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Purpose

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.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
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.
  • Drug: 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.
    Other names:
    • RO7197597
    • RG6171
    • GDC-9545
  • Drug: 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.
  • Drug: 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.
  • Drug: 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.
  • Drug: 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.
  • Diagnostic Test: 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]).
    Other names:
    • F1LCDx
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.
  • Drug: 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.
  • Drug: 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.
  • Drug: 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.
  • Drug: 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.
  • Drug: 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.
  • Diagnostic Test: 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]).
    Other names:
    • F1LCDx

Recruiting Locations

Southern Cancer Center
Daphne 4058219, Alabama 4829764 36526

La Hematology Oncology Medical Group
Glendale 5352423, California 5332921 91260

Marin Cancer Care Inc
Greenbrae 5354013, California 5332921 94904

Kaiser Permanente - Harbor City
Harbor City 5355325, California 5332921 90710

USC Norris Comprehensive Cancer Center
Los Angeles 5368361, California 5332921 90033

USC Norris Cancer Center
Newport Beach 5376890, California 5332921 92663

The Lundquist Institute for BioMedical Innovation at Harbor-UCLA Medical Cente
Torrance 5403022, California 5332921 90502

Rocky Mountain Cancer Centers
Littleton 5429032, Colorado 5417618 80120-4413

Georgetown University Medical Center
Washington D.C. 4140963, District of Columbia 4138106 20007

MedStar Washington Hosp Center
Washington D.C. 4140963, District of Columbia 4138106 20010

AdventHealth Altamonte
Altamonte Springs 4145941, Florida 4155751 32701

Florida Cancer Specialists - Broadway
Fort Myers 4155995, Florida 4155751 33901

Cancer Specialists of North Florida
Jacksonville 4160021, Florida 4155751 32256

Comprehensive Hematology Oncology
St. Petersburg 4171563, Florida 4155751 33709

Florida Cancer Specialists - Tampa
Tampa 4174757, Florida 4155751 33603

Florida Cancer Specialists - EAST - SCRI - PPDS
West Palm Beach 4177887, Florida 4155751 33401-3406

Grady Health System
Atlanta 4180439, Georgia 4197000 30303

Winship Cancer Institute of Emory University
Atlanta 4180439, Georgia 4197000 30329

Advocate Lutheran General Hospital
Park Ridge 4905367, Illinois 4896861 60068

Springfield Clinic
Springfield 4250542, Illinois 4896861 62702

Mission Cancer + Blood - IMMC
Des Moines 4853828, Iowa 4862182 50309

Baptist Health Lexington
Lexington 4297983, Kentucky 6254925 40503

Baptist Health Hamburg
Lexington 4297983, Kentucky 6254925 40509

Baptist Health Louisville
Louisville 4299276, Kentucky 6254925 40207

New England Cancer Specialists
Scarborough 4977882, Maine 4971068 04074

Maryland Oncology Hematology
Annapolis 4347242, Maryland 4361885 21401

Dana Farber Cancer Institute
Boston 4930956, Massachusetts 6254926 02215

Henry Ford Hospital
Detroit 4990729, Michigan 5001836 48202

HCA Midwest Division
Kansas City 4393217, Missouri 4398678 64132

Cancer Care Center of O'Fallon
O'Fallon 4401242, Missouri 4398678 62269

Oncology Hematology West - Grand Island
Grand Island 5069297, Nebraska 5073708 68803

Oncology Hematology West - Legacy
Omaha 5074472, Nebraska 5073708 68130-2042

Astera Cancer Care East Brunswick
East Brunswick 5097402, New Jersey 5101760 08816

Queens Hospital Cancer Center
Jamaica 5122520, New York 5128638 11432

Duke Women Cancer Care
Raleigh 4487042, North Carolina 4482348 27607

Asante Rogue Regional Medical Center
Medford 5740099, Oregon 5744337 97504-8332

Alliance Cancer Specialists
Bensalem 5179995, Pennsylvania 6254927 19020

Ann B. Barshinger Cancer Institute
Lancaster 5197079, Pennsylvania 6254927 17604

Abramson Cancer Center; Univ of Pennsylvania; Clinical Research Unit
Philadelphia 4560349, Pennsylvania 6254927 19106

WellSpan Oncology Research
York 4562407, Pennsylvania 6254927 17403

Brown University Health
Providence 5224151, Rhode Island 5224323 02905

Medical University of South Carolina
Charleston 4574324, South Carolina 4597040 29425

Avera Cancer Institute - Aberdeen
Aberdeen 5225857, South Dakota 5769223 57401

Avera Cancer Institute
Sioux Falls 5231851, South Dakota 5769223 57105

West Cancer Center
Germantown 4624601, Tennessee 4662168 38138

SCRI Oncology Partners
Nashville 4644585, Tennessee 4662168 37203

Texas Oncology Cancer Center
Austin 4671654, Texas 4736286 78731

JPS Oncology & Infusion Center
Fort Worth 4691930, Texas 4736286 76104

Texas Oncology - DFW
Irving 4700168, Texas 4736286 75063

Virginia Cancer Specialists, PC
Fairfax 4758023, Virginia 6254928 22031

Virginia Commonwealth University - Massey Cancer Center
Richmond 4781708, Virginia 6254928 23219

Northwest Medical Specialties
Tacoma 5812944, Washington 5815135 98405

West Virginia University Hospitals Inc
Morgantown 4815352, West Virginia 4826850 26056

Aurora BayCare Medical Center
Green Bay 5254962, Wisconsin 5279468 54311

Aurora St Lukes Medical Center
Milwaukee 5263045, Wisconsin 5279468 53215

PanOncology Trials
San Juan 4568127, Puerto Rico 00935

More Details

Status
Recruiting
Sponsor
Hoffmann-La Roche

Study Contact

Reference Study ID Number: CO44657 https://forpatients.roche.com/
888-662-6728 (U.S. Only)
global-roche-genentech-trials@gene.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.