Phase I trial of LB2501: Novel in vivo CD19/CD20 CAR T-cell therapy for R/R B-NHL

Preliminary results from an ongoing, phase I, first-in-human, open-label, multicenter, dose-escalation study (NCT07002112), evaluating LB2501, a third-generation, self-inactivating, CD19/CD20 dual-target chimeric antigen receptor (CAR) T-cell therapy that uses a lentiviral vector (LVV) to generate CAR T-cells in vivo without lymphodepletion, in adults with relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL), were presented by Lei Fan at the European Hematology Association (EHA) 2026 Congress, June 11–14, 2026, Stockholm, SE. As of April 1, 2026, 12 patients had received LB2501 across dose level (DL) 1 (2 × 10⁸–5 × 10⁸ transducing units [TU]; n = 6, including four at 2 × 10⁸ TU and two at 5 × 10⁸ TU) and DL2 (1 × 10⁹ TU; n = 6) in a 3 + 3 design with backfilling. The primary endpoints were safety, recommended phase II dose (RP2D), and pharmacokinetics (PK) of the LVV and generated CAR T-cells.

Key data: All patients experienced treatment-emergent adverse events (TEAEs), with Grade ≥3 TEAEs reported in 91.7% of patients (DL1, 83.3%; DL2, 100%). No dose-limiting toxicities (DLTs), serious AEs (SAEs), immune effector cell-associated neurotoxicity syndrome (ICANS), non-ICANS neurotoxicity, or deaths were reported. Grade ≥3 cytopenias were manageable and transient. Infusion-related reactions (IRRs) and cytokine release syndrome (CRS) occurred in 75.0% and 66.7% of patients, respectively (all Grade 1–2). At DL1, no responses were observed, while at DL2, the overall response rate (ORR) was 100%, including complete response (CR) in 83.3% of patients; all responses were ongoing at data cutoff. CAR T-cell expansion was detected in 11/12 patients (DL1, 83%; DL2, 100%) in a dose-dependent manner. At DL2, median peak CAR T-cell expansion (C_max) was 109,117.5 copies/µg genomic DNA and median time to peak expansion (T_max) was 15.0 days; viral copy number became undetectable within 24 hours. Vector integration was polyclonal and diverse, with no evidence of non-specific transduction in non-T-lymphocyte populations.

Key learning: These preliminary phase I data support continued evaluation of LB2501 as a potential first-in-class, off-the-shelf, single-infusion, outpatient use, in vivo CAR T-cell therapy in R/R B-NHL.