A Study to Compare the Efficacy and Safety of BMS-986353 (Zolacabtagene- Autoleucel / Zola-cel), CD19-CAR T Cells, Versus Standard of Care in Participants With Active Systemic Sclerosis

Participants in Arm B may receive BMS-986353 following confirmation of progression on standard of care.

• BMS-986353 (Drug), also known as CC-97540: Specified dose on specified days
• Fludarabine (Drug): Specified dose on specified days
• Cyclophosphamide (Drug): Specified dose on specified days
• Tocilizumab (Drug): Specified dose on specified days
• Rituximab (Drug): Specified dose on specified days
• Nintedanib (Drug): Specified dose on specified days

Primary outcomes

• The absolute change from baseline in Forced Vital Capacity (FVC) in mL [At 12 months]

Secondary outcomes

• The absolute change from baseline in Modified Rodnan Skin Score (mRSS) [At month 12]
• The absolute change from baseline in Quantitative Interstitial Lung Disease-Whole Lung (QILD-WL) score [Up to month 36]
• Time to progression, defined as the time from randomization to progressive disease [Approximately 54 months]
• The change from baseline in Patient-Reported Outcomes Measurement Information System (PROMIS)-Fatigue [Up to month 36]
• The change from baseline in Scleroderma Clinical Index (ScleroID) [Up to month 36]
• The change from baseline in Scleroderma Health Assessment Questionnaire - Disability Index (SHAQ-DI) [Up to month 36]
• The change from baseline in PROMIS-29 [Up to month 36]
• The change from baseline in St. George's Respiratory Questionnaire (SGRQ) [Up to month 36]
• The change from baseline in EuroQol 5 Dimensions 5 Level (EQ-5D-5L) visual analog scale [Up to month 36]
• The change from baseline in EQ-5D-5L Utility Index [Up to month 36]
• The absolute change from baseline in FVC in mL [Up to month 36]
• The absolute change from baseline in FVC in mL/year [Up to month 36]
• The absolute change from baseline in Percent Predicted Forced Vital Capacity (ppFVC) [Up to month 36]
• The relative change from baseline in ppFVC [Up to month 36]
• The absolute change from baseline in diffusing capacity of the lung for carbon monoxide (DLCO) [Up to month 36]

Sex: All, ages: 16 Years to any

Inclusion Criteria

\- Participants must fulfill the 2013 American College of Rheumatology (ACR) / European League Against Rheumatism (EULAR) classification criteria for Systemic Sclerosis (SSc), and additionally have the following:.

i) Positive Antinuclear Antibodies (ANA) with nucleolar pattern and/or anti-Topoisomerase I (anti-Scl-70) antibodies.

ii) Confirmation of Interstitial Lung Disease (ILD) on centrally read High-Resolution Computed Tomography (HRCT) with ≥ 10% total lung involvement, with at least one of the following attributed to active SSc:.

A. Arthritis.

B. Myositis.

C. Carditis.

D. Progressive skin disease.

E. Elevated inflammatory markers.

\- Participants must have a non-response or intolerance despite ≥ 6 months of treatment with at least one immunomodulatory drug. Non-response is defined as a patient, who in the opinion of the investigator, is not adequately controlled/treated and requires treatment escalation.

Exclusion Criteria

* Participants must not have a requirement for supplemental oxygen therapy and/or Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO) ≤ 40% (Hemoglobin (Hgb) corrected) at screening.
* Participants must not have moderate to severe Pulmonary Arterial Hypertension (PAH) requiring PAH-specific combination treatment
* Participants must not have pulmonary comorbidity including chronic obstructive pulmonary disease or asthma requiring daily oral corticosteroids, cigarette smoking (including e-cigarettes) within 3 months before screening or unwilling to avoid smoking throughout the study, and/or clinically significant abnormalities on HRCT not attributable to SSc assessed by the central reader at screening.
* Participants must not have gastrointestinal (GI) dysmotility requiring Total Parenteral Nutrition (TPN).
* Participants must not have current gangrene of a digit
* Other protocol-defined Inclusion/Exclusion criteria apply.

• Bristol-Myers Squibb, Study director, Bristol-Myers Squibb

NIH grants: 2025