Clinical trial Recruiting at 179 sites Phase 3 Interventional Ages 18 and up

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.

More Breast Neoplasms trials

Quick facts

PhasePhase 3
Study typeInterventional
Ages18 Years and up
SexAll
Enrollment800 (estimated)
SponsorEli Lilly and Company
Industry-sponsored
Drugs / interventionschemotherapy, prednisone
Locations364 sites (Anchorage, Alaska and 363 other locations)
StatusRecruiting
StartedDecember 22, 2025
Main results expectedMay 2029
Study endsMay 2033
Registry record updatedNovember 4, 2026
Trial IDNCT07174336 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

  • 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
  • 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

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Other studies for the same condition or treatment. Recruiting studies are listed first.

How to take part

  1. Review the eligibility criteria above with your treating physician.
  2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
  3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.
Last reviewed 2026-11-14 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.