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)
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
University of California, Irvine
🇺🇸Orange, California, United States
UCSF Medical Center at Mission Bay
🇺🇸San Francisco, California, United States
Mayo Clinic in Florida
🇺🇸Jacksonville, Florida, United States
Lake Nona DDU
🇺🇸Orlando, Florida, United States
Winship Cancer Center Emory University
🇺🇸Atlanta, Georgia, United States
Community Cancer Center North
🇺🇸Indianapolis, Indiana, United States
Scroll for more (62 remaining)Banner MD Anderson Cancer Center🇺🇸Gilbert, Arizona, United States