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)

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 (ASBMT consensus grading), which was manageable in all cases and resolved after treatment. No Grade 5, ICANs or aGvHD were observed. Conclusion: The allogeneic off-the-shelf TruUCAR™ CAR-T GC027 shows promising efficacy as standalone therapy in heavily pretreated R/R T-ALL pts with a manageable safety profile. A single infusion of GC027 was able to induce deep, durable responses, with the longest duration of response (MRD-CR) 18 months post treatment still ongoing without any additional therapy during remission. GC027 warrants further evaluation in larger clinical studies. Citation Format: Shiqi Li, Lei Gao, Zhongtao Yuan, Kun Wu, Lin Liu, Le Luo, Yao Liu, Cheng Zhang, Yu Li, Duanpeng Wang, Zhimin Li, Xu Tan, Ruihao Huang, Dingsong Zhang, Youcheng Wang, Xinxin Wang, Jia Liu, Martina Sersch, Sanbin Wang, Xi Zhang. 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) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB147.