Abstract LB147: Updates on clinical safety and efficacy result of GC027, the first-in-human, “Off-the-Shelf” CD7 CAR-T stand-alone therapy for adult patients with relapsed/refractory T-cell lymphoblastic leukemia (r/r T-ALL)

• Published in: Cancer research (Chicago, Ill.) Ill.), 2021-07, Vol.81 (13_Supplement), p.LB147-LB147
• Main Authors: Li, Shiqi, Gao, Lei, Yuan, Zhongtao, Wu, Kun, Liu, Lin, Luo, Le, Liu, Yao, Zhang, Cheng, Li, Yu, Wang, Duanpeng, Li, Zhimin, Tan, Xu, Huang, Ruihao, Zhang, Dingsong, Wang, Youcheng, Wang, Xinxin, Liu, Jia, Sersch, Martina, Wang, Sanbin, Zhang, Xi
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2021-LB147

Introduction: T-ALL represents an area of high unmet medical need. Once relapsed, patients have limited treatment options. We first reported data from a single-arm, open-label, multi-center, investigator-initiated study in adults with r/r T-ALL (ChiCTR1900025311) treated with TruUCAR™ GC027, an off-the-shelf CAR-T product at AACR 2020. Here we report long term follow-up results and preliminary results of additional patients treated. Methods: Between July 2019 to Feb 2021, a total of 6 r/r T-ALL patients (19-38 yrs) with a median of 6 prior lines were treated with a single infusion of GC027 at 3 different dose levels after Lymphodepletion over 6 days: DL1 (6x106 cells/kg, n=2), DL2 (1x107 cells/kg, n=3), DL3 (1.5x107 cells/kg, n=1) including a primary refractory T-ALL pt with extramedullary (EM) disease. Results: All 6 pts treated showed molecular expansions of CAR-T cells and peaked day 6-11 in peripheral blood (by qPCR, median 416,905 copies/ug DNA). Robust cellular expansion (by FACS) was observed in 5 pts (median 648 cells/ul). Clinically, 5/6 pts achieved MRD-CR/CRi at the month 1 assessment, including 1 pt with EM disease at several locations including neck, axilla, mediastinum and pancreas. His EM lesions were reassessed by PET-Scan on day 47 after treatment, confirming a complete response. Long-term follow-up (n=5): All pts evaluable at day 28 (n=4) reconstituted all blood cell lineages as assessed by blood cell count. At 6 months, 3/5 pts had maintained MRD- CR. At data cut-off Feb. 4, 2021, 1 pt continued to be in MRD-CR at 16.8 months (day 505) post treatment. 1 pt maintained CR until day 267, when he was found CD7 partial negative (by FACS) relapsed (BM). 1 pt with primary refractory disease (no response to VDP) maintained MRD- CR until month 7 (day 217) and was found relapsed by BM and PB assessment with CD7 partial negative (FACS). He received HSCT on day 255, achieved MRD- CR but relapsed again 5 months post HSCT. Safety (n=6): Overall safety findings were consistent with previous observations reported. TEAEs occurred were grade 3 febrile neutropenia (6/6), grade 4 neutropenia (4/6), grade 4 thrombocytopenia (4/6) and grade 3 anemia (3/6). All TEAE resolved after treatment with SOC and best supportive care, neutropenia improved with G-CSF treatment. Non-hematological TEAE presented as grade≤2 hypoalbuminemia (6/6), grade 3 pulmonary infection (3/6), grade≤2 AST increase (4/6) and grade≤2 ALT increase (3/6). 6/6 pts developed grade ≥ 3 CRS (AS