A Study to Evaluate the Tolerance, Efficacy and Pharmacokinetics of TQB3558 Tablets

Study Overview
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Brief Summary
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This is a study to evaluate the maximum tolerated dose (MTD) , occurrence of all adverse events (AE) and serious adverse events (SAE) , pharmacokinetic parameters and antitumor effect of TQB3558 tablets in Chinese adult patients with advanced solid tumors .The study is divided into phase Ia and phase Ib. Phase Ia: dose escalation period, to evaluate the safety and tolerability of TQB3558 tablets, determine MTD; Phase Ib: effectiveness exploration period, to expand the safe and effective dose group, recommend appropriate dosage and method for subsequent clinical research.

Official Title
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A Phase I, Open-label, Dose Escalation and Expansion Study to Evaluate the Tolerance, Efficacy and Pharmacokinetics of TQB3558 Tablets

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Drug: TQB3558


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Histologically or cytologically confirmed advanced malignant solid tumors, without conventional treatment methods or fail or relapse after treatment. 2. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1; Life expectancy ≥12 weeks. 3. Has at least one measurable lesion (based on RECIST 1.1) or bone metastases. 4. Adequate organ system function. 5. Patients need to adopt effective methods of contraception. 6. Understood and signed an informed consent form. Exclusion Criteria: 1. Has received TRK inhibitors. 2. Has participated in any other clinical trials, or used other anti-cancer drugs, or received major surgical operations within 4 weeks before first administration. 3. Has received local radiotherapy within 7 days or bone marrow radiotherapy within 4 weeks before the first administration. 4. Has other malignant tumors in 2 years, except for cured or locally curable cancers. 5. Has known spinal cord compression and cancerous meningitis. 6. Has interstitial lung disease, drug-induced interstitial lung disease, history of radiation lung disease requiring steroid therapy. 7. Uncontrollable pleural effusion, pericardial effusion or ascites requiring repeated drainage. 8. Obvious cardiovascular diseases. 9. Has a history of autoimmune disease, immunodeficiency. 10. Lactating women. 11. According to the judgement of the researchers, there are other factors that subjects are not suitable for 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: TQB3558 Tablets<br>TQB3558 tablets administered orally once. Then TQB3558 tablet administered orally, once daily in 28-day cycle after 4 days of first administration. | Drug: TQB3558<br>* TQB3558 is a kinase inhibitor of the TRK protein family.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose (MTD) | MTD was defined as the dose in which more than 2 of up to 6 patients developed a DLT. | Baseline up to 28 days | 
| Adverse events (AE) and serious adverse events (SAE) | The occurrence of all adverse events (AE) and serious adverse events (SAE). | Baseline up to 28 days | 
| Overall response rate (ORR) | Percentage of participants achieving complete response (CR) and partial response (PR). | up to 96 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tmax | To characterize the pharmacokinetics of TQB3558 by assessment of time to reach maximum plasma concentration. | 15minutes, 30minutes, 1hour, 2hour, 4hour, 6hour, 8hour,10hour, 24hour, 48hour post-dose on day 1 and day 11; 30minutes pre-dose on day 1, day 5, day 7,day 8 ,day 9 and day 11. | 
| Cmax | Cmax is the maximum plasma concentration of TQB3558 or metabolite(s). | 15minutes, 30minutes, 1hour, 2hour, 4hour, 6hour, 8hour,10hour, 24hour, 48hour post-dose on day 1 and day 11; 30minutes pre-dose on day 1, day 5, day 7,day 8 ,day 9 and day 11. | 
| AUC0-t | To characterize the pharmacokinetics of TQB3558 by assessment of area under the plasma concentration time curve from zero to infinity. | 15minutes, 30minutes, 1hour, 2hour, 4hour, 6hour, 8hour,10hour, 24hour, 48hour post-dose on day 1 and day 11; 30minutes pre-dose on day 1, day 5, day 7,day 8 ,day 9 and day 11. | 
| CL/f | CL/f is total clearance rate for TQB3558. | 15minutes, 30minutes, 1hour, 2hour, 4hour, 6hour, 8hour,10hour, 24hour, 48hour post-dose on day 1 and day 11; 30minutes pre-dose on day 1, day 5, day 7,day 8 ,day 9 and day 11. | 
| Disease control rate（DCR） | Percentage of participants achieving Complete Response (CR) and Partial Response (PR) and Stable Disease (SD). | up to 96 weeks | 
| Progression-free survival (PFS) | PFS defined as the time from first dose to the first documented progressive disease (PD) or death from any cause. | up to 96 weeks | 
| Duration of Response (DOR) | DOR defined as time from earliest date of disease response to earliest date of disease progression based on radiographic assessment. | up to 96 weeks |