Targeting CD19/CD20 Dual-targeted Cell in Patients With Relapsed/Refractory B-cell Non-Hodgkin Lymphoma

This is an open-label, dose-escalation/dose extension study to assess the safety, tolerability, and efficacy of LUCAR-G39D in the patient ≥ 18 years of age with relapsed or refractory B-cell non-Hodgkin lymphoma. Subjects who meet the eligibility criteria will receive a single dose of LUCAR-G39D injection. The study will include the following sequential phases: screening, pre-treatment (lymphodepleting chemotherapy), treatment, and follow-up.

Inclusion criteria

• Subjects have fully understood the possible risks and benefits of participating in this study, are willing to follow and able to complete all trial procedures, and have signed informed consent.
• Aged 18-75 years (inclusive).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Histologically confirmed B-cell non-Hodgkin Lymphoma that expresses at least one of CD19/CD20.
• At least one evaluable tumor lesion according to Lugano 2014 criteria.

Response to prior therapy is consistent with one of the following:

• Primary refractory.
• Relapsed or refractory after 2 or more lines of therapy.
• For LBCL, 3B FL. t-iNHL:

• Relapse within 12 months after first-line chemoimmunotherapy to achieve CR;
• Progression or relapse within 12 months after autologous hematopoietic stem cell transplantation;

• Life expectancy≥ 3 months 8. Clinical laboratory values meet screening visit criteria

Exclusion criteria

Subject eligible for this study must not meet any of the following criteria:

• Prior antitumor therapy with insufficient washout period ; 2. Patients who received autologous CAR-T cell therapy (except CD19-targeted) or autologous gene therapy; 3. Patients who received allogeneic hematopoietic stem cell transplantation or allogeneic therapy; 5. Patients who are positive for any index of hepatitis B surface antigen (HBsAg), hepatitis B virus deoxyribonucleic acid (HBV DNA), hepatitis C antibody (HCV-Ab), hepatitis C virus ribonucleic acid (HCV RNA), or human immunodeficiency virus antibody (HIV- Ab).

• Known life-threatening allergies, hypersensitivity, or intolerance to LUCAR-G39D CAR-T cell or its excipients, including DMSO.

• Pregnant or lactating women;