MedPath

GB491 Combined With Fulvestrant for HR+ HER2- Locally Advanced or Metastatic Breast Cancer

Phase 3
Completed
Conditions
Locally Advanced or Metastatic Breast Cancer
Interventions
Drug: Placebo+Fulvestrant
Registration Number
NCT05054751
Lead Sponsor
Genor Biopharma Co., Ltd.
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
275
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
GB491+ FulvestrantGB491+ Fulvestrant-
Placebo+FulvestrantPlacebo+Fulvestrant-
Primary Outcome Measures
NameTimeMethod
PFS assessed by the investigatorApproximately 1.5 years

To assess the PFS assessed by the investigator

Secondary Outcome Measures
NameTimeMethod
PFS assessed by the blinded independent central review (BICR)Approximately 1.5 years

To assess the PFS assessed by the BICR

OSApproximately 3 years

To assess the overall survival (OS)

ORRApproximately 1.5 years

To assess the objective response rate (ORR)

DORApproximately 1.5 years

To assess the duration of response

DCRApproximately 1.5 years

To assess the disease control rate

CBRApproximately 1.5 years

To assess the clinical benefit rate

Safety and tolerabilityApproximately 3 years

To assess the safety and tolerability assessed by incidence and severity of adverse events (AEs) and serious AEs (SAEs) according to NCI-CTCAE version 5.0

PKFrom Cycle 1 to Cycle 4, approximately 4 months

To assess the PK assessed by population pharmacokinetic analysis based on plasma concentrations of GB491

Trial Locations

Locations (54)

Sun Yat-sen University Cancer Center

🇨🇳

Guangzhou, Guangdong, China

The First Affiliated Hospital of Bengbu Medical College

🇨🇳

Bengbu, Anhui, China

Anhui Provincial Cancer Hospital

🇨🇳

Hefei, Anhui, China

The Second Hospital of Anhui Medical University

🇨🇳

Hefei, Anhui, China

Beijing Chaoyang Hospital of Capital Medical University

🇨🇳

Beijing, Beijing, China

Cancer hospital Chinese Academy of Medical Sciences

🇨🇳

Beijing, Beijing, China

Chinese PLA General Hospital

🇨🇳

Beijing, Beijing, China

Beijing Tiantan Hospital , Capital Medical University

🇨🇳

Beijing, Beijing, China

Chongqing University Cancer Hospital

🇨🇳

Chongqing, Chongqing, China

The First Affiliated Hospital of Chongqing Medical University

🇨🇳

Chongqing, Chongqing, China

Chognqing University Three Gorges Hospital

🇨🇳

Chongqing, Chongqing, China

Fujian Medical University Union Hospital

🇨🇳

Fuzhou, Fujian, China

First Affiliated Hospital of Xiamen University

🇨🇳

Xiamen, Fujian, China

The First people's hospital of Foshan

🇨🇳

Foshan, Guangdong, China

The First Affiliated Hospital, Sun Yat-sen University

🇨🇳

Guangzhou, Guangdong, China

Guangdong provincial TCM hospital

🇨🇳

Guangzhou, Guangdong, China

Meizhou People's Hospital

🇨🇳

Meizhou, Guangdong, China

Cancer Hospital Chinese Academy of Medical Sciences,Shenzhen Center Shenzhen Cancer Hospital

🇨🇳

Shenzhen, Guangdong, China

Hainan General Hospital

🇨🇳

Haikou, Hainan, China

Hainan Third People's Hospital

🇨🇳

Sanya, Hainan, China

The Fourth Hospital of Hebei Medical University

🇨🇳

Shijiazhuang, Hebei, China

Affiliated hospital of Hebei University

🇨🇳

Shijiazhuang, Hebei, China

Harbin Medcial Univercity cancer hospital

🇨🇳

Haerbin, Heilongjiang, China

Henan Cancer Hospital

🇨🇳

Zhengzhou, Henan, China

The First Affiliated Hospital of Zhengzhou University

🇨🇳

Zhengzhou, Henan, China

Tongji Medical College of Huazhong University of Science and Technology

🇨🇳

Wuhan, Hubei, China

Renmin Hospital of Wuhan University

🇨🇳

Wuhan, Hubei, China

Hubei Cancer Hospital

🇨🇳

Wuhan, Hubei, China

The Affiliated hospital of Inner Mongolia Medical University

🇨🇳

Hohhot, Inner Mongolia, China

Jiangsu Province Hospital

🇨🇳

Nanjing, Jiangsu, China

Jiangxi Provincial Hospital

🇨🇳

Nanchang, Jiangxi, China

Jilin Cancer Hospital

🇨🇳

Changchun, Jilin, China

The Second Hospital of Jilin University

🇨🇳

Changchun, Jilin, China

Bethune First Hospital Of Jilin University

🇨🇳

Changchun, Jillin, China

Shengjing Hospital of China Medical University

🇨🇳

Shenyang, Liaoning, China

Liaoning Cancer hospital & Institute

🇨🇳

Shenyang, Liaoning, China

General Hospital of Ningxia Medical University

🇨🇳

Yinchuan, Ningxia, China

Central Hospital Affiliated to Shandong First Medical University

🇨🇳

Jinan, Shandong, China

Shandong Provincial Qianfoshan Hospital

🇨🇳

Jinan, Shandong, China

Shandong Provincial Hospital

🇨🇳

Jinan, Shandong, China

Shandong Cancer Hospital

🇨🇳

Jinan, Shandong, China

Affiliated hospital of Jining Medical University

🇨🇳

Jining, Shandong, China

Liaocheng People's Hospital

🇨🇳

Liaocheng, Shandong, China

The Affiliated Hospital of Qingdao University

🇨🇳

Qingdao, Shandong, China

Taian City Central Hospital

🇨🇳

Taian, Shandong, China

Yantai Yuhuangding Hospital

🇨🇳

Yantai, Shandong, China

Zhongshan Hospital Fudan University

🇨🇳

Shanghai, Shanghai, China

The first hospital of Shanxi Medical University

🇨🇳

Taiyuan, Shanxi, China

West China School of Medicine

🇨🇳

Chengdu, Sichuan, China

Tianjin Medical University Cancer Institute & Hospital

🇨🇳

Tianjin, Tianjin, China

Affiliated Cancer Hospital of Xinjiang Medical University

🇨🇳

Urumqi, Xinjiang, China

The Third Affiliated Hospital of Kunming Medical University

🇨🇳

Kunming, Yunnan, China

The Second Affiliated Hospital, Zhejiang University School of Medicine

🇨🇳

Hangzhou, Zhejiang, China

Zhejiang Cancer Hospital

🇨🇳

Hangzhou, Zhejiang, China

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