Home › Trials › NCT07174336

Tersolisib plus standard anti-cancer medicines for advanced HR+/HER2- breast cancer with a PIK3CA change

A 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)

PHASE3 · Eli Lilly and Company · NCT07174336

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

PhasePHASE3
Study typeInterventional
Enrollment920 (estimated)
Ages18 Years and up
SexAll
SponsorEli Lilly and Company (industry)
Drugs / interventionschemotherapy, prednisone
Locations317 sites (Anchorage, Alaska and 316 other locations)
Trial IDNCT07174336 on ClinicalTrials.gov

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.

Who should consider this trial

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.

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.

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 performed: 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.

Eligibility criteria

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 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.

Where this trial is running

Anchorage, Alaska and 316 other locations

+267 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.

View on ClinicalTrials.gov →

Conditions: Breast Neoplasms, Neoplasm Metastasis, STX-478, PI3K

Last reviewed 2026-05-15 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.