Recruiting

Phase 3

Giredestrant vs. FulvestrantA Study to Evaluate Efficacy and Safety of Giredestrant Compared With Fulvestrant (Plus a CDK4/6 Inhibitor), in Participants With ER-Positive, HER2-Negative Advanced Breast Cancer Resistant to Adjuvant Endocrine Therapy (pionERA Breast Cancer)

Sponsor:

Hoffmann-La Roche

Code:

NCT06065748

Conditions

Estrogen Receptor-Positive, HER2-Negative Advanced Breast Cancer

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Giredestrant

Fulvestrant

Abemaciclib

Palbociclib

Ribociclib

Study Details

Brief summary:

This is a Phase III, randomized, open-label multicenter study that will evaluate the efficacy and safety of giredestrant compared with fulvestrant, both in combination with the investigator's choice of a CDK4/6 inhibitor (palbociclib, ribociclib or abemaciclib), in participants with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer who have developed resistance to adjuvant endocrine therapy.

Conditions

Estrogen Receptor-Positive, HER2-Negative Advanced Breast Cancer

Study ID

NCT06065748

Start date

Dec 11, 2023

Status verified date

Aug, 2026

Completion date

Feb 12, 2029

Anticipated

Primary completion date

Feb 19, 2027

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

Locally advanced or metastatic adenocarcinoma of the breast, not amenable to treatment with curative intent
Documented estrogen receptor-positive (ER+), HER2-negative (HER2-) tumor assessed locally on the most recent tumor biopsy (or an archived tumor sample if a recent tumor sample is not available for testing)
Confirmed ESR1 mutation status (ESR1m versus ESR1nmd) in baseline circulating tumor DNA (ctDNA) through central laboratory testing
Resistance to prior adjuvant endocrine therapy (ET), which is defined as having relapsed with prior standard adjuvant ET, on-treatment after >/=12 months or off-treatment within 12 months of completion. Prior use of adjuvant CDK4/6i is allowed (if relapse occurred >/=12 months since completion).
No prior systemic anti-cancer therapy for advanced disease
Measurable disease as defined per RECIST v.1.1 or non-measurable (including bone-only) disease
Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-1
For pre/perimenopausal women and for men: willing to undergo and maintain treatment with approved LHRH agonist therapy (as per local guidelines) for the duration of study treatment

Exclusion Criteria:

Prior systemic therapy (e.g., prior chemotherapy, immunotherapy, or biologic therapy) for locally advanced unresectable or metastatic breast cancer
Prior treatment with another SERD (e.g., fulvestrant, oral SERDs) or novel ER-targeting agents
Advanced, symptomatic, visceral spread that is at risk of life-threatening complications in the short term
Active cardiac disease or history of cardiac dysfunction
Clinically significant history of liver disease

Study Design

Enrollment

1050 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Giredestrant + Investigator's Choice of CDK4/6i

Participants in the experimental arm will receive giredestrant plus the investigator's choice of CDK4/6 inhibitor (CDK4/6i): palbociclib, ribociclib, or abemaciclib.

active comparator: Fulvestrant + Investigator's Choice of CDK4/6i

Participants in the control arm will receive fulvestrant plus the investigator's choice of CDK4/6 inhibitor (CDK4/6i): palbociclib, ribociclib, or abemaciclib.

Interventions

Giredestrant

Giredestrant 30 milligrams (mg) orally (PO) once a day (QD) on Days 1-28 of each 28-day cycle until progressive disease (PD) or unacceptable toxicity.

Fulvestrant

Fulvestrant 500 mg intramuscularly (IM) on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent 28-day cycle until PD or unacceptable toxicity.

Abemaciclib

If chosen by the investigator as the CDK4/6i, participants will receive abemaciclib 150 mg PO twice per day (BID) on Days 1-28 of each 28-day cycle until PD or unacceptable toxicity.

Palbociclib

If chosen by the investigator as the CDK4/6i, participants will receive palbociclib 125 mg PO QD on Days 1-21 of each 28-day cycle until PD or unacceptable toxicity.

Ribociclib

If chosen by the investigator as the CDK4/6i, participants will receive ribociclib 600 mg PO QD on Days 1-21 of each 28-day cycle until PD or unacceptable toxicity.

LHRH Agonist

Only pre/perimenopausal female participants and male participants will receive a luteinizing hormone-releasing hormone (LHRH) agonist locally approved for use in breast cancer on Day 1 of each 28-day treatment cycle.

FoundationOne Liquid CDx Assay (F1LCDx)

F1LCDx is a next-generation sequencing (NGS)-based in vitro diagnostic test that detects and analyses genomic alterations in circulating cell-free DNA (cfDNA) isolated from plasma derived from the anti-coagulated peripheral whole blood of cancer patients. It will be used to determine the eligibility of participants requiring confirmation of ESR1 mutation status (mutation detected \[ESR1m\] vs. no mutation detected \[ESR1nmd\]).

Primary outcome measure

Progression-Free Survival (PFS) in the ESR1 mutation (ESR1m) Subgroup [ Time Frame: From randomization to first occurrence of progressive disease (PD) or death (up to 5 years) ]
PFS in the Full Analysis Set (FAS) Population [ Time Frame: From randomization to first occurrence of PD or death (up to 5 years) ]

Central Contacts and Locations

Central contacts

Reference Study ID Number: CO44657 https://forpatients.roche.com/ No attachments to email below.

888-662-6728 (U.S. Only)global-roche-genentech-trials@gene.com

Locations

Southern Cancer Center

Recruiting

Daphne, Alabama, United States, 36526

La Hematology Oncology Medical Group

Recruiting

Glendale, California, United States, 91260

Marin Cancer Care Inc

Recruiting

Greenbrae, California, United States, 94904

Kaiser Permanente - Harbor City

Recruiting

Harbor City, California, United States, 90710

USC Norris Comprehensive Cancer Center

Recruiting

Los Angeles, California, United States, 90033

The Lundquist Institute for BioMedical Innovation at Harbor-UCLA Medical Cente

Recruiting

Torrance, California, United States, 90502

Rocky Mountain Cancer Centers

Recruiting

Littleton, Colorado, United States, 80120-4413

Georgetown University Medical Center

Recruiting

Washington D.C., District of Columbia, United States, 20007

MedStar Washington Hosp Center

Recruiting

Washington D.C., District of Columbia, United States, 20010

AdventHealth Altamonte

Recruiting

Altamonte Springs, Florida, United States, 32701

Florida Cancer Specialists - Broadway

Recruiting

Fort Myers, Florida, United States, 33901

Cancer Specialists of North Florida

Recruiting

Jacksonville, Florida, United States, 32256

Florida Cancer Specialists - North;725 6th Ave South (St. Petersburg)

Recruiting

St. Petersburg, Florida, United States, 33701-4553

Comprehensive Hematology Oncology

Recruiting

St. Petersburg, Florida, United States, 33709

Florida Cancer Specialists - EAST - SCRI - PPDS

Recruiting

West Palm Beach, Florida, United States, 33401-3406

Winship Cancer Institute of Emory University

Recruiting

Atlanta, Georgia, United States, 30329

Advocate Lutheran General Hospital

Recruiting

Park Ridge, Illinois, United States, 60068

Springfield Clinic

Recruiting

Springfield, Illinois, United States, 62702

Baptist Health Lexington

Recruiting

Lexington, Kentucky, United States, 40503

Baptist Health Hamburg

Recruiting

Lexington, Kentucky, United States, 40509

Baptist Health Louisville

Recruiting

Louisville, Kentucky, United States, 40207

New England Cancer Specialists

Recruiting

Scarborough, Maine, United States, 04074

Maryland Oncology Hematology

Recruiting

Annapolis, Maryland, United States, 21401

Dana Farber Cancer Institute

Recruiting

Boston, Massachusetts, United States, 02215

Henry Ford Hospital

Recruiting

Detroit, Michigan, United States, 48202

HCA Midwest Division

Recruiting

Kansas City, Missouri, United States, 64132

Oncology Hematology West - Grand Island

Recruiting

Grand Island, Nebraska, United States, 68803

Oncology Hematology West - Legacy

Recruiting

Omaha, Nebraska, United States, 68130-2042

Astera Cancer Care East Brunswick

Recruiting

East Brunswick, New Jersey, United States, 08816

Queens Hospital Cancer Center

Recruiting

Jamaica, New York, United States, 11432

Duke Women Cancer Care

Recruiting

Raleigh, North Carolina, United States, 27607

Asante Rogue Regional Medical Center

Recruiting

Medford, Oregon, United States, 97504-8332

Alliance Cancer Specialists

Recruiting

Bensalem, Pennsylvania, United States, 19020

Ann B. Barshinger Cancer Institute

Recruiting

Lancaster, Pennsylvania, United States, 17604

Abramson Cancer Center; Univ of Pennsylvania; Clinical Research Unit

Recruiting

Philadelphia, Pennsylvania, United States, 19106

Brown University Health

Recruiting

Providence, Rhode Island, United States, 02905

Avera Cancer Institute

Recruiting

Sioux Falls, South Dakota, United States, 57105

West Cancer Center

Recruiting

Germantown, Tennessee, United States, 38138

SCRI Oncology Partners

Recruiting

Nashville, Tennessee, United States, 37203

Texas Oncology Cancer Center

Recruiting

Austin, Texas, United States, 78731

Texas Oncology - DFW

Recruiting

Irving, Texas, United States, 75063

Virginia Cancer Specialists, PC

Recruiting

Fairfax, Virginia, United States, 22031

Virginia Commonwealth University - Massey Cancer Center

Recruiting

Richmond, Virginia, United States, 23219

Northwest Medical Specialties

Recruiting

Tacoma, Washington, United States, 98405

West Virginia University Hospitals Inc

Recruiting

Morgantown, West Virginia, United States, 26056

Aurora BayCare Medical Center

Recruiting

Green Bay, Wisconsin, United States, 54311

Aurora St Lukes Medical Center

Recruiting

Milwaukee, Wisconsin, United States, 53215

More Information

Sponsor

Hoffmann-La Roche

Last update posted

Aug 5, 2026

Last verified

Aug, 2026

Keywords

oral Selective Estrogen Receptor Degrader (SERD)
CDK4/6 inhibitor (CDK4/6i)
ESR1 mutation

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-04. This information was provided to ClinicalTrials.gov by Hoffmann-La Roche on 2026-08-05.