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)
NCT ID: NCT05306340
Last Updated: 2025-11-12
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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ACTIVE_NOT_RECRUITING
PHASE3
373 participants
INTERVENTIONAL
2022-08-03
2026-10-15
Brief Summary
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Giredestrant plus Everolimus
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).
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.
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.
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.
Physician's Choice of Endocrine Therapy plus Everolimus
The physician's choice of endocrine therapy is defined as either exemestane, fulvestrant, or tamoxifen.
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.
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.
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.
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.
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.
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.
Interventions
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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).
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.
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.
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.
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.
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.
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.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
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 study treatment
Exclusion Criteria
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
18 Years
ALL
No
Sponsors
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Genentech, Inc.
INDUSTRY
Responsible Party
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Principal Investigators
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Clinical Trials
Role: STUDY_DIRECTOR
Genentech, Inc.
Locations
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Alabama Oncology - Bruno Cancer Center
Birmingham, Alabama, United States
Alaska Oncology & Hematology, LLC
Anchorage, Alaska, United States
The Dignity Health Cancer Institute
Phoenix, Arizona, United States
Arizona Oncology Associates, PC-CASA
Tucson, Arizona, United States
Genesis Cancer Center
Hot Springs, Arkansas, United States
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States
Pacific Cancer Medical Center
Anaheim, California, United States
Alta Bates Summit Medical Center
Berkeley, California, United States
Beverly Hills Cancer Center
Beverly Hills, California, United States
TOI Clinical Research
Cerritos, California, United States
Newport Beach UC Irvine Medical Center
Costa Mesa, California, United States
Women's Cancer Care
Fresno, California, United States
Scripps Health
La Jolla, California, United States
Los Angeles Hematology Oncology Medical Group
Los Angeles, California, United States
University of California, Irvine Medical Center
Orange, California, United States
Emad Ibrahim, Md, Inc
Redlands, California, United States
Brian LeBerthon, Med Corp
West Covina, California, United States
Yale Cancer Center
New Haven, Connecticut, United States
Broward Health Medical Center (BHMC) (Broward General Medical Center (BGMC))
Fort Lauderdale, Florida, United States
Mount Sinai Medical Center
Miami Beach, Florida, United States
Orlando Health Cancer Institute
Orlando, Florida, United States
Cancer Care Centers of Brevard
Palm Bay, Florida, United States
Tampa General Hospital Cancer Institute
Tampa, Florida, United States
Florida Cancer Specialists
West Palm Beach, Florida, United States
Northwest Georgia Oncology Centers PC - Marietta
Marietta, Georgia, United States
Summit Cancer Care PC
Savannah, Georgia, United States
St Luke?s Cancer Institute
Boise, Idaho, United States
Northwestern University
Chicago, Illinois, United States
Springfield Clinic
Springfield, Illinois, United States
Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, United States
Mission Cancer + Blood - IMMC
Des Moines, Iowa, United States
University of Kansas Cancer Center
Westwood, Kansas, United States
Pikeville Medical Center
Pikeville, Kentucky, United States
Our Lady of the Lake Physicians Group
Baton Rouge, Louisiana, United States
Woman's Hospital
Baton Rouge, Louisiana, United States
Pontchartrain Cancer Center
Covington, Louisiana, United States
Eastern Maine Medical Center
Brewer, Maine, United States
New England Cancer Specialists
Scarborough, Maine, United States
Anne Arundel Health System Research Institute
Annapolis, Maryland, United States
University of Maryland Greenebaum Cancer Center
Baltimore, Maryland, United States
Mercy Medical Center
Baltimore, Maryland, United States
Dana Farber Cancer Institute
Boston, Massachusetts, United States
Dana-Farber/Brigham and Women's Cancer Center at Milford Regional Medical Center
Milford, Massachusetts, United States
Metro-Minnesota Community Oncology Research Consortium
Saint Louis Park, Minnesota, United States
Oncology Hematology West PC
Grand Island, Nebraska, United States
Oncology Hematology West, PC dba Nebraska Cancer Specialists
Omaha, Nebraska, United States
Renown Regional Medical Center
Reno, Nevada, United States
Memorial Sloan Kettering - Basking Ridge
Basking Ridge, New Jersey, United States
Summit Medical Group
Florham Park, New Jersey, United States
Memorial Sloan Kettering - Monmouth
Middletown, New Jersey, United States
Memorial Sloan-Kettering Cancer Center
Montvale, New Jersey, United States
San Juan Oncology Associates
Farmington, New Mexico, United States
Memorial Sloan Kettering
Commack, New York, United States
Memorial Sloan Kettering Cancer Center at Westchester
Harrison, New York, United States
Memorial Sloan Kettering Cancer Center
Long Island City, New York, United States
The Blavatnik Family ? Chelsea Medical Center at Mount Sinai
New York, New York, United States
Icahn School of Medicine at Mount Sinai
New York, New York, United States
Icahn School of Medicine at Mount Sinai
New York, New York, United States
Memorial Sloan-Kettering Cancer Center
New York, New York, United States
Stony Brook University Medical Center
Stony Brook, New York, United States
Memorial Sloan Kettering Cancer Center at Nassau
Uniondale, New York, United States
SCRI Mark H. Zangmeister Center
Columbus, Ohio, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States
Oklahoma Cancer Specialists and Research Institute
Tulsa, Oklahoma, United States
St Charles Medical Center Bend
Bend, Oregon, United States
Abramson Cancer Center
Philadelphia, Pennsylvania, United States
UPMC Hillman Cancer Center - Magee-Women?s Hospital
Pittsburgh, Pennsylvania, United States
Abramson Cancer Center Chester County Hospital
West Chester, Pennsylvania, United States
McGlinn Cancer Institute at Reading Hospital
West Reading, Pennsylvania, United States
Avera Cancer Institute
Sioux Falls, South Dakota, United States
West Cancer Center
Germantown, Tennessee, United States
Thompson Cancer Survival Center
Knoxville, Tennessee, United States
Texas Oncology P.A - Beaumont
Beaumont, Texas, United States
Texas Oncology - Baylor Charles A. Sammons Cancer Center
Bedford, Texas, United States
Texas Oncology - Baylor Charles A. Sammons Cancer Center
Dallas, Texas, United States
Texas Oncology-Denton South
Denton, Texas, United States
Texas Oncology, P.A. - El Paso
El Paso, Texas, United States
Houston Methodist Cancer Center
Houston, Texas, United States
Millennium Research & Clinical Development
Houston, Texas, United States
Texas Oncology P.A.
San Antonio, Texas, United States
Inova Fairfax Hospital
Fairfax, Virginia, United States
Virginia Cancer Specialists
Fairfax, Virginia, United States
Virginia Oncology Associates
Norfolk, Virginia, United States
Northwest Medical Specialties, PLLC
Tacoma, Washington, United States
Instituto de Oncología Ángel H. Roffo
Agronomía, Ciudad Autónoma de BuenosAires, Argentina
Fundación CENIT para la Investigación en Neurociencias
Recoleta, Ciudad Autónoma de BuenosAires, Argentina
Consultorios Médicos Dr. Doreski
Ciudad Autonoma Buenos Aires, , Argentina
Centro Medico Privado CEMAIC
Córdoba, , Argentina
Fundacion Centro Oncologico de Integracion Regional (COIR)
Mendoza, , Argentina
Instituto Medico de la Fundacion Estudios Clinicos
Rosario, , Argentina
Sanatorio Parque S.A.
Rosario, , Argentina
Hospital Provincial del Centenario
Rosario, , Argentina
Instituto de Oncologia de Rosario
Rosario, , Argentina
Centro Polivalente de Asistencia e Investigacion Clinica - CER San Juan
San Juan, , Argentina
Organizacion Medica de Investigacion
San Nicolás, , Argentina
Centro de Investigación Clínica ? Clínica Viedma
Viedma, , Argentina
Marienhospital Bottrop
Bottrop, , Germany
Universitatsklinikum Erlangen
Erlangen, , Germany
Kliniken Essen-Mitte
Essen, , Germany
Universitätsklinikum Heidelberg
Heidelberg, , Germany
Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz
Mainz, , Germany
University of Athens, Hematological Clinic,
Athens, , Greece
Attikon University General Hospital
Athens, , Greece
Metropolitan General Hospital
Cholargós, , Greece
University General Hospital of Heraklion
Heraklio, , Greece
University General Hospital of Larissa
Larissa, , Greece
IASO Obstetrics Gynecology Clinic
Marousi, , Greece
Agios Loucas Clinic SA
Panórama, , Greece
Olympion Clinic
Pátrai, , Greece
Metaxa Cancer Hospital of Piraeus
Piraeus, , Greece
Interbalkan Medical Center of Thessaloniki
Thessaloniki, , Greece
Azienda Ospedaliero - Universitaria di Modena Policlinico
Modena, Emilia-Romagna, Italy
Istituto Nazionale Tumori Regina Elena IRCCS
Rome, Lazio, Italy
Ospedale Policlinico San Martino
Genoa, Liguria, Italy
Asst Grande Ospedale Metropolitano Niguarda
Milan, Lombardy, Italy
Azienda Ospedaliero Universitaria Ospedali Riuniti
Torrette Di Ancona, The Marches, Italy
"Azienda Ospedaliera Universitaria Integrata Verona Ospedale Borgo Trento"
Verona, Veneto, Italy
Aichi Cancer Center
Aichi, , Japan
Nagoya University Hospital
Aichi, , Japan
Chiba Cancer Center
Chiba, , Japan
National Cancer Center Hospital East
Chiba, , Japan
Shikoku Cancer Center
Ehime, , Japan
Hiroshima City Hiroshima Citizens Hospital
Hiroshima, , Japan
Hiroshima University Hospital
Hiroshima, , Japan
Hokkaido University Hospital
Hokkaido, , Japan
Hyogo Cancer Center
Hyōgo, , Japan
University of Tsukuba Hospital
Ibaraki, , Japan
Kanagawa Cancer Center
Kanagawa, , Japan
Tokai University Hospital
Kanagawa, , Japan
Kumamoto University Hospital
Kumamoto, , Japan
Niigata Cancer Center Hospital
Niigata, , Japan
National Hospital Organization Osaka National Hospital
Osaka, , Japan
Juntendo University Hospital
Tokyo, , Japan
The Cancer Institute Hospital of JFCR
Tokyo, , Japan
National University Hospital
Singapore, , Singapore
Oncocare Cancer Centre
Singapore, , Singapore
Medical Oncology Centre of Rosebank
Johannesburg, , South Africa
Chungbuk National University Hospital
Cheongju-si, , South Korea
Soon Chun Hyang University Cheonan Hospital
Dongnam-gu, Cheonan-si, , South Korea
National Cancer Center
Goyang-si, , South Korea
Seoul National University Bundang Hospital
Seongnam-si, , South Korea
Seoul National University Hospital
Seoul, , South Korea
Severance Hospital Yonsei University Health System - PPDS
Seoul, , South Korea
Korea University Guro Hospital
Seoul, , South Korea
Complejo Hospitalario Universitario A Coruña (CHUAC, Materno Infantil), Oncología
A Coruña, LA Coruna, Spain
Hospital Dexeus
Barcelona, , Spain
Hospital Clinic de Barcelona
Barcelona, , Spain
C.H. Regional Reina Sofia - PPDS
Córdoba, , Spain
Hospital General Universitario Gregorio Marañon
Madrid, , Spain
Hospital Universitario Ramón y Cajal
Madrid, , Spain
Hospital Clinico San Carlos
Madrid, , Spain
Hospital Universitario 12 de Octubre
Madrid, , Spain
Hospital General Universitario J.M Morales Meseguer
Murcia, , Spain
Hospital Clinico Universitario de Valencia
Valencia, , Spain
Changhua Christian Hospital
Chang-hua, , Taiwan
Chang Gung Memorial Hospital
Kaohsiung Country, , Taiwan
National Cheng Kung University Hospital
Tainan, , Taiwan
National Taiwan University Hospital
Taipei, , Taiwan
Koo Foundation Sun Yat-Sen Cancer Center
Taipei, , Taiwan
Chang Gung Memorial Hospital - Linkou Branch
Taipei, , Taiwan
Memorial Ankara Hastanesi
Ankara, , Turkey (Türkiye)
SAKARYA University Medical Faculty
Sakarya, , Turkey (Türkiye)
Dorset County Hospital
Dorchester, , United Kingdom
North Middlesex Uni Hospital
London, , United Kingdom
The Christie NHS Foundation Trust
Manchester, , United Kingdom
Nottingham City Hospital
Nottingham, , United Kingdom
Countries
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Other Identifiers
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2022-000199-20
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
2023-506821-12-00
Identifier Type: REGISTRY
Identifier Source: secondary_id
ML43171
Identifier Type: -
Identifier Source: org_study_id