This project is an open, dose escalation and expansion phase I clinical study. The first phase is a dose escalation study, and the second phase is a dose expansion study based on the Maximum tolerated dose (MTD) / Recommended Phase II Dose (RP2D) obtained in the first phase. The purpose is to evaluate the tolerability and preliminary efficacy of TQB3702 tablets in hematological tumor subjects.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
137
TQB3702 tablets are selective BTK inhibitors.
The First Affiliated Hospital of Nanchang University
Nanchang, Jiangxi, China
The Cancer Hospital Affiliated to Shandong First Medical University
Jinan, Shandong, China
Maximum tolerated dose (MTD)
To evaluate the maximum tolerated dose of TQB3702 tablets in the treatment of relapsed/refractory hematologic tumors.
Time frame: Baseline up to 104 weeks
Dose limited toxicity (DLT)
To evaluate the dose-limiting toxic dose of TQB3702 tablets in the treatment of relapsed/refractory hematologic tumors.
Time frame: Baseline up to 104 weeks
Recommended Phase II Dose (RP2D)
To evaluate the phase II recommended dose of TQB3702 tablets in the treatment of relapsed/refractory hematological tumors.
Time frame: Baseline up to 104 weeks
Time to Reach the Maximum Plasma Concentration (Tmax)-single dose
Time to Reach the Maximum Plasma Concentration after single dose
Time frame: before administration, 0.25, 0.5, 0.75, 1, 2, 4, 6, 12, 24, 48, 72hours after administration.
Time to Reach the Maximum Plasma Concentration (Tmax)-multiple dose
Time to Reach the Maximum Plasma Concentration after multiple dose
Time frame: before administration (-1~0h), 0.25, 0.5, 0.75, 1, 2, 4, 6, 12, 24 hours after administration at Day 8/15/28 of Cycle1, Day 28 of Cycle 6; when withdrawn from the group due to disease progression or at the end of study treatment.
Maximum plasma concentration (Cmax)-Single dose
Cmax is the maximum plasma concentration of TQB3702 after single dose
Time frame: before administration, 0.25, 0.5, 0.75, 1, 2, 4, 6, 12, 24, 48, 72hours after administration.
Maximum plasma concentration (Cmax)-Multiple dose
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Cmax is the maximum plasma concentration of TQB3702 after multiple dose
Time frame: before administration (-1~0h), 0.25, 0.5, 0.75, 1, 2, 4, 6, 12, 24 hours after administration at Day 8/15/28 of Cycle1, Day 28 of Cycle 6; when withdrawn from the group due to disease progression or at the end of study treatment.
Elimination half-life (t1/2)-Single dose
t1/2 is time it takes for the blood concentration of TQB3702 or metabolite(s) to drop by half after single dose.
Time frame: before administration, 0.25, 0.5, 0.75, 1, 2, 4, 6, 12, 24, 48, 72 hours after administration.
Elimination half-life (t1/2)-Multiple dose
t1/2 is time it takes for the blood concentration of TQB3702 or metabolite(s) to drop by half after multiple dose.
Time frame: before administration (-1~0h), 0.25, 0.5, 0.75, 1, 2, 4, 6, 12, 24 hours after administration at Day 8/15/28 of Cycle1, Day 28 of Cycle 6; when withdrawn from the group due to disease progression or at the end of study treatment.
Area under the plasma concentration-time curve from time zero to time t (AUC0-t)-Single dose
To characterize the pharmacokinetics of TQB3702 by assessment of area under the plasma concentration time curve from the first dose to a certain time.
Time frame: before administration, 0.25, 0.5, 0.75, 1, 2, 4, 6, 12, 24, 48, 72hours after administration.
Area under the plasma concentration-time curve from time zero to time t (AUC0-t)-Multiple dose
To characterize the pharmacokinetics of TQB3702 by assessment of area under the plasma concentration time curve from the first dose to a certain time.
Time frame: before administration (-1~0h), 0.25, 0.5, 0.75, 1, 2, 4, 6, 12, 24 hours after administration at Day 8/15/28 of Cycle1, Day 28 of Cycle 6; when withdrawn from the group due to disease progression or at the end of study treatment.
Maximum (peak) steady-state plasma drug concentration during a dosage interval (Cmax,ss)-Single dose
Maximum (peak) steady-state plasma drug concentration during a dosage interval (Cmax,ss) after Single dose
Time frame: before administration, 0.25, 0.5, 0.75, 1, 2, 4, 6, 12, 24, 48, 72hours after administration.
Maximum (peak) steady-state plasma drug concentration during a dosage interval (Cmax,ss)-Multiple dose
Maximum (peak) steady-state plasma drug concentration during a dosage interval (Cmax,ss) after Multiple dose
Time frame: before administration (-1~0h), 0.25, 0.5, 0.75, 1, 2, 4, 6, 12, 24 hours after administration at Day 8/15/28 of Cycle1, Day 28 of Cycle 6; when withdrawn from the group due to disease progression or at the end of study treatment.
steady state area under the concentration-time curve over a dosing interval (AUCtau, ss)-single dose
steady state area under the concentration-time curve over a dosing interval (AUCtau, ss) after single dose
Time frame: before administration, 0.25, 0.5, 0.75, 1, 2, 4, 6, 12, 24, 48, 72hours after administration.
steady state area under the concentration-time curve over a dosing interval (AUCtau, ss)-multiple dose
steady state area under the concentration-time curve over a dosing interval (AUCtau, ss) after multiple dose
Time frame: before administration (-1~0h), 0.25, 0.5, 0.75, 1, 2, 4, 6, 12, 24 hours after administration at Day 8/15/28 of Cycle1, Day 28 of Cycle 6; when withdrawn from the group due to disease progression or at the end of study treatment.
Minimum steady-state plasma drug concentration during a dosage interval (Css-min)-Single dose
Minimum steady-state plasma drug concentration during a dosage interval (Cmin-ss) after Single dose
Time frame: before administration, 0.25, 0.5, 0.75, 1, 2, 4, 6, 12, 24, 48, 72hours after administration.
Minimum steady-state plasma drug concentration during a dosage interval (Css-min)-multiple dose
Minimum steady-state plasma drug concentration during a dosage interval (Cmin-ss) after multiple dose
Time frame: before administration (-1~0h), 0.25, 0.5, 0.75, 1, 2, 4, 6, 12, 24 hours after administration at Day 8/15/28 of Cycle1, Day 28 of Cycle 6; when withdrawn from the group due to disease progression or at the end of study treatment.
Objective Response Rate (ORR)
The proportion of patients with tumor size reduction of a predefined amount and for a minimum time period
Time frame: Baseline up to 104 weeks
Complete Remission Rate (CRR)
The proportion of tumors that have a complete response after treatment
Time frame: Baseline up to 104 weeks
Disease Control Rate (DCR)
The percentage of patients with advanced or metastatic cancer who have achieved complete response, partial response and stable disease to a cancer treatment in clinical trials.
Time frame: Baseline up to 104 weeks
Duration of Response (DOR)
The time from the date of first documentation of a CR or PR or PD to the date of first documentation of tumor progression.
Time frame: Baseline up to 104 weeks
Progression Free Survival (PFS)
The time from the first dose to the first documentation of progressive disease (PD) or death from any cause, whichever occurs first
Time frame: Baseline up to 104 weeks
Overall Survival (OS)
the time from start of study treatment to date of death due to any cause
Time frame: Baseline up to 104 weeks
Adverse events (AE)
The occurrence of all adverse events (AE)
Time frame: Baseline up to 104 weeks
Serious adverse events (SAE)
The occurrence of all serious adverse events (SAE)
Time frame: Baseline up to 104 weeks
Bruton's tyrosine kinase (BTK) occupancy
The BTK occupancy in peripheral blood mononuclear cell (PMBC)
Time frame: Baseline up to 104 weeks