A Clinical Study to Evaluate the Tolerability and Pharmacokinetics of TQB3617 Capsule in Patients With Advanced Malignant Tumors

Study Overview
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Brief Summary
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TQB3617 is a bromodomain and extra-terminal (BET) inhibitor that can competitively bind to bromodomains (BRDs) with Acetylated lysine(Kac) and block or partially block the role of KAc in subsequent gene transcription and regulation of chromatin structure, thereby playing an anti-tumor role.

Official Title
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Phase I Clinical Study to Evaluate the Tolerability and Pharmacokinetics of TQB3617 Capsule in Patients With Advanced Malignant Tumors

Conditions
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Advanced Malignant Tumors

Intervention / Treatment
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* Drug: TQB3617


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged: ≥18 years old. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. Life expectancy ≥ 3 months. Patients with advanced malignancy tumor who have failed standard treatment or are unable to receive standard treatment or have no effective treatment. Female and male subjects should agree to use an adequate method of contraception starting with signing informed consent form (ICF) through 180 days after the last dose of study. The women of reproductive age who blood/urine results were positivetherapy before the first study drug is administered within less than 7 days. Exclusion Criteria: Patients has had or is currently having other malignant tumors within 3 years. Patients have multiple factors that affect their oral medication (such as inability to swallow, chronic diarrhea, and intestinal obstruction). The patient had unmitigated toxic reactions due to any prior treatment. Patients underwent major surgical treatment, open biopsy, or significant traumatic injury within 4 weeks prior to the start of study treatment. Patients have long - term unhealed wounds or fractures. Patients were taking Cytochrome P450 3A4, Cytochrome P450 3A5, Cytochrome P450 2A6, Cytochrome P450 2D6 (CYP3A4, CYP3A5, CYP2A6,CYP2D6) inhibitors or inducers before oral medication. Patients who, in the investigator's judgment, have a comorbidity that seriously endangers patient safety or interferes with study completion, or who are considered unsuitable for inclusion for other reasons.

Ages Eligible for Study
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Minimum Age: 18 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: TQB3617<br>0.1mg, once daily, was used as the initial dose, and the medication stage was divided into single administration and continuous administration stages. The single administration was given once, and the continuous administration stage was entered 7 days after drug withdrawal. The drug was administered continuously until the disease progressed. | Drug: TQB3617<br>* TQB3617 is a BET inhibitor.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose (MTD) | The highest dose of a drug or treatment that does not cause unacceptable side effects. | Baseline up to 48 weeks | 
| Adverse events (AEs) and serious adverse events (SAEs) | The occurrence of all AEs and SAEs | Baseline up to 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to reach maximum (peak) plasma concentration following drug administration（Tmax） | To characterize the pharmacokinetics of TQB3617 by assessment of time to reach maximum plasma concentration after single and multiple dosing | Pre-dose, 30 minutes, 1, 2, 3, 4, 6, 8,12, 24, 48, 72, 96, 120,168 hours after oral administration of a single drug delivery; 30 minutes, 1, 2, 3, 4, 6, 8,12, 24 hours of day 28; 30 minutes before oral administration on day 8, day 15, day 22, day 28. | 
| Maximum (peak) plasma drug concentration （Cmax） | Cmax is the maximum plasma concentration of TQB3617 or metabolite(s). | Pre-dose, 30 minutes, 1, 2, 3, 4, 6, 8,12, 24, 48, 72, 96, 120,168 hours after oral administration of a single drug delivery; 30 minutes, 1, 2, 3, 4, 6, 8,12, 24 hours of day 28; 30 minutes before oral administration on day 8, day 15, day 22, day 28. | 
| Elimination half-life (to be used in one-or non- compartmental model) （t1/2） | t1/2 is time it takes for the blood concentration of TQB3617 or metabolite(s) to drop by half. | Pre-dose, 30 minutes, 1, 2, 3, 4, 6, 8,12, 24, 48, 72, 96, 120,168 hours, after oral administration of a single drug delivery. | 
| Maximum (peak) steady-state plasma drug concentration during a dosage interval （Cmax,ss） | Maximum (peak) steady-state plasma drug concentration during a dosage interval | Pre-dose, 30 minutes, 1, 2, 3, 4, 6, 8,12, 24, 48, 72, 96, 120,168 hours after oral administration of a single drug delivery; 30 minutes, 1, 2, 3, 4, 6, 8,12, 24 hours of day 28; 30 minutes before oral administration on day 8, day 15, day 22, day 28. | 
| Minimum steady-state plasma drug concentration during a dosage interval （Css-min） | Minimum steady-state plasma drug concentration during a dosage interval | Pre-dose, 30 minutes, 1, 2, 3, 4, 6, 8,12, 24, 48, 72, 96, 120,168 hours after oral administration of a single drug delivery; 30 minutes, 1, 2, 3, 4, 6, 8,12, 24 hours of day 28; 30 minutes before oral administration on day 8, day 15, day 22, day 28. | 
| Concentration at the end of the dosing interval AUCtau,ss | To characterize the pharmacokinetics of TQB3617 by assessment of area the concentration at the end of the administration interval | Pre-dose, 30 minutes, 1, 2, 3, 4, 6, 8,12, 24, 48, 72, 96, 120,168 hours after oral administration of a single drug delivery; 30 minutes, 1, 2, 3, 4, 6, 8,12, 24 hours of day 28; 30 minutes before oral administration on day 8, day 15, day 22, day 28. | 
| Overall response rate (ORR) | Percentage of participants achieving complete response (CR) and partial response (PR). | up to 96 weeks | 
| Progress Free Survival（PFS） | From the start of randomization to the first tumor progression or time of death. | up to 96 weeks | 
| Disease control rate（DCR） | Percentage of participants achieving complete response (CR) and partial response (PR) and stable disease (SD). | up to 96 weeks | 
| Duration of Response (DOR) | The time when the participants first achieved complete or partial remission to disease progression. | up to 96 weeks | 
| Overall Survival（OS） | From date of first administration of test drug until the date of death from any cause， | assessed up to 100 months |