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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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.
Primary outcome measure(s)
(Part 1): Overall Response Rate (ORR): Percentage of Participants with Confirmed Complete Response (CR) or Partial Response (PR) — Baseline through disease progression or death (Estimated up to 5 years) As determined by the investigator based on Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1
(Part 2): Progression-Free Survival — Baseline to objective progression or death due to any cause (Estimated up to 5 years) Investigator-assessed
Trial sites (360)
Facility
City
Region
Status
Alaska Oncology and Hematology
Anchorage
Alaska
Not Yet Recruiting
Ironwood Cancer & Research Centers
Chandler
Arizona
Recruiting
Mayo Clinic in Arizona - Phoenix
Phoenix
Arizona
Not Yet Recruiting
The University of Arizona Cancer Center - North Campus
Tucson
Arizona
Recruiting
Genesis Cancer and Blood Institute
Hot Springs
Arkansas
Not Yet Recruiting
Highlands Oncology Group
Springdale
Arkansas
Recruiting
Community Cancer Institute
Clovis
California
Not Yet Recruiting
City of Hope
Duarte
California
Recruiting
Epic Care - Emeryville
Emeryville
California
Not Yet Recruiting
Marin Cancer Care
Greenbrae
California
Recruiting
Chao Family Comprehensive Cancer Center and Ambulatory Care (CIACC) - Irvine
Irvine
California
Not Yet Recruiting
City of Hope Orange County Lennar Foundation Cancer Center
Irvine
California
Recruiting
Moores Cancer Center
La Jolla
California
Not Yet Recruiting
USC/Norris Comprehensive Cancer Center
Los Angeles
California
Not Yet Recruiting
Hoag Memorial Hospital Presbyterian
Newport Beach
California
Not Yet Recruiting
Kaiser Permanente Oakland
Oakland
California
Not Yet Recruiting
Profound Research LLC
Oceanside
California
Recruiting
University of California, Irvine (UCI) Health - UC Irvine Medical Center
Orange
California
Not Yet Recruiting
Desert Regional Medical Center
Palm Springs
California
Not Yet Recruiting
Stanford Cancer Center
Palo Alto
California
Not Yet Recruiting
Kaiser Permanente
Roseville
California
Not Yet Recruiting
Kaiser Permanente
San Francisco
California
Not Yet Recruiting
UCSF Medical Center at Mission Bay
San Francisco
California
Not Yet Recruiting
Kaiser Permanente
Santa Clara
California
Not Yet Recruiting
UCLA Hematology/Oncology - Parkside
Santa Monica
California
Not Yet Recruiting
Providence Medical Foundation
Santa Rosa
California
Recruiting
Kaiser Permanente
Vallejo
California
Not Yet Recruiting
Kaiser Permanente Walnut Creek
Walnut Creek
California
Not Yet Recruiting
UCHealth Harmony
Fort Collins
Colorado
Not Yet Recruiting
Cancer Centers of Colorado St. Mary's Regional Hospital
Grand Junction
Colorado
Not Yet Recruiting
Banner MD Anderson Cancer Center at North Colorado Medical Center
Greeley
Colorado
Not Yet Recruiting
Banner MD Anderson Cancer Center at McKee Medical Center
Loveland
Colorado
Not Yet Recruiting
MedStar Washington Hospital Center
Washington D.C.
District of Columbia
Recruiting
AdventHealth Altamonte Springs
Altamonte Springs
Florida
Not Yet Recruiting
Clermont Oncology Center
Clermont
Florida
Recruiting
Florida Oncology & Hematology
Fort Myers
Florida
Not Yet Recruiting
Mayo Clinic in Florida
Jacksonville
Florida
Not Yet Recruiting
University of Miami Hospital and Clinics, Sylvester Cancer Center
Miami
Florida
Not Yet Recruiting
Mid Florida Hematology and Oncology Center
Orange City
Florida
Recruiting
Moffitt Cancer Center, Richard M. Shulze Family Foundation Outpatient Center
Tampa
Florida
Not Yet Recruiting
+ 320 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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