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)

Conditions

• Estrogen Receptor-Positive, HER2-Negative Advanced Breast Cancer

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• 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 \[ESR1nmd\]).

Study Details

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.

Key Dates

Start date

Dec 11, 2023

Status verified

Jun 2026

Primary completion

Feb 19, 2027

Completion

Feb 12, 2029

Study Design

Enrollment

1,050 participants (estimated)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

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.

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) ]

Central Contacts

• Reference Study ID Number: CO44657 https://forpatients.roche.com/
  888-662-6728 (U.S. Only)
  [email protected]
• Fastest response: use the inquiry form. No email attachments. https://www.gene.com/contact-us/submit-medical-inquiry

Locations (61)

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