This is the first-in-human clinical study of TQB3217, aiming to evaluate the safety, tolerability, and pharmacokinetic characteristics of TQB3217 in advanced solid tumors, and to preliminarily explore its efficacy in solid tumors.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
40
TQB3217 Tablets are ubiquitin specific peptidase 1(USP1)-t inhibitor.
National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Beijing, Beijing Municipality, China
Dose Limiting Toxicity (DLT)
DLT refers to occurrence of drug-related adverse events within the first treatment cycle after subjects receive single-dose or multiple-dose treatment, as defined by the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 toxicity assessment criteria.
Time frame: At the end of Cycle 1 (each cycle is 21 days)
Maximum tolerated dose (MTD)
MTD is defined as the highest dose at which dose-limiting toxicity (DLT) occurred in less than 33% of patients.
Time frame: At the end of Cycle 1 (each cycle is 21 days)
Recommended Phase II Dose (RP2D)
DLT describes side effects of a drug or other treatment that are serious enough to evaluate RP2D of TQB3217 tablets in adult patients with advanced malignant cancer.
Time frame: Baseline up to 24 months
Numbers of participant with Adverse events (AEs) and serious adverse events (SAEs)
The incidence and severity of AEs and SAEs, as well as abnormal laboratory test indicators.
Time frame: 30 days after the last administration
Time to Reach the Maximum Plasma Concentration (Tmax)
To characterize the pharmacokinetics of TQB3217 by assessment of time to reach maximum plasma concentration after single and multiple dosing.
Time frame: Single dose day 1: pre-dose, at 0.5, 1, 1.5,2, 3, 4, 6, 8, 12, 24, 48, 72 hours post dose. Days 7, 14 and 21 of multiple dosing cycle 1: pre-dose. Day 21 of multiple dosing cycle 1: at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post dose (21 days a cycle)
Peak concentration (Cmax)
The maximum observed plasma concentration of TQB3217 tablets.
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Time frame: Single dose day 1: pre-dose, at 0.5, 1, 1.5,2, 3, 4, 6, 8, 12, 24, 48, 72 hours post dose. Days 7, 14 and 21 of multiple dosing cycle 1: pre-dose. Day 21 of multiple dosing cycle 1: at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post dose (21 days a cycle)
Half-life (t1/2)
Terminal phase elimination half-life (T1/2) is the time required for half of the drug to be eliminated from the plasma.
Time frame: Single dose day 1: pre-dose, at 0.5, 1, 1.5,2, 3, 4, 6, 8, 12, 24, 48, 72 hours post dose. Days 7, 14 and 21 of multiple dosing cycle 1: pre-dose. Day 21 of multiple dosing cycle 1: at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post dose (21 days a cycle)
Area under the concentration-time curve (AUC [0-infinity]
To characterize the pharmacokinetics of TQB3217 by assessment of area under the plasma concentration time curve from 0 extrapolated to infinity.
Time frame: Single dose day 1: pre-dose, at 0.5, 1, 1.5,2, 3, 4, 6, 8, 12, 24, 48, 72 hours post dose. Days 7, 14 and 21 of multiple dosing cycle 1: pre-dose. Day 21 of multiple dosing cycle 1: at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post dose (21 days a cycle)
Area under the concentration-time curve (AUC [0-t]
To characterize the pharmacokinetics of TQB3217 by assessment of area under the plasma concentration time curve from the first dose to a certain time point.
Time frame: Single dose day 1: pre-dose, at 0.5, 1, 1.5,2, 3, 4, 6, 8, 12, 24, 48, 72 hours post dose. Days 7, 14 and 21 of multiple dosing cycle 1: pre-dose. Day 21 of multiple dosing cycle 1: at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post dose (21 days a cycle)
Apparent clearance (CL/F)
Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the body.
Time frame: Single dose day 1: pre-dose, at 0.5, 1, 1.5,2, 3, 4, 6, 8, 12, 24, 48, 72 hours post dose. Days 7, 14 and 21 of multiple dosing cycle 1: pre-dose. Day 21 of multiple dosing cycle 1: at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post dose (21 days a cycle)
Apparent Volume of Distribution during the Terminal Phase
Apparent volume of distribution during the Terminal Phase of the TQB3217 in plasma.
Time frame: Single dose day 1: pre-dose, at 0.5, 1, 1.5,2, 3, 4, 6, 8, 12, 24, 48, 72 hours post dose. Days 7, 14 and 21 of multiple dosing cycle 1: pre-dose. Day 21 of multiple dosing cycle 1: at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post dose (21 days a cycle)
Objective Response Rate (ORR)
The percentage of complete response (CR) plus partial response (PR) assessed by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 criteria.
Time frame: Up to 2 years
Disease control rate (DCR)
Defined as the proportion of subjects with Complete Response (CR), Partial Response (PR), or Stable Disease (SD).
Time frame: Up to 2 years
Duration of Response (DOR)
Defined as the time from first documented response to documented disease progression.
Time frame: Up to 2 years
Overall Survival (OS)
the time from start of study treatment to date of death due to any cause.
Time frame: From start of study treatment up to die ,estimated at two years