NCT06065748|RecruitingPhase 3DMCFDA DrugFDA Device

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

Hoffmann-La Roche ClinicalTrials.gov

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2 other identifiers

CO446572022-502980-39-00

Study Type

interventional

Target

1,050

Locations

35 countries

Sites

341

Timeline

RegisteredOct 2023

StartedDec 2023

CompletionFeb 2029

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.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Strong global presence with extensive site network

Enrollment

1,050

participants targeted

Target at P75+ for phase_3

Timeline

34mo left

Started Dec 2023

Longer than P75 for phase_3

Geographic Reach

35 countries

341 active sites

Status

recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

5.2 years study duration

Study Progress46%

Dec 2023Feb 2029

First Submitted

Initial submission to the registry

September 26, 2023

Completed

8 days until next milestone

First Posted

Study publicly available on registry

October 4, 2023

Completed

2 months until next milestone

Study Start

First participant enrolled

December 11, 2023

Completed

3.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 19, 2027

Expected

2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

February 12, 2029

Last Updated

May 5, 2026

Status Verified

May 1, 2026

Enrollment Period

3.2 years

First QC Date

September 26, 2023

Last Update Submit

May 4, 2026

Conditions

Estrogen Receptor-Positive, HER2-Negative Advanced Breast Cancer

Keywords

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

Outcome Measures

Primary Outcomes (2)

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

Secondary Outcomes (14)

PFS in the ESR1 no-mutation-detected (ESR1nmd) Subgroup
From randomization to first occurrence of PD or death (up to 5 years)
Overall Survival (OS)
From randomization until death from any cause (up to 5 years)
Confirmed Objective Response Rate (cORR)
From randomization until treatment discontinuation (up to 5 years)
Duration of Response (DOR)
From the first occurrence of a documented objective response to PD or death (up to 5 years)
Clinical Benefit Rate (CBR)
From randomization until treatment discontinuation (up to 5 years)
+9 more secondary outcomes

Study Arms (2)

Giredestrant + Investigator's Choice of CDK4/6i

EXPERIMENTAL

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

Drug: GiredestrantDrug: AbemaciclibDrug: PalbociclibDrug: RibociclibDrug: LHRH AgonistDiagnostic Test: FoundationOne Liquid CDx Assay (F1LCDx)

Fulvestrant + Investigator's Choice of CDK4/6i

ACTIVE COMPARATOR

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

Drug: FulvestrantDrug: AbemaciclibDrug: PalbociclibDrug: RibociclibDrug: LHRH AgonistDiagnostic Test: FoundationOne Liquid CDx Assay (F1LCDx)

Interventions

GiredestrantDRUG

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.

Also known as: RO7197597, RG6171, GDC-9545

Giredestrant + Investigator's Choice of CDK4/6i

FulvestrantDRUG

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.

Fulvestrant + Investigator's Choice of CDK4/6i

AbemaciclibDRUG

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.