Home › Trials › NCT06065748

Evaluating Giredestrant vs Fulvestrant for Advanced 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

Phase 3 Interventional Hoffmann-La Roche · NCT06065748

This study is testing whether a new drug called giredestrant works better than fulvestrant for people with advanced breast cancer that hasn't responded to previous treatments.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment1050 (estimated)
Ages18 Years and up
SexAll
SponsorHoffmann-La Roche Industry-sponsored
Drugs / interventionschemotherapy, immunotherapy
Locations351 sites (Daphne, Alabama and 350 other locations)
Trial IDNCT06065748 on ClinicalTrials.gov

What this trial studies

This Phase III, randomized, open-label multicenter study aims to assess the efficacy and safety of giredestrant compared to fulvestrant, both combined with a CDK4/6 inhibitor, in patients with estrogen receptor-positive, HER2-negative advanced breast cancer who have shown resistance to prior endocrine therapy. Participants will be selected based on their tumor characteristics, including estrogen receptor status and ESR1 mutation status, and will receive treatment at various clinical sites. The study seeks to determine which treatment option provides better outcomes for this specific patient population.

Who should consider this trial

Good fit: Ideal candidates include individuals with locally advanced or metastatic ER-positive, HER2-negative breast cancer who have developed resistance to prior adjuvant endocrine therapy.

Not a fit: Patients who have received prior systemic anti-cancer therapy for advanced disease may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a more effective treatment option for patients with advanced breast cancer who have become resistant to standard therapies.

How similar studies have performed: Other studies have shown promise with similar approaches, particularly in targeting ESR1 mutations in advanced breast cancer.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* 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).
* No prior systemic anti-cancer therapy for advanced disease
* Measurable disease as defined per RECIST v.1.1 or non-measurable (including bone-only) disease
* Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-1
* For pre/perimenopausal women and for men: willing to undergo and maintain treatment with approved LHRH agonist therapy (as per local guidelines) for the duration of study treatment

Exclusion Criteria:

* 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
* Clinically significant history of liver disease

Where this trial is running

Daphne, Alabama and 350 other locations

+301 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Estrogen Receptor-Positive, HER2-Negative Advanced Breast Canceroral Selective Estrogen Receptor DegraderCDK4/6 inhibitorESR1 mutation
Last reviewed 2026-06-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.