Background/Purpose: CD19 targeting chimeric antigen receptor (CAR) T cells have demonstrated durable drug-free responses and remission in patients with idiopathic inflammatory myopathies (IIM) and systemic lupus erythematosus (SLE) reported from a compassionate use program. As a fully human, autologous 4-1BB anti-CD19-CAR T cell therapy, CABA-201 is being investigated for the treatment of multiple B cell-mediated autoimmune diseases. RESET-Myositis (NCT06154252) and RESET-SLE (NCT06121297) are ongoing phase I/II clinical trials evaluating the safety and efficacy of CABA-201 in 4 independent myositis cohorts of immune-mediated necrotizing myopathy (IMNM), antisynthetase syndrome (ASyS), dermatomyositis, and juvenile IIM as well as 2 independent SLE cohorts of non-renal SLE and lupus nephritis (LN), respectively. We report on the initial results of the first IMNM and first non-renal SLE patients treated with CABA-201.

Methods: For the RESET-Myositis trial, eligible patients are ≥18 and ≤75 years or pediatric patients with a clinical diagnosis of IIM, the presence of serum myositis-specific or myositis-associated antibodies, and evidence of active disease despite standard therapy. For the RESET-SLE study, eligible patients are ≥18 to ≤65 years with an SLE diagnosis, ANA+ or anti-dsDNA+, and SLEDAI 2K ≥8 despite standard therapy (non-renal cohort) or active, biopsy-confirmed LN class III or IV ± V (renal cohort). For both trials, a single infusion of 1×10⁶ CAR T cells/kg is administered following a preconditioning regimen of cyclophosphamide and fludarabine. Per protocol, participants are inpatient for a minimum of 4 days post infusion.

Results: Baseline data on the 2 treated subjects are in Table 1. 

In both subjects, CABA-201 expansion peaked at day 15 and peripheral B cells were rapidly reduced, achieving complete B cell depletion by day 15. At 3 months post infusion, the IMNM subject achieved a meaningful response in the total improvement score, associated with improvements in the CK to 308 and MMT-8 to 134, as well as reduction in anti-SRP and anti-Ro52 levels, while off methotrexate and glucocorticoids. At 1 month post infusion, the SLE subject achieved a SLEDAI-2K improvement of 16 points with resolution of vasculitis, arthritis, and hematuria and reduction in the anti-dsDNA titer, while off mycophenolate and hydroxychloroquine and on a prednisone taper.

Safety outcomes are in Table 2.

Conclusion: Both subjects tolerated CABA-201 treatment with no SAE, CRS, or ICANS. The administered dose of CABA-201 resulted in CAR T cell expansion, peripheral B cell depletion, and biomarker and clinical improvements consistent with the data observed in a previous report in ASyS and SLE/LN patients. These findings support the safety and the potential for favorable outcomes of CABA-201 in patients with SRP+ IMNM and non-renal SLE.  Evaluation of the selected CABA-201 dose continues in the ongoing RESET-Myositis and RESET-SLE clinical trials.

Reference: Müller F, et al. NEJM 2024; 390:687

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/safety-and-efficacy-of-caba-201-a-fully-human-autologous-4-1bb-anti-cd19-car-t-cell-therapy-in-patients-with-immune-mediated-necrotizing-myopathy-and-systemic-lupus-erythematosus-from-the-reset-myos/