A Study Evaluating the Efficacy and Safety of Giredestrant Plus Everolimus Compared With The Physician's Choice of Endocrine Therapy Plus Everolimus in Participants With Estrogen Receptor-Positive, HER2-Negative, Locally Advanced or Metastatic Breast Cancer (evERA Breast Cancer)

A Phase III, Randomized, Open-Label, Multicenter Study Evaluating the Efficacy and Safety of Giredestrant Plus Everolimus Compared With The Physician's Choice of Endocrine Therapy Plus Everolimus in Patients With Estrogen Receptor-Positive, HER2-Negative, Locally Advanced or Metastatic Breast Cancer

This Phase III, randomized, open-label, multicenter study will evaluate the efficacy and safety of giredestrant plus everolimus compared with the physician's choice of endocrine therapy plus everolimus in participants with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer who have had previous treatment with cyclin-dependent kinase 4/6 inhibitors (CDK4/6is) and endocrine therapy, either in the locally advanced/metastatic or the adjuvant setting.

Study Overview

• Status: Recruiting
• Conditions: Estrogen Receptor (ER)-Positive, HER2-negative, Locally Advanced or Metastatic Breast Cancer
• Intervention / Treatment: Drug: LHRH Agonist; Drug: Dexamethasone Mouth Rinse; Drug: Giredestrant; Drug: Everolimus; Drug: Exemestane; Drug: Fulvestrant; Drug: Tamoxifen

• Study Type: Interventional
• Enrollment (Estimated): 320
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Reference Study ID Number: ML43171 https://forpatients.roche.com/; Phone Number: 888-662-6728 (U.S. Only); Email: global-roche-genentech-trials@gene.com

Study Locations

• Argentina
  • Ciudad Autonoma Buenos Aires, Argentina, C1426ABP
    • Recruiting
    • Consultorios Médicos Dr. Doreski
  • Ciudad Autonoma Buenos Aires, Argentina, C1417DTB
    • Recruiting
    • Instituto Angel Roffo
  • Ciudad Autonoma de Buenos Aires, Argentina, C1125ABD
    • Recruiting
    • Centro de Neurociencias Invest y Tratamiento
  • Cordoba, Argentina, X5000JHQ
    • Recruiting
    • Sanatorio Allende
  • Cordoba, Argentina, X5008HHW
    • Recruiting
    • Centro médico privado Cemaic
  • Mar Del Plata, Argentina, B7603CBM
    • Recruiting
    • Hospital Privado de la Comunidad
  • Mendoza, Argentina, M5500AYB
    • Recruiting
    • Fundacion Centro Oncologico de Integracion Regional (COIR)
  • Pergamino, Argentina, B2700CPM
    • Recruiting
    • Centro de Investigacion Pergamino SA
  • Rosario, Argentina, S2000DEJ
    • Recruiting
    • Instituto Médico de la Fundación Estudios Clinicos
  • Rosario, Argentina, S2013KZE
    • Recruiting
    • Instituto de Oncología de Rosario
  • Rosario, Argentina, S2002KDS
    • Recruiting
    • Hospital Provincial del Centenario
  • Rosario, Argentina, S2000QGB
    • Recruiting
    • Sanatorio Parque S.A.
  • San Juan, Argentina, J5402DIL
    • Recruiting
    • Centro Polivalente de Asistencia e Investigacion Clinica - CER San Juan
  • San Nicolás, Argentina, C1015ABO
    • Recruiting
    • Organizacion Medica de Investigacion
  • Viedma, Argentina, R8500ACE
    • Recruiting
    • Centro de Investigación Clínica ? Clínica Viedma
• Germany
  • Bottrop, Germany, 46236
    • Recruiting
    • Marienhospital Bottrop
  • Dortmund, Germany, 44137
    • Recruiting
    • St. Johannes-Hospital
  • Erfurt, Germany, 99084
    • Recruiting
    • Frauenarztpraxis Dr. Apel, Dr. Kolpin
  • Erlangen, Germany, 91054
    • Recruiting
    • Universitaetsklinikum Erlangen
  • Essen, Germany, 45136
    • Recruiting
    • Kliniken Essen-Mitte
  • Georgsmarienhutte, Germany, 49124
    • Recruiting
    • Franziskus-Hospital Harderberg
  • Heidelberg, Germany, 69120
    • Recruiting
    • Universitätsklinikum Heidelberg
  • Mainz, Germany, 55101
    • Recruiting
    • Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz
• Greece
  • Athens, Greece, 115 28
    • Recruiting
    • University of Athens Medical School - Regional General Hospital Alexandra
  • Chaidari, Greece, 124 62
    • Recruiting
    • Attikon University General Hospital
  • Cholargos, Greece, 155 62
    • Recruiting
    • Metropolitan General Hospital
  • Heraklio, Greece, 711 10
    • Recruiting
    • University General Hospital of Heraklion
  • Larissa, Greece, 412 21
    • Recruiting
    • University General Hospital of Larissa
  • Marousi, Greece, 151 23
    • Recruiting
    • IASO Obstetrics Gynecology Clinic
  • Panorama, Greece, 552 36
    • Recruiting
    • Agios Loucas Clinic SA
  • Patras, Greece, 265 00
    • Recruiting
    • University General Hospital of Patras
  • Patras, Greece, 264 43
    • Recruiting
    • Olympion Clinic
  • Peiraias, Greece, 185 37
    • Recruiting
    • Metaxa Cancer Hospital of Piraeus
  • Thessaloniki, Greece, 546 39
    • Recruiting
    • Interbalkan Medical Center of Thessaloniki
  • Thessaloniki, Greece, 546 45
    • Recruiting
    • Euromedica PPDS
• Italy
  • Emilia-Romagna
    • Modena, Emilia-Romagna, Italy, 41110
      • Recruiting
      • Azienda Ospedaliero - Universitaria di Modena Policlinico
  • Lazio
    • Roma, Lazio, Italy, 00144
      • Recruiting
      • Istituto Nazionale Tumori Regina Elena Irccs
  • Liguria
    • Genova, Liguria, Italy, 16132
      • Recruiting
      • Ospedale Policlinico San Martino
  • Lombardia
    • Milano, Lombardia, Italy, 20162
      • Recruiting
      • ASST Grande Ospedale Metropolitano Niguarda
    • Monza, Lombardia, Italy, 20900
      • Recruiting
      • Universita Degli Studi Di Milano-Bicocca - Azienda Ospedaliera San Gerardo Di Monza
  • Marche
    • Torrette Di Ancona, Marche, Italy, 60126
      • Recruiting
      • Azienda Ospedaliero Universitaria Ospedali Riuniti
  • Veneto
    • Cona (FE), Veneto, Italy, 44124
      • Recruiting
      • Azienda Ospedaliero Universitaria di Ferrara - U.O. Di Oncologia
    • Verona, Veneto, Italy, 37124
      • Recruiting
      • "Azienda Ospedaliera Universitaria Integrata Verona Ospedale Borgo Trento"
• Japan
  • Aichi, Japan, 464-8681
    • Recruiting
    • Aichi Cancer Center
  • Aichi, Japan, 466-8560
    • Active, not recruiting
    • Nagoya University Hospital
  • Chiba, Japan, 260-8717
    • Recruiting
    • Chiba Cancer Center
  • Chiba, Japan, 277-8577
    • Active, not recruiting
    • National Cancer Center Hospital East
  • Ehime, Japan, 791-0280
    • Recruiting
    • Shikoku Cancer Center
  • Fukushima, Japan, 960-1295
    • Recruiting
    • Fukushima Medical University Hospital
  • Hiroshima, Japan, 730-8518
    • Recruiting
    • Hiroshima City Hiroshima Citizens Hospital
  • Hiroshima, Japan, 734-8551
    • Recruiting
    • Hiroshima University Hospital
  • Hokkaido, Japan, 060-8648
    • Recruiting
    • Hokkaido University Hospital
  • Hyogo, Japan, 673-0021
    • Active, not recruiting
    • Hyogo Cancer Center
  • Ibaraki, Japan, 305-8576
    • Active, not recruiting
    • University of Tsukuba Hospital
  • Kanagawa, Japan, 259-1193
    • Recruiting
    • Tokai University Hospital
  • Kanagawa, Japan, 241-8515
    • Recruiting
    • Kanagawa Cancer Center
  • Kumamoto, Japan, 860-8556
    • Recruiting
    • Kumamoto University Hospital
  • Kyoto, Japan, 606-8507
    • Recruiting
    • Kyoto University Hospital
  • Niigata, Japan, 951-8566
    • Active, not recruiting
    • Niigata Cancer Center Hospital
  • Okinawa, Japan, 901-0154
    • Recruiting
    • Naha-nishi Clinic
  • Osaka, Japan, 541-8567
    • Recruiting
    • Osaka International Cancer Institute
  • Osaka, Japan, 540-0006
    • Recruiting
    • National Hospital Organization Osaka National Hospital
  • Tokyo, Japan, 135-8550
    • Recruiting
    • The Cancer Institute Hospital of JFCR
  • Tokyo, Japan, 113-8431
    • Recruiting
    • Juntendo University Hospital
• Korea, Republic of
  • Cheongju si, Korea, Republic of, 28644
    • Recruiting
    • Chungbuk National University Hospital
  • Dongnam-gu, Cheonan-si, Korea, Republic of, 31151
    • Recruiting
    • Soon Chun Hyang University Cheonan Hospital
  • Goyang-si, Korea, Republic of, 10408
    • Recruiting
    • National Cancer Center
  • Gyeonggi-do, Korea, Republic of, 13496
    • Recruiting
    • Cha Bundang Medical Center
  • Seongnam-si, Korea, Republic of, 463-707
    • Recruiting
    • Seoul National University Bundang Hospital
  • Seoul, Korea, Republic of, 08308
    • Recruiting
    • Korea University Guro Hospital
  • Seoul, Korea, Republic of, 03080
    • Recruiting
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 03722
    • Recruiting
    • Severance Hospital Yonsei University Health System - PPDS
• Singapore
  • Singapore, Singapore, 117599
    • Recruiting
    • National University Hospital
  • Singapore, Singapore, 258499
    • Recruiting
    • Oncocare Cancer Centre
• South Africa
  • Amanzimtoti, South Africa, 4126
    • Recruiting
    • Rainbow Oncology Private Practice
  • City Of Johannesburg, South Africa, 2193
    • Recruiting
    • Wits Health Research
  • Hilton, South Africa, 3245
    • Recruiting
    • Hopelands Cancer Centre
  • Johannesburg, South Africa, 2196
    • Recruiting
    • Medical Oncology Centre of Rosebank; Oncology
  • Pretoria, South Africa, 0001
    • Recruiting
    • Wilgers Oncology Centre
• Spain
  • Barcelona, Spain, 08036
    • Recruiting
    • Hospital Clinic De Barcelona
  • Barcelona, Spain, 08028
    • Recruiting
    • Hospital Dexeus; Oncología
  • Cordoba, Spain, 14004
    • Recruiting
    • C.H. Regional Reina Sofia - PPDS
  • Granada, Spain, 18012
    • Recruiting
    • Hospital Universitario Virgen de las Nieves
  • La Coruña, Spain, 15006
    • Recruiting
    • Complejo Hospitalario Universitario A Coruña (CHUAC, Materno Infantil), Oncología
  • Madrid, Spain, 28034
    • Recruiting
    • Hospital Universitario Ramon Y Cajal
  • Madrid, Spain, 28041
    • Recruiting
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28040
    • Recruiting
    • Hospital Clínico San Carlos
  • Madrid, Spain, 28007
    • Recruiting
    • Hospital General Universitario Gregorio Maranon
  • Murcia, Spain, 30008
    • Recruiting
    • Hospital General Universitario J.M Morales Meseguer; Servicio de Oncologia
  • Valencia, Spain, 46010
    • Recruiting
    • Hospital Clínico Universitario de Valencia
• Taiwan
  • Chang Hua, Taiwan, 500
    • Recruiting
    • Changhua Christian Hospital
  • Kaohsiung Country, Taiwan, 833
    • Recruiting
    • Chang Gung memorial hospital
  • Tainan, Taiwan, 70457
    • Recruiting
    • National Cheng Kung University Hospital
  • Taipei, Taiwan, 10002
    • Recruiting
    • National Taiwan University Hospital
  • Taipei, Taiwan
    • Recruiting
    • Chang Gung Memorial Hospital - Linkou Branch
  • Taipei City, Taiwan, 11259
    • Recruiting
    • Koo Foundation Sun Yat-Sen Cancer Center; Hemato-Oncology
• Turkey
  • Ankara, Turkey, 06520
    • Recruiting
    • Memorial Ankara Hastanesi
  • Diyarbak?r, Turkey, 21280
    • Recruiting
    • Dicle University Medical Faculty
• United Kingdom
  • Dorchester, United Kingdom, DT1 2JY
    • Recruiting
    • Dorset County Hospital
  • London, United Kingdom, N18 1QX
    • Recruiting
    • North Middlesex Uni Hospital; Haematology Dept
  • Manchester, United Kingdom, M20 4BX
    • Recruiting
    • The Christie NHS Foundation Trust
  • Nottingham, United Kingdom, NG5 1PB
    • Recruiting
    • Nottingham City Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • Recruiting
      • Alabama Oncology - Bruno Cancer Center
    • Mobile, Alabama, United States, 36607
      • Recruiting
      • Gulf Health Hospitals, Inc. d/b/a Infirmary Cancer Care
  • Alaska
    • Anchorage, Alaska, United States, 99508
      • Recruiting
      • Alaska Oncology and Hematology
  • Arizona
    • Phoenix, Arizona, United States, 85004
      • Recruiting
      • The Dignity Health Cancer Institute
    • Tucson, Arizona, United States, 85711
      • Recruiting
      • Arizona Oncology Associates, PC-CASA
    • Yuma, Arizona, United States, 85364
      • Withdrawn
      • Yuma Regional Medical Center Cancer Center
  • Arkansas
    • Hot Springs, Arkansas, United States, 71913
      • Recruiting
      • Genesis Cancer Center
    • Little Rock, Arkansas, United States, 72205
      • Recruiting
      • University of Arkansas for Medical Sciences; Winthrop Rockefeller Cancer Institute
  • California
    • Anaheim, California, United States, 92801
      • Recruiting
      • Pacific Cancer Medical Center
    • Berkeley, California, United States, 94704
      • Recruiting
      • Alta Bates Summit Medical Center; Comprehensive Cancer Center
    • Beverly Hills, California, United States, 90211
      • Recruiting
      • Beverly Hills Cancer Center
    • Cerritos, California, United States, 90703
      • Recruiting
      • TOI Clinical Research
    • Costa Mesa, California, United States, 92627
      • Recruiting
      • Newport Beach UC Irvine Medical Center
    • Fresno, California, United States, 93710
      • Recruiting
      • Women's Cancer Care
    • La Jolla, California, United States, 92037
      • Recruiting
      • Scripps Health; Scripps Cancer Center
    • Los Angeles, California, United States, 90017
      • Recruiting
      • Los Angeles Hematology Oncology Medical Group
    • Orange, California, United States, 92868
      • Recruiting
      • University of California, Irvine Medical Center
    • Redlands, California, United States, 92373
      • Recruiting
      • Emad Ibrahim, Md, Inc
    • West Covina, California, United States, 91790-3961
      • Recruiting
      • Brian LeBerthon, Med Corp
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Recruiting
      • Yale Cancer Center; Medical Oncology
    • Norwich, Connecticut, United States, 06360-2740
      • Recruiting
      • Eastern CT Hematology and Oncology Associates
  • Florida
    • Brooksville, Florida, United States, 34613
      • Recruiting
      • ASCLEPES Research Centers - Brooksville
    • Fort Lauderdale, Florida, United States, 33316
      • Recruiting
      • Broward Health Medical Center (BHMC) (Broward General Medical Center (BGMC))
    • Miami Beach, Florida, United States, 33140
      • Recruiting
      • Mount Sinai Medical Center
    • Orlando, Florida, United States, 32806
      • Recruiting
      • Orlando Health Cancer Institute
    • Rockledge, Florida, United States, 32955
      • Recruiting
      • Cancer Care Centers of Brevard
    • West Palm Beach, Florida, United States, 33401
      • Recruiting
      • Florida Cancer Specialists
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Recruiting
      • Piedmont Atlanta Hospital
    • Fayetteville, Georgia, United States, 30214
      • Recruiting
      • Piedmont Fayette Hospital
    • Marietta, Georgia, United States, 30060
      • Recruiting
      • Northwest Georgia Oncology Centers PC - Marietta
    • Newnan, Georgia, United States, 30265
      • Recruiting
      • Piedmont Newnan Hospital
    • Savannah, Georgia, United States, 31405
      • Recruiting
      • Summit Cancer Care PC
    • Stockbridge, Georgia, United States, 30281
      • Recruiting
      • Piedmont Henry Hospital
  • Idaho
    • Boise, Idaho, United States, 83712
      • Recruiting
      • St Luke?s Cancer Institute
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Northwestern University; Robert H. Lurie Comp Can Ctr
    • Springfield, Illinois, United States, 62702
      • Recruiting
      • Springfield Clinic; Department of Hematology and Oncology
    • Springfield, Illinois, United States, 62702
      • Recruiting
      • Southern Illinois University, School of Medicine, Simmons Cancer Institute
    • Tinley Park, Illinois, United States, 60487
      • Recruiting
      • Duly Health and Care
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Recruiting
      • Indiana University Melvin and Bren Simon Cancer Center
  • Iowa
    • Des Moines, Iowa, United States, 50309
      • Recruiting
      • Des Moines Oncology Research Association
  • Kansas
    • Westwood, Kansas, United States, 66205
      • Recruiting
      • University of Kansas Cancer Center
  • Kentucky
    • Pikeville, Kentucky, United States, 41501
      • Recruiting
      • Pikeville Medical Center
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70817
      • Recruiting
      • Woman's Hospital
    • Baton Rouge, Louisiana, United States, 70808
      • Recruiting
      • Our Lady of the Lake Physicians Group; Hematology/Oncology
    • Baton Rouge, Louisiana, United States, 70805
      • Recruiting
      • LSU Health Baton Rouge; North Clinic
    • Covington, Louisiana, United States, 70433
      • Recruiting
      • Pontchartrain Cancer Center
  • Maine
    • Brewer, Maine, United States, 04412
      • Recruiting
      • Northern Light Cancer Center/Oncology Research
    • Scarborough, Maine, United States, 04074
      • Recruiting
      • New England Cancer Specialists
  • Maryland
    • Annapolis, Maryland, United States, 21401
      • Recruiting
      • Anne Arundel Health System Research Institute
    • Baltimore, Maryland, United States, 21202
      • Recruiting
      • Mercy Medical Center
    • Baltimore, Maryland, United States, 21201
      • Recruiting
      • University of Maryland Greenebaum Cancer Center
    • Ocean Pines, Maryland, United States, 21811
      • Recruiting
      • TidalHealth Peninsula Regional; Richard A. Henson Research
    • Randallstown, Maryland, United States, 21133
      • Recruiting
      • Sinai Hospital of Baltimore Inc
    • Salisbury, Maryland, United States, 21801
      • Recruiting
      • TidalHealth Peninsula Regional
    • Westminster, Maryland, United States, 21157
      • Recruiting
      • Sinai Hospital of Baltimore; Wiliam E. Kahlert Regional Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Dana Farber Cancer Institute
    • Foxboro, Massachusetts, United States, 02035
      • Recruiting
      • Dana Farber/Harvard Cancer Center (Foxborough)
    • Milford, Massachusetts, United States, 01757
      • Recruiting
      • Dana Farber/Harvard Cancer Center (Milford)
    • Weymouth, Massachusetts, United States, 02190
      • Recruiting
      • Dana Farber/Harvard Cancer Center (Weymouth)
  • Michigan
    • Farmington Hills, Michigan, United States, 48334
      • Recruiting
      • Michigan Center of Medical Research
  • Minnesota
    • Saint Louis Park, Minnesota, United States, 55416
      • Recruiting
      • Metro-Minnesota Community Oncology Research Consortium
  • Nebraska
    • Grand Island, Nebraska, United States, 68803
      • Recruiting
      • Oncology Hematology West PC
    • Omaha, Nebraska, United States, 68130
      • Recruiting
      • Nebraska Cancer Specialists; Oncology Hematology West, PC
  • Nevada
    • Reno, Nevada, United States, 89502
      • Recruiting
      • Renown Regional Medical Center
  • New Jersey
    • Basking Ridge, New Jersey, United States, 07920
      • Recruiting
      • Memorial Sloan Kettering - Basking Ridge; Pharmacy
    • Florham Park, New Jersey, United States, 07932
      • Recruiting
      • Summit Medical Group; MD Anderson Cancer Center
    • Middletown, New Jersey, United States, 07748
      • Recruiting
      • Memorial Sloan Kettering - Monmouth
    • Montvale, New Jersey, United States, 07645
      • Recruiting
      • Memorial Sloan-Kettering Cancer Center; Hematology/Oncology
  • New Mexico
    • Farmington, New Mexico, United States, 87401
      • Recruiting
      • San Juan Oncology Associates
  • New York
    • Commack, New York, United States, 11725
      • Recruiting
      • Memorial Sloan Kettering
    • Harrison, New York, United States, 10604
      • Recruiting
      • Memorial Sloan Kettering Cancer Center at Westchester
    • Long Island City, New York, United States, 11104
      • Recruiting
      • Memorial Sloan Kettering Cancer Center; Drug Shipment
    • New York, New York, United States, 10029
      • Recruiting
      • Icahn School of Medicine at Mount Sinai
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan-Kettering Cancer Center; Hematology/Oncology
    • New York, New York, United States, 10011
      • Recruiting
      • The Blavatnik Family ? Chelsea Medical Center at Mount Sinai
    • New York, New York, United States, 10029
      • Recruiting
      • Icahn School of Medicine at Mount Sinai; Department of Pharmacy
    • Stony Brook, New York, United States, 11794
      • Recruiting
      • Stony Brook University Medical Center
    • Uniondale, New York, United States, 11553
      • Recruiting
      • Memorial Sloan Kettering Cancer Center at Nassau
  • North Carolina
    • Fayetteville, North Carolina, United States, 28304
      • Withdrawn
      • Cape Fear Valley Medical Center
  • Ohio
    • Canton, Ohio, United States, 44718
      • Recruiting
      • The Gabrail Pharmacology Phase 1 Research Center LLC
    • Columbus, Ohio, United States, 43219
      • Recruiting
      • SCRI Mark H. Zangmeister Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Recruiting
      • University of Oklahoma Health Sciences Center; Peggy and Charles Stephenson Oklahoma Cancer Center
    • Tulsa, Oklahoma, United States, 74146
      • Recruiting
      • Oklahoma Cancer Specialists and Research Institute
  • Oregon
    • Bend, Oregon, United States, 97701
      • Recruiting
      • St Charles Medical Center Bend; ATTN: Research
  • Pennsylvania
    • Harrisburg, Pennsylvania, United States, 17109
      • Recruiting
      • Oncology Research Office
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • Abramson Cancer Center; Univ of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Recruiting
      • UPMC Hillman Cancer Center - Magee-Women?s Hospital
    • West Chester, Pennsylvania, United States, 19380
      • Recruiting
      • Abramson Cancer Center Chester County Hospital; Hematology, Medical Oncology
    • West Reading, Pennsylvania, United States, 19611
      • Recruiting
      • McGlinn Cancer Institute at Reading Hospital
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105
      • Recruiting
      • Avera Cancer Institute
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Recruiting
      • West Cancer Center
    • Knoxville, Tennessee, United States, 37916-2305
      • Recruiting
      • Thompson Cancer Survival Center
  • Texas
    • Beaumont, Texas, United States, 77702
      • Recruiting
      • Texas Oncology P.A - Beaumont
    • Bedford, Texas, United States, 76022
      • Recruiting
      • Texas Oncology
    • Dallas, Texas, United States, 75246
      • Recruiting
      • Texas Oncology - Baylor Charles A. Sammons Cancer Center
    • Denton, Texas, United States, 76201
      • Recruiting
      • Texas Oncology-Denton South
    • El Paso, Texas, United States, 79915
      • Recruiting
      • Texas Oncology, P.A. - El Paso; El Paso Cancer Treatment Center, West
    • Houston, Texas, United States, 77090
      • Recruiting
      • Millennium Research & Clinical Development
    • Houston, Texas, United States, 77030
      • Recruiting
      • Methodist Hospital Research Institute
    • Kingwood, Texas, United States, 77339
      • Recruiting
      • Lumi Research
    • McAllen, Texas, United States, 78503
      • Recruiting
      • Texas Oncology Central - South
    • San Antonio, Texas, United States, 78217
      • Recruiting
      • USOR - Texas Oncology - San Antonio Northeast
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • Virginia Cancer Specialists
    • Falls Church, Virginia, United States, 22031
      • Recruiting
      • Inova Fairfax Hospital
    • Norfolk, Virginia, United States, 23502
      • Recruiting
      • Virginia Oncology Associates
  • Washington
    • Tacoma, Washington, United States, 98405
      • Recruiting
      • Multicare Institute for Research and Innovation
    • Tacoma, Washington, United States, 98405
      • Recruiting
      • Northwest Medical Specialties, PLLC; Research Department
  • Wisconsin
    • Waukesha, Wisconsin, United States, 53188
      • Recruiting
      • UW Cancer Center at ProHealth

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Locally advanced unresectable or metastatic adenocarcinoma of the breast, not amenable to treatment with curative intent
2. Documented estrogen receptor-positive (ER+) tumor and HER2-negative tumor, assessed locally
3. Ability to provide a blood sample for circulating-tumor deoxyribonucleic acid (ctDNA) Estrogen Receptor 1 (ESR1) mutation status determination by central testing

4. Prior endocrine therapy (ET) in combination with cyclin-dependent kinase 4/6 inhibitors in either setting as follows:

   • Metastatic setting: Disease progression after ≥6 months on ET plus CDK4/6 inhibitor in the locally advanced or metastatic setting. If ET plus CDK4/6 inhibitor is not the most recent therapy, then patient must also have had disease progression after ≥4 months on most recent ET
   • Adjuvant Setting: Relapse either while taking or within 12 months of exposure to combination adjuvant ET and CDK4/6 inhibitor. Patients must have taken at least 12 months of adjuvant ET, 6 months of which was in combination with a CDK4/6 inhibitor.
5. Measurable disease as defined per RECIST v.1.1 or evaluable bone metastases. Patients with evaluable bone disease in the absence of measurable disease outside of the bone must have at least one predominantly lytic bone lesion confirmed by computed tomography (CT) or magnetic resonance imaging (MRI) which can be followed
6. Eastern Cooperative Oncology Group Performance Status 0-1
7. For women who are premenopausal or perimenopausal and for men: treatment with approved luteinizing hormone-releasing hormone (LHRH) agonist therapy for the duration of the study treatment

Exclusion Criteria:

1. Prior treatment with another oral selective estrogen receptor degrader (SERD), proteolysis targeting chimera (PROTAC), complete estrogen receptor antagonist (CERAN), novel oral selective estrogen receptor modulator (SERM), or everolimus in any setting. Prior fulvestrant is allowed if treatment was terminated at least 28 days prior to randomization. Prior treatment with tamoxifen is allowed.
2. Progression on more than 2 prior lines of systemic endocrine therapy in the locally advanced unresectable or metastatic breast cancer setting
3. Prior chemotherapy for locally advanced unresectable or metastatic disease
4. Treatment with strong Cytochrome P450 3A4 (CYP3A4) inhibitors or inducers within 14 days or 5 drug elimination half-lives (whichever is longer) prior to randomization
5. Treatment with any investigational therapy within 28 days prior to initiation of study treatment
6. Major surgery, chemotherapy, radiotherapy, or other anti-cancer therapy within 14 days prior to randomization
7. History of any other malignancy other than breast cancer within 5 years prior to screening, except for appropriately treated carcinoma in situ of the cervix, nonmelanoma skin carcinoma, papillary thyroid cancer treated with surgery, Stage I endometrial cancer, or other non-breast cancers at very low risk of recurrence
8. Advanced, symptomatic, visceral spread that is at risk of life-threatening complications in the short term
9. Known active uncontrolled or symptomatic central nervous system (CNS) metastases, carcinomatous meningitis, or leptomeningeal disease
10. Active cardiac disease or history of cardiac dysfunction
11. Known clinically significant history of liver disease consistent with Child-Pugh Class B or C including active viral or other hepatitis virus, current alcohol abuse, or cirrhosis
12. Active inflammatory bowel disease, chronic diarrhea, short bowel syndrome, or major upper gastrointestinal (GI) surgery including gastric resection
13. Interstitial lung disease or severe dyspnea at rest or requiring oxygen therapy
14. Serious infection requiring oral or intravenous (IV) antibiotics, or other clinically significant infection, within 14 days prior to randomization
15. Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study
16. Known allergy or hypersensitivity to any of the study drugs or any of their excipients
17. For premenopausal or perimenopausal women and for men: known hypersensitivity to LHRH agonists
18. Pregnant or breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Giredestrant plus Everolimus	Drug: LHRH Agonist; Only premenopausal/perimenopausal female participants and male participants will receive a luteinizing hormone-releasing hormone (LHRH) agonist on Day 1 of each 28-day treatment cycle. The investigator will determine and supply the appropriate LHRH agonist locally approved for use in breast cancer.; Drug: Dexamethasone Mouth Rinse; A compounded alcohol-free mouthwash of dexamethasone (0.5 mg in 5 mL) will be supplied, where feasible. It is strongly recommended for prophylaxis or treatment of stomatitis/mucositis. Participants should use the alcohol-free mouthwash of dexamethasone four times QD for 8 weeks started concurrently with study treatment, and use it reactively thereafter with the first appearance of symptoms.; Drug: Giredestrant; Participants will receive treatment with giredestrant 30 milligrams (mg) orally once a day (QD) on Days 1-28 of each 28-day cycle until unacceptable toxicity or disease progression as determined by the investigator according to Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1).; Other Names: GDC-9545; RO7197597; RG6171; Drug: Everolimus; Participants will receive treatment with everolimus 10 mg orally QD during each 28-day cycle until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.
Active Comparator: Physician's Choice of Endocrine Therapy plus Everolimus; The physician's choice of endocrine therapy is defined as either exemestane, fulvestrant, or tamoxifen.	Drug: LHRH Agonist; Only premenopausal/perimenopausal female participants and male participants will receive a luteinizing hormone-releasing hormone (LHRH) agonist on Day 1 of each 28-day treatment cycle. The investigator will determine and supply the appropriate LHRH agonist locally approved for use in breast cancer.; Drug: Dexamethasone Mouth Rinse; A compounded alcohol-free mouthwash of dexamethasone (0.5 mg in 5 mL) will be supplied, where feasible. It is strongly recommended for prophylaxis or treatment of stomatitis/mucositis. Participants should use the alcohol-free mouthwash of dexamethasone four times QD for 8 weeks started concurrently with study treatment, and use it reactively thereafter with the first appearance of symptoms.; Drug: Everolimus; Participants will receive treatment with everolimus 10 mg orally QD during each 28-day cycle until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.; Drug: Exemestane; If exemestane is chosen as the physician's choice of endocrine therapy, the participant will receive exemestane at a dose of 25 mg orally once a day (QD) on Days 1-28 of each 28-day cycle or as per local label, until unacceptable toxicity or disease progression as determined by investigator according to RECIST v1.1.; Drug: Fulvestrant; If fulvestrant is chosen as the physician's choice of endocrine therapy, the participant will receive fulvestrant in the clinic at a dose of 500 mg intramuscularly on Day 1 and Day 15 of Cycle 1, then Day 1 of each cycle thereafter (1 cycle is 28 days) or as per local prescribing information, until unacceptable toxicity or disease progression as determined by investigator according to RECIST v1.1.; Drug: Tamoxifen; If tamoxifen is chosen as the physician's choice of endocrine therapy, the participant will receive tamoxifen at a dose of 20 mg orally QD on Days 1-28 of each 28-day cycle or as per local prescribing information, until unacceptable toxicity or disease progression as determined by investigator according to RECIST v1.1.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival, as Determined by the Investigator According to RECIST v1.1, in the ESR1m Subpopulation and ITT Population	The Intent-to-Treat (ITT) population consists of all randomized participants, and the ESR1m subpopulation is defined as participants in the ITT population whose tumors harbor a detectable Estrogen Receptor 1 (ESR1) mutation at baseline as measured in circulating tumor DNA (ctDNA).	From randomization until the first occurrence of disease progression or death from any cause, whichever occurs first (up to 42 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival, in the ESR1m Subpopulation and ITT Population		From randomization until death from any cause (up to 42 months)
Objective Response Rate (ORR), as Determined by the Investigator According to RECIST v1.1, in the ESR1m Subpopulation and ITT Population	The objective response rate 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.	From randomization until progressive disease or death (up to 42 months)
Duration of Response (DOR), as Determined by the Investigator According to RECIST v1.1, in the ESR1m Subpopulation and ITT Population		From the first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first (up to 42 months)
Clinical Benefit Rate (CBR), as Determined by the Investigator According to RECIST v1.1, in the ESR1m Subpopulation and ITT Population	The clinical benefit rate is defined as the percentage of participants with stable disease for at least (≥)24 weeks or a complete response (CR) or partial response (PR) on two consecutive occasions ≥4 weeks apart.	From Baseline until progressive disease or death (up to 42 months)
Time to Confirmed Deterioration in Pain Severity, as Determined Using the Brief Pain Inventory Short-Form (BPI-SF) Worst Pain Item Score, in the ESR1m Subpopulation and ITT Population	Time to confirmed deterioration in pain severity is defined as the time from randomization to the first documentation of ≥2-point increase from baseline on the "worst pain" item score (scale from 0 = "No pain" to 10 = "Pain as bad as you can imagine") held for 2 consecutive time points, or a ≥2-point increase followed by death attributable to cancer progression within 28 days from the last assessment.	From randomization until 90 days after treatment discontinuation (up to 42 months)
Time to Confirmed Deterioration in Pain Presence and Interference, as Determined Using the EORTC QLQ-C30 Questionnaire Linearly Transformed Pain Scale Score, in the ESR1m Subpopulation and ITT Population	Time to confirmed deterioration in pain presence and interference is defined as the time from randomization to the first documentation of ≥10-point increase in pain score held for 2 consecutive time points, or a ≥10-point increase followed by death attributable to cancer progression within 28 days from the last assessment. EORTC QLQ-C30 = European Organisation for Research and Treatment of Cancer Quality of Life-Core 30	From randomization until 90 days after treatment discontinuation (up to 42 months)
Time to Confirmed Deterioration in Physical Functioning (PF), as Determined Using the EORTC QLQ-C30 Questionnaire Linearly Transformed PF Scale Score, in the ESR1m Subpopulation and ITT Population	Time to confirmed deterioration in physical functioning (PF) is defined as the time from randomization to the first documentation of ≥10-point decrease in PF score held for 2 consecutive time points, or a ≥10-point decrease followed by death attributable to cancer progression within 28 days from the last assessment. EORTC QLQ-C30 = European Organisation for Research and Treatment of Cancer Quality of Life-Core 30	From randomization until 90 days after treatment discontinuation (up to 42 months)
Time to Confirmed Deterioration in Role Functioning (RF), as Determined Using the EORTC QLQ-C30 Questionnaire Linearly Transformed RF Scale Score, in the ESR1m Subpopulation and ITT Population	Time to confirmed deterioration in role functioning (RF) is defined as the time from randomization to the first documentation of ≥10-point decrease in RF score held for 2 consecutive time points, or a ≥10-point decrease followed by death attributable to cancer progression within 28 days from the last assessment. EORTC QLQ-C30 = European Organisation for Research and Treatment of Cancer Quality of Life-Core 30	From randomization until 90 days after treatment discontinuation (up to 42 months)
Time to Confirmed Deterioration in Health-Related Quality of Life (HRQoL), as Determined Using the EORTC QLQ-C30 Questionnaire Linearly Transformed Global Health Status (GHS)/QoL Scale Score, in the ESR1m Subpopulation and ITT Population	Time to confirmed deterioration in HRQoL is defined as the time from randomization to the first documentation of ≥10-point decrease in GHS/QoL score held for 2 consecutive time points, or a ≥10-point decrease followed by death attributable to cancer progression within 28 days from the last assessment. EORTC QLQ-C30 = European Organisation for Research and Treatment of Cancer Quality of Life-Core 30	From randomization until 90 days after treatment discontinuation (up to 42 months)
Number of Participants with at Least One Adverse Event, with Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, version 5 (NCI CTCAE v5.0)		From Baseline until 30 days after the final dose of study treatment (up to 42 months)
Number of Participants with Vital Sign Abnormalities Over the Course of the Study	Vital signs include respiratory rate, pulse rate, systolic and diastolic blood pressure while the patient is in a seated position, and temperature.	From Baseline until 30 days after the final dose of study treatment (up to 42 months)
Number of Participants with Clinical Laboratory Test Abnormalities for Hematology Parameters Over the Course of the Study		From Baseline until 30 days after the final dose of study treatment (up to 42 months)
Number of Participants with Clinical Laboratory Test Abnormalities for Biochemistry Parameters Over the Course of the Study		From Baseline until 30 days after the final dose of study treatment (up to 42 months)
Plasma Concentration of Giredestrant at Specified Timepoints		Predose and 3 hours postdose on Days 1 and 15 of Cycle 1, and predose on Day 1 of Cycles 2 and 3 (1 cycle is 28 days)

Collaborators and Investigators

• Sponsor: Genentech, Inc.
• Investigators: Study Director: Clinical Trials, Genentech, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 3, 2022
• Primary Completion (Estimated): October 3, 2024
• Study Completion (Estimated): March 31, 2026

Study Registration Dates

• First Submitted: March 23, 2022
• First Submitted That Met QC Criteria: March 23, 2022
• First Posted (Actual): April 1, 2022

Study Record Updates

• Last Update Posted (Actual): April 9, 2024
• Last Update Submitted That Met QC Criteria: April 8, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protein Kinase Inhibitors; Hormone Antagonists; Bone Density Conservation Agents; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Estrogen Receptor Antagonists; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; MTOR Inhibitors; Dexamethasone; Fulvestrant; Tamoxifen; Everolimus; Exemestane
• Other Study ID Numbers: ML43171; 2022-000199-20 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

For eligible studies, qualified researchers may request access to individual patient level data through the request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/).

For further details on Roche's Global Policy on Sharing of Clinical Study Information and how to request access to related clinical study documents, see here (https://www.roche.com/innovation/process/clinical-trials/data-sharing/).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No