Abstract CT052: Clinical safety and efficacy study of TruUCAR™ GC027: The first-in-human, universal CAR-T therapy for adult relapsed/refractory T-cell acute lymphoblastic leukemia (r/r T-ALL)

Introduction: Patients with T cell malignancies usually have high relapse and mortality rates. Due to shared common surface antigen and potential contamination by malignant cells, development of CAR-T therapies for r/r T-ALL has been lagged, regardless of the costly and lengthy process of autologous CAR-T production. To overcome these challenges, we developed a universal CAR-T platform (TruUCAR™) that displayed superior expansion in patients without using preconditioning biologics such as αCD52 antibody. Here we report results from a prospective study of GC027, the first-in-human, universal CAR-T therapy for treating adult patients with r/r T-ALL to evaluate the safety and clinical efficacy. Methods: TruUCART™ GC027 contains a second-generation CAR with genomic disruption of TCRα and CD7 by CRISPR/Cas9 system to avoid GvHD and fratricide. It is manufactured using lentivirus and leukopaks from HLA-mismatched healthy donors. A T-ALL xenograft murine model were used to assess anti-leukemic efficacy and expansion. Preliminary safety, anti-leukemic activity and expansion kinetics of GC027 are being evaluated in in a single-arm, open-label, multi-center, prospective study for treating adult r/r T-ALL. To date, a total of 5 patients (age 19-38 yrs, median 24 yrs) were enrolled with marrow tumor load 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. Adverse events, disease response, and expansion kinetics were evaluated in this study. Results: GC027 demonstrated robust anti-leukemic activity and expansion in a highly malignant CCRF-CEM xenograft murine model. All mice infused with GC027 exhibited significantly reduced tumor burden and prolonged survival compared to control groups. As of Feb. 6, 2020, 5 pts had received a single dose of GC027, including 1 at 0.6x107/kg, 3 at 1x107/kg and 1 at 1.5x107/kg. 4 pts achieved MRD negative complete responses (MRD- CR) at D28 evaluation: 3 of them remained MRD- at follow-up re-evaluations (D118, 61, 161, respectively, and none was bridged to HSCT); 1 just achieved MRD- CR at D28 and follow-up results will be updated at the meeting. 1 pt achieved MRD+ CR at D14 but had relapsed disease at D29. In all 4 pts with MRD- CR, peak expansions of GC027 in peripheral blood were observed between week 1-2. In 1 pt with CNS disease, GC027 was detected in specimens from his bone marrow and cerebrospinal fluid (CSF). 4 pts experienced Grade 3 cytok