To evaluate the safety, tolerability, and pharmacokinetic characteristics of SIBP-A19 and determine the maximum tolerable dose (MTD) and phase II recommended dose (RP2D).
This study is an open label, multicenter, dose escalation, dose expansion, and indication expansion study to evaluate safety, tolerability, pharmacokinetics, preliminary anti-tumor efficacy, immunogenicity, impact on QT/QTc interval, and explore potential biomarkers of SIBP-A19 for injection in participants with advanced or metastatic solid tumors. This study is divided into three stages and is planned to be set up eight dose groups, including 1.0, 2.0, 3.2, 4.0, 4.8, 5.6, 6.4 and 8.0 mg/kg. The first stage is the dose escalation stage, which will start from the first and second doses for enrollment. If necessary, a 3+3 dose escalation design will be used. The second stage is the dose expansion stage, where two or more doses are selected to enter the dose expansion phase, and 6-9 participants will be enrolled in each dose group for dose expansion. The third stage is the indication expansion stage, where phase II recommended dose (RP2D) is preliminarily determined based on the escalation and expansion of dosage in the early stage. Using RP2D for indication expansion, the investigators plan to expand three indication cohorts, with at least 30 participants selected for each cohort.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
156
SIBP-A19 formulation for injection. Strength: 1.0, 2.0, 3.2, 4.0, 4.8, 5.6, 6.4 and 8.0 mg/kg. Intravenous infusion administration, with a treatment cycle of every 21 days, administered once on the first day of each cycle. The dose escalation stage, 1mg/kg and 2mg/ kg were subjected to accelerated titration, where the safety was evaluated within 21 days after the first administration to one participant. If dose-limiting toxicity (DLT) occurred, the traditional "3+3" dose escalation method was immediately switched. If DLT does not occur, the next dose group will be explored. The third stage will use RP2D for further exploration.
The Union Hospital affiliated to Fujian Medical University
Fuzhou, Fujian, China
RECRUITINGAE (Adverse Events)
That is adverse events, any adverse events that occurred to the participant during the study period.
Time frame: From day 1 after the first dose to day 28 after the last dose
Phase II recommended dose (RP2D)
RP2D refers to the recommended dose determined through initial dose escalation and toxicity assessment in clinical trials, used for further evaluation of drug efficacy and safety.
Time frame: Day 21 after the last dose in the dose expansion phase
Dose-limiting toxicity (DLT)
DLT is defined as any adverse event related to the drug defined in the protocol that occurs within 21 days of the first cycle after a single administration.
Time frame: Day 21 after each dose in the dose escalation stage
Maximum tolerated dose (MTD)
MTD is defined as the maximum dose at which the number of DLT cases occurring during the DLT observation period within 21 days after a single administration is ≤ 1/6 of the total number of cases.
Time frame: Day 21 after the last dose in the dose escalation stage
AUC (Area Under The Plasma Concentration Versus Time Curve)
It shows the degree to which a drug is absorbed and used in the body.
Time frame: Day 1, Day 22 and Day 63 after the first dose
Cmax (Peak Plasma Concentration)
It shows the highest plasma concentration of a drug that can be achieved after administration.
Time frame: Day 1, Day 22 and Day 63 after the first dose
Tmax (Peak Time)
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That is peak time of drug action, it shows the time required to reach the maximum concentration on the participant plasma concentration curve after administration.
Time frame: Day 1, Day 22 and Day 63 after the first dose
ORR (Objective Response Rate)
The proportion of participants whose tumor volume shrinks to a predetermined value and maintains the minimum time limit and is the sum of complete and partial responses.
Time frame: 6 weeks after the last evaluation
DCR (Disease control rate)
In clinical trials, the percentage of participants with advanced cancer who responded fully to cancer treatment, partially responded, and had stable disease.
Time frame: 6 weeks after the last evaluation
PFS (Progression-free survival)
The time between the onset of randomization and the onset (of any aspect) of tumor progression or death (from any cause).
Time frame: 6 weeks after the last evaluation
OS (overall survival)
From randomization to time of death due to any cause.
Time frame: 6 weeks after the last evaluation