Clinical trial NCT04188548: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Breast Cancer
Advanced Breast Cancer
Metastatic Breast Cancer
Endometrial Cancer
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2019-12-06
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Number of Participants with Dose Limiting Toxicities (DLTs) and DLT-Equivalent Toxicities
timeFrame: Baseline through Cycle 1 (21/28 Day Cycle)
Secondary outcomes:
measure: Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of LY3484356
timeFrame: Predose Cycle 1 Day 1 through Predose Cycle 2 Day 1 (21/28 Day Cycles)
measure: PK: Maximum Concentration (Cmax) of LY3484356
timeFrame: Predose Cycle 1 Day 1 through Predose Cycle 2 Day 1 (21/28 Day Cycles)
measure: PK: AUC of LY3484356 in Combination with Other Anticancer Therapies
timeFrame: Predose Cycle 1 Day 1 through Predose Cycle 2 Day 1 (21/28 Day Cycles)
measure: PK: Cmax of LY3484356 in Combination with Other Anticancer Therapies
timeFrame: Predose Cycle 1 Day 1 through Predose Cycle 2 Day 1 (21/28 Day Cycles)
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
timeFrame: Baseline through Disease Progression or Death (Estimated up to 28 Months)
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
timeFrame: Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Estimated up to 28 Months)
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
timeFrame: Baseline through Measured Progressive Disease (Estimated up to 28 Months)
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
timeFrame: Baseline through Measured Progressive Disease (Estimated up to 28 Months)
measure: Progression Free Survival (PFS): Time From Baseline to the Date of Objective Progression or Death Due to Any Cause, Whichever is Earlier
timeFrame: Baseline to Objective Progression or Death Due to Any Cause (Estimated up to 28 Months)
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center
state: Arizona
city: Phoenix
country: United States
facility: Mayo Clinic in Arizona - Phoenix
state: Arizona
city: Springdale
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Beverly Hills
country: United States
facility: Beverly Hills Cancer Center
state: California
city: Orange
country: United States
facility: University of California, Irvine
state: California
city: San Francisco
country: United States
facility: UCSF Medical Center at Mission Bay
state: California
city: Jacksonville
country: United States
facility: Mayo Clinic in Florida
state: Florida
city: Orlando
country: United States
facility: Lake Nona DDU
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Center Emory University
state: Georgia
city: Indianapolis
country: United States
facility: Community Cancer Center North
state: Indiana
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Minneapolis
country: United States
facility: Minnesota Oncology/Hematology PA
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Montvale
country: United States
facility: Memorial Sloan Kettering - Bergen
state: New Jersey
city: Commack
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Rochester
country: United States
facility: Wilmot Cancer Institute
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University Medical Center
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center, Stephenson Cancer Center
state: Oklahoma
city: Medford
country: United States
facility: Asante Rogue Regional Medical Center
state: Oregon
city: Harrisburg
country: United States
facility: UPMC Hillman Cancer Center Harrisburg
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Nashville
country: United States
facility: Vanderbilt Health One Hundred Oaks
state: Tennessee
city: Nashville
country: United States
facility: SCRI Oncology Partners
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology Nashville
state: Tennessee
city: Dallas
country: United States
facility: UT Southwestern Med Center
state: Texas
city: Dallas
country: United States
facility: Texas Oncology-Baylor Charles A. Sammons Cancer Center
state: Texas
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutics (START)
state: Texas
city: The Woodlands
country: United States
facility: Minnesota Oncology/Hematology PA
state: Texas
city: The Woodlands
country: United States
facility: Oncology and Hematology Associates of Southwest Virginia Inc
state: Texas
city: The Woodlands
country: United States
facility: Texas Oncology - San Antonio Medical Center
state: Texas
city: The Woodlands
country: United States
facility: US Oncology
state: Texas
city: The Woodlands
country: United States
facility: USO-Rocky Mountain Cancer Center
state: Texas
city: Tyler
country: United States
facility: Texas Oncology - Tyler
state: Texas
city: Burlington
country: United States
facility: The University of Vermont Medical Center Inc.
state: Vermont
city: Fairfax
country: United States
facility: Inova Schar Cancer Institute
state: Virginia
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Darlinghurst
country: Australia
facility: St Vincent's Hospital Sydney
state: New South Wales
city: Waratah
country: Australia
facility: Calvary Mater Newcastle
state: New South Wales
city: Adelaide
country: Australia
facility: Cancer Research SA
state: South Australia
city: Nedlands
country: Australia
facility: Breast Cancer Research Centre-WA
state: Western Australia
city: Nedlands
country: Australia
facility: Linear Clinical Research
state: Western Australia
city: Edegem
country: Belgium
facility: Antwerp University Hospital
state: Antwerpen
city: Anderlecht
country: Belgium
facility: Institut Jules Bordet
state: Bruxelles-Capitale, Région De
city: Leuven
country: Belgium
facility: UZ Leuven
state: Vlaams-Brabant
city: Paris
country: France
facility: Institut Curie
city: Strasbourg
country: France
facility: Institut de cancérologie Strasbourg Europe (ICANS)
city: Akashi
country: Japan
facility: Hyogo Cancer Center
state: Hyogo
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
state: Korea
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
state: Seoul, Korea
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
state: Seoul-teukbyeolsi [Seoul]
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Barcelona
country: Spain
facility: Hospital Clínic de Barcelona
state: Catalunya [Cataluña]
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
state: Madrid, Comunidad De
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
state: Valenciana, Comunitat
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario Fundación Jiménez Díaz
city: Madrid
country: Spain
facility: Hospital Universitario HM Sanchinarro
city: Valencia
country: Spain
facility: Fundación Instituto Valenciano de Oncología
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Tainan
country: Taiwan
facility: National Cheng-Kung Uni. Hosp.
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Mackay Memorial Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References: