Updated clinical results of first-in-human study of CD19/BCMA dual-targeting fast CAR-T GC012F for patients with relapsed/refractory B-cell non-Hodgkin’s lymphoma.

person Xinfeng Chen Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China info_outline Xinfeng Chen, Ping Yu, Ling Li, Lei Zhang, Xudong Zhang, Jianmin Huang, Jia Liu, Gui Li, Jiaping He, Hua Zhang, Wei Zhao, Lihong Weng, Wenjie Yin, Lianjun Shen, Wei Cao, Wenling Li, Mingzhi Zhang, Yi Zhang

Authors person Xinfeng Chen Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China info_outline Xinfeng Chen, Ping Yu, Ling Li, Lei Zhang, Xudong Zhang, Jianmin Huang, Jia Liu, Gui Li, Jiaping He, Hua Zhang, Wei Zhao, Lihong Weng, Wenjie Yin, Lianjun Shen, Wei Cao, Wenling Li, Mingzhi Zhang, Yi Zhang Organizations Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China, Gracell Biotechnologies Ltd, Shanghai, China, Gracell Biotechnologies, Ltd, Shanghai, China Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Gracell Biotechnology (Shanghai) Co., LTD Background: CD19-directed CAR-T cell therapy has been demonstrated to be a valuable treatment option for relapsed/refractory B-cell non-Hodgkin’s lymphoma (r/r B-NHL). It has been shown that 39% to 97% of clinical samples of B-NHL also express BCMA. To further improve safety and efficacy, we have developed a CD19 and BCMA dual-targeting CAR-T, GC012F, manufactured on the novel next-day FasT CAR-T process, for the treatment of r/r B-NHL. The initial 3-patient data of an investigator-initiated trial (ChiCTR2100047061) was reported at EHA 2022 (#2938). Here, we present updated results of this ongoing IIT trial. Methods: From October 2021 to January 2023, nine eligible r/r DLBCL pts were enrolled and treated with a single infusion of GC012F in escalating dosing cohorts after a standard lymphodepletion regimen. The primary objectives of this study were safety and tolerability; the secondary were pharmacokinetics and efficacy. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were graded by ASBMT 2019, adverse effects were evaluated according to CTCAE 5.0. Efficacy assessment of GC012F was referred to the Lugano criteria. Expansion of CAR-T cells and CAR copy numbers were measured by flow cytometry and qPCR, respectively. Results: As of data cut-off of January 16 th , 2023, with a median of 207 days (range 94-460) of follow-up, all nine pts received single GC012F infusions at dose levels from 3.7×10 4 to 3×10 5 CAR-T/kg, and completed at least 3 months of follow-up. All pt lymphoma samples expressed CD19, and 6 out of 7 expressed BCMA. The median SPD was 2690.81 mm 2 (408.3-13325.96). Pts received a median of 2 prior lines (range 2-3) of therapy including rituximab and anthracyclines. Two pts received prior auto-HSCT. The ORR in nine pts was 100% (9/9) at month 3, CR rate was 77.8% (7/9) at month 3 and 71.4% (5/7) at month 6, respectively. To date, the longest duration of remission was 14.4 months. No dose-limiting toxicities were observed. One pt had grade 3 CRS over 2 days. No ICANS were observed. Of the 9 treated pts, ≥ grade 3 TEAEs were neutropenia (7/9), leukopenia (5/9) and thrombocytopenia (3/9). All TEAEs were resolved after treatment with standard of care and supportive care. The median peak copy number of CAR-T cells in peripheral blood was 71,000 copies/μg DNA (range 9263 -185,039), and the median peak time was 14 days (range 9 - 21). CAR-T cells were also detected in tumor biopsies from all five pts tested. Conclusions: This first-in-human trial of GC012F for the treatment of r/r B-NHL showed a manageable safety profile and promising clinical responses. The ORR was 100% at M3 with 77.8% (7/9) achieving CR. GC012F CAR-T cells were detectable in the tumor biopsies, indicating the infiltration of CAR-T cells into the tumor lesions. Study with larger cohort and longer follow-up is ongoing. Clinical trial information: ChiCTR2100047061.

Clinical