In Vivo CD19/CD20 CAR T-Cell Therapy for Relapsed/Refractory B-Cell Lymphoma

This Phase 1, open-label, single-arm, dose-escalation study is designed to evaluate the safety and tolerability of SL1617 Injection in patients with relapsed or refractory B-cell lymphoma. SL1617 Injection is an investigational in vivo CAR T-cell immunotherapy targeting CD19 and CD20, based on an engineered lentiviral vector system. The vector is designed to specifically target and transduce T cells and NK cells in vivo, enabling in situ generation of functional CAR-expressing immune cells following a single intravenous infusion SL1617 Injection will be administered as a single intravenous infusion. Dose escalation will follow a traditional 3+3 design. The planned starting dose is 1.0 × 10\^9 transducing units (TU), followed sequentially by dose levels of 3.0 × 10\^9 TU and 6.0 × 10\^9 TU. At each dose level, three participants will initially be enrolled. If none of the first three participants experiences a dose-limiting toxicity (DLT), enrollment may proceed to the next dose level. If two or more of the first three participants experience a DLT, further dose escalation will be stopped. If one of the first three participants experiences a DLT, three additional participants will be enrolled at the same dose level. Dose escalation may proceed if none of the three additional participants experiences a DLT. Dose escalation will be stopped if at least one of the three additional participants experiences a DLT, resulting in DLTs in at least two of six participants at that dose level. If the maximum tolerated dose (MTD) is not reached after completion of the DLT observation period for the 6.0 × 10\^9 TU dose cohort, the investigators may explore higher dose levels based on cumulative safety data and pharmacodynamic evidence. The primary objective is to evaluate the safety of SL1617 Injection, including the incidence and severity of cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, hematologic toxicity, organ toxicity, and other treatment-related adverse events. Secondary objectives include assessment of preliminary antitumor activity using objective response rate, complete response rate, partial response rate, overall survival, progression-free survival, and event-free survival. Exploratory objectives include characterization of in vivo CAR-T cell kinetics (CAR copy number, Cmax, Tmax, and AUC28d) and clonal evolution.