This Phase I, open-label, multicenter study evaluates the safety, tolerability, pharmacokinetics, and preliminary efficacy of SYS6005 in advanced malignancies, comprising dose-escalation and expansion phases. The escalation phase employs a BOIN design with accelerated titration across seven dose levels, featuring a 21-day DLT observation period in Cycle 1, with dose adjustments guided by a Safety Monitoring Committee. In the expansion phase, one or more dosing regimens and tumor types will be selected, and participants will receive SYS6005 R2PD for further exploration and validation. Treatment continues until disease progression, unacceptable toxicity, or other discontinuation criteria. Safety monitoring includes AEs, labs, and ECOG PS, while efficacy is assessed via imaging. PK and immunogenicity samples are collected, and survival is tracked quarterly until death or study end. The study aims to determine the maximum tolerance dose (MTD)/recommended phase 2 dose (RP2D) and characterize SYS6005's clinical profile.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
132
SYS6005 administered via IV infusion on , Day 1 of each 21-day cycle
Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
Tianjin, China
RECRUITINGIncidence of Dose limiting toxicities (for dose escalation part)
A DLT is defined as a protocol pre-specified treatment-emergent adverse event (TEAE) that occurs in Cycle 1 of SYS6005 therapy and is considered drug-related.
Time frame: each cycle is 21 days
Recommended Phase 2 Dose(RP2D) of SYS6005 (for dose escalation part)
The selection of RP2D will be based on consideration of overall safety information together with available pharmacokinetic, pharmacodynamic, and efficacy data. The RP2D may be the MTD or may be a lower dose within the tolerable dose range.
Time frame: About up to 6 months
Incidence and severity of adverse events (for both dose escalation and expansion part)
Time frame: About up to 12 months
Overall response (for dose expansion part)
Time frame: About up to 12 months
Complete remission (for dose expansion part)
Time frame: About up to 12 months
Pharmacokinetic (P K) profiles of SYS6005 including AUClast, AUCinf, Cmax, Tmax, t1/2, and CL, etc.
Time frame: About up to 12 months
Immunogenicity of SYS6005: incidence and titer of ADAs, and incidence of neutralizing antibodies (Nabs) (if applicable)
Time frame: About up to 12 months
Area Under the Concentration-Time Curve from Time Zero to the Last Quantifiable Concentration (AUClast) of SYS6005
AUClast reflects total drug exposure from administration to the last measurable concentration, calculated using the linear trapezoidal method.
Time frame: Cycle 1: Pre-dose, end of infusion (0,4,12,24,48,96,168,240,336 hours post); Cycle 2: Pre-dose, 0 hour post; Cycle 3: Pre-dose, end of infusion (0,4,12,24,48,96,168,240,336 hours post); Cycle 4: Pre-dose, 0 hour post
Area Under the Concentration-Time Curve from Time Zero Extrapolated to Infinity (AUCinf) of SYS6005
AUCinf estimates total exposure by extrapolating AUClast using the terminal elimination rate (λz)
Time frame: Cycle 1: Pre-dose, end of infusion (0,4,12,24,48,96,168,240,336 hours post); Cycle 2: Pre-dose, 0 hour post; Cycle 3: Pre-dose, end of infusion (0,4,12,24,48,96,168,240,336 hours post); Cycle 4: Pre-dose, 0 hour post
Maximum Observed Plasma Concentration (Cmax) of SYS6005
Peak plasma concentration, directly indicating the rate and extent of absorption
Time frame: Cycle 1: Pre-dose, end of infusion (0,4,12,24,48,96,168,240,336 hours post); Cycle 2: Pre-dose, 0 hour post; Cycle 3: Pre-dose, end of infusion (0,4,12,24,48,96,168,240,336 hours post); Cycle 4: Pre-dose, 0 hour post
Time to Reach Maximum Plasma Concentration (Tmax) of SYS6005
Time point at which Cmax occurs, reflecting absorption kinetics.
Time frame: Cycle 1: Pre-dose, end of infusion (0,4,12,24,48,96,168,240,336 hours post); Cycle 2: Pre-dose, 0 hour post; Cycle 3: Pre-dose, end of infusion (0,4,12,24,48,96,168,240,336 hours post); Cycle 4: Pre-dose, 0 hour post
Terminal Elimination Half-Life (t1/2) of SYS6005
Time for plasma concentration to reduce by 50% in the elimination phase, calculated as ln(2)/λz
Time frame: Cycle 1: Pre-dose, end of infusion (0,4,12,24,48,96,168,240,336 hours post); Cycle 2: Pre-dose, 0 hour post; Cycle 3: Pre-dose, end of infusion (0,4,12,24,48,96,168,240,336 hours post); Cycle 4: Pre-dose, 0 hour post
Systemic Clearance (CL) of SYS6005
Volume of plasma cleared of drug per unit time (CL = Dose/AUCinf for IV administration).
Time frame: Cycle 1: Pre-dose, end of infusion (0,4,12,24,48,96,168,240,336 hours post); Cycle 2: Pre-dose, 0 hour post; Cycle 3: Pre-dose, end of infusion (0,4,12,24,48,96,168,240,336 hours post); Cycle 4: Pre-dose, 0 hour post
Incidence of Anti-Drug Antibodies (ADAs) Against SYS6005
Proportion of subjects who develop detectable ADAs at any time during the study, expressed as a percentage.
Time frame: Pre-dose on Day 1 of Cycles 1, 2, 3, 4; Pre-dose on Cycle 6; Pre-dose every 4 cycles thereafter (e.g., Cycle 10, 14, 18…); 30 days after last dose (follow-up).
Titer of Anti-Drug Antibodies (ADAs) Against SYS6005
Magnitude of ADA response (e.g., reported as geometric mean titer or median titer in ADA-positive subjects).
Time frame: Pre-dose on Day 1 of Cycles 1, 2, 3, 4; Pre-dose on Cycle 6; Pre-dose every 4 cycles thereafter (e.g., Cycle 10, 14, 18…); 30 days after last dose (follow-up).
Incidence of Neutralizing Antibodies (NAbs) Against SYS6005 (if applicable)
Proportion of subjects with NAbs capable of inhibiting SYS6005's pharmacological activity in a cell-based or competitive ligand-binding assay.
Time frame: Pre-dose on Day 1 of Cycles 1, 2, 3, 4; Pre-dose on Cycle 6; Pre-dose every 4 cycles thereafter (e.g., Cycle 10, 14, 18…); 30 days after last dose (follow-up).
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