Examining safety and durable disease remission in R/R B-ALL after autologous CD19-directed CAR T cells produced by novel PRIMCAR manufacture platform.

person Zhi Yang Chongqing Precision Biotech Co., Ltd., Chongqing, China info_outline Zhi Yang, Shiqi Li, Yu Li, Lin Liu, Zhongtao Yuan, Yingzi Zhang, Le Luo, Lihua Zhang, Yingnian Chen, Qianzhen Zhang, Junjie Shen, Yunyan Li, Linling Wang, Meiling Wang, Wei Zhu, Xiao He, Youcheng Wang, Yancheng Dong, Sanbin Wang, Cheng Qian

Authors person Zhi Yang Chongqing Precision Biotech Co., Ltd., Chongqing, China info_outline Zhi Yang, Shiqi Li, Yu Li, Lin Liu, Zhongtao Yuan, Yingzi Zhang, Le Luo, Lihua Zhang, Yingnian Chen, Qianzhen Zhang, Junjie Shen, Yunyan Li, Linling Wang, Meiling Wang, Wei Zhu, Xiao He, Youcheng Wang, Yancheng Dong, Sanbin Wang, Cheng Qian Organizations Chongqing Precision Biotech Co., Ltd., Chongqing, China, 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China, Kunming, China Abstract Disclosures Research Funding Pharmaceutical/Biotech Company ChongQing Precision Biotech Co., Ltd Background: CD19 chimeric antigen receptor (CAR) T cell therapy has shown promising efficacy in the r/r B-ALL. However, the life-threatening side effect and disease relapse limited its wide application. To overcome these limitations, we established a novel PrimeCAR platform (PRIMCAR) and reported the preliminary safety and effectiveness data of MC-1-50 CAR-T cells before (Shiqi Li, et al. J Clin Oncol 2022; 40 [suppl 16]. Abstract 7008). Here, we present updated data. Methods: In this Phase I /II study (NCT04271410), MC-1-50 CAR T cells were manufactured by the PRIMCAR platform, which reduces manufacture periods to about 2 days. Patients (pts) received single-dose of MC-1-50 at dose ranged 1-5×10 5 CAR+/kg (Level 1, 1×10 5 CAR+/kg; Level 2, 2×10 5 CAR+/kg; Level 3, 3×10 5 CAR+/kg; Level 4, 5×10 5 CAR+/kg). Pts were pre-conditioned with fludarabine (25-30 mg/m 2 ) and cyclophosphamide (200-300 mg/m 2 ) daily for 3 days. Toxicity was graded by CTCAE, CRS and ICANS were graded by ASTCT criteria. Results: 19 pts with r/r B-ALL were infused. Disease characteristics and outcomes are shown in the table. No DLTs were reported. 18 pts (94.7%) experienced CRS, including 10 (52.6%) at grade 1, 7 (36.8%) at grade 2, 1 (5.3%) at grade 3, and no ≥ 4 CRS were observed. Three pts (15.8%) experienced ICANS, including 2 (10.5%) at grade 1, 1(5.3%) at grade 2, and no ≥ 3 ICANS occurred. All patients achieved CR/CRi (BM MRD-) in the first month. All patients received no other anti-tumor therapy until relapse was confirmed. The median DOR was not reached. 6 patients confirmed relapse, including 4 were CD19 negative and 2 were CD19 positive but with CD19 gene mutation at the time of relapse. All patients in 4 dose levels had good CAR-T expansion and exhibited long persistence features. Only 3 patients experienced the loss of CAR-T. Conclusions: Treatment of r/r B-ALL at a very low dose resulted in excellent safety profiles while exhibiting a high and durable efficacy. That makes this PRIMCAR platform potential for outpatient administration in the future. Clinical trial information: NCT04271410. Disease characteristics and safety outcomes. ID Age Gender Prior HSCT Tumor burden (%) Dose (×10 5 /kg) CRS ICANS ALL01-01 17 M Y 71.1 1 2 / ALL01-02 39 M N 82.8 1 1 / ALL01-03 26 M N 51.7 1 1 / ALL01-04 38 F N 30.2 1 1 / ALL01-05 8 M Y 25.4 1 2 1 ALL01-06 71 M N 83.0 1 / / ALL02-01 34 M N 68.8 2 2 / ALL02-02 52 F N 58.4 2 1 / ALL02-03 22 F N 34.6 2 1 / ALL02-04 70 F N 44.5 2 2 1 ALL02-05 25 F N 77.3 2 1 / ALL02-06 24 M Y 83.0 2 3 / ALL02-07 36 F N 33.6 2 1 / ALL03-01 39 F N 79.3 3 2 / ALL03-02 21 M N 79.0 3 1 / ALL03-03 23 F N 83.0 3 1 / ALL03-04 48 M N 3.3 3 1 / ALL04-01 29 F Y 0 a 5 2 2 ALL04-02 6 M N 28.0 5 2 / a The patient has only extramedullary lesions.

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