Abstract Introduction CART19/20 was developed by engineering autologous naïve/memory T (TN/MEM) cells with a bispecific anti-CD19/CD20 chimeric antigen receptor (CAR) with the goal of overcoming resistance to single-target CD19-directed CAR-T cells. We report an update of a first-in-human phase 1 clinical trial of CART19/20 for patients with relapsed/refractory non-Hodgkin lymphoma (R/R NHL) and small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL) (NCT04007029) with a median follow-up of over 4 years. Methods Eligible patients were ≥18 years old with R/R NHL and SLL/CLL, with ECOG 0 or 1. Patients were included if they had 2 or more prior lines of therapy with diffuse large B cell lymphoma (DLBCL) and primary mediastinal B cell lymphoma (PMBCL) and 3 or more prior lines for CLL/SLL, follicular lymphoma (FL), and mantle cell lymphoma (MCL). Autologous leukocytes were obtained by leukapheresis and sorted for CD62L+ TN/MEM cells, followed by lentiviral transduction of the bispecific CD19/CD20 CAR, and subsequent expansion of gene-modified T-cells. The primary end point was safety, and secondary endpoints were clinical response, progression free survival (PFS), overall survival (OS), and CART19/20 persistence. Results As of the data cutoff of November 25, 2025, 15 patients had received CAR-T 19/20 cells (6 DLBCL, 4 FL, 4 MCL, 1 HGBCL). Patients were treated at two dose levels, either 50x106 +/- 30% CAR+ cells (12 patients) or 200 x106 +/- 30% CAR+ cells (3 patients). The median age was 60 (range 29 to 70). Patients had received a median of 4 prior lines of therapy (range 2 to 8). All patients except one had stage IV disease, and 11 of 15 received bridging therapy. The CART19/20 cells were enriched with central-memory T cells (TCM: CD45RA–/CD45RO+/CD62L+). Maximum CRS was grade 2 which occurred in one patient. There were 9 patients that experienced max grade 1 CRS and no ICANS or neurotoxicity. There were 12 serious adverse events and two dose limiting toxicities. Fourteen of fifteen patients achieved an objective response (93% ORR), with 12 patients (80%) achieving a complete response (CR). With a median follow up of 51 months (range: 6.4 – 73.1), the median PFS was 37.5 months (95% CI 4.8 – not estimable) and the median OS was not yet reached. The median peak CAR-T19/20 cell expansion was 592,500 cells/mL whole blood, with mean persistence of CART 19/20 from date of infusion to last date of measurable CART19/20 cells of 526 days. Conclusion Overall, this phase 1 trial demonstrates that CART19/20 is a safe and effective therapy with the potential to overcome common resistance mechanisms of CAR-T cell therapy. Citation Format: Sophie Carlson, Benjamin Puliafito, Christopher M. Walthers, Brenda Ji, Jacob Naparstek, Jia Chen, Mobina Roshandell, Caitlin Harris, Mobina Khericha Gandhi, Melanie Ayala Ceja, Christy Sidhu, Karla Nawaly, Martin Allen-Auerbach, Sven De Vos, Patricia Young, Caspian Oliai, Gary Schiller, John Timmerman, Antoni Ribas, Yvonne Chen, Sarah Larson. Phase 1 Trial of Bispecific CART19/20 Cells for Relapsed or Refractory Non-Hodgkin Lymphoma: Updated Results with Over Four Years Median Follow Up abstract. In: Proceedings of the AACR Immuno-Oncology Conference (AACR IO): Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2026 Feb 18-21; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2026;14(2 Suppl):Abstract nr LB-C001.
Carlson et al. (Thu,) studied this question.