A Clinical Trial of TQB3015 Tablets in Patients With Advanced Malignant Cancer

Study Overview
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Brief Summary
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This study is divided into two stages: dose escalation and dose extension, including a single dose and a multiple dose clinical study. This is a single-center, open, non randomized, single arm study to the safety and tolerability of TQB3015 tables in patients with advanced malignant cancer.

Official Title
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A Phase I Study to Evaluate the Safety and Tolerance of TQB3015 Tablets With Advanced Malignant Cancer.

Conditions
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Advanced Malignant Neoplasm

Intervention / Treatment
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* Drug: TQB3015 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; an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; Advanced malignant tumors confirmed by tissue or cellular pathology and the routine standard treatment was ineffective or lack of effective treatment plans, or patients cannot tolerate the standard treatment; Has at least one assessable lesion according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 criteria; The main organs function well; Female patient had no plans to become pregnant and voluntarily took effective contraceptive measures during the study period and until at least 6 months after the last dose of study drug. Exclusion Criteria: Concomitant disease and medical history: There were other malignant tumors occured within 3 years before the first dose of study drug. Has multiple factors affecting oral medication; Unalleviated toxicity ≥ grade 1 according to CTCAE v5.0 due to any previous therapy, excluding hair loss; Major surgical treatment, open biopsy and obvious traumatic injury were performed within 28 days before the study, or have not fully recovered from previous surgery, or are expected to require major surgical surgery during the study period; Arteriovenous thrombotic events occurred within 6 months before the first dose, such as cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep venous thrombosis and pulmonary embolism; Have a history of psychotropic drug abuse and can not quit or have mental disorders; Subjects with any severe and/or uncontrolled disease including active hepatitis, immunodeficiency; Tumor-related symptoms and treatment: Has known symptomatic central nervous system metastases and/or cancerous meningitis; Have received surgery, chemotherapy, radiation therapy (2 weeks for brain radiation therapy) or other anti-cancer therapies within 4 weeks prior to the first dose. Thoracic/abdominal/pericardial effusion with clinical symptoms or requiring repeated drainage, or drainage for the purpose of receiving treatment within one month after receiving the investigational drug for the first time. 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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All

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: TQB3015 tablets<br>TQB3015 tables is administered as a single dose or multiple dose, 2-40mg once a day; Oral administration on fast condition, 21 days as a cycle. | Drug: TQB3015 tablets<br>* TQB3015 is a protein inhibitor<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 Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 toxicity, 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 (Day 21). | 
| 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 (Day 21). | 
| Recommended Phase II Dose (RP2D) | DLT describes side effects of a drug or other treatment that are serious enough to evaluate RP2D of TQB3015 tablets in adult patients with Advanced Malignant Cancer. | Baseline up to 24 months | 
| Incidence of abnormal clinical laboratory | Incidence of participants with clinical laboratory abnormalities | 30 days after the last administration. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events (AE) | The occurrence of all adverse events (AE). | 30 days after the last administration. | 
| Serious adverse events (SAE) | The occurrence of all serious adverse events (SAE). | 30 days after the last administration. | 
| Time to reach maximum (peak) plasma concentration (Tmax) | To characterize the pharmacokinetics of TQB3015 by assessment of time to reach maximum plasma concentration after single and multiple dosing. | Pre-dose, at 0.5, 1, 2, 3,4, 6, 8, 11, 24, 48, 72 hours after single administration dose. Pre-dose on Cycle 1 Day 7,Cycle 1 Day 14, Cycle 1 Day21; 0.5, 1, 2, 3, 4, 6, 8, 11, 24 hours after-dose on Cycle 1 Day 21. Each cycle is 21 days. | 
| Peak concentration (Cmax) | The maximum observed plasma concentration of study drug. | Pre-dose, at 0.5, 1, 2, 3,4, 6, 8, 11, 24, 48, 72 hours after single administration dose. Pre-dose on Cycle 1 Day 7,Cycle 1 Day 14, Cycle 1 Day21; 0.5, 1, 2, 3, 4, 6, 8, 11, 24 hours after-dose on Cycle 1 Day 21. Each cycle is 21 days. | 
| Half-life (t1/2) | The time required for half of the drug to be eliminated from the plasma. | Pre-dose, at 0.5, 1, 2, 3,4, 6, 8, 11, 24, 48, 72 hours after single administration dose. Pre-dose on Cycle 1 Day 7,Cycle 1 Day 14, Cycle 1 Day21; 0.5, 1, 2, 3, 4, 6, 8, 11, 24 hours after-dose on Cycle 1 Day 21. Each cycle is 21 days. | 
| Area under the concentration-time curve from zero to infinity (AUC0-∞) | To characterize the pharmacokinetics of TQB3015 by assessment of area under the plasma concentration time curve from 0 extrapolated to infinity. | Pre-dose, at 0.5, 1, 2, 3,4, 6, 8, 11, 24, 48, 72 hours after single administration dose. Pre-dose on Cycle 1 Day 7,Cycle 1 Day 14, Cycle 1 Day21; 0.5, 1, 2, 3, 4, 6, 8, 11, 24 hours after-dose on Cycle 1 Day 21. Each cycle is 21 days. | 
| Area under the concentration-time curve from zero to last observation (AUC [0-t]) | To characterize the pharmacokinetics of TQB3015 by assessment of area under the plasma concentration time curve from the first dose to a certain time point. | Pre-dose, at 0.5, 1, 2, 3,4, 6, 8, 11, 24, 48, 72 hours after single administration dose. Pre-dose on Cycle 1 Day 7,Cycle 1 Day 14, Cycle 1 Day21; 0.5, 1, 2, 3, 4, 6, 8, 11, 24 hours after-dose on Cycle 1 Day 21. Each cycle is 21 days. | 
| Apparent clearance (CL/F) | Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the body. | Pre-dose, at 0.5, 1, 2, 3,4, 6, 8, 11, 24, 48, 72 hours after single administration dose. Pre-dose on Cycle 1 Day 7,Cycle 1 Day 14, Cycle 1 Day21; 0.5, 1, 2, 3, 4, 6, 8, 11, 24 hours after-dose on Cycle 1 Day 21. Each cycle is 21 days. | 
| Apparent volume of distribution (Vd/F) | Apparent volume of distribution of the TQB3015 in plasma. | Pre-dose, at 0.5, 1, 2, 3,4, 6, 8, 11, 24, 48, 72 hours after single administration dose. Pre-dose on Cycle 1 Day 7,Cycle 1 Day 14, Cycle 1 Day21; 0.5, 1, 2, 3, 4, 6, 8, 11, 24 hours after-dose on Cycle 1 Day 21. Each cycle is 21 days. | 
| Objective response rate (ORR) | The percentage of patients with complete response (CR) and/or partial response (PR) assessed by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 | 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. |