A Clinical Trial of TQB3909 Tablets in Patients With Breast Cancer

Study Overview
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Brief Summary
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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.

Official Title
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A Phase Ib/II Study to Investigate the Safety, Tolerance and Pharmacokinetics of TQB3909 With HR-positive, HER2-negative Advanced Breast Cancer

Conditions
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Advanced Breast Cancer

Intervention / Treatment
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* Drug: TQB3909 tablets


Participation Criteria
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Eligibility Criteria
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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: There were other malignant tumors in 3 years before the first medication. Has multiple factors affecting oral medication; Unalleviated toxicity ≥ grade 1 due to any previous therapy; 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: Has central nervous system metastases (CNS) and/or cancerous meningitis or leptomeningeal carcinomatosis; have received radiotherapy, other antineoplastic therapy within 2 weeks prior to the first dose; 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TQB3909 tablets<br>200-1000mg of TQB3909 tablets once a day; Oral administration under fast condition, 28 days as a cycle. | Drug: TQB3909 tablets<br>* TQB3909 is an inhibitor targeting BCL-2 protein<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose Limiting Toxicity (DLT) | 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. | At the end of Cycle 1 (Cycle 1, Day 28) | 
| Maximum tolerated dose (MTD) | MTD was defined as the highest dose at which dose-limiting toxicity (DLT) occurred in less than 33% of patients. | At the end of Cycle 1 (Cycle 1, Day 28) | 
| Recommended Phase II Dose (RP2D) | 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 | Baseline up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to reach maximum (peak)plasma concentration (Tmax) | To characterize the pharmacokinetics of TQB3909 by assessment of time to reach maximum plasma concentration after single and multiple dosing. | 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. | 
| Peak concentration (Cmax) | Maximum observed concentration (Cmax) of TQB3909 | 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. | 
| Terminal half-life (T1/2) | Pharmacokinetics parameters to evaluate the half life of TQB3909 (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. | 
| Area under the plasma concentration-time curve from time zero to time t (AUC0-t) | 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. | 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 (peak) steady-state plasma drug concentration during a dosage interval (Cmax,ss) | Cmax,ss is the steady state maximum concentration of TQB3909. | 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. | 
| Minimum steady-state plasma drug concentration during a dosage interval (Cmin,ss) | Cmin,ss is the minimum plasma concentration of TQB3909. | 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. | 
| Clinilca Benefit Rate (CBR) | Percentage of participants achieving complete response (CR) and partial response (PR) and stable disease (SD). | 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. | 
| Objective Response Rate (ORR) | Defined as the percentage of Complete Response (CR) plus partial response (PR) assessed by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 criteria | 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. |