Testing TRS005 for patients with recurrent CD20-positive B-cell lymphoma

A Multicenter, Single-arm, Dose-escalating Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Effectiveness of TRS005 in Patients With Relapsed or Refractory CD20-positive B-NHL

This study is testing a new treatment called TRS005 to see if it can help people with recurrent CD20-positive B-cell lymphoma feel better and how safe it is.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 152 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Zhejiang Teruisi Pharmaceutical Inc. (Industry-sponsored)
• Drugs / interventions: rituximab, CAR-T, chemotherapy, immunotherapy, prednisone
• Locations: 6 sites (Beijing, Beijing and 5 other locations)
• Trial ID: NCT05395533 on ClinicalTrials.gov

What this trial studies

This is a multicenter, open-label, single-arm Phase 1 clinical trial designed to evaluate the safety, tolerability, and pharmacokinetics of TRS005, a recombinant CD20 monoclonal antibody-MMAE conjugate, in patients with recurrent or refractory CD20-positive B-cell non-Hodgkin lymphoma. The trial employs a dose-escalation approach using the '3 + 3' rule, where patients receive increasing doses of TRS005, starting from 0.1 mg/kg up to 2.3 mg/kg, based on safety and tolerability assessments. Participants will undergo a single dose followed by multiple continuous doses over a total of six cycles, with careful monitoring of their response and side effects. The study aims to determine the maximum tolerated dose and gather data on the drug's pharmacokinetic profile.

Who should consider this trial

Good fit: Ideal candidates are adults with histologically confirmed CD20-positive B-cell non-Hodgkin lymphoma who have relapsed or are refractory after at least two standard treatment regimens.

Not a fit: Patients who have not received prior anti-tumor treatment or those with non-CD20-positive B-cell non-Hodgkin lymphoma may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with difficult-to-treat CD20-positive B-cell non-Hodgkin lymphoma.

How similar studies have performed: Other studies involving monoclonal antibodies for similar conditions have shown promising results, indicating potential for success with this approach.

Eligibility 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。

Where this trial is running

Beijing, Beijing and 5 other locations

• Chinese Academy of Medical Sciences, Cancer Hospital — Beijing, Beijing, China (Recruiting)
• Sun Yat-sen University Cancer Center (SYSUCC) — Guangzhou, Guangdong, China (Recruiting)
• Henan Cancer Hospital (Affiliated Cancer Hospital of Zhengzhou University) — Zhengzhou, Henan, China (Recruiting)
• The First Affiliated Hospital of Zhengzhou University — Zhengzhou, Henan, China (Recruiting)
• Second Affiliated Hospital of Soochow University — Suzhou, Jiangsu, China (Recruiting)
• Tianjin Medical University Cancer Institute & Hospital (TMUCIH) — Tianjin, Tianjin, China (Recruiting)

Study contacts

• Principal investigator: Yuankai Shi, MD — Cancer Institute and Hospital, Chinese Academy of Medical Sciences
• Study coordinator: Jian Zhang, MD

Conditions CD20-positive B-cell Non-Hodgkin Lymphoma