Estrogen Receptor (ER)-Positive, HER2-negative, Locally Advanced or Metastatic Breast CancerPhase 3NCT05306340
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 3 study testing Giredestrant, Exemestane and Fulvestrant in people with Estrogen Receptor (ER)-Positive, HER2-negative, Locally Advanced or Metastatic Breast Cancer, run by Genentech, Inc. at 136 sites in 13 countries.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Estrogen Receptor (ER)-Positive, HER2-negative, Locally Advanced or Metastatic Breast Cancer
- What is being tested?
- Giredestrant, Exemestane and Fulvestrant
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 373 participants
- Where
- 136 sitesin 13 countries
- Study dates
- 3 Aug 2022to 15 Jun 2027
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Locally advanced unresectable or metastatic adenocarcinoma of the breast, not amenable to treatment with curative intent
- Documented estrogen receptor-positive (ER+) tumor and HER2-negative tumor, assessed locally
- Ability to provide a blood sample for circulating-tumor deoxyribonucleic acid (ctDNA) Estrogen Receptor 1 (ESR1) mutation status determination by central testing
- 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.
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- 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
- Eastern Cooperative Oncology Group Performance Status 0-1
- 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
Who cannot join
- 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.
- Progression on more than 2 prior lines of systemic endocrine therapy in the locally advanced unresectable or metastatic breast cancer setting
- Prior chemotherapy for locally advanced unresectable or metastatic disease
- 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
- Treatment with any investigational therapy within 28 days prior to initiation of study treatment
- Major surgery, chemotherapy, radiotherapy, or other anti-cancer therapy within 14 days prior to randomization
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- 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
- Advanced, symptomatic, visceral spread that is at risk of life-threatening complications in the short term
- Known active uncontrolled or symptomatic central nervous system (CNS) metastases, carcinomatous meningitis, or leptomeningeal disease
- Active cardiac disease or history of cardiac dysfunction
- 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
- Active inflammatory bowel disease, chronic diarrhea, short bowel syndrome, or major upper gastrointestinal (GI) surgery including gastric resection
- Interstitial lung disease or severe dyspnea at rest or requiring oxygen therapy
- Serious infection requiring oral or intravenous (IV) antibiotics, or other clinically significant infection, within 14 days prior to randomization
- 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
- Known allergy or hypersensitivity to any of the study drugs or any of their excipients
- For premenopausal or perimenopausal women and for men: known hypersensitivity to LHRH agonists
- Pregnant or breastfeeding
Trial locations and contacts
136 sites in 13 countries.
136 sites in 13 countries
United States55 sites
Alaska Oncology & Hematology, LLC
Anchorage, Alaska, 99508
Anne Arundel Medical Center
Annapolis, Maryland, 21401
University of Maryland Greenebaum Cancer Center
Baltimore, Maryland, 21201
Mercy Medical Center
Baltimore, Maryland, 21202
Memorial Sloan Kettering - Basking Ridge
Basking Ridge, New Jersey, 07920
Texas Oncology - Baylor Charles A. Sammons Cancer Center
Bedford, Texas, 76022
St Charles Medical Center Bend
Bend, Oregon, 97701
Alta Bates Summit Medical Center
Berkeley, California, 94704
Beverly Hills Cancer Center
Beverly Hills, California, 90211
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
Eastern Maine Medical Center
Brewer, Maine, 04412
TOI Clinical Research
Cerritos, California, 90703
Northwestern University
Chicago, Illinois, 60611
SCRI Mark H. Zangmeister Center
Columbus, Ohio, 43219
Texas Oncology - Baylor Charles A. Sammons Cancer Center
Dallas, Texas, 75246
Texas Oncology-Denton South
Denton, Texas, 76201
Texas Oncology, P.A. - El Paso
El Paso, Texas, 79902
Inova Fairfax Hospital
Fairfax, Virginia, 22031
Virginia Cancer Specialists
Fairfax, Virginia, 22031
San Juan Oncology Associates
Farmington, New Mexico, 87401
Women's Cancer Care
Fresno, California, 93710
West Cancer Center
Germantown, Tennessee, 38138
Houston Methodist Cancer Center
Houston, Texas, 77030
Millennium Research & Clinical Development
Houston, Texas, 77090
Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, 46202
Scripps Health
La Jolla, California, 92037
University of Arkansas for Medical Sciences
Little Rock, Arkansas, 72205-7199
Los Angeles Hematology Oncology Medical Group
Los Angeles, California, 90017
Northwest Georgia Oncology Centers PC - Marietta
Marietta, Georgia, 30060
Mount Sinai Medical Center
Miami Beach, Florida, 33140
Memorial Sloan Kettering - Monmouth
Middletown, New Jersey, 07748
Yale Cancer Center
New Haven, Connecticut, 06520
The Blavatnik Family ? Chelsea Medical Center at Mount Sinai
New York, New York, 10011
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065
Virginia Oncology Associates
Norfolk, Virginia, 23502
Oncology Hematology West, PC dba Nebraska Cancer Specialists
Omaha, Nebraska, 68103
University of California, Irvine Medical Center
Orange, California, 92868
Orlando Health Cancer Institute
Orlando, Florida, 32806
Abramson Cancer Center
Philadelphia, Pennsylvania, 19104
UPMC Hillman Cancer Center - Magee-Women?s Hospital
Pittsburgh, Pennsylvania, 15213
Renown Regional Medical Center
Reno, Nevada, 89502
Metro-Minnesota Community Oncology Research Consortium
Saint Louis Park, Minnesota, 55416
Texas Oncology P.A.
San Antonio, Texas, 78229
Summit Cancer Care PC
Savannah, Georgia, 31405
New England Cancer Specialists
Scarborough, Maine, 04074
Avera Cancer Institute
Sioux Falls, South Dakota, 57105
Springfield Clinic
Springfield, Illinois, 62702
Stony Brook University Medical Center
Stony Brook, New York, 11794
Northwest Medical Specialties, PLLC
Tacoma, Washington, 98405
Arizona Oncology Associates, PC-CASA
Tucson, Arizona, 85711
Oklahoma Cancer Specialists and Research Institute
Tulsa, Oklahoma, 74146
Abramson Cancer Center Chester County Hospital
West Chester, Pennsylvania, 19380
McGlinn Cancer Institute at Reading Hospital
West Reading, Pennsylvania, 19611
University of Kansas Cancer Center
Westwood, Kansas, 66205
Japan17 sites
Aichi Cancer Center
Aichi, 464-8681
Nagoya University Hospital
Aichi, 466-8560
Chiba Cancer Center
Chiba, 260-8717
National Cancer Center Hospital East
Chiba, 277-8577
Shikoku Cancer Center
Ehime, 791-0280
Hiroshima City Hiroshima Citizens Hospital
Hiroshima, 730-8518
Hiroshima University Hospital
Hiroshima, 734-8551
Hokkaido University Hospital
Hokkaido, 060-8648
Hyogo Cancer Center
Hyōgo, 673-0021
University of Tsukuba Hospital
Ibaraki, 305-8576
Kanagawa Cancer Center
Kanagawa, 241-8515
Tokai University Hospital
Kanagawa, 259-1193
Kumamoto University Hospital
Kumamoto, 860-8556
Niigata Cancer Center Hospital
Niigata, 951-8566
National Hospital Organization Osaka National Hospital
Osaka, 540-0006
Juntendo University Hospital
Tokyo, 113-8431
The Cancer Institute Hospital of JFCR
Tokyo, 135-8550
Argentina11 sites
Instituto de Oncología Ángel H. Roffo
Agronomía, Ciudad Autónoma de BuenosAires, C1417DTB
Centro de Investigaciones Médicas y Desarrollo LC S.R.L
Buenos Aires, Ciudad Autónoma de BuenosAires, C1113AAE
Consultorios Médicos Dr. Doreski
Ciudad Autonoma Buenos Aires, C1426ABP
Centro Medico Privado CEMAIC
Córdoba, Córdoba Province, X5008AAC
Fundacion Centro Oncologico de Integracion Regional (COIR)
Mendoza, M5500AYB
Instituto Medico de la Fundacion Estudios Clinicos
Rosario, S2000DEJ
Hospital Provincial del Centenario
Rosario, S2002KDS
Instituto de Oncologia de Rosario
Rosario, S2013KZE
Centro Polivalente de Asistencia e Investigacion Clinica - CER San Juan
San Juan, J5402DIL
Organizacion Medica de Investigacion
San Nicolás, C1015ABO
Centro de Investigación Clínica ? Clínica Viedma
Viedma, R8500ACE
Greece10 sites
University of Athens, Hematological Clinic,
Athens, 115 27
Attikon University General Hospital
Athens, 12464
Metropolitan General Hospital
Cholargós, 155 62
University General Hospital of Heraklion
Heraklio, 711 10
University General Hospital of Larissa
Larissa, 412 21
IASO Obstetrics Gynecology Clinic
Marousi, 151 23
Agios Loucas Clinic SA
Panórama, 552 36
Olympion Clinic
Pátrai, 264 43
Metaxa Cancer Hospital of Piraeus
Piraeus, 185 37
Interbalkan Medical Center of Thessaloniki
Thessaloniki, 546 39
Spain10 sites
Complejo Hospitalario Universitario A Coruña (CHUAC, Materno Infantil), Oncología
A Coruña, LA CORUNA, 15006
Hospital Dexeus
Barcelona, BARCELONA, 08028
Hospital Clinic de Barcelona
Barcelona, BARCELONA, 08036
C.H. Regional Reina Sofia - PPDS
Córdoba, CORDOBA, 14004
Hospital General Universitario Gregorio Marañon
Madrid, Madrid, 28007
Hospital Universitario Ramón y Cajal
Madrid, Madrid, 28034
Hospital Clinico San Carlos
Madrid, Madrid, 28040
Hospital Universitario 12 de Octubre
Madrid, Madrid, 28041
Hospital General Universitario J.M Morales Meseguer
Murcia, Murcia, 30008
Hospital Clinico Universitario de Valencia
Valencia, Valencia, 46010
South Korea7 sites
Chungbuk National University Hospital
Cheongju-si, 28644
Soon Chun Hyang University Cheonan Hospital
Dongnam-gu, Cheonan-si, 31151
National Cancer Center
Goyang-si, 10408
Seoul National University Bundang Hospital
Seongnam-si, 13620
Seoul National University Hospital
Seoul, 03080
Severance Hospital Yonsei University Health System - PPDS
Seoul, 03722
Korea University Guro Hospital
Seoul, 08308
Italy6 sites
IRCCS AOM Azienda Ospedaliera Metropolitana
Genoa, Liguria, 16132
Asst Grande Ospedale Metropolitano Niguarda
Milan, Lombardy, 20162
Azienda Ospedaliero - Universitaria di Modena Policlinico
Modena, Emilia-Romagna, 41110
Istituto Nazionale Tumori Regina Elena IRCCS
Rome, Lazio, 00144
Azienda Ospedaliero Universitaria Ospedali Riuniti
Torrette Di Ancona, The Marches, 60126
"Azienda Ospedaliera Universitaria Integrata Verona Ospedale Borgo Trento"
Verona, Veneto, 37124
Taiwan6 sites
Changhua Christian Hospital
Chang-hua, 500
Chang Gung Memorial Hospital
Kaohsiung Country, 833
National Cheng Kung University Hospital
Tainan, 70457
National Taiwan University Hospital
Taipei, 100229
Koo Foundation Sun Yat-Sen Cancer Center
Taipei, 112
Chang Gung Memorial Hospital - Linkou Branch
Taipei
Germany5 sites
Knappschaft Kliniken Marienhospital Bottrop
Bottrop, 46236
Universitatsklinikum Erlangen
Erlangen, 91054
Kliniken Essen-Mitte
Essen, 45136
Universitätsklinikum Heidelberg
Heidelberg, 69120
Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz
Mainz, 55101
United Kingdom4 sites
Dorset County Hospital
Dorchester, DT1 2JY
North Middlesex Uni Hospital
London, N18 1QX
The Christie NHS Foundation Trust - SSC Parent
Manchester, Manchester, M20 4BX
Nottingham City Hospital
Nottingham, NG5 1PB
Singapore2 sites
National University Hospital
Singapore, 117599
Oncocare Cancer Centre
Singapore, 258500
Turkey (Türkiye)2 sites
Memorial Ankara Hastanesi
Ankara, 06520
SAKARYA University Medical Faculty
Sakarya, 811
South Africa1 site
Medical Oncology Centre of Rosebank
Johannesburg, 2196
About this study
Official title: 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.
- Conditions
- Estrogen Receptor (ER)-Positive, HER2-negative, Locally Advanced or Metastatic Breast Cancer
- Being tested
- Giredestrant, Exemestane, Fulvestrant, Tamoxifen, Everolimus
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GiredestrantDrug
Also called GDC-9545, RO7197597, RG6171
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).
ExemestaneDrug
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.
FulvestrantDrug
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.
TamoxifenDrug
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.
EverolimusDrug
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 AgonistDrug
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 RinseDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Giredestrant plus Everolimus | Experimental | Not described Receives: Drug: Giredestrant; Drug: Everolimus; Drug: LHRH Agonist; Drug: Dexamethasone Mouth Rinse |
| Physician's Choice of Endocrine Therapy plus Everolimus | Active comparator | The physician's choice of endocrine therapy is defined as either exemestane, fulvestrant, or tamoxifen. Receives: Drug: Exemestane; Drug: Fulvestrant; Drug: Tamoxifen; Drug: Everolimus; Drug: LHRH Agonist; Drug: Dexamethasone Mouth Rinse |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: From randomization until the first occurrence of disease progression or death from any cause, whichever occurs first (up to 42 months)
Secondary outcomes (14)
Overall Survival, in the ESR1m Subpopulation and ITT Population
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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)
Measured: 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.
Measured: 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
Measured: 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
Measured: From Baseline until 30 days after the final dose of study treatment (up to 42 months)
Plasma Concentration of Giredestrant at Specified Timepoints
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Apr 2022
- Study start3 Aug 2022
- Primary completion16 Jul 2025
- Study completion15 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Estrogen Receptor (ER)-Positive, HER2-negative, Locally Advanced or Metastatic Breast CancerStudies of the same condition, open and under way.
- More trials run by Genentech, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 373 participants (actual)
Sponsor and investigators
- Lead sponsor
- Genentech, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Genentech, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05306340
- Sponsor's protocol ID
- ML43171
- Other IDs
- 2022-000199-20, 2023-506821-12-00, 2023
- Status last verified
- Oct 2026
- First submitted
- 23 Mar 2022
- Last updated
- 3 Nov 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data\_sharing
- Expanded access
- Available
Publications
Mayer EL, Tolaney SM, Martin M, Vidal GA, Moscetti L, Jhaveri KL, Brufsky A, Gradishar WJ, Schneeweiss A, Niikura N, Favret A, Alfie M, Lee KS, Khan S, Feldman MB, Day BM, Lam LH, Darbonne WC, Shah MD, Griffiths KL, DiLallo G, Perez-Moreno PD, Rugo HS; evERA Breast Cancer Investigators. Giredestrant plus Everolimus in Advanced Breast Cancer. N Engl J Med. 2026 Oct 1;395(13):1285-1298. doi: 10.1056/NEJMoa2602457.
PubMed 42814929
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT05306340
- Acronym / sponsor ID
- ML43171
- Conditions
- Estrogen Receptor (ER)-Positive, HER2-negative, Locally Advanced or Metastatic Breast Cancer
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 373 participants (actual)
- Lead sponsor
- Genentech, Inc.Industry (pharma, biotech, devices)
- Study start
- 3 Aug 2022 (actual)
- Primary completion
- 16 Jul 2025 (actual)
- Study completion
- 15 Jun 2027 (estimated)
- First posted
- 1 Apr 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Giredestrant plus Everolimus | Experimental | Drug: Giredestrant, Drug: Everolimus, Drug: LHRH Agonist, Drug: Dexamethasone Mouth Rinse |
| Physician's Choice of Endocrine Therapy plus Everolimus | Active comparator | Drug: Exemestane, Drug: Fulvestrant, Drug: Tamoxifen, Drug: Everolimus, Drug: LHRH Agonist, Drug: Dexamethasone Mouth RinseThe physician's choice of endocrine therapy is defined as either exemestane, fulvestrant, or tamoxifen. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Locally advanced unresectable or metastatic adenocarcinoma of the breast, not amenable to treatment with curative intent
- Documented estrogen receptor-positive (ER+) tumor and HER2-negative tumor, assessed locally
- Ability to provide a blood sample for circulating-tumor deoxyribonucleic acid (ctDNA) Estrogen Receptor 1 (ESR1) mutation status determination by central testing
- Prior endocrine therapy (ET) in combination with cyclin-dependent kinase 4/6 inhibitors in either setting as follows:
- 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
Key exclusion criteria (18 listed)
- 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.
- Progression on more than 2 prior lines of systemic endocrine therapy in the locally advanced unresectable or metastatic breast cancer setting
- Prior chemotherapy for locally advanced unresectable or metastatic disease
- 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
- Treatment with any investigational therapy within 28 days prior to initiation of study treatment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GiredestrantAlso: GDC-9545, RO7197597, RG6171Participants 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). | Drug | Giredestrant plus Everolimus |
| ExemestaneIf 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 | Physician's Choice of Endocrine Therapy plus Everolimus |
| FulvestrantIf 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 | Physician's Choice of Endocrine Therapy plus Everolimus |
| TamoxifenIf 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. | Drug | Physician's Choice of Endocrine Therapy plus Everolimus |
| EverolimusParticipants 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 | Giredestrant plus Everolimus, Physician's Choice of Endocrine Therapy plus Everolimus |
| LHRH AgonistOnly 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 | Giredestrant plus Everolimus, Physician's Choice of Endocrine Therapy plus Everolimus |
| Dexamethasone Mouth RinseA 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 plus Everolimus, Physician's Choice of Endocrine Therapy plus Everolimus |
Primary outcome
Progression-Free Survival, as Determined by the Investigator According to RECIST v1.1, in the ESR1m Subpopulation and ITT Population
Time frame: From randomization until the first occurrence of disease progression or death from any cause, whichever occurs first (up to 42 months)
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).
14 secondary outcomes
Overall Survival, in the ESR1m Subpopulation and ITT Population
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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 frame: 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 frame: 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 frame: 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 frame: 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 frame: 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)
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: From Baseline until 30 days after the final dose of study treatment (up to 42 months)
Plasma Concentration of Giredestrant at Specified Timepoints
Time frame: 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)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Nov 2026.
- Derived from this study: PubMed 42814929Mayer EL, Tolaney SM, Martin M, Vidal GA, Moscetti L, Jhaveri KL, Brufsky A, Gradishar WJ, Schneeweiss A, Niikura N, Favret A, Alfie M, Lee KS, Khan S, Feldman MB, Day BM, Lam LH, Darbonne WC, Shah MD, Griffiths KL, DiLallo G, Perez-Moreno PD, Rugo HS; evERA Breast Cancer Investigators. Giredestrant plus Everolimus in Advanced Breast Cancer. N Engl J Med. 2026 Oct 1;395(13):1285-1298. doi: 10.1056/NEJMoa2602457.
- Individual participant dataSharing planned: Yes. For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Genentech, Inc.
136 sites in 13 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Giredestrant, Exemestane and Fulvestrant in people with Estrogen Receptor (ER)-Positive, HER2-negative, Locally Advanced or Metastatic Breast Cancer, run by Genentech, Inc. at 136 sites in 13 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 3 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 136 sites in United States, Japan, Argentina, Greece, Spain and 8 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-Free Survival, as Determined by the Investigator According to RECIST v1.1, in the ESR1m Subpopulation and ITT Population (time frame: From randomization until the first occurrence of disease progression or death from any cause, whichever occurs first (up to 42 months)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05306340, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Nov 2026.