Locally Advanced or Metastatic Breast Cancer
Conditions
Keywords
CDK4/6, Phase III, GB491
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.
Interventions
DRUGGB491+ Fulvestrant
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.
DRUGPlacebo+Fulvestrant
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.
Sponsors
Genor Biopharma Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PFS assessed by the investigator | Approximately 1.5 years | To assess the PFS assessed by the investigator |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| OS | Approximately 3 years | To assess the overall survival (OS) |
| ORR | Approximately 1.5 years | To assess the objective response rate (ORR) |
| DOR | Approximately 1.5 years | To assess the duration of response |
| PFS assessed by the blinded independent central review (BICR) | Approximately 1.5 years | To assess the PFS assessed by the BICR |
| CBR | Approximately 1.5 years | To assess the clinical benefit rate |
| Safety and tolerability | Approximately 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 |
| PK | From Cycle 1 to Cycle 4, approximately 4 months | To assess the PK assessed by population pharmacokinetic analysis based on plasma concentrations of GB491 |
| DCR | Approximately 1.5 years | To assess the disease control rate |
Countries
China
Outcome results
None listed