This trial is a multicenter, open-label, single-arm, dose-escalation and dose-expansion clinical trial. The dose was increased according to the "3 + 3" rule. Patients with previously untreated patients with CD20-positive DLBCL were selected to evaluate the safety, tolerance (DLT, MTD), pharmacokinetics, and anti-tumor activity of TRS005 in combination with standard doses of cyclophosphamide, doxorubicin, and prednisone(T-CHP) by intravenous drip every 3 weeks.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
66
TRS005 will be administered at a starting dose of 0.8mg/kg IV every 3 weeks (starting from Cycle 1 Day 1), for 6 cycles (up to 8).
Cyclophosphamide will be administered at 750 milligrams per square meter (mg/m\^2) IV every 3 weeks (starting from Cycle 1 Day 1), for 6 cycles.
Doxorubicin will be administered at 50 mg/m\^2 IV every 3 weeks (starting from Cycle 1 Day 1), for 6 cycles.
Prednisolone will be administered at 100 mg orally daily for 5 days every 3 weeks (starting from Cycle 1 Day 1), for 6 cycles.
Chinese Academy of Medical Sciences, Cancer Hospital
Beijing, Beijing Municipality, China
Part I: Dose Limiting Toxicities (DLTs) and Maximum Tolerated Dose (MTD)
All dose-escalation cohorts will consist of at least 3 participants. If a DLT is observed in 1 participant at a given dose level during the DLT observation period before dose escalation, additional participants will be enrolled at that dose level for a total of at least 6 participants. DLT assessment forms part of determining the Maximum Tolerated Dose (MTD). The highest dose level resulting in DLTs in less than one-third of a minimum of 6 participants will be declared the MTD.
Time frame: Cycle 1 Day 1 (C1D1) to Cycle 1 Day 21 (C1D21)
Part I and II: Adverse Events
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: Day 1 up to approximately 6 months
Overall Response Rate (ORR)
The overall response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) based on Lugano 2014 criteria
Time frame: At the end of treatment (Month 6)
Duration of Response (DOR)
Duration of Overall Response (DOR), estimated using the Kaplan Meier method, is measured from Lugano 2014 criteria are met for CR or PR (whichever is first recorded) , until the first date that recurrent or progressive disease is objectively documented. Patients without progressive disease are censored at the date of last disease assessment.
Time frame: Up to 24 months
Progression-Free Survival (PFS)
Progression-free survival based on the Kaplan-Meier method is defined as the duration between randomization and documented disease progression (PD) per Lugano criteria or death, or is censored at time of last disease assessment.
Time frame: Up to 24 months
Overall Survival (OS)
Overall Survival (OS) based on the Kaplan-Meier method is defined as the time from study entry to death or censored at date last known alive.
Time frame: Up to 24 months
Immunogenicity
ADA will be assessed in all participants. NAb will be assessed in samples that are ADA positive.
Time frame: At the end of treatment (Month 6)
Serum concentration
Total TRS005, TRS005 unconjugated MMAE, and antibody-conjugated Mono-Methyl Auristatin E \[acMMAE\]
Time frame: At the end of cycle 4 (each cycle is 21 days)
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