Recruiting NCT07174336

A Study of Tersolisib (LY4064809/STX-478) With Other Anti-Cancer Treatments in Participants With Advanced Breast Cancer With a Genetic Change (PIK3CA)

Phase III Interventional Breast Neoplasms Neoplasm Metastasis

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied: The protocol lists: LY4064809, Placebo, Ribociclib, Palbociclib.
Who it may be relevant to: Registry conditions: Breast Neoplasms, Neoplasm Metastasis. Basic parameters: from 18 years · All.
What needs checking: Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place: United States, Argentina, Australia, Belgium, Brazil +13
Next step: Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

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)

Overview

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.

Interventions

Drug LY4064809
Administered orally
Drug Placebo
Administered orally
Drug Ribociclib
Administered orally
Drug Palbociclib
Administered orally
Drug Abemaciclib
Administered orally
Drug Anastrozole
Administered orally
Drug Letrozole
Administered orally
Drug Exemestane
Administered orally
Drug Fulvestrant
Administered intramuscular

Primary outcome measures

(Part 1): Overall Response Rate (ORR): Percentage of Participants with Confirmed Complete Response (CR) or Partial Response (PR) [Time frame: Baseline through disease progression or death (Estimated up to 5 years)]
(Part 2): Progression-Free Survival [Time frame: Baseline to objective progression or death due to any cause (Estimated up to 5 years)]

Secondary outcome measures (12)

(Part 1): Disease Control Rate (DCR) [Time frame: Baseline through measured progressive disease (Estimated up to 5 years)]
(Part 1): Time to Response (TTR) [Time frame: Baseline until the date that measurement criteria for CR or PR (whichever is first recorded) are first met (Estimated as approximately 5 years)]
(Parts 1 and 2): Duration of Response (DOR) [Time frame: Date of CR or PR to date of objective disease progression or death due to any cause (Estimated up to 5 years)]
(Part 1): PFS [Time frame: Baseline to objective progression or death due to any cause (Estimated up to 5 years)]
(Parts 1 and 2): Overall Survival (OS) [Time frame: Baseline to deaths from any cause (Estimated up to 7 years)]
(Parts 1 and 2): Clinical Benefit Rate (CBR): Percentage of Participants with a BOR of CR or PR, or SD Lasting Greater than or Equal to Six Months [Time frame: Baseline to disease progression or death from any cause (Estimated up to 5 years)]
(Parts 1 and 2): PK: Average Plasma Concentrations of tersolisib [Time frame: Baseline to last PK sample collection up to 5 months]
(Part 2): Progression-Free Survival after Subsequent Line of Treatment (PFS2) [Time frame: Baseline to disease progression on next line of treatment or death from any cause (Estimated as up to 7 years)]
(Part 2): Progression-Free Survival (PFS) [Time frame: Baseline to objective progression or death from any cause (Estimated up to 5 years)]
(Part 2): Objective Response Rate (ORR) [Time frame: Baseline to disease progression or death from any cause (Estimated up to 5 years)]
(Part 2): Time to Chemotherapy (TTC) [Time frame: Baseline until the start of chemotherapy (Estimated up to 7 years)]
(Part 2): Chemotherapy-Free Survival [Time frame: Baseline until the start of chemotherapy or death from any cause (Estimated up to 7 years)]

Eligibility 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation: Randomized
Model: Parallel assignment
Masking: Double blind
Primary purpose: Treatment