Advanced Breast Cancer
Conditions
Brief summary
TQB3909 is an inhibitor targeting B-cell lymphoma (BCL)-2 protein. By binding to BCL-2 protein, TQB3909 releases Pro apoptotic proteins such as BCL-2-Anatagonist/Killer 1(BAK), BCL-2 associated X (BAX) protein and BCL-2 associated death (BAD) protein, promotes the release of cytochrome c from mitochondria, phosphatidylserine eversion, stimulates caspase 3/7 activity and caspase 3/9 cleavage, and induces apoptosis.
Interventions
DRUGTQB3909 tablets
TQB3909 is an inhibitor targeting BCL-2 protein
Sponsors
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Evidence of a personally signed and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the study. * Age: 18 to 75 years old; female patient, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. * Histopathologically confirmed HR positive and HER2 negative advanced or metastatic breast cancer. * Patients who have been treated with endocrine therapy and have experienced disease progression. * Patients previously treated with any CDK4/6 inhibitor and not treated with BCL-2 inhibitor. * Has at least one measurable lesion according to Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 criteria * The main organs function well; * Female patient had no plans to become pregnant and voluntarily took effective contraceptive measures from agree with the study to at least 6 months after the last dose of study drug.
Exclusion criteria
* 1\. Concomitant disease and medical history: 1. There were other malignant tumors in 3 years before the first medication. 2. Has multiple factors affecting oral medication; 3. Unalleviated toxicity ≥ grade 1 due to any previous therapy; 4. Major surgical treatment, open biopsy and obvious traumatic injury were performed within 28 days before the study; e．Arteriovenous thrombotic events occurred within 6 months before the first medication, such as cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep venous thrombosis and pulmonary embolism; f．Have a history of psychotropic drug abuse and can not quit or have mental disorders; g．Subjects with any severe and / or uncontrolled disease included: Cirrhosis, active hepatitis, history of immunodeficiency; * Tumor-related symptoms and treatment: 1. Has central nervous system metastases (CNS) and/or cancerous meningitis or leptomeningeal carcinomatosis; 2. have received radiotherapy, other antineoplastic therapy within 2 weeks prior to the first dose; 3. Has uncontrollable pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures. * Known hypersensitivity to TQB3909, LHRH agonists (e.g., goserelin), or any excipients. * Subjects who have received the vaccine within 28 days prior to the first dose, or are planning to receive the vaccine during the study period. * Has Participated in other clinical trials within 4 weeks before first dose. * According to the judgement of the investigators, there are other factors that may lead to the termination of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose Limiting Toxicity (DLT) | At the end of Cycle 1 (Cycle 1, Day 28) | DLT will be defined as toxicities that meet pre-defined severity criteria(according to the NCI CTCAE v5.0 toxicity assessment criteria), and assessed as having a suspected relationship to study drug that occurred from the first dose to the end of the first treatment cycle. |
| Maximum tolerated dose (MTD) | At the end of Cycle 1 (Cycle 1, Day 28) | MTD was defined as the highest dose at which dose-limiting toxicity (DLT) occurred in less than 33% of patients. |
| Recommended Phase II Dose (RP2D) | Baseline up to 24 months | DLT describes side effects of a drug or other treatment that are serious enough to evaluate RP2D of TQB3909 tablets in adult patients with Breast cancers |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Terminal half-life (T1/2) | before administration at Day 1, Cycle1 Day7,Cycle1 Day14, Cycle1 Day28; 1, 2, 4, 6, 8, 10,24,48, and 72 hours after-dose at Day 1; 1, 2, 4, 6, 8, 10, and 24 hours after-dose at Cycle 1 Day 28. | Pharmacokinetics parameters to evaluate the half life of TQB3909 (T1/2) |
| Area under the plasma concentration-time curve from time zero to time t (AUC0-t) | before administration at Day 1, Cycle1 Day7,Cycle1 Day14, Cycle1 Day28; 1, 2, 4, 6, 8, 10,24,48, and 72 hours after-dose at Day 1; 1, 2, 4, 6, 8, 10, and 24 hours after-dose at Cycle 1 Day 28. | To characterize the pharmacokinetics of TQB3909 by assessment of area under the plasma concentration time curve from the first dose to a certain time point. |
| Maximum (peak) steady-state plasma drug concentration during a dosage interval (Cmax,ss) | before administration at Day 1, Cycle1 Day7,Cycle1 Day14, Cycle1 Day28; 1, 2, 4, 6, 8, 10,24,48, and 72 hours after-dose at Day 1; 1, 2, 4, 6, 8, 10, and 24 hours after-dose at Cycle 1 Day 28. | Cmax,ss is the steady state maximum concentration of TQB3909. |
| Clinilca Benefit Rate (CBR) | From date of the first dose until the date of first documented progression or date of death from any cause, assessed up to 100 weeks. | Percentage of participants achieving complete response (CR) and partial response (PR) and stable disease (SD). |
| Objective Response Rate (ORR) | From date of the first dose until the date of first documented progression or date of death from any cause, assessed up to 100 weeks. | Defined as the percentage of Complete Response (CR) plus partial response (PR) assessed by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 criteria |
| Minimum steady-state plasma drug concentration during a dosage interval (Cmin,ss) | before administration at Day 1, Cycle1 Day7,Cycle1 Day14, Cycle1 Day28; 1, 2, 4, 6, 8, 10,24,48, and 72 hours after-dose at Day 1; 1, 2, 4, 6, 8, 10, and 24 hours after-dose at Cycle 1 Day 28. | Cmin,ss is the minimum plasma concentration of TQB3909. |
| Time to reach maximum (peak)plasma concentration (Tmax) | before administration at Day 1, Cycle1 Day7,Cycle1 Day14, Cycle1 Day28; 1, 2, 4, 6, 8, 10,24,48, and 72 hours after-dose at Day 1; 1, 2, 4, 6, 8, 10, and 24 hours after-dose at Cycle 1 Day 28. | To characterize the pharmacokinetics of TQB3909 by assessment of time to reach maximum plasma concentration after single and multiple dosing. |
| Peak concentration (Cmax) | before administration at Day 1, Cycle1 Day7,Cycle1 Day14, Cycle1 Day28; 1, 2, 4, 6, 8, 10,24,48, and 72 hours after-dose at Day 1; 1, 2, 4, 6, 8, 10, and 24 hours after-dose at Cycle 1 Day 28. | Maximum observed concentration (Cmax) of TQB3909 |
Countries
China
Outcome results
None listed