CELL INTELLIGENCE · 肿瘤细胞治疗研究

Inclusion Criteria:

1. Subjects voluntarily participate in clinical studies; Fully informed of this study and signed informed consent; Informed consent form must be obtained prior to initiation of any study-related tests or procedures that are not part of the standard treatment for the subject's disease; Good compliance and cooperation with follow-up.
2. Age greater than or equal to 18.
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
4. At least one measurable tumor lesion.
5. Eligible subjects shall meet the criteria and qualification requirements of any one of the expansion cohorts as follows:

   * Cohort 1: Relapsed or refractory large B-cell lymphoma patients who have received at least one line of systemic therapy and have not undergone CAR-T therapy;
   * Cohort 2: High-risk large B-cell lymphoma patients in the first-line setting (who have completed 2 cycles of standard first-line systemic immunochemotherapy);
   * Cohort 3: Relapsed or refractory mantle cell lymphoma patients treated with at least two lines of systemic therapy;
   * Cohort 4: Exploratory cohort including relapsed or refractory indolent lymphoma and other B-cell malignancies.
6. Life expectancy≥ 3 months
7. Clinical laboratory values meet screening visit criteria
8. Adequate organ function;

Exclusion Criteria:

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

1. Prior antitumor therapy with insufficient washout period ;
2. Prior treatment with lentiviral vector-based gene therapies;
3. Patients who are positive for hepatitis B surface antigen (HBsAg), hepatitis B virus deoxyribonucleic acid (HBV DNA), hepatitis C antibody (HCV-Ab), hepatitis C virus ribonucleic acid (HCV RNA), and human immunodeficiency virus antibody (HIV-Ab).
4. Known life-threatening allergic reaction, hypersensitivity reaction, or intolerance to study drug excipients and related excipients, including but not limited to DMSO; or those with a history of severe allergic reactions in the past (such as hypersensitivity reactions, or those with severe immune-related reactions such as the need for glucocorticoids to prevent anaphylaxis as assessed by the investigator).
5. Lactating women;

主要终点：Incidence, severity, and category of treatment-emergent adverse events (TEAEs) · An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. · Through study completion, an average of 2 years afterCD19/CD20 Dual-Target in vivo CAR-T Lentiviral infusion (Day 1)；Objective response rate (ORR) and complete response (CR) rate (or the proportion of subjects achieving very good partial response [VGPR] or better) assessed per protocol-specified efficacy evaluation criteria stratified by disease type · Objective Response Rate (ORR) is defined as the proportion of subjects who achieve CR or PR after treatment via CD19/CD20 Dual-Target in vivo CAR-T Lentiviral cell infusion · Through study completion, an average 2 years after CD19/CD20 Dual-Target in vivo CAR-T Lentiviral infusion (Day 1)
次要终点：Further evaluation of efficacy endpoints stratified by disease subtype: Time to Response (TTR)；Further evaluation of efficacy endpoints stratified by disease subtype: Duration of Response (DOR)；Further evaluation of efficacy endpoints stratified by disease subtype: Progression Free Survival (PFS)；Further evaluation of efficacy endpoints stratified by disease subtype: Overall Survival (OS)；Pharmacokinetics in peripheral blood；Pharmacokinetics in bone marrow；Immunogenicity assessment of CD19/CD20 Dual-Target in vivo CAR-T Lentiviral infusion.

• CD19/CD20 Dual-Target in vivo CAR-T Lentiviral · EXPERIMENTAL · Each subject will receive a single dose of CD19/CD20 Dual-Target in vivo CAR-T Lentiviral product infusion.

Phase Ib Clinical Study to Evaluate the Safety, Tolerability, and Efficacy of the CD19/CD20 Dual-Target in vivo CAR-T Lentiviral product in the Treatment of Relapsed/Refractory B-cell Malignancies