A Study of LY4064809 With Other Anti-Cancer Treatments in Participants With Advanced Breast Cancer With a Genetic Change (PIK3CA)
- Conditions
- Breast NeoplasmsNeoplasm Metastasis
- Interventions
- Registration Number
- NCT07174336
- Lead Sponsor
- Eli Lilly and Company
- Brief Summary
The purpose of the study is to assess the efficacy and safety of the addition of LY4064809 to other anti-cancer drugs as first treatment for advanced hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer. Participants can remain in the study as long as the drug is helping the cancer without unbearable side effects.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 920
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If assigned female at birth, pre-/peri- and postmenopausal status is allowed. Those with pre- or peri-menopausal status at study entry must agree to use ovarian function suppression with any locally approved gonadotropin-releasing hormone (GnRH) agonist.
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If assigned male at birth with an estrogen receptor positive (ER+) breast cancer diagnosis, they must agree to use hormone suppression with a GnRH agonist.
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Have histologically or cytologically confirmed breast cancer, defined as individuals with
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locally advanced breast cancer not amenable to curative therapy (for example, surgery) or metastatic disease, and
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hormone receptors (HR)+/human epidermal growth factor receptor 2 (HER2)- or HR+/HER low defined by American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) Guidelines
- HR status: Documented ER+ and/or progesterone receptor-positive (PR+) tumor according to ASCO/CAP Guidelines, defined as greater than or equal to (≥)1 percent (%) of tumor cells stained positive based on the most recent tumor biopsy and assessed locally
- HER status: immunohistochemistry score of 1+ or score of 2+ with a negative Fluorescence In Situ Hybridization (FISH) based on local results as defined in the ASCO/CAP Guidelines
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Have evidence of an activating PIK3CA mutation, detected in tumor or blood samples using an appropriate assay.
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Have measurable disease or non-measurable, evaluable bone disease
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Part 1:
- Received 0-2 prior systemic treatments for advanced breast cancer not amenable to curative therapy (for example, surgery) or metastatic disease.
- Up to 1 of these prior systemic treatments may contain chemotherapy
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Part 2:
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Received 0 prior systemic treatment for advanced breast cancer not amenable to curative therapy (for example, surgery) or metastatic disease.
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Individuals who are eligible are either
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Population 1 (P1): Endocrine sensitive
- newly diagnosed with advanced breast cancer (de novo)
- relapsed with documented evidence of progression greater than (>)12 months from completion of (neo)adjuvant ET ± cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor, or
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Population 2 (P2): Endocrine resistant
- relapsed with documented evidence of progression less than or equal to (≤)12 months of completing (neo)adjuvant ET ± CDK4/6 inhibitor.
- if a CDK4/6 inhibitor was included as part of neoadjuvant or adjuvant therapy, progression event must be >12 months since completion of CDK4/6 inhibitor portion of neoadjuvant or adjuvant therapy.
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Have an established diagnosis of Type 1 diabetes mellitus or Type 2 diabetes mellitus with hemoglobin A1c (HbA1c) ≥8%, fasting blood glucose (FBG) ≥140 milligrams per deciliter (mg/dL) (7.7 millimoles per liter [mmol/L]), or requiring insulin.
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Have inflammatory or metaplastic breast cancer.
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History of leptomeningeal disease or carcinomatous meningitis.
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Have known and untreated or active central nervous system (CNS) metastases. Exception: Asymptomatic brain or spinal metastases if treated by surgery, surgery plus radiotherapy, or radiotherapy alone with no evidence of radiographic progression or hemorrhage within at least 28 days before randomization and no requirement for anticonvulsants or systemic corticosteroids for at least 28 days before randomization.
- Have received treatment with any local or systemic antineoplastic therapy or investigational anticancer agent within 14 days or 4 half-lives, whichever is longer, prior to randomization up to a maximum washout period of 28 days.
- Have a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (dose more than 10 milligrams [mg] daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to randomization.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description LY4064809 + CDK4/6 Inhibitor + Endocrine Therapy (ET) (Part 1) LY4064809 LY4064809 given orally in one of two doses in combination with investigator's choice of CDK4/6 inhibitor given orally and ET given orally or intramuscularly LY4064809 + CDK4/6 Inhibitor + Endocrine Therapy (ET) (Part 1) Ribociclib LY4064809 given orally in one of two doses in combination with investigator's choice of CDK4/6 inhibitor given orally and ET given orally or intramuscularly LY4064809 + CDK4/6 Inhibitor + Endocrine Therapy (ET) (Part 1) Palbociclib LY4064809 given orally in one of two doses in combination with investigator's choice of CDK4/6 inhibitor given orally and ET given orally or intramuscularly LY4064809 + CDK4/6 Inhibitor + Endocrine Therapy (ET) (Part 1) Abemaciclib LY4064809 given orally in one of two doses in combination with investigator's choice of CDK4/6 inhibitor given orally and ET given orally or intramuscularly LY4064809 + CDK4/6 Inhibitor + Endocrine Therapy (ET) (Part 1) Anastrozole LY4064809 given orally in one of two doses in combination with investigator's choice of CDK4/6 inhibitor given orally and ET given orally or intramuscularly LY4064809 + CDK4/6 Inhibitor + Endocrine Therapy (ET) (Part 1) Letrozole LY4064809 given orally in one of two doses in combination with investigator's choice of CDK4/6 inhibitor given orally and ET given orally or intramuscularly LY4064809 + CDK4/6 Inhibitor + Endocrine Therapy (ET) (Part 1) Exemestane LY4064809 given orally in one of two doses in combination with investigator's choice of CDK4/6 inhibitor given orally and ET given orally or intramuscularly LY4064809 + CDK4/6 Inhibitor + Endocrine Therapy (ET) (Part 1) Fulvestrant LY4064809 given orally in one of two doses in combination with investigator's choice of CDK4/6 inhibitor given orally and ET given orally or intramuscularly LY4064809 + CDK4/6 Inhibitor + Endocrine Therapy (ET) (Part 2) LY4064809 LY4064809 given orally in combination with CDK4/6 inhibitor given orally and ET given orally or intramuscularly LY4064809 + CDK4/6 Inhibitor + Endocrine Therapy (ET) (Part 2) Palbociclib LY4064809 given orally in combination with CDK4/6 inhibitor given orally and ET given orally or intramuscularly LY4064809 + CDK4/6 Inhibitor + Endocrine Therapy (ET) (Part 2) Anastrozole LY4064809 given orally in combination with CDK4/6 inhibitor given orally and ET given orally or intramuscularly LY4064809 + CDK4/6 Inhibitor + Endocrine Therapy (ET) (Part 2) Letrozole LY4064809 given orally in combination with CDK4/6 inhibitor given orally and ET given orally or intramuscularly LY4064809 + CDK4/6 Inhibitor + Endocrine Therapy (ET) (Part 2) Exemestane LY4064809 given orally in combination with CDK4/6 inhibitor given orally and ET given orally or intramuscularly LY4064809 + CDK4/6 Inhibitor + Endocrine Therapy (ET) (Part 2) Fulvestrant LY4064809 given orally in combination with CDK4/6 inhibitor given orally and ET given orally or intramuscularly Placebo + CDK4/6 Inhibitor + Endocrine Therapy (ET) (Part 2) Placebo Placebo given orally in combination with CDK4/6 inhibitor given orally and ET given orally or intramuscularly Placebo + CDK4/6 Inhibitor + Endocrine Therapy (ET) (Part 2) Palbociclib Placebo given orally in combination with CDK4/6 inhibitor given orally and ET given orally or intramuscularly Placebo + CDK4/6 Inhibitor + Endocrine Therapy (ET) (Part 2) Anastrozole Placebo given orally in combination with CDK4/6 inhibitor given orally and ET given orally or intramuscularly Placebo + CDK4/6 Inhibitor + Endocrine Therapy (ET) (Part 2) Letrozole Placebo given orally in combination with CDK4/6 inhibitor given orally and ET given orally or intramuscularly Placebo + CDK4/6 Inhibitor + Endocrine Therapy (ET) (Part 2) Exemestane Placebo given orally in combination with CDK4/6 inhibitor given orally and ET given orally or intramuscularly Placebo + CDK4/6 Inhibitor + Endocrine Therapy (ET) (Part 2) Fulvestrant Placebo given orally in combination with CDK4/6 inhibitor given orally and ET given orally or intramuscularly
- Primary Outcome Measures
Name Time Method (Part 1): Overall Response Rate (ORR): Percentage of Participants with Confirmed Complete Response (CR) or Partial Response (PR) Baseline through disease progression or death (Estimated up to 5 years) As determined by the investigator based on Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1
(Part 2): Progression-Free Survival Baseline to objective progression or death due to any cause (Estimated up to 5 years) Investigator-assessed
- Secondary Outcome Measures
Name Time Method (Part 1): Disease Control Rate (DCR) Baseline through measured progressive disease (Estimated up to 5 years) per RECIST v1.1
(Part 1): Time to Response (TTR) Baseline until the date that measurement criteria for CR or PR (whichever is first recorded) are first met (Estimated as approximately 5 years) per RECIST v1.1
(Parts 1 and 2): Duration of Response (DOR) Date of CR or PR to date of objective disease progression or death due to any cause (Estimated up to 5 years) per RECIST v1.1
(Part 1): PFS Baseline to objective progression or death due to any cause (Estimated up to 5 years) per RECIST v1.1
(Parts 1 and 2): Overall Survival (OS) Baseline to deaths from any cause (Estimated up to 7 years) (Part 1): Best Overall Response (BOR) Baseline to disease progression or death from any cause (Estimated up to 5 years) (Parts 1 and 2): Clinical Benefit Rate (CBR): Percentage of Participants with a BOR of CR or PR, or SD Lasting Greater than or Equal to Six Months Baseline to disease progression or death from any cause (Estimated up to 5 years) per RECIST v1.1
(Parts 1 and 2): PK: Average Plasma Concentrations of LY4064809 Baseline to last PK sample collection up to 5 months (Part 2): Progression-Free Survival after Subsequent Line of Treatment (PFS2) Baseline to disease progression on next line of treatment or death from any cause (Estimated as up to 7 years) Investigator-assessed
(Part 2): Progression-Free Survival (PFS) Baseline to objective progression or death from any cause (Estimated up to 5 years) By BICR
(Part 2): Objective Response Rate (ORR) Baseline to disease progression or death from any cause (Estimated up to 5 years) By investigator and blinded independent central review (BICR)
(Part 2): Time to Chemotherapy (TTC) Baseline until the start of chemotherapy (Estimated up to 7 years) (Part 2): Chemotherapy-Free Survival Baseline until the start of chemotherapy or death from any cause (Estimated up to 7 years) (Part 2): Change in Overall Health-related Quality of Life (HRQoL) as measured by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status/Quality of Life Subscale Baseline until disease progression or death (Estimated up to 7 years) The EORTC QLQ-C30 is a 30-question patient-reported instrument used to assess multidimensional HRQoL in cancer patients. Overall HRQoL is measured by the EORTC QLQ-C30 Global Health Status/Quality of Life Subscale (two items). Response options range from 1) "very poor" to 7) "excellent." Score is linearly transformed to the range 0 - 100. Higher score represents better overall HRQoL.
(Part 2): Change in Physical Function as measured by the EORTC QLQ-C30 Physical Functioning Subscale Baseline until disease progression or death (Estimated up to 7 years) The EORTC QLQ-C30 is a 30-question patient-reported instrument used to assess multidimensional HRQoL in cancer patients. Physical function is measured by the EORTC QLQ-C30 Physical Functioning subscale (five items). Response options range from 1) "not at all" to 4) "very much." Score is linearly transformed to the range 0 - 100. Higher score represents better overall physical function.
Trial Locations
- Locations (30)
Highlands Oncology Group
🇺🇸Springdale, Arkansas, United States
Summit Cancer Care, PC
🇺🇸Savannah, Georgia, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Good Samaritan Regional Medical Center
🇺🇸Corvallis, Oregon, United States
Parkland Health and Hospital System
🇺🇸Dallas, Texas, United States
UT Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Anyang Cancer Hospital
🇨🇳Anyang, China
Beijing Cancer hospital
🇨🇳Beijing, China
The First Hospital of Jilin University
🇨🇳Changchun, China
Scroll for more (20 remaining)Highlands Oncology Group🇺🇸Springdale, Arkansas, United StatesJoseph BeckPrincipal Investigator