A Study of LY3484356 in Participants With Advanced or Metastatic Breast Cancer or Endometrial Cancer
- Conditions
- Metastatic Breast CancerBreast CancerAdvanced Breast CancerEndometrial Cancer
- Interventions
- Drug: Aromatase Inhibitor (AI)
- Registration Number
- NCT04188548
- Lead Sponsor
- Eli Lilly and Company
- 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 available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 500
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
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part B: Dose Expansion: Cohort E4: LY3484356 + Everolimus LY3484356 LY3484356 and everolimus given orally. Part B: Dose Expansion: Cohort E5: LY3484356 + Alpelisib LY3484356 LY3484356 and alpelisib given orally. Part B: Dose Expansion: Cohort E3: LY3484356 LY3484356 LY3484356 given orally. Part C:Dose Expansion: LY3484356 + Trastuzumab +/- Abemaciclib LY3484356 LY3484356 administered orally in combination with trastuzumab intravenously with or without Abemaciclib. Part A: Dose Expansion: LY3484356 + Abemaciclib +/- AI Aromatase Inhibitor (AI) LY3484356 and abemaciclib given orally in combination with or without Aromatase Inhibitor (AI) of physician's choice (Anastrozole, Exemestane, or Letrozole) administered orally. Part E: Dose Expansion: LY3484356 + Trastuzumab + Pertuzumab LY3484356 LY3484356 administered orally in combination with trastuzumab and pertuzumab administered intravenously. Dose Escalation LY3484356 LY3484356 LY3484356 given orally. Part D: Dose Expansion: LY3484356 +/- Abemaciclib LY3484356 LY3484356 and Abemaciclib given orally with trastuzumab administered intravenously. Part A: Dose Expansion: LY3484356 + Abemaciclib +/- AI LY3484356 LY3484356 and abemaciclib given orally in combination with or without Aromatase Inhibitor (AI) of physician's choice (Anastrozole, Exemestane, or Letrozole) administered orally. Part B: Dose Expansion: Cohort E4: LY3484356 + Everolimus Everolimus LY3484356 and everolimus given orally. Part A: Dose Expansion: LY3484356 + Abemaciclib +/- AI Abemaciclib LY3484356 and abemaciclib given orally in combination with or without Aromatase Inhibitor (AI) of physician's choice (Anastrozole, Exemestane, or Letrozole) administered orally. Part B: Dose Expansion: Cohort E5: LY3484356 + Alpelisib Alpelisib LY3484356 and alpelisib given orally. Part C:Dose Expansion: LY3484356 + Trastuzumab +/- Abemaciclib Abemaciclib LY3484356 administered orally in combination with trastuzumab intravenously with or without Abemaciclib. Part C:Dose Expansion: LY3484356 + Trastuzumab +/- Abemaciclib Trastuzumab LY3484356 administered orally in combination with trastuzumab intravenously with or without Abemaciclib. Part D: Dose Expansion: LY3484356 +/- Abemaciclib Abemaciclib LY3484356 and Abemaciclib given orally with trastuzumab administered intravenously. Part E: Dose Expansion: LY3484356 + Trastuzumab + Pertuzumab Trastuzumab LY3484356 administered orally in combination with trastuzumab and pertuzumab administered intravenously. Part E: Dose Expansion: LY3484356 + Trastuzumab + Pertuzumab Pertuzumab LY3484356 administered orally in combination with trastuzumab and pertuzumab administered intravenously.
- Primary Outcome Measures
Name Time Method Number of Participants with Dose Limiting Toxicities (DLTs) and DLT-Equivalent Toxicities Baseline through Cycle 1 (21/28 Day Cycle) Number of Participants with DLTs and DLT-Equivalent Toxicities
- Secondary Outcome Measures
Name Time Method PK: Maximum Concentration (Cmax) of LY3484356 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 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
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 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
Progression Free Survival (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) PFS: Time From Baseline to the Date of Objective Progression or Death Due to Any Cause, Whichever is Earlier
Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of LY3484356 Predose Cycle 1 Day 1 through Predose Cycle 2 Day 1 (21/28 Day Cycles) PK: AUC of LY3484356
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 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 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
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) PK: Cmax of LY3484356 in Combination with Other Anticancer Therapies
Clinical Benefit Rate (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) CBR: Percentage of Participants with a BOR of CR or PR, or SD lasting ≥24 weeks as per RECIST v1.1
Trial Locations
- Locations (72)
Winship Cancer Center Emory University
🇺🇸Atlanta, Georgia, United States
Johns Hopkins University
🇺🇸Baltimore, Maryland, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Ohio State University Medical Center
🇺🇸Columbus, Ohio, United States
Community Cancer Center North
🇺🇸Indianapolis, Indiana, United States
South Texas Accelerated Research Therapeutics (START)
🇺🇸San Antonio, Texas, United States
Duke University
🇺🇸Durham, North Carolina, United States
Breast Cancer Research Centre-WA
🇦🇺Nedlands, Western Australia, Australia
UCSF Medical Center at Mission Bay
🇺🇸San Francisco, California, United States
University of Oklahoma Health Sciences Center, Stephenson Cancer Center
🇺🇸Oklahoma City, Oklahoma, United States
Vanderbilt Health One Hundred Oaks
🇺🇸Nashville, Tennessee, United States
SCRI Oncology Partners
🇺🇸Nashville, Tennessee, United States
Tennessee Oncology Nashville
🇺🇸Nashville, Tennessee, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Hospital Universitario HM Sanchinarro
🇪🇸Madrid, Spain
Kaohsiung Medical University Hospital
🇨🇳Kaohsiung, Taiwan
University of California, Irvine
🇺🇸Orange, California, United States
Banner MD Anderson Cancer Center
🇺🇸Gilbert, Arizona, United States
Mayo Clinic in Arizona - Phoenix
🇺🇸Phoenix, Arizona, United States
Highlands Oncology Group
🇺🇸Springdale, Arkansas, United States
Beverly Hills Cancer Center
🇺🇸Beverly Hills, California, United States
Mayo Clinic in Florida
🇺🇸Jacksonville, Florida, United States
Washington University
🇺🇸Saint Louis, Missouri, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Minnesota Oncology/Hematology PA
🇺🇸The Woodlands, Texas, United States
Memorial Sloan Kettering - Bergen
🇺🇸Montvale, New Jersey, United States
Wilmot Cancer Institute
🇺🇸Rochester, New York, United States
UPMC Hillman Cancer Center Harrisburg
🇺🇸Harrisburg, Pennsylvania, United States
Asante Rogue Regional Medical Center
🇺🇸Medford, Oregon, United States
UT Southwestern Med Center
🇺🇸Dallas, Texas, United States
Texas Oncology-Baylor Charles A. Sammons Cancer Center
🇺🇸Dallas, Texas, United States
Texas Oncology - San Antonio Medical Center
🇺🇸The Woodlands, Texas, United States
Oncology and Hematology Associates of Southwest Virginia Inc
🇺🇸The Woodlands, Texas, United States
US Oncology
🇺🇸The Woodlands, Texas, United States
Texas Oncology - Tyler
🇺🇸Tyler, Texas, United States
USO-Rocky Mountain Cancer Center
🇺🇸The Woodlands, Texas, United States
The University of Vermont Medical Center Inc.
🇺🇸Burlington, Vermont, United States
Inova Schar Cancer Institute
🇺🇸Fairfax, Virginia, United States
Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States
Cancer Research SA
🇦🇺Adelaide, South Australia, Australia
Calvary Mater Newcastle
🇦🇺Waratah, New South Wales, Australia
St Vincent's Hospital Sydney
🇦🇺Darlinghurst, New South Wales, Australia
Linear Clinical Research
🇦🇺Nedlands, Western Australia, Australia
UZ Leuven
🇧🇪Leuven, Vlaams-Brabant, Belgium
Institut Curie
🇫🇷Paris, France
Institut de cancérologie Strasbourg Europe (ICANS)
🇫🇷Strasbourg, France
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Seoul, Korea, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Hospital Clínic de Barcelona
🇪🇸Barcelona, Catalunya [Cataluña], Spain
Hospital Clínico Universitario de Valencia
🇪🇸Valencia, Valenciana, Comunitat, Spain
Asan Medical Center
🇰🇷Seoul, Seoul-teukbyeolsi [Seoul], Korea, Republic of
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Madrid, Comunidad De, Spain
Hospital Universitario Ramón y Cajal
🇪🇸Madrid, Spain
Hospital General Universitario Gregorio Marañon
🇪🇸Madrid, Spain
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Clinico San Carlos
🇪🇸Madrid, Spain
Hospital Universitario Fundación Jiménez Díaz
🇪🇸Madrid, Spain
Fundación Instituto Valenciano de Oncología
🇪🇸Valencia, Spain
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan
University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Institut Jules Bordet
🇧🇪Anderlecht, Bruxelles-Capitale, Région De, Belgium
National Cancer Center Hospital
🇯🇵Chuo-ku, Tokyo, Japan
China Medical University Hospital
🇨🇳Taichung, Taiwan
National Cheng-Kung Uni. Hosp.
🇨🇳Tainan, Taiwan
Mackay Memorial Hospital
🇨🇳Taipei, Taiwan
Antwerp University Hospital
🇧🇪Edegem, Antwerpen, Belgium
Hyogo Cancer Center
🇯🇵Akashi, Hyogo, Japan
Lake Nona DDU
🇺🇸Orlando, Florida, United States
Rhode Island Hospital
🇺🇸Providence, Rhode Island, United States