en.Wedoany.com Reported - Legend Biotech Corporation presented Phase 1 clinical proof-of-concept data (Abstract #LB5006) for its investigational in vivo CAR-T cell therapy LB2501 in a late-breaking session at the European Hematology Association (EHA) 2026 Congress. Results showed that in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (R/R B-NHL), LB2501 achieved a 100% objective response rate (ORR) and an 83.3% complete response rate (CR) at the higher dose level without the need for lymphodepletion.
This Phase 1 study is an open-label, multicenter, dose-escalation trial designed to evaluate the safety, recommended Phase 2 dose, pharmacokinetics, and preliminary efficacy of LB2501 in adult patients with R/R B-NHL. A total of 12 patients were enrolled and treated at two dose levels: Dose Level 1 (DL1, n=6) and Dose Level 2 (DL2, n=6). Patients had received a median of 3 prior lines of therapy, and 58.3% were refractory to their most recent treatment.
In the DL2 cohort, all 6 patients achieved an objective response, with 5 patients attaining a complete response. Responses were observed in patients with diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), and follicular lymphoma (FL). Across both dose levels combined, the ORR was 50.0% (6/12) and the CR rate was 41.7% (5/12). As of the data cutoff date, all responses in the DL2 cohort were ongoing.
LB2501 demonstrated a favorable safety profile. No dose-limiting toxicities (DLTs), serious adverse events (SAEs), immune effector cell-associated neurotoxicity syndrome (ICANS), or deaths were reported in the study. Infusion-related reactions (IRRs) and cytokine release syndrome (CRS) were the most common adverse events of special interest, all of which were Grade 1-2. The overall IRR incidence was 75.0% (9/12), with a median onset time of 1.4 hours post-infusion and a median recovery time of 18.6 hours. The overall CRS incidence was 66.7% (8/12), with a median onset time of Day 11 and a median duration of 4.5 days. No patients required corticosteroids for CRS management, and 4 patients received tocilizumab.
Pharmacokinetic analysis showed dose-dependent in vivo CAR-T expansion in 100% (6/6) of patients in the DL2 cohort and 83% (5/6) in the DL1 cohort. CAR-T cells were detectable in peripheral blood for up to 116 days. Peripheral blood viral copy numbers peaked immediately post-infusion and decreased to undetectable concentrations within 24 hours. Additional translational analyses revealed no evidence of non-specific transduction in NK cells or other non-T/B/NK lymphocyte populations, and vector integration was highly polyclonal and diverse, supporting the proof of concept for in vivo T-cell engineering.
Dr. Ying Huang, CEO of Legend Biotech, stated that in vivo CAR-T cell therapy aims to generate CAR-T cells directly within the patient's body, potentially simplifying treatment and expanding accessibility. These early data, showing deep responses following a single infusion in patients, give the company confidence in the path forward.
Professor Lei Fan, Administrative Director of the Department of Hematology at Jiangsu Province Hospital, noted that the 100% objective response rate observed at the higher dose level, combined with the favorable safety profile and the absence of a need for lymphodepletion, supports further investigation of LB2501 as a novel in vivo CAR-T approach. The pharmacokinetic and translational findings presented at EHA further support the feasibility of generating CAR-T cells directly within the patient's body.
LB2501 is an investigational, potentially first-in-class CD19/CD20 bispecific in vivo CAR-T therapy designed to generate CAR-T cells directly within the patient's body via a single intravenous infusion. The therapy is currently being evaluated in a Phase 1 open-label study (NCT07002112) in patients with relapsed/refractory B-cell malignancies.
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