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)

A Phase III Randomized, Open-Label Study Evaluating Efficacy and Safety of Giredestrant Compared With Fulvestrant, Both Combined With a CDK4/6 Inhibitor, in Patients With Estrogen Receptor-Positive, HER2-Negative Advanced Breast Cancer With Resistance to Prior Adjuvant Endocrine Therapy

• Status: Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 1,050 (estimated)
• Sponsor: Hoffmann-La Roche · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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

Interventions

Type	Name	Description
DRUG	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.
DRUG	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.
DRUG	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.
DRUG	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.
DRUG	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.
DRUG	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.
DIAGNOSTIC_TEST	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 \[ESR1nmd\]).

Timeline

• Start date: 2023-12-11
• Primary completion: 2027-02-19
• Completion: 2029-02-12
• First posted: 2023-10-04
• Last updated: 2026-04-06

Locations

351 sites across 37 countries: United States, Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, China, Colombia, Costa Rica, Finland, France, Germany, Greece, Guatemala, Hong Kong, Hungary, India, Israel, Italy, Kenya, Mexico, New Zealand, Peru, Poland, Portugal, Puerto Rico, Romania, Singapore, Slovenia, South Africa, South Korea, Spain, Taiwan, Thailand, Turkey (Türkiye)

Regulatory

• FDA-regulated drug study
• FDA-regulated device study