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

NCT07523542 | Recruiting Phase 1 DMC

• 1 other identifier: EB-SLE-CART-SELECT-001
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

REFRACTORY SYSTEMIC LUPUS ERYTHEMATOSUS; Lupus Nephritis

Keywords

autologous T cells; B-cell depletion; BCMA; biomarker-guided therapy; CAR-T; CD19; immune reset; lupus nephritis; plasma-cell depletion; refractory lupus

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (1)

• Complete renal response in LN subgroup

  52 weeks

Study Arms (2)

CD19-selected

EXPERIMENTAL

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).; Drug: Fludarabine; Drug: Cyclophosphamide

BCMA-Selected CAR-T

EXPERIMENTAL

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).; Drug: Fludarabine; Drug: Cyclophosphamide

Interventions

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). BIOLOGICAL

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.

BCMA-Selected CAR-T; CD19-selected

Fludarabine DRUG

30 mg/m2/day IV on Days -5 to -3.

BCMA-Selected CAR-T; CD19-selected

Cyclophosphamide DRUG

300 mg/m2/day IV on Days -5 to -3.

BCMA-Selected CAR-T; CD19-selected

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Age 18 to 70 years at consent. 2. Meets 2019 EULAR/ACR classification criteria for SLE, with total score \>= 10.
• \. 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.
• \. 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%.
• \. Adequate venous access and eligibility for leukapheresis. 9. Negative pregnancy test and agreement to use effective contraception for 12 months after infusion.
• \. 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.

You may not qualify if:

• \. Active uncontrolled infection, including active tuberculosis, hepatitis B or C with active replication, or HIV.
• \. 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.
• \. 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.
• \. Uncontrolled psychiatric disease, active substance misuse, or social circumstances that would impair adherence.
• \. Any condition that, in the investigator's judgment, makes participation unsafe or confounds interpretation of the study endpoints.

Sponsors & Collaborators

• Beijing Biotech: lead

Study Sites (1)

Peking University Shenzhen Hospital

Shenzhen, Guangdong, 518036, China

RECRUITING

MeSH Terms

Conditions

Lupus Erythematosus, Systemic; Lupus Nephritis

Interventions

fludarabine; Cyclophosphamide

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Central Study Contacts

shan S Lu, Phd

CONTACT

+86 13076790030; Seni-Lu@beijing-biotech.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: Open-label conduct is required because the assigned CAR-T product is individualized, target selection is biomarker-driven, and early toxicity management requires full knowledge of the product received.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Two experimental arms run in parallel. A pre-specified target-selection algorithm assigns each participant to the CD19 arm or BCMA arm after screening based on flow-cytometry target expression, serologic activity, prior response to B-cell-depleting therapy, and renal/plasma-cell biomarkers where relevant. Each arm includes a dose-finding safety lead-in followed by cohort expansion at the selected dose.

Study Record Dates

• First Submitted: April 5, 2026
• First Posted: April 13, 2026
• Study Start: March 2, 2026
• Primary Completion (Estimated): March 14, 2027
• Study Completion (Estimated): October 17, 2028
• Last Updated: April 13, 2026

Record last verified: 2026-04

Locations

CN (1)