Clinical trial NCT05054751: GB491 Combined With Fulvestrant for HR+ HER2- Locally Advanced or Metastatic Breast Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Locally Advanced or Metastatic Breast Cancer
Keywords: CDK4/6
Phase III
GB491
Lead sponsor: Genor Biopharma Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2021-09-23
Enrollment: 275
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Key Inclusion Criteria:

1. Females or males of 18 years of age or older and less than 75 years of age at study screening
2. Histologically or cytologically confirmed locally advanced or metastatic breast cancer that is not amenable to curative surgical resection or radiation therapy
3. Patients have been diagnosed with ER-positive breast cancer in the local laboratory
4. Patents have been diagnosed with HER2-negative breast cancer in the local laboratory
5. Menopausal status is not limited (including Premenopausal/perimenopausal/postmenopausal state)
6. Prior endocrine therapy and chemotherapy, the following are permitted:

1) 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.

Key Exclusion Criteria:

1. Previous treatment with fulvestrant, everolimus or any other CDK4/6 inhibitors
2. Patients with known hypersensitivity to any component of GB491 or Fulvestrant
3. 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
4. Visceral crisis
5. Patients with skin lesion only and radiographically non-measurable at baseline
6. Persistent toxicities (CTCAE Grade \>2) caused by previous anticancer therapy, excluding alopecia
7. Patients who have been on bisphosphonates and denosumab therapy at a stable dose for less than 7 days prior to randomization
8. 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
9. 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
10. Patients with long-term systematic use of corticosteroids
11. Any severe and/or uncontrollable medical conditions
12. Patients with severely impaired lung function
13. Known history of HIV infection or history of HIV seropositivity
14. Patients have significant hepatic disease

Primary outcomes:
measure: PFS assessed by the investigator
timeFrame: Approximately 1.5 years
Secondary outcomes:
measure: PFS assessed by the blinded independent central review (BICR)
timeFrame: Approximately 1.5 years
measure: OS
timeFrame: Approximately 3 years
measure: ORR
timeFrame: Approximately 1.5 years
measure: DOR
timeFrame: Approximately 1.5 years
measure: DCR
timeFrame: Approximately 1.5 years
measure: CBR
timeFrame: Approximately 1.5 years
measure: Safety and tolerability
timeFrame: Approximately 3 years
measure: PK
timeFrame: From Cycle 1 to Cycle 4, approximately 4 months
Other outcomes:
Locations:
city: Bengbu
country: China
facility: The First Affiliated Hospital of Bengbu Medical College
state: Anhui
city: Hefei
country: China
facility: Anhui Provincial Cancer Hospital
state: Anhui
city: Hefei
country: China
facility: The Second Hospital of Anhui Medical University
state: Anhui
city: Beijing
country: China
facility: Beijing Chaoyang Hospital of Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Cancer hospital Chinese Academy of Medical Sciences
state: Beijing
city: Beijing
country: China
facility: Chinese PLA General Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Tiantan Hospital , Capital Medical University
state: Beijing
city: Chongqing
country: China
facility: Chongqing University Cancer Hospital
state: Chongqing
city: Chongqing
country: China
facility: The First Affiliated Hospital of Chongqing Medical University
state: Chongqing
city: Chongqing
country: China
facility: Chognqing University Three Gorges Hospital
state: Chongqing
city: Fuzhou
country: China
facility: Fujian Medical University Union Hospital
state: Fujian
city: Xiamen
country: China
facility: First Affiliated Hospital of Xiamen University
state: Fujian
city: Foshan
country: China
facility: The First people's hospital of Foshan
state: Guangdong
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital, Sun Yat-sen University
state: Guangdong
city: Guangzhou
country: China
facility: Guangdong provincial TCM hospital
state: Guangdong
city: Meizhou
country: China
facility: Meizhou People's Hospital
state: Guangdong
city: Shenzhen
country: China
facility: Cancer Hospital Chinese Academy of Medical Sciences,Shenzhen Center Shenzhen Cancer Hospital
state: Guangdong
city: Haikou
country: China
facility: Hainan General Hospital
state: Hainan
city: Sanya
country: China
facility: Hainan Third People's Hospital
state: Hainan
city: Shijiazhuang
country: China
facility: The Fourth Hospital of Hebei Medical University
state: Hebei
city: Shijiazhuang
country: China
facility: Affiliated hospital of Hebei University
state: Hebei
city: Haerbin
country: China
facility: Harbin Medcial Univercity cancer hospital
state: Heilongjiang
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Wuhan
country: China
facility: Tongji Medical College of Huazhong University of Science and Technology
state: Hubei
city: Wuhan
country: China
facility: Renmin Hospital of Wuhan University
state: Hubei
city: Wuhan
country: China
facility: Hubei Cancer Hospital
state: Hubei
city: Hohhot
country: China
facility: The Affiliated hospital of Inner Mongolia Medical University
state: Inner Mongolia
city: Nanjing
country: China
facility: Jiangsu Province Hospital
state: Jiangsu
city: Nanchang
country: China
facility: Jiangxi Provincial Hospital
state: Jiangxi
city: Changchun
country: China
facility: Jilin Cancer Hospital
state: Jilin
city: Changchun
country: China
facility: The Second Hospital of Jilin University
state: Jilin
city: Changchun
country: China
facility: Bethune First Hospital Of Jilin University
state: Jillin
city: Shenyang
country: China
facility: Shengjing Hospital of China Medical University
state: Liaoning
city: Shenyang
country: China
facility: Liaoning Cancer hospital & Institute
state: Liaoning
city: Yinchuan
country: China
facility: General Hospital of Ningxia Medical University
state: Ningxia
city: Jinan
country: China
facility: Central Hospital Affiliated to Shandong First Medical University
state: Shandong
city: Jinan
country: China
facility: Shandong Provincial Qianfoshan Hospital
state: Shandong
city: Jinan
country: China
facility: Shandong Provincial Hospital
state: Shandong
city: Jinan
country: China
facility: Shandong Cancer Hospital
state: Shandong
city: Jining
country: China
facility: Affiliated hospital of Jining Medical University
state: Shandong
city: Liaocheng
country: China
facility: Liaocheng People's Hospital
state: Shandong
city: Qingdao
country: China
facility: The Affiliated Hospital of Qingdao University
state: Shandong
city: Taian
country: China
facility: Taian City Central Hospital
state: Shandong
city: Yantai
country: China
facility: Yantai Yuhuangding Hospital
state: Shandong
city: Shanghai
country: China
facility: Zhongshan Hospital Fudan University
state: Shanghai
city: Taiyuan
country: China
facility: The first hospital of Shanxi Medical University
state: Shanxi
city: Chengdu
country: China
facility: West China School of Medicine
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute & Hospital
state: Tianjin
city: Urumqi
country: China
facility: Affiliated Cancer Hospital of Xinjiang Medical University
state: Xinjiang
city: Kunming
country: China
facility: The Third Affiliated Hospital of Kunming Medical University
state: Yunnan
city: Hangzhou
country: China
facility: The Second Affiliated Hospital, Zhejiang University School of Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
Study officials:
affiliation: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
name: Binghe Xu, PhD
role: PRINCIPAL_INVESTIGATOR
References: