A Clinical Study of TQB3824 in Subjects With Advanced Cancer

Study Overview
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Brief Summary
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TQB3824 blocks function of a specific protein called Cell Division Cycle 7 (CDC7) kinase in the human body, which plays important roles in the maintenance of DNA replication forks and DNA damage response pathways. This study will evaluate the safety, tolerability and pharmacokinetics of TQB3824.

Official Title
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A Phase I Study to Evaluate the Safety and Pharmacokinetics of TQB3824 in Subjects With Advanced Cancer

Conditions
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Advanced Cancer

Intervention / Treatment
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* Drug: TQB3824 tablets


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Understood and signed an informed consent form; Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1; Life expectancy >=3 months; Progressed after standard treatment or no standard treatment with an established survival benefit is available; Adequate organ/system function; Female patients of childbearing age should agree to use contraceptive measures during the study period and for at least 6 months after study is stopped; male patients should agree to use contraception during the study period and for at least 6 months after study is stopped. Exclusion Criteria: Diagnosed and/or treated additional malignancy within 3 years before the first dose; With factors affecting oral medication; Toxicity that is >=Grade 2 caused by previous cancer therapy; Received major surgical treatment, open biopsy or obvious traumatic injury within 28 days before the first dose; Arterial thromboembolism and/or venous thromboembolism within 6 months; A history of psychotropic drug abuse or have a mental disorder; Any severe and/or uncontrolled disease; Has received surgery, chemotherapy, radiotherapy or other anticancer therapies 4 weeks before the first dose; Has received Chinese patent medicines with anti-tumor indications that National Medical Products Administration (NMPA) approved within 2 weeks before the first dose; Has received CDC7 inhibitors; Pleural effusion, pericardial effusion or ascites that cannot be controlled and need repeated drainage; Brain metastases ; Has participated in other clinical studies 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: 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: TQB3824 tablets<br>TQB3824 tablets orally administrated orally on Days 1-21 of each 21-day treatment cycle. Dose escalation of TQB3824 will be based on evaluation of clinical safety and tolerability and guided by accumulating PK data | Drug: TQB3824 tablets<br>* TQB3824 is a CDC7 inhibitor, which plays important roles in the maintenance of DNA replication forks and DNA damage response pathways.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limiting toxicity (DLT) | DLT describes side effects of a drug or other treatment that are serious enough to prevent an increase in dose or level of that treatment. | up to 18 months | 
| Maximum Tolerated Dose (MTD) | The maximum Dose at which less than 33% subjects experiencing DLT | up to 18 months | 
| Recommended Phase II Dose (RP2D) | RP2D will be based on evaluation of clinical safety and tolerability and guided by accumulating PK data | up to 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration-time curve (AUC) | Concentration Uncer Curve | up to 18 months | 
| Maximum (peak) plasma drug concentration (Cmax) | Maximum plasma concentration of drug | up to 18 months | 
| Time to reach maximum(peak )plasma concentration following drug administration (Tmax) | Time to Reach the Maximum Plasma Concentration | up to 18 months | 
| Overall response rate (ORR) | The sum of percentage of participants with complete response rate and partial response rate | Baseline up to 12 months | 
| Disease Control Rate (DCR ) | percentage of participants with complete response (CR), partial response (PR) plus stable disease (SD) | Baseline up to 12 months | 
| Duration of Response (DOR) | the time from the date of first documentation of a CR or PR to the date of first documentation of tumor progression | Baseline up to 12 months | 
| Progression-free survival (PFS) | Time from the first dose to the first documentation of PD or death from any cause, whichever occurs first | Baseline up to 12 months | 
| Overall survival (OS) | the time from start of study treatment to date of death due to any cause | Baseline up to 12 months |