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Clinical Trials in the USA / NCT05306340
Active, not recruiting Phase 3

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)

NCT05306340 · tracked via the Priya Life Science USA tracker
Sponsor
Genentech, Inc.
Phase
Phase 3
Started
2022-08-03
Last updated
2026-06-17

Condition(s) studied

Estrogen Receptor (ER)-Positive, HER2-negative, Locally Advanced or Metastatic Breast Cancer

Investigational drug(s) / intervention(s)

GiredestrantExemestaneFulvestrantTamoxifenEverolimusLHRH AgonistDexamethasone Mouth Rinse

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.

Study 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 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.

Eligibility

Sex
ALL
Min age
18 Years
Max age
Healthy volunteers
No
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 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

Primary outcome measure(s)

Trial sites (136)

FacilityCityRegionStatus
Alaska Oncology & Hematology, LLC Anchorage Alaska
Arizona Oncology Associates, PC-CASA Tucson Arizona
University of Arkansas for Medical Sciences Little Rock Arkansas
Alta Bates Summit Medical Center Berkeley California
Beverly Hills Cancer Center Beverly Hills California
TOI Clinical Research Cerritos California
Women's Cancer Care Fresno California
Scripps Health La Jolla California
Los Angeles Hematology Oncology Medical Group Los Angeles California
University of California, Irvine Medical Center Orange California
Yale Cancer Center New Haven Connecticut
Mount Sinai Medical Center Miami Beach Florida
Orlando Health Cancer Institute Orlando Florida
Northwest Georgia Oncology Centers PC - Marietta Marietta Georgia
Summit Cancer Care PC Savannah Georgia
Northwestern University Chicago Illinois
Springfield Clinic Springfield Illinois
Indiana University Melvin and Bren Simon Cancer Center Indianapolis Indiana
University of Kansas Cancer Center Westwood Kansas
Eastern Maine Medical Center Brewer Maine
New England Cancer Specialists Scarborough Maine
Anne Arundel Medical Center Annapolis Maryland
University of Maryland Greenebaum Cancer Center Baltimore Maryland
Mercy Medical Center Baltimore Maryland
Dana Farber Cancer Institute Boston Massachusetts
Metro-Minnesota Community Oncology Research Consortium Saint Louis Park Minnesota
Oncology Hematology West, PC dba Nebraska Cancer Specialists Omaha Nebraska
Renown Regional Medical Center Reno Nevada
Memorial Sloan Kettering - Basking Ridge Basking Ridge New Jersey
Memorial Sloan Kettering - Monmouth Middletown New Jersey
San Juan Oncology Associates Farmington New Mexico
The Blavatnik Family ? Chelsea Medical Center at Mount Sinai New York New York
Icahn School of Medicine at Mount Sinai New York New York
Memorial Sloan-Kettering Cancer Center New York New York
Stony Brook University Medical Center Stony Brook New York
SCRI Mark H. Zangmeister Center Columbus Ohio
Oklahoma Cancer Specialists and Research Institute Tulsa Oklahoma
St Charles Medical Center Bend Bend Oregon
Abramson Cancer Center Philadelphia Pennsylvania
UPMC Hillman Cancer Center - Magee-Women?s Hospital Pittsburgh Pennsylvania

+ 96 more sites — see the full list on the official registry below.

More Genentech, Inc. trials in the USA

Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT05306340 on ClinicalTrials.gov ↗ ← All trials in the USA