PO:11:273 CD19 NEX-T® (BMS-986353), a chimeric antigen receptor (CAR) T cell therapy, for active SLE with inadequate response to glucocorticoids and at least 2 immunosuppressants: a phase 2 trial in progress

Objectives Systemic lupus erythematosus (SLE) is characterized by aberrant B-cell activity and systemic inflammation, leading to organ damage, reduced quality of life, and premature death. Treatments that can achieve long-term disease remission without glucocorticoids (GC) and immunosuppressants (IS) are needed. Previous reports observed that a single infusion of CD19-directed CAR T cell therapy induces deep B-cell depletion, followed by repopulation with naive B cells, suggesting long-term, drug-free remission may be possible. However, current autologous cell therapy trials for SLE carry unique challenges, including manufacturing efficiency, scalability and access, defining the most suitable patient population, evaluation of long-term treatment effects, appropriateness of outcome measures, and lack of control group.BMS-986353 is a CD19-directed CAR T cell therapy, manufactured using the next-generation T cell (NEX-T) process, which aims to reduce manufacturing time and optimize phenotypic attributes. In Breakfree-1 (NCT05869955), BMS-986353 showed promising early safety and efficacy in severe refractory SLE.The multicenter, open-label, phase 2 Breakfree-SLE trial (NCT07015983) will evaluate the efficacy and safety of BMS-986353 in refractory SLE.Methods Eligible patients have active SLE, inadequate response to GC and at least 2 IS; and cannot have uncontrolled central nervous system pathology or prior CAR T cell therapy. Approximately 80 patients will receive a single BMS-986353 infusion at 10×10^6 CAR+ T cells after lymphodepletion ( figure 1) and will be followed for 60 months.Primary endpoint is drug-free achievement of Definition Of Remission In SLE (DORIS) at 6 months. Additional endpoints assessed up to 60 months: complete renal response in patients with lupus nephritis, drug-free DORIS, lupus low disease activity state, SLE Responder Index-4, incidence and severity of flares, SLICC damage index, duration of response, safety, autoantibodies, complement factors, patient-reported outcomes (PROs), and pharmacokinetics. Independent experts will adjudicate disease activity scoring. An evidence-based historical control group will be used.Results N/A Abstract PO:11:273 Figure 1Conclusions Breakfree-SLE aims to address key limitations in CAR T cell development for SLE with improved manufacturing, expanded study population to reflect real-world unmet needs, comprehensive disease scoring, and assessment of PROs and durability of response. It represents a meaningful step in generating critical evidence for novel treatment development and potentially sustained drug-free remission in SLE.