This trial is a multicenter, open, single arm, dose increasing and extended clinical trial. The dose was increased according to the "3 + 3" rule. Patients with recurrent or refractory CD20 positive B-cell non-Hodgkin's lymphoma were selected to evaluate the safety, tolerance (DLT, MTD) and pharmacokinetic (PK) characteristics of TRS005 by intravenous drip.
The subjects were screened and examined according to the protocol before enrollment. The dose of the enrolled subjects was increased according to the following 6 dose groups: 0.1mg/kg, 0.5mg/kg, 1.0mg/kg, 1.5mg/kg, 1.8mg/kg, 2.1mg/kg. The incremental process is divided into groups according to the principle of 3 + 3 dose increment. The subjects randomly receive intravenous drip of TRS005 in chronological order. Each subject first carries out a single dose study, and then carries out multiple continuous doses. The first dose is given once in D1. After 21 days of observation, it is decided whether to continue multiple continuous doses according to the situation. They are given once in C2D1, C3D1, C4D1, C5D1, C6D1, or more cycles respectively, and received treatment until progressive disease or unacceptable toxicity. During the dose escalation process, the investigators will perform dose expansion according to the clinical benefits of different dose groups.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
147
The dose of the enrolled subjects was increased according to the following 6 dose groups: 0.1mg/kg, 0.5mg/kg, 1.0mg/kg, 1.5mg/kg, 1.8mg/kg, and 2.1mg/kg.
Chinese Academy of Medical Sciences, Cancer Hospital
Beijing, Beijing Municipality, China
Sun Yat-sen University Cancer Center (SYSUCC)
Guangzhou, Guangdong, China
Henan Cancer Hospital (Affiliated Cancer Hospital of Zhengzhou University)
Zhengzhou, Henan, China
The First Affiliated Hospital of Zhengzhou University
Zhengzhou, Henan, China
Number of Participants With Dose-limiting Toxicity
DLTs were defined as specific events which occurred in the 21-day DLT evaluation period of the dose escalation part, except any events that were clearly due to underlying disease or extraneous causes. The grading and severity of events were based on the guidelines provided in the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Time frame: Cycle 1(Days 1-21)
MTD,Maximum Tolerated Dose
After the dose increment is completed, the incidence of DLT in each dose group is summarized and analyzed. The highest dose group closest to 1 / 3 of the preset incidence of DLT is MTD
Time frame: Cycle 1(Days 1-21)
Number of Participants With Treatment-emergent Adverse Event (TEAE)
An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. AEs were reported based on the national cancer institute common terminology criteria for AEs, Version 5.0 (NCI-CTCAE, v5.0). Reported are the number of subjects with AEs, Grade 3-5 AEs, and Serious Adverse Events (SAEs).
Time frame: Baseline up to approximately 5 years
Number of Participants With ADA/Nab
Evaluate the changes of anti drug antibody and neutralizing antibody produced by the subjects.
Time frame: Baseline up to approximately 5 years
ORR, overall response rate
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Second Affiliated Hospital of Soochow University
Suzhou, Jiangsu, China
Tianjin Medical University Cancer Institute & Hospital (TMUCIH)
Tianjin, Tianjin Municipality, China
Summarize the number and percentage of objective remission (Complete remission (CR) or Partial remission (PR))
Time frame: Baseline up to approximately 5 years
DOR, duration of response
DOR was defined as the time from the documentation of first tumor response (CR or PR) to disease progression or death.
Time frame: Baseline up to approximately 5 years
PFS, progression-free survival
PFS was defined as the time between start of treatment and the first documentation of progression, or death.
Time frame: Baseline up to approximately 5 years
OS, overall survival
OS was defined as the time between the start of treatment and death from any cause.
Time frame: Baseline up to approximately 5 years
Cmax
Peak concentration. Obtained directly from the measured data of blood drug concentration-time.
Time frame: At the day3/day5/day8/day15 in cycle 1and 4;and at the first day of Cycle 1-5 (each cycle is 21 days)
AUC0-t
Area under the curve from zero to the lowest detectable plasma concentration. Calculated by linear trapezoidal rule: AUC(i, i+1)=(Ti+1-Ti)(Ci+Ci+1)/2, AUC 0-t is the sum of all AUC (I, I + 1).
Time frame: At the day3/day5/day8/day15 in cycle 1and 4;and at the first day of Cycle 1-5 (each cycle is 21 days)
AUC0-∞
Area under the curve extrapolated from zero to infinity time. AUC0-∞=AUC0-t+Ct/λ z(Ct is the last measurable plasma concentration)
Time frame: At the day3/day5/day8/day15 in cycle 1and 4;and at the first day of Cycle 1-5 (each cycle is 21 days)
Tmax
Peak time. Obtained directly from the measured data of blood drug concentration-time.
Time frame: At the day3/day5/day8/day15 in cycle 1and 4;and at the first day of Cycle 1-5 (each cycle is 21 days)