A Clinical Trial of TQB3909 Tablets in Patients With Breast Cancer
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Phase 1/Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: TQB3909 tablets 200-1000mg of TQB3909 tablets once a day; Oral administration under fast condition, 28 days as a cycle. |
Drug: TQB3909 tablets
TQB3909 is an inhibitor targeting BCL-2 protein
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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
- 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.
- 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.
- 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
Eligibility Criteria
Criteria
Inclusion Criteria:
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Evidence of a personally signed and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the study.
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Age: 18 to 75 years old; female patient, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
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Histopathologically confirmed HR positive and HER2 negative advanced or metastatic breast cancer.
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Patients who have been treated with endocrine therapy and have experienced disease progression.
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Patients previously treated with any CDK4/6 inhibitor and not treated with BCL-2 inhibitor.
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Has at least one measurable lesion according to Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 criteria
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The main organs function well;
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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:
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- Concomitant disease and medical history:
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There were other malignant tumors in 3 years before the first medication.
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Has multiple factors affecting oral medication;
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Unalleviated toxicity ≥ grade 1 due to any previous therapy;
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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:
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Has central nervous system metastases (CNS) and/or cancerous meningitis or leptomeningeal carcinomatosis;
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have received radiotherapy, other antineoplastic therapy within 2 weeks prior to the first dose;
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Has uncontrollable pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures.
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Known hypersensitivity to TQB3909, LHRH agonists (e.g., goserelin), or any excipients.
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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.
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Has Participated in other clinical trials within 4 weeks before first dose.
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According to the judgement of the investigators, there are other factors that may lead to the termination of the study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Hunan Cancer Hospital | Changsha | Hunan | China | 410013 |
Sponsors and Collaborators
- Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- TQB3909-Ib/II-01