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ABCL-853: Vispa-Cel, an Allogeneic Anti-CD19 CAR-T Therapy With a PD-1 Knockout, in Patients With Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma (ANTLER Phase 1 Clinical Trial)
Abstract   Peer reviewed

ABCL-853: Vispa-Cel, an Allogeneic Anti-CD19 CAR-T Therapy With a PD-1 Knockout, in Patients With Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma (ANTLER Phase 1 Clinical Trial)

Mohamad Cherry, Houston Holmes, James Essell, Ayad Hamdan, Boyu Hu, Elizabeth Brem, Rushang D Patel, Sunita Nasta, Costas K Yannakou, Don A Stevens, …
Clinical lymphoma, myeloma and leukemia, Vol.26(Suppl 1), pp.S924-S925
08/2026
DOI: 10.1016/S2152-2650(26)02597-8

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Abstract

Objectives: Vispacabtagene regedleucel (vispa-cel, CB-010) is an allogeneic anti-CD19 CAR-T therapy manufactured from healthy donors. Cas9 chRDNA genome editing technology is used for three genome edits: (1) KOof TRAC to reduce GVHDrisk, (2) insertion of a CD19-specific CAR (FMC63, 4-1BB), and (3) KO of PD-1 to prevent premature CAR-T cell exhaustion and potentially enhance antitumor activity. The ANTLER phase 1 trial (NCT04637763) evaluated safety and efficacy of vispa-cel in relapsed/refractory B-cell non-Hodgkin lymphoma. Design: Patients received lymphodepletion of sequential cyclophosphamide (60 mg/kg/day × 2 days) then fludarabine (25 mg/m2/day × 5 days) followed by a single vispa-cel infusion of 40 million (M), 80 M, or 120 M cells. Results: As of September 2, 2025, 84 patients received vispa-cel (63 for 2L LBCL, CD19-naive). Their median age was 66 years. Vispa-cel was generally well tolerated with no GVHD. CRS occurred in 55% of patients (grade ≥3, 1%), ICANS occurred in 14% of patients (grade ≥3, 4%), infections occurred in 51% of patients (grade ≥3, 25%), grade ≥3 prolonged cytopenias occurred in 28% of patients, and immune effector cell–associated hemophagocytic lymphohistiocytosis syndrome occurred in 2% of patients (all grade ≥3). By day 60, neutropenia and thrombocytopenia recovered to grade ≤2 by 95% and 86%, respectively. Five deaths occurred due to adverse events (one related, one possibly related, three unrelated). The 80-M cell dose was selected as the RP2D. Patients who received optimized vispacel (donor age, <30 years; ≥2 human leukocyte antigen-matched alleles; n = 35) had 86% ORR and 63% CR rate. The median PFS and DoR were not reached, with a 12-month PFS of 53%. Patients who received optimized vispa-cel at RP2D (n = 27) had 82% ORR and 63% CR. Updated data from patients who received optimized vispa-cel will be presented. Conclusions: Vispa-cel demonstrates deep, durable responses in 2L LBCL, on par with approved autologous CAR-T therapies, with well-tolerated safety. A randomized pivotal trial is planned for 2L LBCL patients not eligible for transplant and not candidates or not eligible for autologous CAR-T therapy based on access challenges or medical criteria, including the need for urgent therapy. 2L LBCL: second-line large B-cell lymphoma, CAR-T: chimeric antigen receptor T-cell, CD19: cluster of differentiation 19, chRDNA: chemically modified RNADNA hybrid, CR: complete response, CRS: cytokine release syndrome, DoR: duration of response, GVHD: graft-versus-host disease, ICANS: immune effector cell–associated neurotoxicity syndrome, KO: knockout, ORR: objective response rate, PD-1: programmed death-1, PFS: progression-free survival, RP2D: recommended phase 2 dose, TRAC: T-cell receptor alpha constant.
 ABCL aggressive B-cell lymphoma allogeneic CAR-T CD19 diffuse large B-cell lymphoma genome editing phase 1

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