CD19/BCMA dual-targeting FasTCAR-T GC012F for patients with relapsed/refractory B-cell non-Hodgkin lymphoma: An update.
Authors: Xinfeng Chen, Ping Yu, Ling Li, Lei Zhang, Xudong Zhang, Jianmin Huang, Jia Liu, Gui Li, Lihong Weng, Huan Shi, Wenjie Yin, Lianjun Shen, Wenling Li, Wei Cao, Mingzhi Zhang, Yi Zhang
Journal: Journal of Clinical Oncology (2024)

e19045 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 between 39% and 97% of clinical samples of B-NHL also express BCMA. To further improve safety and efficacy, we have developed GC012F, a CD19 and BCMA dual-targeting CAR-T, manufactured using the novel next-day FasT CAR-T process, for the treatment of r/r B-NHL. The data from an investigator-initiated trial of GC012F for r/r B-NHL were reported at ASCO 2023 (# 7562). Here, we present updated results of the trial, including more pts and a longer follow-up period. Methods: This is a single-arm, open label trial (ChiCTR2100047061). The patients (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. Results: As of data cut-off on January 30 th , 2024, with a median of 410.5 days (range: 28 - 839) of follow-up, all pts received single GC012F infusions at dose levels ranging from 3.7×10 4 to 3×10 5 CAR-T/kg. The median age was 49.5 years (range: 18 - 67). Ten pts were Ann Arbor stage III/IV disease. All pts lymphoma samples expressed CD19, and 9 out of 11 expressed BCMA. Ptsreceived a median of 2 prior lines (range: 2 - 3) of therapy including rituximab and anthracyclines. Two ptsreceived the auto-HSCT previously. 91.7% (11/12) of the pts achieved ORR at month 3 post GC012F infusion; 66.7% (8/12) CR at month 6 and 60% (6/10) CR at month 12, respectively. To date, the longest duration of remission is 27.0 months. No dose-limiting toxicities were observed. One pt had grade 3 CRS and recovered within 2 days. No ICANS were observed. Grade ≥ 3 hematologic toxicities included lymphocytopenia (11/12), neutropenia (11/12) and leukopenia (10/12). All TEAEs were resolved after treatment with standard of care and supportive care. The median peak copy number of CAR-T cells in the peripheral blood was 70,083 copies/μg DNA (range: 6,876 - 185,039), and the median peak time was 14 days (range: 9 - 21). CAR-T cells were also detected in tumor biopsies from all six pts tested. In five pts at progressive disease, the primary or new lesions were CD19 positive, and no CAR-T cells were detected. Conclusions: This first-in-human trial of GC012F for the treatment of r/r DLBCL showed a manageable safety profile and promising clinical responses and a long-lasting duration of a remission. Overall, CD19-BCMA dual targeting CAR-T product GC012F is a promising therapy for r/r DLBCL pts and longer follow-up is ongoing. Clinical trial information: ChiCTR2100047061 .