Meeting
2023 ASCO Annual Meeting
Examining safety and durable disease remission in R/R B-ALL after autologous CD19-directed CAR T cells produced by novel PRIMCAR manufacture platform.
Authors
Zhi Yang
Chongqing Precision Biotech Co., Ltd., Chongqing, China
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
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 1-5×105 CAR+/kg (Level 1, 1×105 CAR+/kg; Level 2, 2×105 CAR+/kg; Level 3, 3×105 CAR+/kg; Level 4, 5×105 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: 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.
| ID | Age | Gender | Prior HSCT | Tumor burden (%) | Dose (×105/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 | 0a | 5 | 2 | 2 | |
| ALL04-02 | 6 | M | N | 28.0 | 5 | 2 | / | |
aThe patient has only extramedullary lesions.
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Abstract Details
Session Type
Poster Session
Session Title
Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant
Track
Hematologic Malignancies
Sub Track
Acute Leukemia
Clinical Trial Registration Number
NCT04271410
Citation
J Clin Oncol 41, 2023 (suppl 16; abstr 7026)
DOI
10.1200/JCO.2023.41.16_suppl.7026
Abstract #
7026
Poster Bd #
156
Abstract Disclosures
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