Advanced Breast Cancer
Conditions
Brief summary
GB491-005 is a multicenter, open-label, phase Ib Clinical Trial study to evaluate the safety, pharmacokinetic (PK), pharmacodynamic (PD) activity, and preliminary anti-tumor activity of GB491 in combination with Letrozole in Previously Untreated Patients with HR-positive, HER2-negative Advanced Breast Cancer
Interventions
DRUGGB491+Letrozole
Drug：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
Sponsors
Genor Biopharma Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Females 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. The subject has HER2-negative breast cancer in the local laboratory 5. Menopausal status is not limited (including Premenopausal/perimenopausal/postmenopausal state) 6. No previous systemic anti-tumor treatment for locally advanced or metastatic breast cancer; 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 only bone metastases are present, 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. 10. The subject of childbearing potential must use one highly effective birth control method from the total duration of the study and 6 months after the last dose of study intervention. 11. Provide informed consent
Exclusion criteria
1. Previous treatment with CDK4/6 inhibitors 2. Subjects with known hypersensitivity to any component of GB491 or Letrozole 3. Patients with disease progression or recurrence during or within 1 year after completion of previous endocrine neoadjuvant or adjuvant therapy 4. 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 5. Visceral crisis 6. Patients with skin lesion only and radiographically non-measurable at baseline 7. Persistent toxicities (CTCAE Grade ≥ 2) caused by previous anticancer therapy, excluding alopecia 8. Major surgical procedure within 4 weeks of the first dose of study treatment or an anticipated need for major surgery, chemotherapy, radiotherapy, any other investigational drug or other anti-cancer therapy during the study 9. Patients who have been on bisphosphonates and denosumab therapy at a stable dose for less than 14 days prior to randomization 10. 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 11. 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 12. Patients with long-term systematic use of corticosteroids 13. Any severe and/or uncontrollable medical conditions 14. Patients with severely impaired lung function 15. Known history of HIV infection or history of HIV seropositivity 16. Resting QTcF \> 480 msec or there is a medical history of QTcF prolongation 17. Subjects have significant hepatic disease 18. Coagulation abnormalities 19. Refractory nausea and vomiting, inability to swallow the formulated product, or other disease or clinical status would preclude adequate absorption, distribution, metabolism, or excretion of GB491 20. Previous allogeneic bone marrow transplant 21. Inflammatory breast cancer; 22. Subjects with a history of other primary malignancies, except for non-melanoma skin cancer and cervical cancer in situ disease-free status ≥ 3 years 23. Lactating women 24. Unlikely to comply with study procedures, restrictions, and requirements 25. Judgment by the investigator that the patient should not participate into the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| DLT | During Cycle 1 (up to 28 days) | Number of Participants with Dose-Limiting Toxicities for GB491 in Combination with Letrozole |
| AE | From Baseline until 30 days after the last treatment | Number of Participants with Adverse Events by Severity, According to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE v5.0) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| DOR | Approximately 2 years | To assess the duration of response for GB491 in Combination with Letrozole |
| DCR | Approximately 2 years | To assess the disease control rate for GB491 in Combination with Letrozole |
| PFS | Approximately 2 years | To assess the progression free survival assessed by investigator |
| Plasma Concentration of GB491 | At predefined intervals from Cycle 1, Day 1 & Day 15; Cycle 2, Day 1 (each cycle is 28 days) | Plasma Concentration of GB491 Over Time |
| Plasma Concentration of Letrozole | At predefined intervals from Cycle 1, Day 1 & Day 15; Cycle 2, Day 1 (each cycle is 28 days) | Plasma Concentration of Letrozole Over Time |
| CBR | Approximately 2 years | To assess the clinical benefit rate for GB491 in Combination with Letrozole by investigator |
| ORR | Approximately 2 years | To assess the objective response rate for GB491 in Combination with Letrozole |
Countries
China
Contacts
Primary ContactShawn Yu
Outcome results
None listed