Background/Purpose: GC012F (AZD0120) is a CD19/B cell maturation antigen (BCMA) dual-targeting chimeric antigen receptor T-cell (CAR-T) developed on the novel FasTCAR-T platform with next-day manufacturing, designed to improve depth and duration of B-cell depleting response. We present interim results here from a dose escalation investigator initiative trial (IIT) (NCT05858684) to evaluate the safety and efficacy of GC012F CAR-T cell therapy in resetting humoral immunity in patients with refractory systemic lupus erythematosus (SLE).

Methods: Ten patients with refractory SLE (SLEDAI-2K score range 8-20) were enrolled in this investigator-initiated, open-label, single-center Phase I study. All patients received a single infusion of autologous CD19-BCMA dual chimeric antigen receptor (CAR) T cells at one of three different dose levels following preconditioning with fludarabine and cyclophosphamide. The primary endpoint was safety and tolerability, assessed by the percentage of subjects experiencing dose-limiting toxicity (DLT) within 28 days and the percentage of subjects reporting adverse events (AEs) within 12 weeks. Efficacy was assessed using the SLE Responder Index (SRI-4), the Definition of Remission in SLE (DORIS) criteria and renal response rate. Safety parameters, including cytokine release syndrome and infections, were systematically recorded and evaluated.

Results: The median follow-up duration was 448.5 days (range, 336-612 days), with a mean duration of B-cell aplasia of 126 days (range, 84–168 days). All patients achieved an SRI-4 response in week 24. Five patients met DORIS remission by week 24, six by week 36 and week 48. All patients discontinued immunosuppressive drugs during the follow-up period. One patient experienced a disease flare at week 40. Four patients exhibited residual proteinuria, and repeat kidney biopsies were performed in three of them. The biopsy results primarily showed persistent fibrosis and podocyte injury, with resolution of acute inflammation, significant reduction in immune complex deposition, and absorption or dissipation of electron-dense deposits. No DLTs were observed. Six patients experienced grade 1 CRS, and one patient experienced grade 2 CRS. No cases of immune effector cell-associated neurotoxicity syndrome (ICANS) or grade ≥3 CRS were reported. Other common AEs included hematologic abnormalities, hypogammaglobulinemia, and infections. No fatal adverse events occurred.

Conclusion: GC012F CAR-T cell therapy was well tolerated and demonstrated high efficacy in patients with refractory SLE. A multicenter phase1/2 study (NCT06530849) is ongoing to further evaluate the safety and efficacy of GC012F in a broader range of patients with SLE.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/cd19-bcma-dual-targeting-fastcar-t-cells-gc012f-azd0120-in-patients-with-refractory-systemic-lupus-erythematosusm-an-open-label-single-center-phase-i-study/