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

Genor Biopharma Co., Ltd.54 sites in 1 country275 target enrollmentSeptember 10, 2021

ConditionsLocally Advanced or Metastatic Breast Cancer

InterventionsGB491+ Fulvestrant Placebo+Fulvestrant

DrugsPlacebo+Fulvestrant GB491+ Fulvestrant

Overview

Phase: Phase 3
Intervention: GB491+ Fulvestrant
Conditions: Locally Advanced or Metastatic Breast Cancer
Sponsor: Genor Biopharma Co., Ltd.
Enrollment: 275
Locations: 54
Primary Endpoint: PFS assessed by the investigator
Status: Completed
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials Related News

Overview

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.

Registry

clinicaltrials.gov

Start Date

September 10, 2021

End Date

March 30, 2024

Last Updated

last year

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Genor Biopharma Co., Ltd.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•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.

Exclusion Criteria

•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

Arms & Interventions

GB491+ Fulvestrant

Intervention: GB491+ Fulvestrant

Placebo+Fulvestrant

Intervention: Placebo+Fulvestrant

Outcomes

Primary Outcomes

PFS assessed by the investigator

Time Frame: Approximately 1.5 years

To assess the PFS assessed by the investigator

Secondary Outcomes

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)
CBR(Approximately 1.5 years)
Safety and tolerability(Approximately 3 years)
PK(From Cycle 1 to Cycle 4, approximately 4 months)