A Phase 2 Clinical Trial of Anti-CD19 CAR-T (pCAR-19B) in Chinese Pediatric and Young Adult with Relapsed/Refractory (R/R) CD19+ B-ALL: The First Pivotal Study in an Asian Population
Year: 2024
Type: conference-abstract
Abstract: Introduction: Acute lymphoblastic leukemia (ALL) is one of the most common malignant tumors in children and a leading cause of mortality in children and adolescents. The chimeric antigen receptor (CAR-T) cell therapy has revolutionized the treatment of relapsed/refractory (R/R) B-cell ALL, with the first FDA-approved product, Kymriah (tisagenlecleucel) developed by Novartis, significantly improving remission rates and survival times. pCAR-19B is an autologous CAR-T cell product with an optimized humanized CD19-specific single-chain variable fragment (scFv) designed to address safety concerns. pCAR-19B has been granted “Breakthrough Therapy Designation” by the China National Medical Products Administration for treating B-ALL. This report presents the efficacy and safety outcomes of pCAR-19B in a pivotal clinical trial involving Chinese pediatric and young adult patients with R/R B-cell ALL. Methods: This phase 2 trial (NCT05334823) was a single-arm, open-label, multicenter study. Patients aged ≥ 3 and ≤ 21 years at screening with confirmed CD19+ R/R B-ALL were included. The primary endpoint was the overall remission rate (ORR), defined as complete remission (CR) plus CR with incomplete blood recovery (CRi) within 3 months post-infusion. Results: As of April 18th, 2024, 89 patients had been enrolled and underwent leukapheresis, with 64 patients receiving pCAR-19B infusion. There were no cases of manufacturing failure. Among the infused patients, 6.25%(4/64）were refractory and 93.75%(60/64) had relapsed to multiple lines of prior therapy or allogeneic stem cell transplant. The median age was 11 years (range 3-21), and 56.25% (36/64) were male. Additionally, 75% (48/64) of the patients carried at least one high-risk gene. The median bone marrow (BM) blast burden at baseline was 58.3% (range 5%-98%) with a heavy BM blast burden (≥50%) observed in 56.25% of the patients. At a median follow-up of 211 days (range 35-750), the best ORR was 90.63% (58/64), with 78.13% of patients (50/64) achieving CR and 12.5% of patients (8/64) achieving CRi, surpassing the efficacy of the commercial anti-CD19 CAR-T therapy products reported in R/R B-ALL. 98.27% (57/58) of patients with ORR achieved negative minimal residual disease (MRD)-negative remission. The ORR at 3 months was 76.56% (49/64). The median duration of response (DOR) was 10.61 months (95% confidence interval 7.66-20.96). The median overall survival (OS) was 23.92 months (95% confidence interval 9.86-NR). Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 98.44% and 50% of patients, respectively. Grade ≥3 CRS and ICANS were observed in 29.69% and 39.06% of patients, respectively. The median duration of Grade ≥3 CRS and ICANS was 4 days and 3 days, respectively. There were no deaths attributed to CRS or ICANS. Conclusions: Despite a heavy burden of BM blasts and a high risk of genetic variations, pCAR-19B demonstrated high remission rates, achieved a high rate of MRD-negative remission, durable responses, and a tolerable safety profile. This study represents the first pivotal clinical trial of childhood B-ALL in an Asian population, offering a new treatment option for Chinese pediatric and young adult patients with R/R B-ALL.
Source: Blood
Authors: Ruidong Zhang, Yang Cao, Xiaofan Zhu, Zhenya Hong, Jianwen Xiao, Fei Li, Ju Gao, Hongling Peng, Yongmin Tang, Runming Jin, Sixi Liu, Yajuan Cui, Shaoyan Hu, Min Yu, Xiaojun Xu, Xiaoyan Wu, Xiaoxi Lu, Huirong Mai, Xiaoxi Zhou, Yingzi Zhang, Zhi Yang, Yufeng Huang, Xiao He, Liang Huang, Cheng Qian, Yicheng Zhang, Tianyou Wang
Institutions: Capital Medical University, Beijing Children’s Hospital, Tongji Hospital, Huazhong University of Science and Technology, Chinese Academy of Medical Sciences & Peking Union Medical College, Institute of Hematology & Blood Diseases Hospital, Children's Hospital of Chongqing Medical University, Chongqing Medical University, Nanchang University, First Affiliated Hospital of Nanchang University, Sichuan University, West China Second University Hospital of Sichuan University, Second Xiangya Hospital of Central South University, Children's Hospital of Zhejiang University, Zhejiang University, Shenzhen Children's Hospital, Soochow University, Wuhan Union Hospital, Chongqing Precision Biotech Co., Ltd. (China)
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4405040806