A Study of Tersolisib (LY4064809) and Abemaciclib With Hormone Therapies in Participants With PIK3CA-Mutated Early Breast Cancer (PIKALO-3)

November 9, 2026 updated by: Eli Lilly and Company

A Phase 2, Open-label, Randomized Study Investigating the Tolerability of Concurrent Versus Staggered Administration of Abemaciclib and Endocrine Therapy With Tersolisib in Patients With HR+, HER2- Node-Positive, PIK3CA-Mutated Early Breast Cancer.

The main purpose of this study is to compare two ways of giving the anti-cancer medicines abemaciclib and hormone therapy with tersolisib in participants with early breast cancer that has a genetic mutation (PIK3CA mutation).

For each participant, the study will last up to 56 weeks and include 12 visits.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

120

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

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

Study Contact Backup

Study Locations

  • United States
    • California
      • Los Alamitos, California, United States, 90720
        • Cancer and Blood Specialty Clinic
        • Principal Investigator:
          • Sassan Farjami
    • Colorado
      • Lakewood, Colorado, United States, 80228
        • USO - Rocky Mountain Cancer Centers
        • Principal Investigator:
          • Sara Robinson
    • Georgia
      • Atlanta, Georgia, United States, 30308
        • Winship Cancer Institute, Emory University
        • Principal Investigator:
          • Manali Bhave
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Dana-Farber Cancer Institute
        • Principal Investigator:
          • Erica Mayer
    • Ohio
      • Columbus, Ohio, United States, 43212
        • Stefanie Spielman Comprehensive Breast Center
        • Principal Investigator:
          • Robert Wesolowski
    • Texas
      • Amarillo, Texas, United States, 79106
        • Texas Oncology - West Texas
        • Principal Investigator:
          • Ines Sanchez-Rivera
      • Austin, Texas, United States, 78731
        • Texas Oncology - Balcones
        • Principal Investigator:
          • Kathryn Hudson
      • San Antonio, Texas, United States, 78229-3307
        • South Texas Accelerated Research Therapeutics (START)
        • Principal Investigator:
          • Amita Patnaik
    • Virginia
      • Reston, Virginia, United States, 20190
        • USO - Virginia Cancer Specialists
        • Principal Investigator:
          • Isabelle Le

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Have histologically or cytologically confirmed breast cancer, defined as individuals with:

    • early stage, resected, invasive breast cancer without evidence of distant metastasis, and

    • have confirmed hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) status defined by

      • Hormone Receptor (HR) status: documented estrogen receptor positive (ER+) and/or progesterone receptor+ tumor, defined as greater than or equal to (≥) 1% of tumor cells stained positive, assessed locally on primary disease specimen, as defined by American Society of Clinical Oncology College of American Pathologists (ASCO/CAP) Guidelines
      • HER status: fulfill the requirement of HER2- disease by local testing on primary disease specimen; tumor must be HER2- according to ASCO/CAP guidelines for HER2 testing

  • Have evidence of an activating phosphatidylinositol-3-kinase catalytic subunit alpha (PIK3CA) mutation in tumor tissue.

  • Must have undergone definitive locoregional therapy, defined as surgery of the primary breast tumor(s), with or without radiation therapy, and/or systemic therapy (neo/adjuvant chemotherapy and or Endocrine Therapy (ET)) per standard guidelines.

  • Individuals with bilateral breast cancer (diagnosis of invasive tumors in both breasts simultaneously or within 6 months of each other) may be eligible if all lesions tested on both sides are HR+ HER2- and adequate surgery has been performed for both breasts.

  • Tumor involvement in at least 1 axillary lymph node (ALN).

    • ≥ ipsilateral positive ALN, OR

    • 1 to 3 ipsilateral positive ALN and either:

      • tumor size ≥5cm, or
      • histologic Grade 3 tumor (as defined by a combined score of at least 8 points per the modified Bloom-Richardson grading system or equivalent

  • Individuals must be randomized within 16 months from the time of definitive breast cancer surgery.

  • May have received up to 12 weeks of ET with AIs or tamoxifen until randomization following the last non-ET (surgery, chemotherapy, or radiation), whichever is last.

  • Are willing to follow contraception requirements.

Exclusion Criteria:

  • Have evidence of

    • metastatic disease
    • inflammatory breast cancer at primary breast cancer diagnosis
    • breast cancer recurrence (local, regional, or distant), or
    • a history of previous invasive breast cancer

  • Has an established diagnosis of type 1 diabetes mellitus or type 2 diabetes mellitus with Hemoglobin A1c (HbA1c) ≥8 percent (%), fasting plasma glucose ≥140 mg/dL (7.7 mmol/L), or requiring insulin.

  • Has a history of malignancy other than breast cancer

  • Have active Hepatitis B Virus (HBV)

  • Have active Hepatitis C Virus (HCV)

  • Have untreated Human Immunodeficiency Virus (HIV) infection

  • Have any other active systemic infection requiring system therapy

  • Have a history of Kaposi sarcoma or multicentric Castleman disease

  • Have a serious cardiac condition

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm A: Abemaciclib and Endocrine Therapy (ET) + Tersolisib - Staggered

Abemaciclib in combination with physician's choice of endocrine therapy (ET). Tersolisib will be added in a staggered approach after 2 cycles of abemaciclib and ET. All drugs will be administered orally.
Drug: Abemaciclib

Administered orally

Drug: Anastrozole

Administered orally

Drug: Letrozole

Administered orally

Drug: Exemestane

Administered orally

Drug: Tersolisib

Administered orally

Other Names:
  • LY4064809
Experimental: Arm B: Abemaciclib and Endocrine Therapy (ET) + Tersolisib - Concurrent

Abemaciclib and tersolisib will be administered concurrently in combination with physician's choice of ET. All drugs will be administered orally.
Drug: Abemaciclib

Administered orally

Drug: Anastrozole

Administered orally

Drug: Letrozole

Administered orally

Drug: Exemestane

Administered orally

Drug: Tersolisib

Administered orally

Other Names:
  • LY4064809

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Rate of Participants who Discontinue Tersolisib Due to Treatment Emergent Adverse Events (TEAEs).
Time Frame: Cycle 1 through study completion (estimated as 56 weeks)
Cycle 1 through study completion (estimated as 56 weeks)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Duration of Exposure to Study Intervention
Time Frame: Start of study intervention through study completion (estimated as 56 weeks)

Study intervention start is defined as Cycle -1 for Arm A and Cycle 1 for Arm B. Arm A includes an additional 8 weeks.
Start of study intervention through study completion (estimated as 56 weeks)
Number of Study Intervention Dose Adjustments
Time Frame: Start of study intervention through study completion (estimated as 56 weeks)

Study intervention start is defined as Cycle -1 for Arm A and Cycle 1 for Arm B. Arm A includes an additional 8 weeks.
Start of study intervention through study completion (estimated as 56 weeks)
Pharmacokinetics (PK): Predose Plasma Concentrations (Cmax) of Tersolisib
Time Frame: Day 15 through study completion (estimated as 56 weeks)
Day 15 through study completion (estimated as 56 weeks)
Change from Baseline in Side-Effect Burden as Measured by Functional Assessment of Cancer Therapy - General Item GP5 (FACT-GP5)
Time Frame: Baseline to end of study completion (estimated as 56 weeks)
Baseline to end of study completion (estimated as 56 weeks)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Eli Lilly and Company

Investigators

  • Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 8 AM - 8 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

December 1, 2026

Primary Completion (Estimated)

December 1, 2027

Study Completion (Estimated)

January 1, 2028

Study Registration Dates

First Submitted

November 9, 2026

First Submitted That Met QC Criteria

November 9, 2026

First Posted (Actual)

November 13, 2026

Study Record Updates

Last Update Posted (Actual)

November 13, 2026

Last Update Submitted That Met QC Criteria

November 9, 2026

Last Verified

November 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 27842
  • 2026-526410-87-00 (Ctis)
  • J6M-MC-JSGH (Other Identifier: Eli Lilly and Company)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

IPD Sharing Time Frame

Data are available 6 months after the primary publication or approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.

IPD Sharing Access Criteria

A research proposal should be approved by an independent review panel and researchers should sign a data sharing agreement.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe