This study is an open-label, multicenter, dose-escalation and dose-expansion, non-randomized phase I clinical study evaluating the safety, tolerability, pharmacokinetic characteristics and preliminary efficacy of SI-B036 bispecific antibody injection in patients with locally advanced or metastatic urological tumors and other solid tumors.
The study consists of two phases: a dose-escalation phase (Phase Ia) and a dose-expansion phase (Phase Ib).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
Administration by intravenous infusion for a cycle of 3 weeks.
Peking University First Hospital
Beijing, Beijing Municipality, China
Phase Ia: Dose limiting toxicity (DLT)
DLTs are assessed according to NCI-CTCAE v5.0 during the first cycle and defined as occurrence of any of the toxicities in DLT definition if judged by the investigator to be possibly, probably or definitely related to study drug administration.
Time frame: Up to 21 days after the first dose
Phase Ia: Maximum tolerated dose (MTD)
MTD is defined as the highest dose level at which no more than 1 in 6 participants experienced a DLT during the first cycle.
Time frame: Up to 21 days after the first dose
Phase Ib: Recommended Phase II Dose (RP2D)
The RP2D is defined as the dose level chosen by the sponsor (in consultation with the investigators) for phase II study, based on safety, tolerability, efficacy, PK, and PD data collected during the dose escalation study of SI-B036.
Time frame: Up to approximately 24 months
Treatment-Emergent Adverse Event (TEAE)
TEAE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally emerging, or any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition during the treatment of SI-B036. The type, frequency and severity of TEAE will be evaluated during the treatment of SI-B036.
Time frame: Up to approximately 24 months
Cmax
Cmax is defined as the maximum observed drug concentration in plasma after administration.
Time frame: Up to approximately 24 months
Tmax
Tmax is defined as the time required to reach the maximum drug concentration in plasma following drug administration.
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Time frame: Up to approximately 24 months
T1/2
T1/2 is defined as the time required for the plasma concentration of a drug to decrease by 50% during the elimination phase.
Time frame: Up to approximately 24 months
AUC0-t
AUC0-t is defined as area under the serum concentration-time curve from time 0 to the time of the last measurable concentration.
Time frame: Up to approximately 24 months
CL (Clearance)
Clearance (CL) is the volume of plasma from which a drug is completely removed per unit time.
Time frame: Up to approximately 24 months
Ctrough
Ctrough is defined as the lowest serum concentration prior to the next dose will be administered.
Time frame: Up to approximately 24 months
Anti-drug Antibody (ADA)
Frequency of anti-SI-B036 antibody (ADA) will be investigated.
Time frame: Up to approximately 24 months
Progression-free Survival (PFS)
Progression-free survival (PFS) as assessed by BICR is defined as the time between the date subjects were randomized and the first observation of disease progression (based on BICR's image-based assessment) or death.
Time frame: Up to approximately 24 months
Objective Response Rate (ORR)
Objective response rate (ORR) is defined as the number of CR and PR in the treatment and control groups divided by the number of that group in the full analysis set (FAS).
Time frame: Up to approximately 24 months
Disease Control Rate (DCR)
Disease Control Rate (DCR) : Percentage of all randomized subjects who rated the best overall response (BOR) as complete response (CR), partial response (PR), and disease stabilization (SD) according to RECIST 1.1 criteria.
Time frame: Up to approximately 24 months
Duration of Response (DOR)
Duration of Response (DOR) : defined as the period from the date when tumor response is first recorded to the date when objective tumor progression is first recorded or the date of death.
Time frame: Up to approximately 24 months