FIRST-IN-HUMAN, UNIVERSAL ANTI-CD7 CAR-T THERAPY FOR RELAPSED AND REFRACTORY T-CELL ACUTE LYMPHOBLASTIC LEUKEMIA (R/R T-ALL)
Author(s): ,
Xinxin Wang
Affiliations:
Gracell Biotechnologies Co., Ltd.,Shanghai,China
,
Shiqi Li
Affiliations:
920th Hospital of Joint Logistics Support Force of People's Liberation Army of China,Kunming,China
,
Lei Gao
Affiliations:
The Second Affiliated Hospital of Army Medical University,Chongqing,China
,
Zhongtao Yuan
Affiliations:
920th Hospital of Joint Logistics Support Force of People's Liberation Army of China,Kunming,China
,
Kun Wu
Affiliations:
The First Affiliated Hospital of Kunming Medical University,Kunming,China
,
Lin Liu
Affiliations:
920th Hospital of Joint Logistics Support Force of People's Liberation Army of China ,Kunming,China
,
Le Luo
Affiliations:
920th Hospital of Joint Logistics Support Force of People's Liberation Army of China,Kunming,China
,
Yao Liu
Affiliations:
The Second Affiliated Hospital of Army Medical University ,Chongqing,China
,
Cheng Zhang
Affiliations:
The Second Affiliated Hospital of Army Medical University ,Chongqing,China
,
Jia Liu
Affiliations:
Gracell Biotechnologies Co., Ltd. ,Shanghai,China
,
Chunhui Yang
Affiliations:
Gracell Biotechnologies Co., Ltd.,Shanghai,China
,
Yu Li
Affiliations:
920th Hospital of Joint Logistics Support Force of People's Liberation Army of China ,Kunming,China
,
Jiaping He
Affiliations:
Gracell Biotechnologies Co., Ltd.,Shanghai,China
,
Xun Ye
Affiliations:
Gracell Biotechnologies Co., Ltd.,Shanghai,China
,
Zhimin Li
Affiliations:
Gracell Biotechnologies Co., Ltd. ,Shanghai,China
,
Duanpeng Wang
Affiliations:
Gracell Biotechnologies Co., Ltd.,Shanghai,China
,
Jianning Ge
Affiliations:
Gracell Biotechnologies Co., Ltd. ,Shanghai,China
,
Xu Tan
Affiliations:
The Second Affiliated Hospital of Army Medical University,Chongqing,China
,
Ruihao Huang
Affiliations:
The Second Affiliated Hospital of Army Medical University,Chongqing,China
,
Cong Han
Affiliations:
Gracell Biotechnologies Co., Ltd.,Shanghai,China
,
Yu Han
Affiliations:
Gracell Biotechnologies Co., Ltd.,Shanghai,China
,
Martina Sersch
Affiliations:
Gracell Biotechnologies Co., Ltd.,Shanghai,China
,
Dingsong Zhang
Affiliations:
920th Hospital of Joint Logistics Support Force of People's Liberation Army of China,Kunming,China
,
Youcheng Wang
Affiliations:
920th Hospital of Joint Logistics Support Force of People's Liberation Army of China,Kunming,China
,
Lihua Fang
Affiliations:
920th Hospital of Joint Logistics Support Force of People's Liberation Army of China,Kunming,China
,
Yingnian Chen
Affiliations:
920th Hospital of Joint Logistics Support Force of People's Liberation Army of China,Kunming,China
,
Wei Cao
Affiliations:
Gracell Biotechnologies Co., Ltd.,Shanghai,China
,
Sanbin Wang
Affiliations:
920th Hospital of Joint Logistics Support Force of People's Liberation Army of China,Kunming,China
Xi Zhang
Affiliations:
The Second Affiliated Hospital of Army Medical University,Chongqing,China
(Abstract release date: 05/14/20) EHA Library. Wang X. 06/12/20; 294935; S115
Xinxin Wang
Xinxin Wang
Contributions
Abstract

Abstract: S115

Type: Oral Presentation

Session title: Cellular, antibody and targeted therapy

Background

T-ALL in adults is an aggressive malignancy with low long-term remission rates and high relapse and mortality rates. As a potential target for CAR-T therapy, CD7 is present on >95% T-ALL samples and has restricted expression on the lymphoid (T and NK) lineage. However, autologous CAR-T development for r/r T-ALL has been limited by CD7 expression on normal T cells, potential contaminations by T-ALL cells and high manufacturing cost. TruUCAR GC027 is a CD7 targeted, universal CAR-T product for r/r T-ALL. It is manufactured using lentivirus and leukopheresis products from HLA-mismatched healthy donors, which demonstrated robust expansion and superior anti-leukemia activity in preclinical studies.

Aims

To assess the clinical safety and preliminary efficacy of GC027 in r/r T-ALL, a single-arm, open-label, multi-center, prospective study has been conducted in patients with r/r T-ALL (Clinical trial information: ChiCTR1900025311). 

Methods

TruUCART™ GC027 contains a second-generation CAR, and the expression of TCRα and CD7 has been disrupted by CRISPR/Cas9 system to avoid GvHD and fratricide. To date, a total of 5 patients (age 19-38 yrs, median 27.8 yrs, all males) were enrolled with a marrow tumor load between 4-80.2% (median prior lines 5). All 5 pts have received a 6-day enhanced preconditioning chemotherapy followed by a single infusion of GC027. No other biologics such as anti-CD52 antibody was given as immune suppressant. No patient has been bridged to HSCT to date. Adverse events, disease response, and expansion kinetics were evaluated in this study.

Results

As of Feb. 6, 2020, 5 pts had been enrolled and received a single dose of GC027: 1 at 0.6x107/kg, 3 at 1x107/kg, 1 at 1.5x107/kg. 3 pts achieved MRD negative complete responses (MRD- CR, <0.01% assessed by flow cytometry) at D28 evaluation and remained MRD- at follow-up re-evaluations (161, D118, 61, respectively) without bridging to HSCT. As of data cut-off, 1 pt just achieved D28 MRD- CR and follow-up result will be presented. 1 pt achieved MRD+ CR at D14, but his disease progressed at D29 and deceased due to relapse. Patients’ peripheral blood was analyzed by flow cytometry and Q-PCR. GC027 had robust expansion in all 4 pts with MRD- CR and peaked around day 10. Grade 3 cytokine release syndrome (CRS) occurred in 4 pts and Grade 4 CRS occurred in 1 pt (ASBMT Consensus Grading). CRS symptoms including febrile and low systolic blood pressure were manageable and resolved after anti-CRS treatment and supportive care. No patient developed neurotoxicity or GvHD.

Conclusion

GC027 shows promising efficacy treating adult r/r T-ALL. With a single infusion of GC027, 80% of patients had robust CAR-T cell expansion and achieved a durable MRD- CR (161 days and response still ongoing) without using any biologics as part of the preconditioning therapy or bridging to HSCT. GC027 has demonstrated superior clinical efficacy and induced deep response in patients with acceptable safety profile. The trial is ongoing and updated data will be presented at the meeting. 

Session topic: 02. Acute lymphoblastic leukemia - Clinical

Keyword(s): Allogeneic, CAR-T, T-ALL

Abstract: S115

Type: Oral Presentation

Session title: Cellular, antibody and targeted therapy

Background

T-ALL in adults is an aggressive malignancy with low long-term remission rates and high relapse and mortality rates. As a potential target for CAR-T therapy, CD7 is present on >95% T-ALL samples and has restricted expression on the lymphoid (T and NK) lineage. However, autologous CAR-T development for r/r T-ALL has been limited by CD7 expression on normal T cells, potential contaminations by T-ALL cells and high manufacturing cost. TruUCAR GC027 is a CD7 targeted, universal CAR-T product for r/r T-ALL. It is manufactured using lentivirus and leukopheresis products from HLA-mismatched healthy donors, which demonstrated robust expansion and superior anti-leukemia activity in preclinical studies.

Aims

To assess the clinical safety and preliminary efficacy of GC027 in r/r T-ALL, a single-arm, open-label, multi-center, prospective study has been conducted in patients with r/r T-ALL (Clinical trial information: ChiCTR1900025311). 

Methods

TruUCART™ GC027 contains a second-generation CAR, and the expression of TCRα and CD7 has been disrupted by CRISPR/Cas9 system to avoid GvHD and fratricide. To date, a total of 5 patients (age 19-38 yrs, median 27.8 yrs, all males) were enrolled with a marrow tumor load between 4-80.2% (median prior lines 5). All 5 pts have received a 6-day enhanced preconditioning chemotherapy followed by a single infusion of GC027. No other biologics such as anti-CD52 antibody was given as immune suppressant. No patient has been bridged to HSCT to date. Adverse events, disease response, and expansion kinetics were evaluated in this study.

Results

As of Feb. 6, 2020, 5 pts had been enrolled and received a single dose of GC027: 1 at 0.6x107/kg, 3 at 1x107/kg, 1 at 1.5x107/kg. 3 pts achieved MRD negative complete responses (MRD- CR, <0.01% assessed by flow cytometry) at D28 evaluation and remained MRD- at follow-up re-evaluations (161, D118, 61, respectively) without bridging to HSCT. As of data cut-off, 1 pt just achieved D28 MRD- CR and follow-up result will be presented. 1 pt achieved MRD+ CR at D14, but his disease progressed at D29 and deceased due to relapse. Patients’ peripheral blood was analyzed by flow cytometry and Q-PCR. GC027 had robust expansion in all 4 pts with MRD- CR and peaked around day 10. Grade 3 cytokine release syndrome (CRS) occurred in 4 pts and Grade 4 CRS occurred in 1 pt (ASBMT Consensus Grading). CRS symptoms including febrile and low systolic blood pressure were manageable and resolved after anti-CRS treatment and supportive care. No patient developed neurotoxicity or GvHD.

Conclusion

GC027 shows promising efficacy treating adult r/r T-ALL. With a single infusion of GC027, 80% of patients had robust CAR-T cell expansion and achieved a durable MRD- CR (161 days and response still ongoing) without using any biologics as part of the preconditioning therapy or bridging to HSCT. GC027 has demonstrated superior clinical efficacy and induced deep response in patients with acceptable safety profile. The trial is ongoing and updated data will be presented at the meeting. 

Session topic: 02. Acute lymphoblastic leukemia - Clinical

Keyword(s): Allogeneic, CAR-T, T-ALL

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