Breast Cancer, Advanced Breast Cancer, Metastatic Breast Cancer, Endometrial Cancer
Conditions
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.
Interventions
DRUGPertuzumab
Administered intravenously
DRUGLY3484356
Administered orally
DRUGAbemaciclib
Administered orally
DRUGEverolimus
Administered orally
DRUGAlpelisib
Administered orally
DRUGTrastuzumab
Administered intravenously
Anastrozole or Exemestane or Letrozole administered orally (physician choice)
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
Countries
Australia, Belgium, France, Japan, South Korea, Spain, Taiwan, United States
Outcome results
None listed