Recruiting
PHASE3
INTERVENTIONAL
NCT06065748
A 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)
View on ClinicalTrials.gov
Updated Dec 15, 2025
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.
Interventions
Name:
Giredestrant
Type:
DRUG
Description:
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.
Name:
Fulvestrant
Type:
DRUG
Description:
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.
Name:
Abemaciclib
Type:
DRUG
Description:
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.
Name:
Palbociclib
Type:
DRUG
Description:
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.
Name:
Ribociclib
Type:
DRUG
Description:
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.
Name:
LHRH Agonist
Type:
DRUG
Description:
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.
Name:
FoundationOne Liquid CDx Assay (F1LCDx)
Type:
DIAGNOSTIC_TEST
Description:
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 Outcomes
Measure:
Progression-Free Survival (PFS) in the ESR1 mutation (ESR1m) Subgroup
TimeFrame:
From randomization to first occurrence of progressive disease (PD) or death (up to 5 years)
Description:
PFS is defined as the time from randomization to the first occurrence of PD, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1), or death from any cause during the study.
Measure:
PFS in the Full Analysis Set (FAS) Population
TimeFrame:
From randomization to first occurrence of PD or death (up to 5 years)
Description:
Trial Information
NCT ID
NCT06065748
Status
Recruiting
Study Type
INTERVENTIONAL
Phases
PHASE3
Sponsor
Hoffmann-La Roche
Last Updated
December 15, 2025