is Earlier	PFS: Time From Baseline to the Date of Objective Progression or Death Due to Any Cause, Whichever is Earlier	Baseline to Objective Progression or Death Due to Any Cause (Estimated up to 28 Months)

External Links

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