Background/Purpose: BMS-986353 (CC-97540) is an investigational CD19-directed T-cell therapy expressing the chimeric antigen receptor (CAR) used in globally-approved lisocabtagene maraleucel; it is manufactured via the NEX-T™ process to shorten manufacturing time and optimize phenotypic attributes. Early data from Breakfree-1 trial (NCT05869955) in severe, refractory autoimmune diseases (ADs) showed promising efficacy and manageable safety with BMS-986353.1 Here, we report updated data on BMS-986353 in the SSc cohort.

Methods: This phase 1 study assesses safety and efficacy in patients (pts) with severe, refractory ADs, including recently progressing diffuse SSc or limited SSc with interstitial lung disease (ILD) and inadequate response to ≥ 1 immunosuppressant. All SSc-directed therapies were discontinued before BMS-986353 infusion. Pts received a single infusion of BMS-986353 at 10×106 (dose level [DL] 1) or 25×106 (DL2) CAR+ T cells after lymphodepletion. Primary endpoint was safety.

Results: As of April 7, 2025, 14 pts with SSc were enrolled; 9 pts received BMS-986353 (DL1, n = 8; DL2, n = 1), with a median follow-up of 115.5 days (range 42–295) for DL1 and 168 days for DL2. Median age: 54.5 years for DL1, 41 years for DL2. Prior therapies: median 2 (range 1–5) for DL1 and 3 for DL2. At baseline, DL1 pts had a median modified Rodnan skin score (mRSS) of 18.0 and Physician’s Global Assessment (PGA) score of 7.0; scores for the DL2 pt were 7.0 and 4.0, respectively. ILD was present in 6 pts. Eight pts were efficacy evaluable (7 DL1, 1 DL2).All inflammatory AEs (iAE) reported were low grade. In DL1, 50.0% of pts had cytokine release syndrome (CRS; 3 grade 1, 1 grade 2) with a median duration of 2.0 days; 1 pt had grade 1 immune effector cell-associated neurotoxicity syndrome (ICANS) that resolved in 3 days (Table). There were 4 transient, self-resolving grade ≥ 3 hematologic TEAEs in DL1 pts; none in DL2. There were no prolonged grade ≥ 3 cytopenias, dose-limiting toxicities, or treatment-related infections.In DL1, median increase from baseline in absolute forced vital capacity in all patients was 3.0% on day 85 (n = 3) and 7.0% at day 169 (n = 3). In DL1, median reduction in mRSS across all pts with diffuse cutaneous SSc regardless of baseline mRSS was 14.0 points at day 85 (n = 3) and 11.5 at day 169 (n = 2) (Figure 1). Median reduction in PGA from baseline was 3.0 points on day 85 (DL1 n = 4; DL2 n = 1) and 4.5 on day 169 (DL1 n = 2). Improvement from baseline in revised Composite Response Index in Systemic Sclerosis was achieved in 3/3 pts at day 85 and day 169. All pts had robust CAR T cell expansion and achieved complete peripheral B-cell depletion (Figure 2).

Conclusion: BMS-986353 showed an acceptable safety profile and preliminary meaningful improvement in skin thickening and lung function in pts with severe, refractory SSc. iAEs were grade 1/2 and resolved quickly. Updated safety, efficacy, and translational data will be presented. Reference: 1. Schett G, et al. Arthritis Rheumatol 2024;76(suppl 9):1753.Medical writing: Joaquin Jaramillo, MD (Caudex, an IPG Health company), funded by Bristol Myers Squibb.

Table. CRS and ICANS by DL. a: Multiple events occurring within 7 days from each other are considered as 1 episode. CRS, cytokine release syndrome; DL, dose level; ICANS, immune effector cell-associated neurotoxicity syndrome.

Figure 1. (A) mRSS and (B) FVC in pts with SSc ≥ 1 month post-BMS-986353 at DL1 and DL2. FVC, forced vital capacity; mRSS, modified Rodnan skin score.

Figure 2. (A) Pharmacokinetic profile compared with lisocabtagene maraleucel and (B) B cell depletion. NHL, non-Hodgkin lymphoma; PK, pharmacokinetic; Q, quartile.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/efficacy-and-safety-of-bms-986353-a-cd19-directed-chimeric-antigen-receptor-t-cell-therapy-manufactured-using-a-next-generation-process-updated-data-from-a-phase-1-trial-in-patients-with-systemic-sc/