Tersolisib plus standard anti-cancer medicines for advanced HR+/HER2- breast cancer with a PIK3CA change
Official title: A Phase 2, Randomized, Open-Label Dose Optimization and Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of LY4064809 Combined With a CDK4/6 Inhibitor and Endocrine Therapy in Adults With HR+, HER2-Advanced Breast Cancer With a PIK3CA Mutation Who Received No Prior Treatment for Advanced Breast Cancer (PIKALO-2)
Run by Eli Lilly and Company · NCT07174336 · Data updated 2026-11-12
This trial tests whether adding tersolisib to standard first-line anti-cancer medicines helps people with advanced hormone receptor–positive, HER2‑negative breast cancer that has a PIK3CA mutation.
Quick facts
| Phase | Phase 3 |
|---|---|
| Study type | Interventional |
| Ages | 18 Years and up |
| Sex | All |
| Enrollment | 800 (estimated) |
| Sponsor | Eli Lilly and Company Industry-sponsored |
| Drugs / interventions | chemotherapy, prednisone |
| Locations | 364 sites (Anchorage, Alaska and 363 other locations) |
| Status | Recruiting |
| Started | December 22, 2025 |
| Main results expected | May 2029 |
| Study ends | May 2033 |
| Registry record updated | November 4, 2026 |
| Trial ID | NCT07174336 on ClinicalTrials.gov |
Is this trial a fit for you?
✓Likely a good fit
Adults with locally advanced or metastatic HR+/HER2‑ breast cancer that harbors a PIK3CA mutation who are starting first-line systemic therapy and can meet contraception and hormonal‑suppression requirements are the intended participants.
✕Probably not a fit
Patients without a PIK3CA mutation, those with HER2‑positive disease, or those who have already had prior systemic therapy for advanced disease are unlikely to benefit from this trial.
A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.
What this trial studies
This Phase 3 trial adds tersolisib (LY4064809/STX-478), a PI3K-pathway targeted agent, to commonly used first-line regimens for advanced HR+/HER2- breast cancer with a PIK3CA genetic change. Participants receive either tersolisib or placebo alongside standard treatments such as CDK4/6 inhibitors (ribociclib, palbociclib, or abemaciclib) and endocrine therapy. Treatment continues while the drug is helping the cancer and side effects remain tolerable, with regular visits for tumor and safety assessments. The trial compares cancer control measures and adverse events between the tersolisib arm and the placebo arm to determine if adding tersolisib improves outcomes.
Why it matters
Potential benefit: If successful, adding tersolisib could extend the time the cancer is controlled and provide a new targeted option for patients with PIK3CA‑mutant HR+/HER2‑ advanced breast cancer.
How similar studies have gone: Other PI3K inhibitors (for example alpelisib) have shown benefit in PIK3CA‑mutant HR+/HER2‑ breast cancer, so this approach builds on prior positive findings though tersolisib itself is in late‑stage testing.
Who can join: the full rules
Show full inclusion / exclusion criteria
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.
Where it's running
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Alaska Oncology and Hematology
Anchorage, Alaska, United States Recruiting -
Ironwood Cancer & Research Centers
Chandler, Arizona, United States Recruiting -
The University of Arizona Cancer Center - North Campus
Tucson, Arizona, United States Recruiting -
Highlands Oncology Group
Springdale, Arkansas, United States Recruiting -
Community Cancer Institute
Clovis, California, United States Recruiting -
City of Hope
Duarte, California, United States Recruiting
Show 44 more locations
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Epic Care - Emeryville
Emeryville, California, United States Recruiting -
Marin Cancer Care
Greenbrae, California, United States Recruiting -
City of Hope Orange County Lennar Foundation Cancer Center
Irvine, California, United States Recruiting -
USC/Norris Comprehensive Cancer Center
Los Angeles, California, United States Recruiting -
Profound Research LLC
Oceanside, California, United States Recruiting -
Stanford Cancer Center
Palo Alto, California, United States Recruiting -
Providence Medical Foundation
Santa Rosa, California, United States Recruiting -
MedStar Washington Hospital Center
Washington D.C., District of Columbia, United States Recruiting -
Clermont Oncology Center
Clermont, Florida, United States Recruiting -
Florida Oncology & Hematology
Fort Myers, Florida, United States Recruiting -
Mid Florida Hematology and Oncology Center
Orange City, Florida, United States Recruiting -
Moffitt Cancer Center, Richard M. Shulze Family Foundation Outpatient Center
Tampa, Florida, United States Recruiting -
Central Georgia Cancer Care
Macon, Georgia, United States Recruiting -
City of Hope National Medical Center, Atlanta Cancer Center
Newnan, Georgia, United States Recruiting -
Summit Cancer Care, PC
Savannah, Georgia, United States Recruiting -
Kaiser Permanente Moanalua Medical Center
Honolulu, Hawaii, United States Recruiting -
City of Hope, Chicago
Chicago, Illinois, United States Recruiting -
University of Illinois at Chicago
Chicago, Illinois, United States Recruiting -
Accellacare of Duly
Lisle, Illinois, United States Recruiting -
Indiana University Health University Hospital
Indianapolis, Indiana, United States Recruiting -
Deaconess GI Specialty Center
Newburgh, Indiana, United States Recruiting -
Saint Elizabeth Medical Center Edgewood
Edgewood, Kentucky, United States Recruiting -
New England Cancer Specialists
Westbrook, Maine, United States Recruiting -
American Oncology Partners, PA
Bethesda, Maryland, United States Recruiting -
James M Stockman Cancer Institute
Frederick, Maryland, United States Recruiting -
Metro-Minnesota Community Clinical Oncology
Saint Louis Park, Minnesota, United States Recruiting -
North Mississippi Hematology and Oncology Associates
Tupelo, Mississippi, United States Recruiting -
Oncology Hematology Associates
Springfield, Missouri, United States Recruiting -
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, United States Recruiting -
Jefferson Health - Cherry Hill
Cherry Hill, New Jersey, United States Recruiting -
Sidney Kimmel Cancer Center - Washington Township
Sewell, New Jersey, United States Recruiting -
Atlantic Health System Overlook Medical Center
Summit, New Jersey, United States Recruiting -
Messino Cancer Centers
Asheville, North Carolina, United States Recruiting -
WakeMed Cancer Care - Waverly Hematology & Medical Oncology
Cary, North Carolina, United States Recruiting -
University of North Carolina Medical Center
Chapel Hill, North Carolina, United States Recruiting -
Carolina Cancer Research Center
Wilson, North Carolina, United States Recruiting -
Gabrail Cancer Center
Canton, Ohio, United States Recruiting -
The James Cancer Hospital and Solove Research Institute at The Ohio State University Comprehensive Cancer -T
Columbus, Ohio, United States Recruiting -
Good Samaritan Regional Medical Center
Corvallis, Oregon, United States Recruiting -
Oncology Associates of Oregon
Eugene, Oregon, United States Recruiting -
Oregon Health and Science University
Portland, Oregon, United States Recruiting -
St. Luke's University Health Network
Bethlehem, Pennsylvania, United States Recruiting -
Thomas Jefferson University - Clinical Research Institute
Philadelphia, Pennsylvania, United States Recruiting -
Jefferson Hospital Northeast
Philadelphia, Pennsylvania, United States Recruiting
+314 more sites. See ClinicalTrials.gov for the full list.
Study contacts
- Study coordinator: Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or
- Email: LillyTrials@Lilly.com
- Phone: 1-317-615-4559
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How to take part
- Review the eligibility criteria above with your treating physician.
- Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
- Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.