Phase 3 Randomized Study of CD19‑Targeted NEX‑T CAR T (CC‑97540) vs Standard‑of‑Care Combination Therapy in Systemic Sclerosis–Associated Interstitial Lung Disease

The primary objective is to assess the efficacy of CD19‑targeted NEX‑T CAR T (BMS‑986353) compared with standard of care in improving pulmonary function in participants with active Systemic Sclerosis and associated interstitial lung disease, reflecting its potential therapeutic benefit on a key organ manifestation.

Secondary objectives include:

• Evaluation of the effect on skin thickening, a frequent manifestation of Systemic Sclerosis.
• Assessment of changes in high‑resolution computed tomography characteristics and additional pulmonary function parameters.
• Determination of the ability of the investigational therapy to prevent disease worsening.

The trial enrolled 55 participants diagnosed with Systemic Sclerosis and associated interstitial lung disease. Both male and female patients were included, with ages ranging from 16 years upward, as defined by the study’s age‑range categories. Eligibility required fulfillment of the ACR/EULAR 2013 criteria for systemic sclerosis, presence of positive auto‑antibodies, and radiographic evidence of active lung involvement on high‑resolution computed tomography. Candidates also needed at least one active disease manifestation (e.g., swollen joints, myositis, myocarditis, worsening skin thickening, or elevated inflammatory markers) and a history of insufficient response or intolerance to at least six months of prior systemic sclerosis therapy. The population comprised individuals classified as patients, including those considered vulnerable, selected solely on the basis of these clinical and laboratory criteria. No specific lifestyle restrictions such as diet or physical activity were stipulated in the provided information.

The study is a Phase 3, randomized, open-label, multicenter trial evaluating the efficacy and safety of CD19‑targeted NEX‑T CAR T cells (BMS‑986353) compared with standard‑of‑care therapies in participants with active Systemic Sclerosis and associated interstitial lung disease. Eligible individuals must be ≥16 years old, meet ACR/EULAR 2013 criteria for systemic sclerosis, have positive auto‑antibodies, demonstrate active lung involvement on high‑resolution CT, present at least one disease‑related manifestation (e.g., arthritis, myositis, myocarditis, skin thickening, elevated inflammatory markers), and have experienced inadequate response or intolerance to at least one prior systemic sclerosis treatment. The primary endpoint is the change in Forced Vital Capacity (mL); secondary endpoints include change in Modified Rodnan Skin Score, percent predicted FVC, DLCO, and time to disease progression. The trial timeline extends from an estimated recruitment start of 20 June 2026 to an anticipated completion date of 11 November 2030. Study visits include a screening visit for eligibility assessment, a baseline visit on day 0 for administration of the investigational cell product or initiation of comparator therapy, and scheduled follow‑up visits at defined intervals (e.g., weeks 2, 4, 8, 12 and then every 3 months) to monitor efficacy, safety, and laboratory parameters, culminating in an end‑of‑study visit for final assessments. Participant involvement therefore spans the entire treatment and follow‑up period until the end‑of‑study visit. Early termination may occur due to serious adverse events, unacceptable toxicity, disease progression requiring alternative therapy, withdrawal of consent, or major protocol violations.

NINTEDANIB is administered orally as a tablet. The protocol permits two dosage strengths, 200 mg and 300 mg, taken once daily by mouth throughout the treatment period.

FLUDARABINE PHOSPHATE is given by intravenous infusion at a dose of 30 mg/m². It is administered as part of the background regimen according to the study schedule.

TOCILIZUMAB is provided in two formulations. Intravenous administration is performed at 24 mg/kg, and a subcutaneous formulation is given at a fixed dose of 162 mg. Both routes are utilized as comparator treatments and are delivered on the days specified in the protocol.

CYCLOPHOSPHAMIDE is delivered by intravenous infusion at 300 mg/m². This agent is used as an auxiliary background therapy according to the predefined dosing calendar.

RITUXIMAB is administered intravenously at a dose of 1000 mg/m². It serves as a comparator treatment and is given on the schedule outlined in the study protocol.

CD19-Targeted NEX‑T CAR T (cell suspension for injection) is infused intravenously. The target dose is 10 × 10⁶ CAR‑T cells (dose unit specified as “Other” in the sponsor documentation). This investigational product is administered as a single infusion following the conditioning regimen.

All study medications are recorded in the source documents, and adherence to the dosing schedule is monitored by site personnel through treatment logs, infusion records, and periodic verification of drug accountability. Compliance assessments include review of administered dose, timing relative to the protocol‑defined window, and documentation of any dose modifications or interruptions.

Efficacy will be evaluated primarily by the change from baseline in Forced Vital Capacity (FVC) measured in milliliters.

Secondary efficacy assessments include the change in Modified Rodnan Skin Score (mRSS), combined evaluations of FVC or mRSS, the change in percent predicted FVC (ppFVC), the change in DLCO, and the time to disease worsening measured from the date of study entry.