LB2501, an investigational in vivo lentiviral vector (LVV) designed to generate CD19/CD20 dual-targeted CAR T cells within a patient following a single infusion, was deemed well tolerated and produced an objective response rate (ORR) of 100% (95% CI, 54.1%-100%) when administered at the second dose level (DL2; n = 6) in patients with relapsed/refractory B-cell non-Hodgkin lymphomas, including diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), and follicular lymphoma, according to data from a phase 1 first-in-human study (NCT07002112).1
Findings presented at the
At DL2 of 8×108 to 1.5×109 transducing units (TU), 5 of 6 responders experienced a complete response (CR; 83.3%; 95% CI, 35.9%-99.6%). At dose level 1 (DL1; 1×10⁸ to 5×10⁸ TU), no responses occurred in evaluable patients (n = 6). Across both dose levels, the ORR was 50.0% (95% CI, 21.1%-78.9%), and the CR rate was 41.7% (95% CI, 15.2%-72.3%). At the April 1, 2026, data cutoff, all DL2 responses were ongoing at a median follow-up of 2.3 months (range, 2.0-4.5).
“These data support the further development of LB2501 as a potential first-in-class, off-the-shelf, single-infusion [CAR T-cell therapy with no] lymphodepletion [and] outpatient use...for relapsed/refractory B-cell lymphoma,” lead study author Lei Fan, MD, PhD, of Jiangsu Province Hospital in Nanjing, China, said in a presentation of the data.
Although autologous CAR T-cell therapies have been integrated into the treatment paradigms across various B-cell non-Hodgkin lymphomas, ex vivo manufacturing remains complex and individualized, leading to treatment delays, high cost, restricted access, and treatment-related mortality, Fan explained.
LB2501 is a third-generation, self-inactivating, replication-incompetent LVV engineered to generate CD19/CD20 dual-target CAR T cells inside the patient.
The ongoing phase 1, open-label, multicenter dose-escalation study is enrolling patients at least 18 years of age with histologically confirmed LBCL, indolent non-Hodgkin lymphoma, MCL, and confirmed chronic lymphocytic leukemia who have received at least 2 prior lines of therapy or were refractory to first-line systemic therapy; notably, prior treatment with autologous CD19-directed CAR T-cell therapy or T-cell engagers is allowed. An ECOG performance status of 0 or 1 is also required.
The dose-escalation portion of the trial is enrolling a maximum of 30 patients, and the study features a 3+3 design with backfill. LB2501 is being evaluated at DL1, DL2, and dose level 3 (2×109 to 4×109 TU). After screening, patients are allowed to receive bridging therapy if applicable. Notably, no lymphodepletion is used prior to LB2501 infusion, although prophylactic medications include nonsteroidal anti-inflammatory drugs and antihistamines; glucocorticoids are not required. LB2501 is given as a single infusion, and follow-up visits occur every 30 days for the first 6 months, then every 90 days thereafter.
In Vivo CD19/CD20 CAR T-Cell Therapy in R/R B-Cell NHL: Early Phase 1 Takeaways
Safety, determining the recommended phase 2 dose, and pharmacokinetics are serving as the trial’s primary end points. Secondary end points include efficacy outcomes, such as ORR, time to response, duration of response, progression-free survival, and overall survival.
Among the 12 evaluable patients treated across DL1 and DL2 prior to data cutoff, the median age was 58.5 years (range, 36-73), and 16.7% were at least 65 years of age. Half of patients had an ECOG performance status of 0, and the other half had a performance status of 1. Disease histology comprised DLBCL (50.0%), follicular lymphoma (25.0%), MCL (16.7%), and primary mediastinal B-cell lymphoma (8.3%). Most patients (66.7%) had Ann Arbor stage III to IV disease. The median absolute lymphocyte count was 1.03 x 109/L (range, 0.58-1.44), and the median CD3-positive cell count was 557 cells/µL (range, 311-1713).
Patients had received a median of 3.0 prior lines of therapy (range, 1-7); 41.7% of patients had relapsed disease following their last line of therapy, and 58.3% of patients were refractory to their last line of therapy. Notably, 8.3% of patients had received a prior CD19-directed CAR T-cell therapy, and 16.7% of patients had received a prior T-cell engager. The median sum of the product of diameters was 921.4 mm2 (range, 144-2540).
Pharmacokinetic analyses demonstrated dose-dependent in vivo CAR T-cell expansion, with CAR T cells detectable via quantitative PCR in 83% of patients treated at DL1 and 100% of patients treated at DL2 patients. At DL2, peak CAR-T expansion (Cmax) reached a median of 109,117.5 copies/µg genomic DNA (range, 32,497-137,457), with a median time to peak expansion (Tmax) of 15.0 days (range, 13-18). These respective values were 1068 copies/µg genomic DNA (range, 51-113,350) and 17.0 days (range, 14-30) at DL1.
Treatment-emergent AEs (TEAEs) of any grade were reported in all patients across both dose levels; grade 3 or higher TEAEs occurred in 83.3% of patients treated at DL1 and 100% of patients treated at DL2. At DL2, the rates of any-grade and grade 3 or higher TEAEs related to LB2501 LVV were 100% and 66.7%, respectively. TEAEs related to the generated CAR T cells occurred at any grade in 100% of patients and at grade 3 or higher in 83.3% of patients treated at DL2.
Infusion-related reactions occurred in 50% of patients treated at DL1 and 100% of patients treated at DL2, although all these AEs were grade 1 or 2. Cytokine release syndrome was reported in 33.3% of patients treated at DL1 and 100% of patients treated at DL2, but these AEs were also all grade 1 or 2.
At DL2, other LB2501 LVV infusion–related TEAEs reported in at least 30% of patients included increased C-reactive protein (CRP) levels (grade 1/2, 83.3%; grade ≥ 3, 0%), decreased lymphocyte count (0%; 66.7%), decreased white blood cell (WBC) count (33.3%; 33.3%), anemia (50.0%; 0%), decreased platelet count (50.0%; 0%), decreased neutrophil count (16.7%; 33.3%), hypoalbuminemia (50.0%; 0%), and increased serum ferritin levels (33.3%; 0%).
Other TEAEs related to the generated CAR T cells reported in at least 30% of patients treated at DL2 comprised decreased lymphocyte count (grade 1/2, 16.7%; grade ≥ 3, 66.7%), decreased WBC count (33.3%; 50.0%), decreased lymphocyte count (50.0%; 16.7%), increased serum ferritin levels (66.7%; 0%), decreased platelet count (83.3%; 0%), increased interleukin levels (83.3%; 0%), increased CRP levels (66.7%; 0%), increased blood lactate dehydrogenase levels (83.3%; 0%), decreased neutrophil count (0%; 83.3%), anemia (66.7%; 0%), and increased fibrin D dimer levels (66.7%; 0%).
