Legend Biotech's in vivo CAR-T LB2501 showed 100% objective response and 83% complete response at the high dose in B-cell NHL, with no serious safety events and no lymphodepletion.
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Legend Biotech reported Phase 1 data for LB2501, an in vivo CD19/CD20 dual-targeting CAR-T therapy, at the EHA congress. A single infusion at the higher dose level (DL2) produced a 100% objective response rate (6 of 6 patients) and an 83.3% complete response rate in relapsed or refractory B-cell non-Hodgkin lymphoma. All responses were ongoing at data cutoff.
The trial treated 12 patients across two doses without the standard lymphodepletion step that current CAR-T products require. The drug is designed to generate CAR-T cells inside the patient after a single intravenous injection, skipping the weeks-long ex vivo manufacturing process.
"In vivo CAR-T represents a compelling frontier in cell therapy, enabling the generation of CAR-T cells directly within the patient," said Ying Huang, Ph.D., CEO of Legend Biotech. "These early data, with deep responses from a single infusion across patients, give us confidence in the path ahead."
At DL2, responses were seen across diffuse large B-cell lymphoma, mantle cell lymphoma, and follicular lymphoma. Across both dose levels the ORR was 50% and the CR rate was 41.7%. Patients had received a median of three prior lines of therapy, and 58.3% were refractory to their most recent treatment.
No dose-limiting toxicities, serious adverse events, ICANS, or deaths were reported. Infusion-related reactions occurred in 75% of patients, all Grade 1-2, with a median onset of 1.4 hours and recovery within 18.6 hours. Cytokine release syndrome occurred in 66.7% of patients, median onset at Day 11, duration 4.5 days. Four patients received tocilizumab; none required glucocorticoids.
CAR-T cells expanded in 100% of patients at DL2 and 83% at DL1. Cells remained detectable in peripheral blood for up to 116 days. Viral copy number peaked immediately after infusion and fell to undetectable within 24 hours. No non-specific transduction was found in NK cells or other non-T populations. Vector integrations were polyclonal and diverse, supporting proof-of-concept for in vivo T-cell engineering.
Lei Fan, M.D., Ph.D., a professor at Jiangsu Province Hospital who consulted for Legend Biotech, said: "The responses observed at the higher dose level achieved a 100% objective response rate, together with a favorable safety profile and the absence of lymphodepletion, support further investigation of LB2501."
Legend Biotech is best known for CARVYKTI, its approved CAR-T for multiple myeloma, developed and marketed with Johnson & Johnson. LB2501 represents a potential next step: an all-in-one therapy that could be administered in a single clinic visit without external manufacturing. If later-stage data hold, the product would compete in a large addressable market – B-cell NHL accounts for roughly 85% of non-Hodgkin lymphoma cases.
The Phase 1 study is still enrolling at higher dose levels. The next data readout will show whether durability and response rates improve further or whether off-target effects emerge at higher doses. For now, the 100% ORR at DL2 provides the first clinical evidence that in vivo CAR-T can match the efficacy of traditional CAR-T without the logistical burden.
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