A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Initial Effectiveness of TRS005 in Patients With Relapsed or Refractory CD20-positive NHL.

• Status: Recruiting
• Trial end date: 2022-11-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Zhejiang Teruisi Pharmaceutical Inc.
• Treatments: Antibodies; Antibodies, Monoclonal

Criteria

Inclusion Criteria:

1. Histologically confirmed CD20-positive B-cell non-Hodgkin lymphoma;

2. Relapse or refractory after receiving at least 2 standard treatment regimens;（Definition of refractory: Patients who did not reach PR in two cycles or CR in four cycles）

3. At least one measurable tumor lesion with the longest transverse diameter ≥ 1.5cm;

4. Previously received anti-tumor treatment (such as radiotherapy, chemotherapy, hormone therapy, biotherapy, immunotherapy) at least 28 days before the first administration of this study;

5. The toxicity of previous anti-tumor treatment has been restored to ≤ grade 1 as defined by NCI-CTCAE v5.0 (except for alopecia)；

6. The laboratory inspection results must meet the following requirements:（It is not allowed to give any blood components, short acting cell growth factor, albumin and other drugs within 7 days before laboratory examination; Long acting cell growth factor is not allowed to be given within the first 14 days）：

• Hematology: white blood cell count (WBC) ≥ 3 × 109 / L, absolute neutrophil count (ANC) ≥ 1.5 × 109 / L, platelet (PLT) ≥ 100 × 109 / L, hemoglobin (HGB) > 90g / L;

• Liver function: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 times the upper limit of normal value, and total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal value;

• Renal function：Serum creatinine (Cr) ≤ 2 times the upper limit of normal value;

• Coagulation function：International normalized ratio (INR) ≤ 1.5 upper limit of normal value and activated partial thromboplastin time (APTT) ≤ 1.5 upper limit of normal value (The patients were not treated with anticoagulation before enrollment);

• Measured value / predicted value of vital capacity (VC) ≥ 60%, or predicted value of carbon monoxide diffusion function (DLCO) ≥ 50%;

7. ≥ 18 years , gender is not limited;

8. ECOG performance status 0-1;

9. Life expectancy of greater than 3 months;

10. 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;

11. Patients voluntarily agree to participate in the study and to sign the informed consent form.

Exclusion Criteria:

Patients who meet any of the following criteria will be excluded:

1. Received rituximab within 3 months before the first medication;

2. Rituximab ADA positive in peripheral blood at the time of screening;

3. The residual concentration of rituximab in peripheral blood > 24ug / ml at screening;

4. A clear history of drug allergy, and a history of ingredient allergy to heterogeneous proteins, biological agents or test drugs;

5. Active hepatitis B or C (HBsAg positive and / or HBcAb positive and HBV DNA ≥ 104 copy number or ≥ 4000IU/ml; HCV antibody positive) or human immunodeficiency virus (HIV) antibody positive;

6. Tumor-infiltrating diseases of the central nervous system;

7. Accompanied by peripheral or central nervous system diseases;

8. Investigator-assessed diabetes uncontrolled by drug therapy;

9. Patients with other malignancies within the past 5 years;

10. With active autoimmune diseases (such as systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, Sjogren's syndrome, autoimmune thrombocytopenia, etc.);

11. Accompanied by the following serious cardiovascular diseases:

1. Myocardial infarction in nearly 6 months of screening period;

2. Unstable angina pectoris in the screening period of nearly 3 months;

3. Cardiac insufficiency (cardiac function grade ≥ NYHA class II);

4. Severe arrhythmia (e.g., persistent ventricular tachycardia, ventricular fibrillation);

5. Prolonged QTc interval (male > 450 ms, female > 470 ms);

6. Second or third degree heart block;

7. Drug-poorly controlled hypertension (systolic blood pressure > 160mmHg or diastolic blood pressure > 100mmHg);

12. Accompanied by other serious diseases and serious active infections (such as pneumonia, active tuberculosis, interstitial lung disease, etc.);

13. Received hematopoietic growth factor treatment within 1 week prior to first administration, including colony stimulating factor, interleukin or blood transfusion;

14. The dosage of steroid hormone (prednisone phase equivalent) used greater than 20mg/ day within 1 month prior to first administration for more than 14 consecutive days or immunosuppressive treatment;

15. Various vaccines were inoculated within 1 month prior to first administration;

16. Major surgery (except diagnostic biopsy) within 1 month prior to first administration;

17. Patients who received autologous stem cell transplantation within 3 months prior to first administration;

18. Patients who have received allogeneic stem cell transplantation in the past;

19. Patients with infusion reaction above grade III after previous monoclonal antibody treatment;

20. Participate in clinical trials of other drugs or medical devices within 1 month prior to first administration;

21. Patients previously treated with CAR-T;

22. Investigators assessed as unsuitable to participate in this study for other reasons。