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Purpose

The purpose of the study is to assess the efficacy and safety of the addition of Tersolisib (LY4064809/STX-478) 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.

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Are willing to follow contraception requirements. Contraceptive use by participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. - 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. - 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. - Have histologically or cytologically confirmed breast cancer, defined as individuals with - locally advanced breast cancer not amenable to curative therapy (for example, surgery) or metastatic disease, and - 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 - Have evidence of an activating PIK3CA mutation, detected in tumor or blood samples using an appropriate assay. - Have measurable disease or non-measurable, evaluable bone disease - 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 - Part 2: - Received 0 prior systemic treatment for advanced breast cancer not amenable to curative therapy (for example, surgery) or metastatic disease. - Individuals who are eligible are either - 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 - 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.

Exclusion Criteria

  • 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. - Have inflammatory or metaplastic breast cancer. - History of leptomeningeal disease or carcinomatous meningitis. - 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. - Are pregnant, breastfeeding, or intend to become pregnant during the study or within 6 months of the last dose of study intervention and at least 2 years after the last dose of fulvestrant and/or CDK4/6 inhibitor after the final administration of study treatment.

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Double (Participant, Investigator)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
LY4064809 + CDK4/6 Inhibitor + Endocrine Therapy (ET) (Part 1) 		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
  • Drug: LY4064809
    Administered orally
    Other names:
    • STX-478
    • Tersolisib
  • Drug: Ribociclib
    Administered orally
  • Drug: Palbociclib
    Administered orally
  • Drug: Abemaciclib
    Administered orally
    Other names:
    • LY2835219
  • Drug: Anastrozole
    Administered orally
  • Drug: Letrozole
    Administered orally
  • Drug: Exemestane
    Administered orally
  • Drug: Fulvestrant
    Administered intramuscular
Experimental
LY4064809 + CDK4/6 Inhibitor + Endocrine Therapy (ET) (Part 2) 		LY4064809 given orally in combination with CDK4/6 inhibitor given orally and ET given orally or intramuscularly
  • Drug: LY4064809
    Administered orally
    Other names:
    • STX-478
    • Tersolisib
  • Drug: Palbociclib
    Administered orally
  • Drug: Anastrozole
    Administered orally
  • Drug: Letrozole
    Administered orally
  • Drug: Exemestane
    Administered orally
  • Drug: Fulvestrant
    Administered intramuscular
Placebo Comparator
Placebo + CDK4/6 Inhibitor + Endocrine Therapy (ET) (Part 2) 		Placebo given orally in combination with CDK4/6 inhibitor given orally and ET given orally or intramuscularly
  • Drug: Placebo
    Administered orally
  • Drug: Palbociclib
    Administered orally
  • Drug: Anastrozole
    Administered orally
  • Drug: Letrozole
    Administered orally
  • Drug: Exemestane
    Administered orally
  • Drug: Fulvestrant
    Administered intramuscular

Recruiting Locations

Highlands Oncology Group
Springdale, Arkansas 72762
Contact:
479-872-8130

Marin Cancer Care
Greenbrae, California 94904

Providence Medical Foundation
Santa Rosa, California 95403

Clermont Oncology Center
Clermont, Florida 34711
Contact:
352-242-1366

Mid Florida Hematology and Oncology Center
Orange City, Florida 32763
Contact:
386-774-1223

Summit Cancer Care, PC
Savannah, Georgia 31405
Contact:
912-651-5771

Indiana University Health University Hospital
Indianapolis, Indiana 46202

Jefferson Health - Cherry Hill
Cherry Hill, New Jersey 08002

Sidney Kimmel Cancer Center - Washington Township
Sewell, New Jersey 08080

Atlantic Health System Overlook Medical Center
Summit, New Jersey 07901

Good Samaritan Regional Medical Center
Corvallis, Oregon 97330

Oncology Associates of Oregon
Eugene, Oregon 97401

Thomas Jefferson University - Clinical Research Institute
Philadelphia, Pennsylvania 19107

Jefferson Hospital Northeast
Philadelphia, Pennsylvania 19114

Asplundh Cancer Pavilion
Willow Grove, Pennsylvania 19090

Sarah Cannon Research Institute SCRI
Nashville, Tennessee 37203

World Research Link
Baytown, Texas 77521
Contact:
833-832-8328

USO - Texas Oncology
Dallas, Texas 75246

UT Southwestern Medical Center
Dallas, Texas 75390
Contact:
214-648-4180

Texas Oncology - West Texas
El Paso, Texas 79902

Oncology Consultants P.A.
Houston, Texas 77030
Contact:
713-600-0900

Nova Oncology
McAllen, Texas 78504
Contact:
281-944-3610

Texas Oncology - San Antonio Medical Center
San Antonio, Texas 78240

US Oncology Research Network
The Woodlands, Texas 77380

More Details

Status
Recruiting
Sponsor
Eli Lilly and Company

Study Contact

Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or
1-317-615-4559
LillyTrials@Lilly.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.