Autologous CD19-directed CAR T cells produced by novel PrimeCAR manufacture platform exhibit safety, efficacy, and long persistence profiles in relapsed/refractory B-lineage acute leukemia (r/r B-ALL).

7008 Background: CD19 chimeric antigen receptor (CAR) T cell therapy has shown promising efficacy in the r/r B-ALL. However, the life-threatening side effects especially high grades of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) limited its wide application. To overcome these limitations, we established a novel PrimeCAR platform based on moderate activation and short expansion to manufacture MC-1-50, an autologous CD19-directed CAR T cell. Our preclinical study showed that MC-1-50 exerted a great efficacy and less cytokines secretion. Methods: In this Phase I /II study (NCT04271410), CAR T cells were manufactured by PrimeCAR platform, which reduces manufacture periods to about 2 days. T cells were transducted with a lentiviral vector encoding a humanized CD19 specific scFv following 4-1BB and CD3ζ cytoplasmic domain. Patients (pts) received single-dose of MC-1-50 at dose level 1 (1×105 CAR+/kg), level 2 (3×105 CAR+/kg), and level 3 (1×107 CAR+ totally, ranged 1.67-3.85×105 CAR+/kg). Pts were pre-conditioned with fludarabine (25-30 mg/m2) and cyclophosphamide (200-300 mg/m2) daily for 3 days. Toxicity was graded by CTCAE, CRS and ICANS were graded by ASTCT criteria. Results: As of Feb 10, 2022, 13 pts with r/r B-ALL were infused with MC-1-50. Disease characteristics and outcomes are shown in the table. No DLTs were reported. Eleven pts (84%) experienced CRS, including 7 (54%) at grade 1 and 4 (30%) at grade 2, no ≥ 3 CRS were observed. One pts (7%) experienced grade 1 ICANS, no ≥ 2 ICANS occurred. The Tmax for IL-6 was detected around day 11 (123.3±165.16 pg/ml). There were similar low secretion features of other cytokines, which is consistent with low CRS and ICANS. In all dose levels, 13 pts finished 1M evaluation and the CR rate in 1M is 100%. Four pts finished 3M evaluation and the CR rate in 3M is 75%, 1 pts relapsed at the month 3 with CD19 mutation. One pts had a CR statue at the month 11. Cmax for CAR copy number in 3 dose levels are similar and the average number of Cmax of CAR is 275901.6 copies/ug genomic DNA. Conclusions: PrimeCAR platform could produce CAR T cells in very short time with high percentage of Tscm. Treatment of r/r B-ALL at very low dose resulted in excellent safety profile, while exhibited a promising efficacy. That make this PrimeCAR platform potential for outpatient administration in the future. Clinical trial information: NCT04271410. [Table: see text]