Legend Biotech’s in vivo CAR-T therapy LB2501 achieved a 100% response rate and 83.3% complete response rate in relapsed/refractory B-cell non-Hodgkin lymphoma, supporting further development in an ongoing Phase 1 study.
Written By: Meghana Jinka, PharmD
Reviewed By: Pharmacally Editorial Team
Legend Biotech has unveiled the first clinical proof-of-concept data for LB2501, an investigational in vivo CD19/CD20 dual-targeting CAR-T therapy, at the European Hematology Association (EHA) 2026 Congress. In an ongoing Phase 1 study, the therapy achieved a 100% objective response rate (ORR) and an 83.3% complete response (CR) rate at the higher dose level, with all responses ongoing at the time of data cutoff. The findings mark an important step toward generating CAR-T cells directly within patients and could reshape how cell therapies are delivered in the future.
Trial Design and Patient Population
The ongoing first-in-human Phase 1 dose-escalation study (NCT07002112) enrolled 12 patients with relapsed or refractory B-cell non-Hodgkin lymphoma (R/R B-NHL) across two dose levels. Participants had received a median of three prior therapies, and nearly 60% were refractory to their most recent treatment. The study included patients with diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), and follicular lymphoma (FL).
The open-label, multicenter trial is evaluating the safety, tolerability, pharmacokinetics, recommended Phase 2 dose, and preliminary efficacy of LB2501. Notably, treatment was administered without lymphodepletion.
Efficacy Results
At the higher dose level (DL2), LB2501 achieved a 100% ORR and an 83.3% CR rate among six treated patients. Responses were observed across DLBCL, MCL, and FL, and all responses remained ongoing at the time of analysis.
Across both dose levels, the ORR was 50.0% and the CR rate was 41.7%. While the findings are preliminary, the depth of response observed after a single infusion supports continued clinical evaluation of the platform. Longer follow-up will be required to determine the durability of these responses.
Safety Profile
LB2501 demonstrated a favorable safety profile. Investigators reported no dose-limiting toxicities, serious adverse events, immune effector cell-associated neurotoxicity syndrome (ICANS), or treatment-related deaths.
Infusion-related reactions occurred in 75.0% of patients and cytokine release syndrome (CRS) occurred in 66.7%. All events were Grade 1 or 2. No patients required glucocorticoids for CRS management, although four patients received tocilizumab.
The absence of severe CRS, neurotoxicity, or treatment-related mortality is notable given the therapy generated CAR-T cells directly within patients without lymphodepleting chemotherapy.
Pharmacokinetics and Translational Insights
Pharmacokinetic analyses confirmed successful in vivo CAR-T generation following a single infusion. Dose-dependent CAR-T expansion was observed in all patients treated at DL2 and in five of six patients treated at DL1.
Viral vector levels in peripheral blood peaked immediately after infusion and became undetectable within 24 hours, while CAR-T cells remained detectable for up to 116 days. These findings suggest efficient in vivo CAR-T generation despite rapid vector clearance.
Additional translational studies further supported the platform’s safety profile. Researchers detected no evidence of non-specific transduction in natural killer cells or other non-target immune cell populations. Vector integration patterns were highly polyclonal and diverse, supporting controlled in vivo T-cell engineering.
Platform Significance
LB2501 delivers a viral vector that programs T cells directly inside the patient to recognize both CD19 and CD20, eliminating the need for ex vivo cell collection and manufacturing.
Conventional autologous CAR-T therapies require individualized cell harvesting, manufacturing, and lymphodepletion, processes that can delay treatment and limit patient access. By generating CAR-T cells directly within the body through a single infusion, LB2501 could simplify treatment logistics, shorten treatment timelines, and broaden access to cellular therapies.
The study also provides early clinical validation of the broader in vivo CAR-T concept, an emerging field that seeks to overcome many of the operational challenges associated with current CAR-T approaches.
Researchers and company executives said the findings support further development of LB2501, citing the combination of deep responses, a favorable safety profile, and the feasibility of generating CAR-T cells directly within patients without lymphodepletion.
Path Forward
Legend Biotech will continue dose escalation and further evaluate LB2501 in the ongoing Phase 1 study. While longer follow-up is needed to assess response durability, the early efficacy, favorable safety profile, dose-dependent CAR-T expansion, and rapid vector clearance provide initial clinical validation of the in vivo CAR-T approach and support its continued development across B-cell malignancies.
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About the Writer
Meghana Jinka (LinkedIn) is a Pharm.D graduate with a strong interest in clinical pharmacy, clinical research, pharmacovigilance, and medical writing. She has developed expertise in evaluating scientific literature, interpreting clinical data, and communicating complex medical information in a clear and accessible manner. Through clinical training, patient counseling, and healthcare awareness activities, she has gained practical experience in evidence-based medicine and patient-centered care. Passionate about healthcare communication, Meghana is committed to developing accurate, engaging, and evidence-based healthcare documents that support healthcare professionals and the wider community.