Diffuse Large B-Cell Lymphoma (DLBCL)
Conditions
Brief summary
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.
Interventions
DRUGTRS005
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).
DRUGCyclophosphamide
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.
DRUGDoxorubicin
Doxorubicin will be administered at 50 mg/m\^2 IV every 3 weeks (starting from Cycle 1 Day 1), for 6 cycles.
DRUGPrednisolone
Prednisolone will be administered at 100 mg orally daily for 5 days every 3 weeks (starting from Cycle 1 Day 1), for 6 cycles.
Sponsors
Zhejiang Teruisi Pharmaceutical Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 1\. Part I: Age 18 -65 years old; Part II: Aged ≥ 18 years old, both male and female. * 2\. Previously untreated patients with CD20-positive DLBCL diagnoses by 2022 WHO. * 3\. Measurable disease of at least 15mm (node)/10mm (extranodal). * 4\. ECOG performance status 0-2. * 5\. International Prognostic Index (IPI) score of 2-5. * 6\. Estimated survival time ≥6 months. * 7\. Having sufficient organ function. * 8\. Female and male patients of childbearing age and their spouses are willing to carry out adequate contraception throughout the study period, and female patients of childbearing age must have negative serum pregnancy test within 7 days before the first administration. * 9\. Patients voluntarily agree to participate in the study and to sign the informed consent form.
Exclusion criteria
* 1\. Contraindication to any of the individual components of study drugs, including prior receipt of xenoproteins, biological agents. * 2\. Serologic evidence of chronic hepatitis B virus (HBV) infection and unable or unwilling to receive standard prophylactic antiviral therapy or with detectable HBV viral load; Serologic evidence of hepatitis C virus (HCV) infection without completion of curative treatment or with detectable HCV viral load; Human immunodeficiency virus (HIV) seropositive. * 3\. Clinically apparent central nervous system (CNS) lymphoma. * 4\. Patient has ≥ Grade 2 peripheral neuropathy. * 5\. Investigator-assessed diabetes uncontrolled by drug therapy. * 6\. Clinically significant third space fluid accumulation. * 7\. Patients with other malignancies within the past 5 years. * 8\. With active autoimmune diseases. * 9\. Accompanied by serious cardiovascular diseases. * 10\. Accompanied by serious diseases and serious active infections. * 11\. The dosage of steroid hormone (prednisone phase equivalent) used greater than 20mg/ day within 28 days prior to first administration for more than 14 consecutive days, or immunosuppressive treatment. * 12\. Various vaccines were inoculated within 28 days prior to first administration; * 13\. Major surgery (except diagnostic biopsy) within 28 days prior to first administration or during the study period. * 14\. Participate in clinical trials of other drugs or medical devices within 28 days prior to first administration. * 15\. Serious medical or psychiatric illness likely to interfere with participation in this study. * 16\. Investigators assessed as unsuitable to participate in this study for other reasons.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part I: Dose Limiting Toxicities (DLTs) and Maximum Tolerated Dose (MTD) | Cycle 1 Day 1 (C1D1) to Cycle 1 Day 21 (C1D21) | 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. |
| Part I and II: Adverse Events | Day 1 up to approximately 6 months | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | Up to 24 months | 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. |
| Overall Survival (OS) | Up to 24 months | 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. |
| Duration of Response (DOR) | Up to 24 months | 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. |
| Serum concentration | At the end of cycle 4 (each cycle is 21 days) | Total TRS005, TRS005 unconjugated MMAE, and antibody-conjugated Mono-Methyl Auristatin E \[acMMAE\] |
| Immunogenicity | At the end of treatment (Month 6) | ADA will be assessed in all participants. NAb will be assessed in samples that are ADA positive. |
| Overall Response Rate (ORR) | At the end of treatment (Month 6) | 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 |
Countries
China
Contacts
Primary ContactChen Wang
Outcome results
None listed