CD19/BCMA dual-targeting FasTCAR-T GC012F for patients with relapsed/refractory B-cell non-Hodgkin lymphoma: An update.

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 .