An Open-label, Single-arm Study of JWCAR201 in the Treatment of Relapsed or Refractory Diffuse Large B-cell Lymphoma

This is an open-label, single-arm study to investigate the efficacy and safety signals of JWCAR201 amongst subjects with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

This is an open-label, single-arm, investigator-initiated study (IIT) to evaluate the safety an JWCAR201 in adult patients with relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL). The study employs a two-stage, Continual Reassessment Method (CRM)-like dose escalation design. In the first stage, each dose cohort will use an accelerated titration approach, escalating to the dose level at which a Dose-Limiting Toxicity (DLT) occurs or the 50 × 10\^6 CAR+ T-cell dose level (whichever is reached first). The second stage will start at observed DLT dose level or the 50\^6 CAR+ T-cell dose level, an model-based CRM method using a single-parameter Logistic model will be used to describe the relationship between the JWCAR201 dose and the probability of observed DLTs. The Maximum Tolerated Dose (MTD) is defined as the highest an estimated DLT probability below the 25% target toxicity level. For each dose level, a prior mean DLT risk (skeleton) will be set based on historical data. After enrolling ≥3 patients perort, the prior DLT risk will be updated based on the available study data, and the DLT risk will be communicated to the Data Safety Monitoring Committee to recommend the next cohort dose. The study plans to start at 25 × 10\^6 CAR+ T cells as the initial dose, with exploration across three dose levels (25 × 10\^6, 50 × 10\^6, 75 × 10\^6 CAR+ T cells), and 15 × 10\^6 CAR+ T cells or lower and 100 × 10\^6 CAR+ T cells or higher as backup doses, aiming to evaluate the safety, tolerability of JWCAR201 in r/r DLBCL and determine the recommended dose for expansion. Additionally, pharmacokinetic and pharmacodynamic characteristics are also study objectives.

Eligibility Criteria:
Inclusion Criteria:

1. Age ≥18
2. Voluntarily willing to participate in the study and sign the written informed consent form
3. Histologically confirmed diffuse large B-cell lymphoma (DLBCL) with immunohistochemistry (IHC) CD20-positive
4. Patients must be priorly treated by Anthracyclines and anti-CD20-targeted regimens, and must be refractory or relapsed to at least ≥2 treatment lines of standard of care or autologous hematopoietic stem-cell transplantation (HSCT)
5. At least one measurable lesion by CT or PET per Lugano criteria
6. Eastern Cooperative Oncology Group (ECOG) performance status scale ≤1
7. Adequate organ functions
8. Adequate venous access for apheresis
9. Women of childbearing potential must agree to use an effective and reliable contraceptive method till 1-year post-infusion
10. Male patients who have not undergone vasectomy and have sexual activity with women of childbearing potential must agree to the use of a barrier contraceptive till 1-year post-infusion

Exclusion Criteria:

1. Primary central nervous system lymphoma
2. Another primary malignancy within 2 years
3. Active infections of hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), or syphilis
4. With severe active deep venous thrombosis or pulmonary embolism within 3 months
5. Treated with anti-coagulations (except for prophylaxis use) due to severe active deep venous thrombosis or pulmonary embolism within 3 months
6. Uncontrolled or active infection
7. Acute or chronic graft-versus-host disease (GvHD)
8. With severe cardiovascular diseases within 6 months
9. With severe clinically-significant central nervous system disorders within 6 months
10. Pregnant or lactating women
11. Not satisfying pre-defined wash-out period for apheresis
12. Unable or unwilling to comply with the study protocol, judged by the investigator, or other situations implying that the subject might not be appropriate to participate in the study
13. Previously treated with any genetically engineered modified T-cell therapy nor other cell-gene therapy