Health Trials

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)

ConditionEstrogen Receptor-Positive, HER2-Negative Advanced Breast Cancer
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age18+
SponsorHoffmann-La Roche

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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).

Disqualifiers

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

Trial design

Design model

Parallel

Treatments tested in this trial

  • Giredestrant

    Drug

    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

    Drug

    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

    Drug

    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

    Drug

    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

    Drug

    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

    Drug

    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)

    Diagnostic test

    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 \[ESR1nmd\]).

Treatment groups

1,050 Participants
are divided into 2 treatment groups
Group A: Giredestrant + Investigator's Choice of CDK4/6iExperimental treatment 6 interventions
Group B: Fulvestrant + Investigator's Choice of CDK4/6iActive comparator 6 interventions

Trial outcomes

Primary outcomes

1

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.

Time frame
From randomization to first occurrence of progressive disease (PD) or death (up to 5 years)
2

PFS in the Full Analysis Set (FAS) Population

Time frame
From randomization to first occurrence of PD or death (up to 5 years)

Secondary outcomes

1

PFS in the ESR1 no-mutation-detected (ESR1nmd) Subgroup

Time frame
From randomization to first occurrence of PD or death (up to 5 years)
2

Overall Survival (OS)

OS is defined as the time from randomization to death from any cause. It will be analyzed in the FAS and in the ESR1m and ESR1nmd subgroups.

Time frame
From randomization until death from any cause (up to 5 years)
3

Confirmed Objective Response Rate (cORR)

The cORR is defined as the percentage of participants with a complete response (CR) or partial response (PR) on two consecutive occasions at least 4 weeks apart, as determined by the investigator according to RECIST v1.1. It will be analyzed in the FAS and in the ESR1m and ESR1nmd subgroups.

Time frame
From randomization until treatment discontinuation (up to 5 years)
4

Duration of Response (DOR)

DOR is defined as the time from the first occurrence of a documented objective response to PD, as determined by the investigator according to RECIST v1.1, or death from any cause (whichever occurs first). It will be analyzed in the FAS and in the ESR1m and ESR1nmd subgroups.

Time frame
From the first occurrence of a documented objective response to PD or death (up to 5 years)

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Hoffmann-La Roche

Lead sponsor

Source ClinicalTrials.gov
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