Developing a Novel Anti-CD19/CD20 Bi-Specific Chimeric Antigen Receptor T (CAR-T) Cell Therapy for Relapsed/Refractory (r/r) B-Cell NHL
Author:
Zhou Lili1, Huang Jiaqi2, Zhu Shigui2, Yao Xin2, Ye Shiguang1, Zhu Judy3, Zheng Chengxiao3, Chen Shiyi3, Li Yanfeng3, Lan Liping3, Chen Shicheng3, Guo Lin3, Zhang Qingsong3, Zheng Jiangqin3, Wang Rirfei3, Hong Yi3, Ren Jiaqiang2, Zhang Li2, Zhang Wenjun1, Tang Xiaochen1, Wang Junbang1, Liu Jie1, Humphries Michael3, Li Ping1, Yao Yihong2, Liang Aibin1
Affiliation:
1. School of Medicine, Tongji Hospital of Tongji University, Shanghai, China 2. Cellular Biomedicine Group Inc, Gaithersburg, MD 3. Cellular Biomedicine Group Inc, Shanghai, China
Abstract
Background:
Aiming to improve both the response rate and durability of response while limiting antigen escape of CD-19 following anti-CD-19 CAR-T therapy, C-CAR039 has been developed as a 2nd generation 4-1BB novel bi-specific chimeric antigen receptor T (CAR-T) therapy targeting both CD19 and CD20 antigens.
Methods:
NCT04317885 is a single arm, single-center, non-randomized phase I clinical trial designed to evaluate the safety and efficacy of C-CAR039 in treatment of relapsed or refractory NHL (r/r NHL) patients. The primary objective of the study is to evaluate incidence and severity of treatment emergent adverse events. The secondary objectives include determining overall response rate (ORR), progression-free survival, and overall survival.
Results:
In preclinical studies, human T cells transduced with the lentiviral vector encoding C-CAR039in vitroshowed CAR-T proliferation, cytokine production, cytotoxicity to CD19, and CD20 single positive and double positive tumor cells. C-CAR039 can eradicate CD19/CD20 positive tumor cellsin vivobased on our animal model study.
A Phase 1 trial was conducted in Shanghai Tongji Hospital in patients with r/r NHL to assess the safety and efficacy of C-CAR039 (NCT04317885). Following apheresis to harvest T cells, C-CAR039 was manufactured and infused as a single intravenous dose after a standard 3-day cyclophosphamide/fludarabine conditioning regimen. C-CAR039 was manufactured in a serum free, semi-automated, and digitally closed system with median vein to vein time of 18 days. The manufacturing success rate was 100%. As of Aug 3, 2020, 16 patients were infused with C-CAR039 with a dose range of 1.0 x 106 to 5.0 x 106 CAR-T cells/kg. 14 patients had at least one-month evaluable safety data and 13 patients (11 DLBCL, 2 FL patients) had one-month or longer efficacy data. C-CAR039 treatment was well tolerated with no grade 3 or higher cytokine release syndrome(CRS) and no neurotoxicity event. Reversible grade 1~2 CRS was observed in 12 (86%) of patients. Cytopenias due to the conditioning regimen were common and reversible. At the one-month evaluation, 12/13 patients showed clinical improvement (ORR=92%) and 11/11 of DLBCL patients responded to the treatment (ORR=100%). Median follow-up was 70 days (range: 35-257 days). The best overall response (BOR) includes 10 complete responses (CRs) and 2 partial responses (PRs). Furthermore, C-CAR039 proliferation and expansion in the peripheral blood positively correlated with tumor regression.
Conclusion:
C-CAR039 shows promising efficacy and a favorable safety profile in the early clinical trial in patients with r/r NHL. The early clinical efficacy signal is encouraging and compares favorably to anti-CD19 CAR-T therapies. These findings need to be evaluated in more patients with longer follow-up to confirm safety, efficacy and duration of response.
Disclosures
Huang: Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Zhu:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Yao:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Zhu:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Zheng:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Chen:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Li:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Lan:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Chen:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Guo:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Zhang:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Zheng:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Wang:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Hong:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Ren:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Zhang:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Humphries:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Yao:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.
Publisher
American Society of Hematology
Subject
Cell Biology,Hematology,Immunology,Biochemistry
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