A Study of LY3484356 in Participants With Advanced or Metastatic Breast Cancer or Endometrial Cancer (EMBER)
Breast Cancer, Advanced Breast Cancer, Metastatic Breast Cancer
About this trial
This is an interventional treatment trial for Breast 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
Sites / Locations
- Banner MD Anderson Cancer Center
- Mayo Clinic Hospital
- Highlands Oncology Group
- Beverly Hills Cancer Center
- Univ of California Irvine College of Medicine
- Univ of California San Francisco
- Rocky Mountain Cancer Center
- Mayo Clinic in Florida
- Lake Nona DDU
- Winship Cancer Center Emory University
- Northwestern University
- Community Health Network
- Johns Hopkins University
- Massachusetts General Hospital
- Dana-Farber Cancer Institute
- Minnesota Oncology/Hematology PA
- Mayo Clinic
- Washington University Medical School
- Memorial Sloan Kettering Cancer Center
- Memorial Sloan Kettering Cancer Center
- University of Rochester School of Medicine
- University of North Carolina
- Duke University Medical Center
- Ohio State University Medical Center
- Peggy and Charles Stephenson Oklahoma Cancer Center
- Asante Rogue Regional Medical Center
- University of Pittsburgh Medical Center
- Rhode Island Hospital
- Sarah Cannon Research Institute SCRI
- Tennessee Oncology PLLC
- Henry-Joyce Cancer Clinic
- Texas Oncology-Baylor Charles A. Sammons Cancer Center
- UT Southwestern Med Center
- University of Texas MD Anderson Cancer Center
- South Texas Accelerated Research Therapeutics (START)
- Texas Oncology - San Antonio Medical Center
- US Oncology
- Texas Oncology - Tyler
- University of Vermont Medical Center
- Inova Schar Cancer Institute
- Oncology and Hematology Associates of Southwest Virginia Inc
- Seattle Cancer Care Alliance
- St Vincent's Hospital Sydney
- Calvary Mater Newcastle
- Ashford Cancer Centre Research
- Breast Cancer Research Centre-WA
- Linear Clinical Research
- Institut Jules Bordet
- Universitair Ziekenhuis Antwerpen
- Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
- Institut Curie
- Institut de Cancérologie de l'Ouest Centre René Gauducheau
- ICANS_Institut de Cancerologie Strasbourg Europe
- Gustave Roussy
- Hyogo Cancer Center
- National Cancer Center Hospital
- Severance Hospital, Yonsei University Health System
- Seoul National University Hospital
- Asan Medical Center
- Samsung Medical Center
- Hospital Universitari Vall d'Hebron
- Hospital Clinic I Provincial
- Hospital General Universitario Gregorio Marañon
- Hospital Universitario Ramón y Cajal
- Hospital Clinico San Carlos
- Hospital Universitario 12 de Octubre
- Fundación Jiménez Díaz-Oncology
- Hospital Madrid Norte Sanchinarro
- Fundación Instituto Valenciano de Oncología
- Hospital Clínico Universitario de Valencia
- Kaohsiung Medical University Chung-Ho Memorial Hospital
- China Medical University Hospital
- National Cheng-Kung Uni. Hosp.
- National Taiwan University Hospital
- Mackay Memorial Hospital
- Taipei Veterans General Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Dose Escalation LY3484356
Part A: Dose Expansion: LY3484356 + Abemaciclib +/- AI
Part B: Dose Expansion: Cohort E3: LY3484356
Part B: Dose Expansion: Cohort E4: LY3484356 + Everolimus
Part B: Dose Expansion: Cohort E5: LY3484356 + Alpelisib
Part C:Dose Expansion: LY3484356 + Trastuzumab +/- Abemaciclib
Part D: Dose Expansion: LY3484356 +/- Abemaciclib
Part E: Dose Expansion: LY3484356 + Trastuzumab + Pertuzumab
LY3484356 given orally.
LY3484356 and abemaciclib given orally in combination with or without Aromatase Inhibitor (AI) of physician's choice (Anastrozole, Exemestane, or Letrozole) administered orally.
LY3484356 given orally.
LY3484356 and everolimus given orally.
LY3484356 and alpelisib given orally.
LY3484356 administered orally in combination with trastuzumab intravenously with or without Abemaciclib.
LY3484356 and Abemaciclib given orally with trastuzumab administered intravenously.
LY3484356 administered orally in combination with trastuzumab and pertuzumab administered intravenously.