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The trial was divided into two phases: dose escalation and dose expansion. The dosing regimens were single-dose study and continuous dosing study. A single-center, open, non-randomized, single-arm clinical trial design was adopted. Subjects with advanced malignant tumors were selected to take TQB3019 capsules orally to evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy of TQB3019 capsules.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| TQB3019 capsules | Experimental | Single or continuous administration, 50-600 mg each time TQB3019 capsule is taken orally once a day on an empty stomach, and each cycle is 28 days. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| TQB3019 capsules | Drug | TQB3019 capsule is a targeted protein degrader |
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| Measure | Description | Time Frame |
|---|---|---|
| Dose Limiting Toxicity (DLT) | DLT will be defined as toxicities that meet pre-defined severity criteria(according to the NCI Common Terminology Criteria for Adverse Events(CTCAE) version5.0 toxicity assessment criteria), and assessed as having a suspected relationship to study drug that occurred from first medication to the end of the first treatment cycle. | At the end of Cycle 1 (Each cycle is 28 days) |
| 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 (Each cycle is 28 days) |
| Recommended Phase II Dose (RP2D) | DLT describes side effects of a drug or other treatment that are serious enough to evaluate RP2D of TQB3019 capsules in adult patients with Advanced Malignant Cancer. | Baseline up to 24 months |
| Maximum assessed dose (MAD) | Recommendations made by the investigator and sponsor based on clinical safety, efficacy, pharmacokinetic, and pharmacodynamic data will be considered the highest dose level to complete dose exploration in the absence of an MTD | Baseline up to 24 months |
| Adverse events (AEs) | The occurrence of all adverse events (AEs) | From the time the subject receives TQB3019 to 28 days after the last dose or until the start of other anti-tumor treatment (whichever occurs first, up to approximately 3 years) |
| Serious adverse events (SAEs) | The occurrence of all serious adverse events (SAEs) . |
| Measure | Description | Time Frame |
|---|---|---|
| Tmax | Time to Reach the Maximum Plasma Concentration. | Single Day1/First dose: pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48 hours post dose Cycle 1 Day 8, 15, 28: pre-dose; 0.5, 1, 2, 4, 6, 8, 12, 24 hours at days 28 post dose, each cycle is 28 days |
| Cmax |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Zengjun Li, Doctor | Contact | +86-13642138692 | zengjunli@163.com | |
| Yvping Sun, Doctor | Contact | +86-13370582181 | 13370582181@163.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cancer Institute & Hospital.Chinese Academy of Medical Sciences | Not yet recruiting | Beijing | Beijing Municipality | 100021 | China |
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| From the time the subject receives TQB3019 to 28 days after the last dose or until the start of other anti-tumor treatment (whichever occurs first, up to approximately 3 years) |
| Abnormal incidence of laboratory test indicators | Incidence and severity of abnormal laboratory values | From the time the subject receives TQB3019 to 28 days after the last dose or until the start of other anti-tumor treatment (whichever occurs first, up to approximately 3 years) |
| Overall response rate (ORR) | The proportion of subjects with best response of Complete Response (CR), Partial Response (PR), Partial Response with Lymphocytosis (PR-L), Very Good Partial Response (VGPR), and Minimal Response (MR). | From date of the first dose until the date of first documented progression or date of death from any cause, up to approximately 3 years |
Cmax is the maximum plasma concentration of TQB3019. |
| Single Day1/First dose: pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48 hours post dose Cycle1 Day 8, 15, 28: pre-dose; 0.5, 1, 2, 4, 6, 8, 12, 24 hours at days 28 post dose, each cycle is 28 days |
| Elimination half-life (t1/2) | To evaluate the Elimination half-life (t1/2) after oral dose of TQB3019 capsules to subjects. | Single Day1/First dose: pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48 hours post dose Cycle1 Day 8, 15, 28: pre-dose; 0.5, 1, 2, 4, 6, 8, 12, 24 hours at days 28 post dose, each cycle is 28 days |
| Area under the plasma concentration-time curve from time zero to time t (AUC0-t) | To characterize the pharmacokinetics of TQB3019 by assessment of area under the plasma concentration time curve from the first dose to a certain time. | Single Day1/First dose: pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48 hours post dose Cycle1 Day 8, 15, 28: pre-dose; 0.5, 1, 2, 4, 6, 8, 12, 24 hours at days 28 post dose, each cycle is 28 days |
| Apparent clearance (CL/F) | Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the body.. | Single Day1/First dose: pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48 hours post dose Cycle1 Day 8, 15, 28: pre-dose; 0.5, 1, 2, 4, 6, 8, 12, 24 hours at days 28 post dose, each cycle is 28 days |
| Apparent volume of distribution (Vd/F) | Apparent volume of distribution of the TQB3019 in plasma. | Single Day1/First dose: pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48 hours post dose Cycle1 Day 8, 15, 28: pre-dose; 0.5, 1, 2, 4, 6, 8, 12, 24 hours at days 28 post dose, each cycle is 28 days |
| Minimum concentration (Cmin) | Minimum observed concentration (Cmin) of TQB3019 | Single Day1/First dose: pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48 hours post dose Cycle1 Day 8, 15, 28: pre-dose; 0.5, 1, 2, 4, 6, 8, 12, 24 hours at days 28 post dose, each cycle is 28 days |
| Bruton's tyrosine kinase (BTK) protein levels | BTK protein levels in peripheral blood mononuclear cells (PMBCs) | Single Day1/First dose: pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48 hours post dose Cycle1 Day 8, 15, 28: pre-dose; 0.5, 1, 2, 4, 6, 8, 12, 24 hours at days 28 post dose, each cycle is 28 days |
| Complete Remission Rate (CRR) | The proportion of tumors that have a complete response after treatment. | Single Day1/First dose: pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48 hours post dose Cycle1 Day 8, 15, 28: pre-dose; 0.5, 1, 2, 4, 6, 8, 12, 24 hours at days 28 post dose, each cycle is 28 days |
| Disease Control Rate (DCR) | The percentage of patients with advanced or metastatic cancer who have achieved complete response, partial response and stable disease to a cancer treatment in clinical trials. | Single Day1/First dose: pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48 hours post dose Cycle1 Day 8, 15, 28: pre-dose; 0.5, 1, 2, 4, 6, 8, 12, 24 hours at days 28 post dose, each cycle is 28 days |
| Duration of Response (DOR) | The time from the date of first documentation of a CR or PR or PD to the date of first documentation of tumor progression. | From date of the first dose until the date of first documented progression or date of death from any cause, assessed up to 100weeks |
| Progression Free Survival (PFS) | The time from the first dose to the first documentation of progressive disease (PD) or death from any cause, whichever occurs first | Single Day1/First dose: pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48 hours post dose Cycle1 Day 8, 15, 28: pre-dose; 0.5, 1, 2, 4, 6, 8, 12, 24 hours at days 28 post dose, each cycle is 28 days |
| Overall Survival (OS) | the time from start of study treatment to date of death due to any cause | Single Day1/First dose: pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48 hours post dose Cycle1 Day 8, 15, 28: pre-dose; 0.5, 1, 2, 4, 6, 8, 12, 24 hours at days 28 post dose, each cycle is 28 days |
| Nanfang Hospital of Southern Medical University | Not yet recruiting | Guangzhou | Guangdong | 510515 | China |
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| The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital | Recruiting | Zhengzhou | Henan | 450000 | China |
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| Jiangsu Province Hospital | Not yet recruiting | Nanjing | Jiangsu | 210029 | China |
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| The First Affiliated Hospital of Nanchang University | Not yet recruiting | Nanchang | Jiangxi | 330006 | China |
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| The First Affiliated Hospital of Xi'an Jiaotong University | Not yet recruiting | Xi'an | Shaanxi | 710061 | China |
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| Heze Municipal Hospital | Not yet recruiting | Heze | Shandong | 27400 | China |
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| The Cancer Hospital Affiliated to Shandong First Medical University | Not yet recruiting | Jinan | Shandong | 250117 | China |
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| The Affiliated Hospital of Qingdao University | Not yet recruiting | Qingdao | Shandong | 266075 | China |
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| Tongji Hospital of Tongji University | Not yet recruiting | Shanghai | Shanghai Municipality | 200065 | China |
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| The Affiliated Hospital of Southwest Medical University | Not yet recruiting | Luzhou | Sichuan | 646099 | China |
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| Mianyang Central Hospital | Not yet recruiting | Mianyang | Sichuan | 621000 | China |
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| Affiliated Hospital of North sichuan Medical college | Not yet recruiting | Nanchong | Sichuan | 637000 | China |
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| TianJin Medical University Cancer Institute&Hospital | Not yet recruiting | Tianjin | Tianjin Municipality | 300000 | China |
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| Institute of Hematology &Blood Diseases Hospital,Chinese Academy of Medical Sciences &Peking Union Medical College | Not yet recruiting | Tianjin | Tianjin Municipality | 301617 | China |
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