A Study to Evaluate the Tolerance and Pharmacokinetics of TQB3474 Injection

Study Overview
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Brief Summary
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This is a study to evaluate the tolerance, dose-limiting toxicity (DLT), phase II recommended dose (RP2D), and maximum tolerated dose (MTD) of single and multiple oral doses of TQB3474 in patients with advanced malignant tumors.

Official Title
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A Phase I, Open-label, Multicenter, Dose Escalation and Expansion Study to Evaluate the Tolerance and Pharmacokinetics of TQB3474 Injection

Conditions
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Advanced Solid Tumor

Intervention / Treatment
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* Drug: TQB3474 injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1.18 and 70 years old. 2. Histologically or cytologically confirmed advanced solid tumors. 3. Has the surgery more than 4 weeks before the first dose. 4. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1. 5. Life expectancy ≥12 weeks. 6. Adequate organ system function. 7. Male or female subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 6 months after the last dose of study. 8. Understood and signed an informed consent form. Exclusion Criteria: Has received chemotherapy or radiotherapy within 4 weeks before the first dose. Hypersensitivity to TQB3474 or its excipient. Has factors that impact on intravenous infusion of drugs and venous blood collection. Has severe gastrointestinal disease within 4 weeks before the first dose. Has severe eye disease. Breastfeeding or pregnant women. Has brain metastases. HCV antibody and HCV-RNA positive; Syphilis positive; HBsAg positive and HBV DNA positive (≥1000 copies /mL). Has infection that need systemic treatment during screening. Has participated in any other clinical trial within 4 weeks before the first dose. 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: 70 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: TQB3474 injection<br>Participants receive TQB3474 injection by intravenous (IV) infusion on Day 1, 8, 15, 22 of each 28 day cycle. | Drug: TQB3474 injection<br>* This is a kind of heat shock protein (HSP90) inhibitor.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limiting toxicity (DLT) | Subjects appear the following toxic reaction relate to the drug after treatment within 28 days ：III °or above of non-hematological toxicity, IV° hematological toxicity , III ° neutropenia associated with fever, III ° thrombocytopenia with bleeding. | Baseline up to 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | Cmax is the maximum plasma concentration of TQB3474 or metabolite(s). | 0hour, 0.5hour, end of infusion, 5minutes, 15minutes, 0.5hour, 1hour, 2hour, 4hour, 7hour, 12hour, 24hour, 48hour, 144hour after infusion of day 1 and day 22; Hour 0, end of infusion of day 8 and day 15, hour 0 of day 29. | 
| Tmax | To characterize the pharmacokinetics of TQB3474 by assessment of time to reach maximum plasma concentration. | 0hour, 0.5hour, end of infusion, 5minutes, 15minutes, 0.5hour, 1hour, 2hour, 4hour, 7hour, 12hour, 24hour, 48hour, 144hour after infusion of day 1 and day 22; Hour 0, end of infusion of day 8 and day 15, hour 0 of day 29. | 
| AUC0-t | To characterize the pharmacokinetics of TQB3474 by assessment of area under the plasma concentration time curve from zero to infinity. | 0hour, 0.5hour, end of infusion, 5minutes, 15minutes, 0.5hour, 1hour, 2hour, 4hour, 7hour, 12hour, 24hour, 48hour, 144hour after infusion of day 1 and day 22; Hour 0, end of infusion of day 8 and day 15, hour 0 of day 29. |