Phase 2 study of anbal‐cel, novel anti‐cd19 car‐t therapy with dual silencing of pd‐1 and tigit in relapsed or refractory large b cell lymphoma ‐ interim analysis result

Introduction: Anbal-cel is a novel autologous anti-CD19 CAR-T cell therapy which has been knocked-down for PD-1 and TIGIT expression using OVIS platform. It demonstrated superior T-cell functionality compared to other marketed CD19 CAR-T cells at preclinical studies. Phase 1 dose escalation study confirmed anbal-cel is safe and potentially effective. Methods: Patients with relapsed or refractory LBCL were enrolled from six Korean investigator sites to receive anbal-cel at a dose of 2 × 106 CAR-T cells/kg. Primary endpoint is objective response rate (ORR) assessed by Independent Review Committee (IRC). Secondary endpoints are progression-free survival (PFS), duration of response (DOR), pharmacokinetics (PK) and safety profiles. Results: As of 28 February 2023, a total of 41 patients were infused and 34 patients completed at least one tumor response evaluation at day 28. With the median age of 63 (range 37–82), 66% of the patients (27/41) were double expressor. Non-GCB type was 76% (31/41) and 42% (17/41) were primary refractory patients. Median follow-up period was 4.6 months. ORR (CR/PR) assessed by investigators was 85.3% and CR rate at day 28 & month 3 were 73.5% (25/34) and 71.4% (22/31) respectively. IRC assessment result was similar and will be presented at the meeting. Among the 41 patients, grade 3 CRS and ICANS were reported from 6 patients (14.6%) and 2 patients (4.9%) respectively. No grade 4 CRS and ICANS was observed. Prolonged neutropenia was observed in 11 patients (26.8%) and thrombocytopenia was observed in 12 patients (29.3%). Three (7.3%) serious infections (1 bacteria and 2 COVID-19 infections) were reported during primary follow-up period. Responder group (CR) reported higher incidence and severity of CRS compared to non-responder group (Non-CR), but it was insignificant. Incidence rate, severity of ICANS and prolonged cytopenia were comparable between the two groups. Among CAR+ T-cells in the anbal-cel product, median CD4:CD8 ratio was 3.6 and CCR7+ memory phenotype CAR T-cells account for 65.8% of CAR-T cells. Median knock-down rates of PD-1 and TIGIT were 65% and 96% respectively. The responder group showed a significantly increased level of CCR7+ memory phenotype (68.6% vs. 44.9%) and PD-1 knock-down rate (71.8% vs. 59.3%) compared to the non-responder group, which showed correlation with increased levels of AUC0-28days and Cmax. Anbal-cel expansion was not correlated to tumor volume measured by SPD and TMTV. In addition, the responder group had notable changes in cytokine levels of IL-2, IL-10, IFN-γ, granzyme, GM-CSF and peak levels of various cytokines were proportional to severity of CRS. Patients with higher levels of IL-15 and MCP-1 at baseline had tendency to experience ICANS. Conclusions: Anbal-cel demonstrated unique characteristics in product profile which demonstrated potential to correlate with treatment outcomes and warrant to confirm with more data. The research was funded by: Curocell Inc. Keywords: aggressive B-cell non-Hodgkin lymphoma, cellular therapies, immunotherapy No conflicts of interests pertinent to the abstract.