Biomarker-guided CAR-T target selection for refractory lupus

A Phase 1/2, Open-Label, Biomarker-Guided, Non-Randomized, Multicenter Study of Autologous CAR-T Cell Therapy Targeting CD19 or BCMA in Adults With Refractory Systemic Lupus Erythematosus With or Without Active Lupus Nephritis.

This trial tests whether using a lab-based immune profile to pick CD19- or BCMA-targeted CAR-T can help adults with refractory lupus, including lupus nephritis, who have not responded to standard treatments.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 24 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Beijing Biotech (industry)
• Drugs / interventions: CAR-T, cyclophosphamide, fludarabine, rituximab
• Locations: 1 site (Shenzhen, Guangdong)
• Trial ID: NCT07523542 on ClinicalTrials.gov

What this trial studies

Adults with refractory SLE undergo centralized immunophenotyping (flow cytometry, autoantibody and complement testing) to identify whether their disease is B-cell-dominant (CD19) or plasma-cell-dominant (BCMA). Participants assigned to the CD19 or BCMA arm undergo leukapheresis, optional short bridging therapy, fludarabine/cyclophosphamide lymphodepletion, and a single infusion of autologous CAR-T cells with a safety lead-in dose-escalation followed by an expansion cohort. Inpatient monitoring is provided after infusion and participants are followed through 52 weeks with separate long-term gene-modified-cell safety surveillance. Primary aims are to characterize safety, define a recommended Phase 2 dose for each arm, and estimate remission rates by Week 24.

Who should consider this trial

Good fit: Adults aged 18–70 with 2019 EULAR/ACR-classified SLE who have active, treatment-refractory disease (insufficient response to at least two prior systemic regimens including an immunosuppressant or biologic) and demonstrable CD19- or BCMA-targetable biology are potential candidates.

Not a fit: Patients without measurable CD19 or BCMA target expression, those with well-controlled disease, or those unable to tolerate leukapheresis, lymphodepletion, or CAR-T therapy are unlikely to benefit from this approach.

Why it matters

Potential benefit: If successful, matching each patient to the CAR-T target that most closely drives their disease could produce deeper, longer-lasting remissions and reduce reliance on other immunosuppression.

How similar studies have performed: Small case series have reported deep remissions after CD19-directed CAR-T in refractory SLE, while BCMA-directed CAR-T is established in myeloma but is less tested for autoimmune disease.

Eligibility criteria

Inclusion Criteria:

* 1\. Age 18 to 70 years at consent. 2. Meets 2019 EULAR/ACR classification criteria for SLE, with total score \>= 10.

  3\. Active refractory disease at screening, defined by SELENA-SLEDAI \>= 8, or at least one BILAG A domain, or at least two BILAG B domains, or active lupus nephritis with significant proteinuria and active urinary sediment.

  4\. Inadequate response, intolerance, or contraindication to at least 2 prior standard systemic regimens, including at least 1 immunosuppressant or biologic used for SLE or lupus nephritis. 5. Demonstrable targetable biology and assignment to one protocol arm: CD19 arm for measurable CD19-positive B-cell / B-cell-dominant disease, or BCMA arm for BCMA-positive plasmablast / plasma-cell-dominant disease and/or persistent serologic activity after prior B-cell depletion. 6. If active lupus nephritis is present, biopsy-proven class III, IV, V, or mixed proliferative / membranous LN within the previous 24 months, or investigator confirmation that repeat biopsy is unsafe but the clinical picture strongly supports active LN. 7. Adequate organ function: hemoglobin \>= 8.5 g/dL, ANC \>= 1.0 x 10\^9/L, platelets \>= 50 x 10\^9/L, AST / ALT \<= 2.5 x ULN, creatinine clearance \>= 30 mL/min, bilirubin \<= 2.0 mg/dL unless otherwise explained, and LVEF \>= 50%.

  8\. Adequate venous access and eligibility for leukapheresis. 9. Negative pregnancy test and agreement to use effective contraception for 12 months after infusion.

  10\. Ability to discontinue prohibited SLE medications per washout rules and willingness to comply with inpatient observation and long-term follow-up. 11. Written informed consent.

Exclusion Criteria:

* 1\. Active uncontrolled infection, including active tuberculosis, hepatitis B or C with active replication, or HIV.

  2\. Prior CAR-T therapy or prior CD19- or BCMA-directed cell therapy. 3. Severe active CNS lupus requiring urgent escalation of immunosuppression, uncontrolled seizure disorder, or stroke within 60 days before screening. 4. End-stage organ failure not expected to improve with immune reset, such as dialysis-dependent kidney failure, uncontrolled advanced heart failure, or ICU-level respiratory instability. 5. Active malignancy or history of malignancy within 5 years, except adequately treated non-melanoma skin cancer, cervical carcinoma in situ, or other low-risk malignancy in durable remission. 6. Pregnant or breastfeeding. 7. Allogeneic hematopoietic stem cell transplant or solid organ transplant history.

  8\. Contraindication to fludarabine, cyclophosphamide, leukapheresis, or standard rescue medications for CRS / ICANS. 9. Live vaccine within 4 weeks before lymphodepletion. 10. Participation in another interventional clinical study within 3 months before enrollment.

  11\. Uncontrolled psychiatric disease, active substance misuse, or social circumstances that would impair adherence.

  12\. Any condition that, in the investigator's judgment, makes participation unsafe or confounds interpretation of the study endpoints.

Where this trial is running

Shenzhen, Guangdong

• Peking University Shenzhen Hospital — Shenzhen, Guangdong, China (RECRUITING)

Study contacts

• Study coordinator: shan S Lu, Phd

Conditions: REFRACTORY SYSTEMIC LUPUS ERYTHEMATOSUS, Lupus Nephritis, autologous T cells, B-cell depletion, BCMA, biomarker-guided therapy, CAR-T, CD19