Meeting
2022 ASCO Annual Meeting
Autologous CD19-directed CAR T cells produced by novel PrimeCARmanufacture platform exhibit safety, efficacy, and long persistence profiles in relapsed/refractory B-lineage acute leukemia (r/r B-ALL).
Authors
Shiqi Li
920th Hospital of Joint Logistics Support Force of People's Liberation Army of China, Kunming, China
Shiqi Li , Zhi Yang , Zucong Chen , Yu Li , Lin Liu , Zhongtao Yuan , Yingzi Zhang , Le Luo , Lihua Fang , Yingnian Chen , Qianzhen Zhang , Junjie Shen , Yunyan Li , Linling Wang , Meiling Wang , Wei Zhu , Sanbin Wang , Cheng Qian
Organizations
920th Hospital of Joint Logistics Support Force of People's Liberation Army of China, Kunming, China, Chongqing Precision Biotech Co., Ltd., Chongqing, China, The People's Hospital of Dehong Prefecture, Dehong, China
Research Funding
Pharmaceutical/Biotech Company
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.
| ID | Age | Gender | Prior HSCT | Tumor burden | Dose | CRS | ICANS |
|---|---|---|---|---|---|---|---|
| 01 | 17 | M | Y | 71% | 1×105/kg | 2 | / |
| 02 | 39 | F | N | 83% | 1×105/kg | 1 | / |
| 03 | 26 | M | N | 52% | 1×105/kg | 1 | / |
| 04 | 34 | M | N | 69% | 3×105/kg | 2 | / |
| 05 | 21 | M | N | 79% | 3×105/kg | 1 | / |
| 06 | 23 | F | N | 83% | 3×105/kg | 1 | / |
| 07 | 39 | F | N | 79% | 1×107 total | 2 | / |
| 08 | 52 | F | N | 58% | 1×107 total | 1 | / |
| 09 | 22 | F | N | 35% | 1×107 total | 1 | / |
| 10 | 70 | F | N | 45% | 1×107 total | / | / |
| 11 | 54 | M | N | 0%a | 1×107 total | / | / |
| 12 | 38 | F | N | 30% | 1×107 total | 1 | / |
| 13 | 8 | M | Yes | 25% | 1×107 total | 2 | 1 |
aThe patient has only extramedullary lesions.
Disclaimer
This material on this page is ©2024 American Society of Clinical Oncology, all rights reserved. Licensing available upon request. For more information, please contact licensing@asco.org
Abstract Details
Session Type
Clinical Science Symposium
Session Title
Beating Bad Blood: The Power of Immunotherapy in Hematologic Malignancies
Track
Hematologic Malignancies,Hematologic Malignancies
Sub Track
Acute Leukemia
Clinical Trial Registration Number
NCT04271410
Citation
J Clin Oncol 40, 2022 (suppl 16; abstr 7008)
DOI
10.1200/JCO.2022.40.16_suppl.7008
Abstract #
7008
Abstract Disclosures
Similar Abstracts
Abstract
2023 ASCO Annual Meeting
Safety and efficacy profile of a very low dose of MC-1-50 for treatment of r/r NHL.
First Author: Shiqi Li
Abstract
2023 ASCO Annual Meeting
Effect of bispecific B7H3 x CD19 CAR T cells on host CD19 expression and CAR T cell engraftment.
First Author: Navin R. Pinto
Abstract
2021 ASCO Annual Meeting
Safety and efficacy of a novel anti-CD20/CD19 bi-specific CAR T-cell therapy (C-CAR039) in relapsed or refractory (r/r) B-cell non-Hodgkin lymphoma (B-NHL).
First Author: Aibin Liang
Abstract
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.
First Author: Zhi Yang