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

Overview

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.

Full Title of Study: “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

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: October 31, 2023

Interventions

  • Drug: GB491+ Fulvestrant
    • GB491: The dose of GB491 is 150 mg, which should be taken with a meal and taken twice daily at approximately the same time each day, approximately 12 hours apart. 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.
  • Drug: Placebo+Fulvestrant
    • Placebo: The dose of Placebo is 150 mg, which should be taken with a meal and taken twice daily at approximately the same time each day, approximately 12 hours apart. 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.

Arms, Groups and Cohorts

  • Experimental: GB491+ Fulvestrant
    • GB491: The dose of GB491 is 150 mg, which should be taken with a meal and taken twice daily at approximately the same time each day, approximately 12 hours apart. 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 Comparator: Placebo+Fulvestrant
    • Placebo: The dose of placebo is 150 mg, which should be taken with a meal and taken twice daily at approximately the same time each day, approximately 12 hours apart. 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.

Clinical Trial Outcome Measures

Primary Measures

  • PFS by BICR.
    • Time Frame: Approximately 1.5 years
    • To assess the progression free survial (PFS), which is assessed by BICR.

Secondary Measures

  • PFS by PI
    • Time Frame: Approximately 1.5 years
    • To assess the progression free survial (PFS), which is assessed by PI.
  • OS
    • Time Frame: Approximately 3 years
    • To assess the overall survival (OS)
  • ORR
    • Time Frame: Approximately 1.5 years
    • To assess the objective response rate (ORR)
  • DOR
    • Time Frame: Approximately 1.5 years
    • To assess the duration of response
  • DCR
    • Time Frame: Approximately 1.5 years
    • To assess the disease control rate
  • CBR
    • Time Frame: Approximately 1.5 years
    • To assess the clinical benefit rate by BICR
  • SAE
    • Time Frame: Approximately 3 years
    • To assess the incidence of SAE by Graded according to the National Cancer Institute (NCI CTCAE)
  • AE
    • Time Frame: Approximately 3 years
    • To assess the incidence of AE by Graded according to the National Cancer Institute (NCI CTCAE)
  • TEAE
    • Time Frame: Approximately 3 years
    • To assess the incidence of TEAE by Graded according to the National Cancer Institute (NCI CTCAE)
  • Cmax
    • Time Frame: On Day15 of Cycle 1 and Day 1 of Cycle 2-4 (each cycle is 28 days)
    • To evaluate the Cmax of GB491 and its metabolites G1T30
  • Tmax
    • Time Frame: On Day15 of Cycle 1 and Day 1 of Cycle 2-4 (each cycle is 28 days)
    • To evaluate the Tmax of GB491 and its metabolites G1T30
  • AUC
    • Time Frame: On Day15 of Cycle 1 and Day 1 of Cycle 2-4 (each cycle is 28 days)
    • To evaluate the AUC of GB491 and its metabolites G1T30

Participating in This Clinical Trial

Inclusion Criteria

1. Females or males of 18 years of age or older at study screening 2. Histologically or cytologically confirmed locally advanced or advanced metastatic breast cancer that is not amenable to curative surgical resection or radiation therapy 3. The subject has been diagnosed with ER-positive breast cancer in the local laboratory 4. Subject has HER2-negative breast cancer in the local laboratory 5. Menopausal status is not limited (including Premenopausal/perimenopausal/postmenopausal state) 6. 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 only bone metastases are present, there must be at least one osteolytic bone lesion that can be evaluated by CT/MRI 7. ECOG performance status of 0 or 1 8. Adequate organ and marrow function. Exclusion Criteria:

1. Previous treatment with fulvestrant, everolimus and any other CDK4/6 inhibitors 2. Subjects 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 14 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. Subjects 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. Subjects have significant hepatic disease 15. Coagulation abnormalities 16. Subjects with a history of other primary malignancies, except for non-melanoma skin cancer and cervical cancer in situ disease-free status ≥ 3 years 17. Lactating women

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Genor Biopharma Co., Ltd.
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Binghe Xu, PhD, Principal Investigator, Chinese Academy of Medical Sciences
  • Overall Contact(s)
    • Shawn YU, MD, 18600332657, shawn.yu@genorbio.com

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