The Safety and Efficacy of p CAR-19B, a Scfv Humanlized CD19-Directed CAR-T for Patients with Relapsed/Refactory (R/R) CD19+ B-ALL

Introduction: Two murine anti-CD19 scFv based chimeric antigen receptors T cell (CAR-T) products have been approved by FDA for children and adults R/R B-ALL patients, with about 50%-70% complete remission (CR) rates. Humoral and/or cellular immune responses against murine scFv may attenuate the efficacy. To reduce immunogenicity of murine scFv, we developed an optimal humanized anti-CD19 CAR-T product named pCAR-19B, which have a CAR structure including humanized CD19 specific scFv following 4-1BB and CD3ζ cytoplasmic domain. Here we report the preliminary safety and efficacy data for the adults R/R B-ALL patients in a phase I clinical trials. Methods: In the phase Istudy (NCT04888442), Eligible patients were histologically confirmed CD19+ B-ALL, KPS＞60, relapsed or refractory to standard therapies. Patients received single-dose of pCAR-19B at dose level 1 (DL1) (0.6×106 CAR/kg), level 2 (DL2) (2×106 CAR/kg) after fludarabine (25-30 mg/m2 × 3 days) and cyclophosphamide (10-20mg/ kg× 3 days) based pre-condition. Toxicity was graded by CTCAE, CRS and ICANS were graded by ASTCT criteria. Primary endpoint is the incidence of dose-limiting toxicities (DLTs) in the first 28 days. Secondary endpoints are cellular kinetics, overall response rate (CR/CRi), duration of response, and overall survival. Results: As of June 30, 2022, nine patients (3 in DL1, 6 in DL2) were infused with pCAR-19B and all patients have finished at least 6 months follow up visit. Demographics, baseline disease, prior treatment and special concerned adverse events are presented in the table. CAR-T-related adverse events occurred in 9 patients (9/9, 100%), no adverse events leading to patient withdrawal from the study occurred. 8 patients (8/9, 89%) experienced cytokine release syndrome (CRS), including 5 (5/9, 56%) grade 1, 3 (3/9, 33%) grade 2, and no grade 3 or higher CRS occurred. Two patients (2/9, 22%) experienced immune effector cell-associated neurotoxicity syndrome (ICANS), including 1 (1/9, 11%) grade 1, 1 (1/9, 11%) grade 2, and no grade 3 or higher ICANS occurred. No DLTs were reported. 100% (9/9) CR/CRi was achieved in the first month after CAR-T infusion. The relapse-free survival (RFS) is presented in the figure. The median OS and RFS is not reached yet. No anti-CAR antibody was detected in any patients in 1M and 3M after CAR-T infusion. Conclusion: pCAR-19B has demonstrated a good safe profile and 100% CR rate in phase I study for adults R/R CD19+ B-ALL. The muti-center pivotal study is going to recruit patients soon in China. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal