Recruiting

Phase 3

LY4064809 with Anti-Cancer DrugsA Study of Tersolisib (LY4064809/STX-478) With Other Anti-Cancer Treatments in Participants With Advanced Breast Cancer With a Genetic Change (PIK3CA)

Sponsor:

Eli Lilly and Company

Code:

NCT07174336

Conditions

Breast Neoplasms

Neoplasm Metastasis

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

LY4064809

Placebo

Ribociclib

Palbociclib

Abemaciclib

Study Details

Brief summary:

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

Breast Neoplasms

Neoplasm Metastasis

Study ID

NCT07174336

Start date

Dec 22, 2025

Status verified date

Aug, 2026

Completion date

May, 2033

Anticipated

Primary completion date

May, 2029

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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 trials.
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)
participants with a history of HR+, HER2- EBC and did not receive SOC adjuvant ET
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.
Have active bacterial or fungal infection that is not recovered at randomization.

Study Design

Enrollment

800 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

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

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

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

Interventions

LY4064809

Administered orally

Placebo

Administered orally

Ribociclib

Administered orally

Palbociclib

Administered orally

Abemaciclib

Administered orally

Anastrozole

Administered orally

Letrozole

Administered orally

Exemestane

Administered orally

Fulvestrant

Administered intramuscular

Primary outcome measure

(Part 1): Overall Response Rate (ORR): Percentage of Participants with Confirmed Complete Response (CR) or Partial Response (PR) [ Time Frame: Baseline through disease progression or death (Estimated up to 5 years) ]
(Part 2): Progression-Free Survival [ Time Frame: Baseline to objective progression or death due to any cause (Estimated up to 5 years) ]

Central Contacts and Locations

Central contacts

Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or

1-317-615-4559 LillyTrials@Lilly.com

Physicians interested in becoming principal investigators please contact

clinical_inquiry_hub@lilly.com

Locations

Ironwood Cancer & Research Centers

Recruiting

Chandler, Arizona, United States, 85224

Principal Investigator:

Jasleen Khanuja

The University of Arizona Cancer Center - North Campus

Recruiting

Tucson, Arizona, United States, 85719

Principal Investigator:

Sima Ehsani

Highlands Oncology Group

Recruiting

Springdale, Arkansas, United States, 72762

Contacts

479-872-8130

Principal Investigator:

Joseph Beck

City of Hope

Recruiting

Duarte, California, United States, 91010

Principal Investigator:

Hope Rugo

Marin Cancer Care

Recruiting

Greenbrae, California, United States, 94904

Principal Investigator:

Cyrus Mazidi

City of Hope Orange County Lennar Foundation Cancer Center

Recruiting

Irvine, California, United States, 92618

Principal Investigator:

Hope Rugo

Profound Research LLC

Recruiting

Oceanside, California, United States, 92056

Principal Investigator:

Catherine Quinn

Providence Medical Foundation

Recruiting

Santa Rosa, California, United States, 95403

Principal Investigator:

Ian Anderson

MedStar Washington Hospital Center

Recruiting

Washington D.C., District of Columbia, United States, 20010

Principal Investigator:

Ami Chitalia

Clermont Oncology Center

Recruiting

Clermont, Florida, United States, 34711

Contacts

352-242-1366

Principal Investigator:

Gopal Kunta

Mid Florida Hematology and Oncology Center

Recruiting

Orange City, Florida, United States, 32763

Contacts

386-774-1223

Principal Investigator:

Santosh Nair

City of Hope National Medical Center, Atlanta Cancer Center

Recruiting

Newnan, Georgia, United States, 30265

Principal Investigator:

Sarah Friend

Summit Cancer Care, PC

Recruiting

Savannah, Georgia, United States, 31405

Contacts

912-651-5771

Principal Investigator:

Alison Spellman

City of Hope, Chicago

Recruiting

Chicago, Illinois, United States, 60611

Principal Investigator:

Ajaz M. Khan

Indiana University Health University Hospital

Recruiting

Indianapolis, Indiana, United States, 46202

Principal Investigator:

Tarah Ballinger

Jefferson Health - Cherry Hill

Recruiting

Cherry Hill, New Jersey, United States, 08002

Principal Investigator:

Steven Manobianco

Sidney Kimmel Cancer Center - Washington Township

Recruiting

Sewell, New Jersey, United States, 08080

Principal Investigator:

Steven Manobianco

Atlantic Health System Overlook Medical Center

Recruiting

Summit, New Jersey, United States, 07901

Principal Investigator:

Bonni Guerin

Messino Cancer Centers

Recruiting

Asheville, North Carolina, United States, 28806

Principal Investigator:

Rachel Raab

Good Samaritan Regional Medical Center

Recruiting

Corvallis, Oregon, United States, 97330

Principal Investigator:

John Strother

Oncology Associates of Oregon

Recruiting

Eugene, Oregon, United States, 97401

Principal Investigator:

Miho Dougherty

Thomas Jefferson University - Clinical Research Institute

Recruiting

Philadelphia, Pennsylvania, United States, 19107

Principal Investigator:

Steven Manobianco

Jefferson Hospital Northeast

Recruiting

Philadelphia, Pennsylvania, United States, 19114

Principal Investigator:

Steven Manobianco

Asplundh Cancer Pavilion

Recruiting

Willow Grove, Pennsylvania, United States, 19090

Principal Investigator:

Steven Manobianco

Sarah Cannon Research Institute SCRI

Recruiting

Nashville, Tennessee, United States, 37203

Principal Investigator:

SMO Sarah Cannon Research Inst.

World Research Link

Recruiting

Baytown, Texas, United States, 77521

Contacts

833-832-8328

Principal Investigator:

Amir Rasheed

USO - Texas Oncology

Recruiting

Dallas, Texas, United States, 75246

Principal Investigator:

Joyce O'Shaughnessy

UT Southwestern Medical Center

Recruiting

Dallas, Texas, United States, 75390

Contacts

214-648-4180

Principal Investigator:

Nisha Unni

Texas Oncology - West Texas

Recruiting

El Paso, Texas, United States, 79902

Principal Investigator:

Ines Sanchez

Oncology Consultants P.A.

Recruiting

Houston, Texas, United States, 77030

Contacts

713-600-0900

Principal Investigator:

Ricardo Alvarez

Nova Oncology

Recruiting

McAllen, Texas, United States, 78504

Contacts

281-944-3610

Principal Investigator:

Raghad Muhsin Abdul Karim, MD

Texas Oncology - San Antonio Medical Center

Recruiting

San Antonio, Texas, United States, 78240

Principal Investigator:

Emmalind Aponte

US Oncology Research Network

Recruiting

The Woodlands, Texas, United States, 77380

Principal Investigator:

SMO Sarah Cannon Research Inst.

UW Medicine Valley Medical Center

Recruiting

Renton, Washington, United States, 98055

Contacts

425-690-3503

Principal Investigator:

Navanshu Arora

More Information

Sponsor

Eli Lilly and Company

Last update posted

Aug 21, 2026

Last verified

Aug, 2026

Keywords

STX-478
PI3K

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Eli Lilly and Company on 2026-08-21.