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Not recruiting
Phase 3

Giredestrant vs. Fulvestrant

Sponsor:

Hoffmann-La Roche

Code:

NCT06065748

Conditions

Estrogen Receptor-Positive, HER2-Negative Advanced Breast Cancer

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Giredestrant

Fulvestrant

Abemaciclib

Palbociclib

Ribociclib

Study Details

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.

Conditions

Estrogen Receptor-Positive, HER2-Negative Advanced Breast Cancer

Study ID

NCT06065748

Start date

Dec 11, 2023

Status verified date

Sep, 2026

Completion date

Feb 12, 2029

Anticipated

Primary completion date

Apr 20, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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

Study Design

Enrollment

1050 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

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.

Interventions

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.

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.

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.

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.

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.

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.

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 \[ESR1nmd\]).

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) ]
  • PFS in the Full Analysis Set (FAS) Population [ Time Frame: From randomization to first occurrence of PD or death (up to 5 years) ]

Central Contacts and Locations

More Information

Sponsor

Hoffmann-La Roche

Last update posted

Sep 14, 2026

Last verified

Sep, 2026

Keywords

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

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-23. This information was provided to ClinicalTrials.gov by Hoffmann-La Roche on 2026-09-14. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.