GB491 Combined With Fulvestrant for HR+ HER2- Locally Advanced or Metastatic Breast Cancer
A Randomized, Double-blind, Placebo-controlled, Phase III Clinical Trial of GB491 Combined With Fulvestrant in Subjects With HR+, HER2- Locally Advanced or Metastatic Breast Cancer Who Have Progressed on Prior Endocrine Therapy
1 other identifier
interventional
275
1 country
54
Brief Summary
GB491-004 is a multicenter, randomized, double-blind, placebo-controlled Phase III study to evaluate the efficacy and safety of GB491 in combination with fulvestrant in patients with HR-positive, HER2-negative locally advanced or metastatic breast cancer who have progressed on prior endocrine therapy.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Sep 2021
Typical duration for phase_3
54 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 13, 2021
CompletedStudy Start
First participant enrolled
September 10, 2021
CompletedFirst Posted
Study publicly available on registry
September 23, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 2, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
March 30, 2024
CompletedOctober 10, 2024
August 1, 2021
1.2 years
August 13, 2021
October 7, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
PFS assessed by the investigator
To assess the PFS assessed by the investigator
Approximately 1.5 years
Secondary Outcomes (8)
PFS assessed by the blinded independent central review (BICR)
Approximately 1.5 years
OS
Approximately 3 years
ORR
Approximately 1.5 years
DOR
Approximately 1.5 years
DCR
Approximately 1.5 years
- +3 more secondary outcomes
Study Arms (2)
GB491+ Fulvestrant
EXPERIMENTALPlacebo+Fulvestrant
PLACEBO COMPARATORInterventions
GB491: The dose of GB491 is 150 mg, BID, which should be taken with a meal. The drug is administered according to the patient's dose group until the progression of disease or an intolerable toxicity occur or meet the criteria for termination of treatment or the patient withdraw informed consent or the sponsor discontinues the trial. Fulvestrant: Intramuscular injection of flurvexine 500mg on day 1 and day 15 of the first cycle, and flurvexine 500mg on day 1 of the second and subsequent cycles. Flurvexine 500mg should be given slowly (1-2 minutes per injection) on both sides of the buttocks, once 250 mg on each side. The drug is administered according to the patient's dose group until the progression of disease or an intolerable toxicity occur or meet the criteria for termination of treatment or the patient withdraw informed consent or the sponsor discontinues the trial.
Placebo: The dose of Placebo is 150 mg, BID, which should be taken with a meal. The placebo is administered according to the patient's dose group until the progression of disease occur or meet the criteria for termination of treatment or the patient withdraw informed consent or the sponsor discontinues the trial. Fulvestrant: Intramuscular injection of flurvexine 500mg on day 1 and day 15 of the first cycle, and flurvexine 500mg on day 1 of the second and subsequent cycles. Flurvexine 500mg should be given slowly (1-2 minutes per injection) on both sides of the buttocks, once 250 mg on each side. The drug is administered according to the patient's dose group until the progression of disease or an intolerable toxicity occur or meet the criteria for termination of treatment or the patient withdraw informed consent or the sponsor discontinues the trial.
Eligibility Criteria
You may qualify if:
- Females or males of 18 years of age or older and less than 75 years of age at study screening
- Histologically or cytologically confirmed locally advanced or metastatic breast cancer that is not amenable to curative surgical resection or radiation therapy
- Patients have been diagnosed with ER-positive breast cancer in the local laboratory
- Patents have been diagnosed with HER2-negative breast cancer in the local laboratory
- Menopausal status is not limited (including Premenopausal/perimenopausal/postmenopausal state)
- Prior endocrine therapy and chemotherapy, the following are permitted:
- \) Prior endocrine adjuvant therapy: a) Radiologic evidence of progressive disease (PD) during or within 12 months following (neo)adjuvant therapy with an aromatase inhibitor (AI) or an anti-estrogen such as tamoxifen, and no subsequent endocrine therapy for locally advanced or metastatic breast cancer; b) Radiologic evidence of PD during or within 12 months following (neo)adjuvant therapy with an AI or an anti-estrogen such as tamoxifen, after receiving the first-line endocrine therapy for locally advanced or metastatic breast cancer, and who developed radiologically documented PD after receiving therapy for ≥ 6 months; c) Radiologically documented PD more than 12 months following the end of adjuvant therapy with AIs or anti-estrogens such as tamoxifen, followed by radiographic progression following first-line therapy with AIs or anti-estrogens for locally advanced or metastatic breast cancer; 2) Progression with radiographic evidence of disease following prior first-line endocrine therapy for locally advanced or metastatic breast cancer in subjects who have not received prior (neo) adjuvant therapy; 3) Prior chemotherapy: In addition to endocrine therapy, subjects are eligible if they received a maximum of 1 prior line of chemotherapy for locally advanced or metastatic breast cancer and discontinued treatment for at least 28 days prior to randomization; 7.According to RECIST V1.1, the patient has at least one measurable lesion that has not been irradiated by radiotherapy and can be evaluated by CT/MRI; If there is no measurable lesion, there must be at least one osteolytic bone lesion that can be evaluated by CT/MRI 8.ECOG performance status of 0 or 1 9.Adequate organ and marrow function.
You may not qualify if:
- Previous treatment with fulvestrant, everolimus or any other CDK4/6 inhibitors
- Patients with known hypersensitivity to any component of GB491 or Fulvestrant
- Known active, uncontrolled, or symptomatic central nervous system metastasis, carcinomatous meningitis, or clinically manifested leptomeningeal disease, cerebral edema, spinal compression or/and tumor progressive growth
- Visceral crisis
- Patients with skin lesion only and radiographically non-measurable at baseline
- Persistent toxicities (CTCAE Grade \>2) caused by previous anticancer therapy, excluding alopecia
- Patients who have been on bisphosphonates and denosumab therapy at a stable dose for less than 7 days prior to randomization
- Patients who have received limited field radiotherapy in 2 weeks or extended field radiotherapy in 4 weeks before randomization or radiation with more than 30% of the bone marrow
- Patients use drugs or fruits containing strong inducers or inhibitors of CYP3A4/5, or drugs with narrow therapeutic window that are mainly metabolized by CYP3A4/5 in 14 days before randomization
- Patients with long-term systematic use of corticosteroids
- Any severe and/or uncontrollable medical conditions
- Patients with severely impaired lung function
- Known history of HIV infection or history of HIV seropositivity
- Patients have significant hepatic disease
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (54)
The First Affiliated Hospital of Bengbu Medical College
Bengbu, Anhui, 233099, China
Anhui Provincial Cancer Hospital
Hefei, Anhui, 230031, China
The Second Hospital of Anhui Medical University
Hefei, Anhui, 230601, China
Beijing Chaoyang Hospital of Capital Medical University
Beijing, Beijing Municipality, 100020, China
Cancer hospital Chinese Academy of Medical Sciences
Beijing, Beijing Municipality, 100021, China
Chinese PLA General Hospital
Beijing, Beijing Municipality, 100039, China
Beijing Tiantan Hospital , Capital Medical University
Beijing, Beijing Municipality, 100050, China
Chongqing University Cancer Hospital
Chongqing, Chongqing Municipality, 400030, China
The First Affiliated Hospital of Chongqing Medical University
Chongqing, Chongqing Municipality, 400042, China
Chognqing University Three Gorges Hospital
Chongqing, Chongqing Municipality, 404000, China
Fujian Medical University Union Hospital
Fuzhou, Fujian, 350001, China
First Affiliated Hospital of Xiamen University
Xiamen, Fujian, 361003, China
The First people's hospital of Foshan
Foshan, Guangdong, 528000, China
Sun Yat-sen University Cancer Center
Guangzhou, Guangdong, 510060, China
The First Affiliated Hospital, Sun Yat-sen University
Guangzhou, Guangdong, 510080, China
Guangdong provincial TCM hospital
Guangzhou, Guangdong, 510120, China
Meizhou People's Hospital
Meizhou, Guangdong, 514031, China
Cancer Hospital Chinese Academy of Medical Sciences,Shenzhen Center Shenzhen Cancer Hospital
Shenzhen, Guangdong, 518172, China
Hainan General Hospital
Haikou, Hainan, 570311, China
Hainan Third People's Hospital
Sanya, Hainan, 572000, China
The Fourth Hospital of Hebei Medical University
Shijiazhuang, Hebei, 50011, China
Affiliated hospital of Hebei University
Shijiazhuang, Hebei, 500311, China
Harbin Medcial Univercity cancer hospital
Haerbin, Heilongjiang, 150081, China
Henan Cancer Hospital
Zhengzhou, Henan, 450003, China
The First Affiliated Hospital of Zhengzhou University
Zhengzhou, Henan, 450052, China
Tongji Medical College of Huazhong University of Science and Technology
Wuhan, Hubei, 430022, China
Renmin Hospital of Wuhan University
Wuhan, Hubei, 430060, China
Hubei Cancer Hospital
Wuhan, Hubei, 430079, China
The Affiliated hospital of Inner Mongolia Medical University
Hohhot, Inner Mongolia, 750306, China
Jiangsu Province Hospital
Nanjing, Jiangsu, 210029, China
Jiangxi Provincial Hospital
Nanchang, Jiangxi, 330029, China
Jilin Cancer Hospital
Changchun, Jilin, 130012, China
The Second Hospital of Jilin University
Changchun, Jilin, 130041, China
Bethune First Hospital Of Jilin University
Changchun, Jillin, 130061, China
Shengjing Hospital of China Medical University
Shenyang, Liaoning, 110022, China
Liaoning Cancer hospital & Institute
Shenyang, Liaoning, 110801, China
General Hospital of Ningxia Medical University
Yinchuan, Ningxia, 750003, China
Central Hospital Affiliated to Shandong First Medical University
Jinan, Shandong, 250013, China
Shandong Provincial Qianfoshan Hospital
Jinan, Shandong, 250013, China
Shandong Provincial Hospital
Jinan, Shandong, 250021, China
Shandong Cancer Hospital
Jinan, Shandong, 250117, China
Affiliated hospital of Jining Medical University
Jining, Shandong, 272007, China
Liaocheng People's Hospital
Liaocheng, Shandong, 252004, China
The Affiliated Hospital of Qingdao University
Qingdao, Shandong, 266003, China
Taian City Central Hospital
Taian, Shandong, 271099, China
Yantai Yuhuangding Hospital
Yantai, Shandong, 264099, China
Zhongshan Hospital Fudan University
Shanghai, Shanghai Municipality, 200030, China
The first hospital of Shanxi Medical University
Taiyuan, Shanxi, 003001, China
West China School of Medicine
Chengdu, Sichuan, 610044, China
Tianjin Medical University Cancer Institute & Hospital
Tianjin, Tianjin Municipality, 300181, China
Affiliated Cancer Hospital of Xinjiang Medical University
Ürümqi, Xinjiang, 830011, China
The Third Affiliated Hospital of Kunming Medical University
Kunming, Yunnan, 650118, China
The Second Affiliated Hospital, Zhejiang University School of Medicine
Hangzhou, Zhejiang, 310003, China
Zhejiang Cancer Hospital
Hangzhou, Zhejiang, 310005, China
Related Publications (1)
Xu B, Zhang Q, Luo Y, Tong Z, Sun T, Shan C, Liu X, Yao Y, Zhao B, Wang S, Zeng X, Hu C, Yan X, Wang X, Jia H, Chen Z, Qiu F, Wu X, Zhang D, Li T. Lerociclib plus fulvestrant in patients with HR+/HER2- locally advanced or metastatic breast cancer who have progressed on prior endocrine therapy: LEONARDA-1 a phase III randomized trial. Nat Commun. 2025 Jan 16;16(1):716. doi: 10.1038/s41467-025-56096-2.
PMID: 39820749DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Binghe Xu, PhD
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 13, 2021
First Posted
September 23, 2021
Study Start
September 10, 2021
Primary Completion
December 2, 2022
Study Completion
March 30, 2024
Last Updated
October 10, 2024
Record last verified: 2021-08
Data Sharing
- IPD Sharing
- Will not share