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Abstract
Objective Patients with severe refractory systemic lupus erythematosus (srSLE) exhibit failure to respond to treatments, progressive organ damage, and high mortality. Traditionally manufactured CD19-directed CAR T-cell therapies have potential to promote full clinical remission in srSLE. YTB323 (rapcabtagene autoleucel) is a novel, rapidly manufactured, autologous CD19-directed CAR T-cell therapy. The objective of this study is to determine the safety, efficacy and cellular kinetics of YTB323 in patients with srSLE.
Methods An open-label, single-arm, multicentre phase 1/2 study (NCT05798117) to assess the safety, efficacy and cellular kinetics of YTB323 in patients with srSLE is currently ongoing. Safety data including adverse events (AEs), severe AEs, deaths, vital signs, electrocardiogram and laboratory assessments and preliminary efficacy data including SLE Disease Activity Index (SLEDAI) and Physician’s Global Assessment (PhGA) were collected. Pharmacokinetics (PK) data monitored by quantitative polymerase chain reaction and flow cytometry, and biomarker data including levels of B cells, T cells, immunoglobulin (Ig)G, IgA, IgM, complement C3 and C4 and anti-dsDNA were also collected.
Results We present safety, preliminary efficacy and biomarker data for six patients (data cutoff: December 2023), and available PK data for two patients who received YTB323 treatment (data cutoff: August 2023). Transient lymphodepletion-related cytopenia (grade 3 or 4) was observed in all six patients, as expected. Hypogammaglobulinaemia, which did not require intravenous immunoglobulin treatment, was a common AE. Cytokine release syndrome (grade 1 [n=1] or 2 [n=3]) was observed in four of six patients, and all events resolved following treatment with tocilizumab. No events of immune cell-associated neurotoxicity syndrome were reported. Infectious complications included pneumonia in one patient (grade 2). Preliminary efficacy and biomarker data for six patients indicated considerable reductions in SLEDAI (figure 1a) and PhGA (figure 1b) accompanied by improvements in relevant disease biomarkers such as anti-dsDNA (figure 1c), complement levels (figure 2a-b), and proteinuria, as well as deep B-cell depletion with subsequent B-cell recovery. PK assessment confirmed CAR T-cell expansion for the two patients with evaluable PK data.
Individual efficacy parameters over time
Complement levels over time
Conclusions Interim data from this clinical trial suggest favourable safety, CAR T-cell expansion, B-cell depletion and initial efficacy of YTB323 in srSLE, supporting its continued evaluation.
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