SELECT-SLE: Biomarker-Guided CAR-T Target Selection for Refractory Lupus (SELECT-SLE)

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.

study evaluates a biomarker-guided strategy to assign adults with refractory SLE to autologous CAR-T therapy targeting either CD19 or BCMA. Participants undergo centralized screening immunophenotyping to determine whether their disease appears B-cell-dominant (CD19-preferred) or plasma-cell-dominant (BCMA-preferred), followed by leukapheresis, lymphodepletion, and a single CAR-T infusion. The main goals are to assess safety, determine a recommended Phase 2 dose within each arm, and estimate remission rates by Week 24.

Study Overview

• Status: Recruiting
• Conditions: Lupus Nephritis; REFRACTORY SYSTEMIC LUPUS ERYTHEMATOSUS
• Intervention / Treatment: Biological: Autologous anti-CD19 CAR-T cells, intravenous single infusion at protocol-defined dose level (1 x 10^6 or 3 x 10^6 CAR-positive viable T cells/kg).; Drug: Fludarabine; Drug: Cyclophosphamide

Detailed Description

SLE is frequently sustained by autoreactive CD19-positive B cells, plasmablasts, and long-lived plasma cells. CD19-directed CAR-T can produce profound B-cell depletion and immune reset, whereas BCMA-directed CAR-T may better address plasma-cell-dominant disease, especially persistent autoantibody production or lupus nephritis after prior B-cell-depleting therapy. This example trial prospectively assigns participants to the target most likely to match their dominant pathogenic compartment. At screening, a central review committee evaluates flow cytometry target expression, serum autoantibody burden, complement levels, immunoglobulins, prior response to rituximab or similar agents, and renal/plasma-cell biomarkers where relevant. Each arm includes a safety lead-in with dose escalation followed by an expansion cohort at the recommended Phase 2 dose. All participants undergo leukapheresis, optional protocol-limited bridging therapy, fludarabine/cyclophosphamide lymphodepletion, single CAR-T infusion, inpatient monitoring, and follow-up through 52 weeks, plus separate long-term gene-modified-cell safety surveillance.

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: shan S Lu, Phd; Phone Number: +86 13076790030; Email: Seni-Lu@beijing-biotech.com

Study Locations

• China
  • Guangdong
    • Shenzhen, Guangdong, China, 518036
      • Recruiting
      • Peking University Shenzhen Hospital
      • Contact: Zhen J Peng, Phd; Phone Number: +86 13076790039; Email: Zhen-Peng@beijing-biotech.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CD19-selected; Participants with a B-cell-dominant disease profile (for example, measurable circulating CD19-positive B cells, active serology, and no strong evidence of plasma-cell-dominant refractory disease) receive autologous anti-CD19 CAR-T cells after lymphodepletion.	Biological: Autologous anti-CD19 CAR-T cells, intravenous single infusion at protocol-defined dose level (1 x 10^6 or 3 x 10^6 CAR-positive viable T cells/kg).; Autologous anti-CD19 CAR-T cells are patient-derived T lymphocytes that are genetically engineered to target CD19-expressing B cells. In clinical trials, a single intravenous infusion is administered at a protocol-defined dose (e.g., 1 × 10⁶ or 3 × 10⁶ CAR-positive viable T cells per kg) to evaluate safety, tolerability, and preliminary efficacy.; Drug: Fludarabine; 30 mg/m2/day IV on Days -5 to -3.; Drug: Cyclophosphamide; 300 mg/m2/day IV on Days -5 to -3.
Experimental: BCMA-Selected CAR-T; Participants with a plasma-cell-dominant or BCMA-preferred profile (for example, persistent autoantibody production after prior B-cell depletion, high plasmablast/plasma-cell markers, or active nephritis with ongoing serologic activity) receive autologous anti-BCMA CAR-T cells after lymphodepletion.	Biological: Autologous anti-CD19 CAR-T cells, intravenous single infusion at protocol-defined dose level (1 x 10^6 or 3 x 10^6 CAR-positive viable T cells/kg).; Autologous anti-CD19 CAR-T cells are patient-derived T lymphocytes that are genetically engineered to target CD19-expressing B cells. In clinical trials, a single intravenous infusion is administered at a protocol-defined dose (e.g., 1 × 10⁶ or 3 × 10⁶ CAR-positive viable T cells per kg) to evaluate safety, tolerability, and preliminary efficacy.; Drug: Fludarabine; 30 mg/m2/day IV on Days -5 to -3.; Drug: Cyclophosphamide; 300 mg/m2/day IV on Days -5 to -3.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-limiting toxicities (DLTs)	Incidence of protocol-defined DLTs, including product-related Grade 3 or higher non-hematologic toxicity and prolonged severe cytopenia.	28 days
Incidence and severity of cytokine release syndrome (CRS)	Incidence and severity of cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, graded by ASTCT criteria.	28
Protocol-defined lupus response	Proportion of participants achieving DORIS remission without rescue therapy or, for those with active baseline LN, complete renal response without rescue therapy.	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete renal response in LN subgroup	Renal response rate in participants with active lupus nephritis at baseline.	52 weeks

Collaborators and Investigators

• Sponsor: Beijing Biotech

Study record dates

Study Major Dates

• Study Start (Actual): March 2, 2026
• Primary Completion (Estimated): March 14, 2027
• Study Completion (Estimated): October 17, 2028

Study Registration Dates

• First Submitted: April 5, 2026
• First Submitted That Met QC Criteria: April 5, 2026
• First Posted (Actual): April 13, 2026

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 5, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: CAR-T; CD19; lupus nephritis; BCMA; B-cell depletion; autologous T cells; biomarker-guided therapy; immune reset; plasma-cell depletion; refractory lupus
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Glomerulonephritis; Nephritis; Skin and Connective Tissue Diseases; Lupus Erythematosus, Systemic; Lupus Nephritis; Organic Chemicals; Hydrocarbons; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Cyclophosphamide; fludarabine
• Other Study ID Numbers: EB-SLE-CART-SELECT-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No