LUCAR-DKS1 for relapsed or treatment-resistant autoimmune diseases

An Open-label Clinical Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of LUCAR-DKS1 in Subjects With Relapsed/Refractory Autoimmune Diseases (r/r AID)

This study will try LUCAR-DKS1, a CAR-NK cell therapy, in adults (18–70) with relapsed or treatment-resistant autoimmune diseases who test positive for CD19 and/or BCMA.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 36 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Nanjing Legend Biotech Co. (Industry-sponsored)
• Drugs / interventions: chimeric antigen receptor, chemotherapy
• Locations: 5 sites (Bengbu, Anhui and 4 other locations)
• Trial ID: NCT07095075 on ClinicalTrials.gov

What this trial studies

This is a prospective, single-arm, open-label, dose-escalation early-phase trial testing LUCAR-DKS1, a chimeric antigen receptor (CAR) NK-cell therapy, in adults with relapsed or refractory autoimmune diseases. Participants will undergo screening, receive lymphodepleting chemotherapy, then a single infusion of LUCAR-DKS1 followed by planned follow-up visits to monitor safety, pharmacokinetics, and signals of efficacy. The protocol enrolls patients meeting disease-specific classification criteria (for SLE, AAV, SSc, or IIM) with relevant antibody or marker positivity and acceptable laboratory parameters. The primary focus is on safety and tolerability, with secondary collection of pharmacologic and preliminary effectiveness data.

Who should consider this trial

Good fit: Ideal candidates are adults 18–70 with relapsed or treatment-refractory SLE, AAV, SSc, or IIM who meet the disease classification criteria, have the required antibody/marker positivity (including CD19 and/or BCMA), and meet laboratory safety criteria.

Not a fit: Patients without CD19 or BCMA positivity, with uncontrolled infections or serious comorbidities, or who do not meet the specific disease classification or laboratory criteria are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, this approach could reduce autoimmune activity and produce durable remissions in patients who have not responded to standard therapies.

How similar studies have performed: Targeting B cells with cellular therapies (notably CAR-T) has shown promising but early results in some refractory autoimmune conditions, while CAR-NK approaches are novel and have only limited clinical data so far.

Eligibility criteria

* Inclusion Criteria:

  1. Subjects voluntary agreement to provide written informed consent.
  2. Aged 18 to 70 years, either sex.
  3. Clinical laboratory values meet screening criteria.
  4. Positive test for CD19 and/ or BCMA

SLE:

* Meets at least 1 classification criteria≥6 months for SLE.
* At screening, antinuclear antibody, and/or anti-dsDNA antibody, and/or anti-Smith antibody should be positive.
* Fulfill relapsed/refractory SLE conditions.

AAV:

* Meets the 2022 ACR/EULAR classification criteria for AAV.
* Positive test for anti-MPO or p-ANCA or anti-PR3 or anti-MPO antibodies at screening.
* Fulfill relapsed/refractory AAV conditions.

SSc:

* Meets the 2013 ACR/EULAR classification criteria for SSc.
* At screening, mRSS is higher than 10.
* Fulfill relapsed/refractory SSc conditions.

IIM:

* Meets 2017 EULAR/ACR classification criteria for IIM.
* Positive test for myositis-associated antibodies or myositis-specific antibodies at screening.
* Fulfill relapsed/refractory IIM conditions. SjS：
* Meets the 2016 ACR/EULAR diagnostic criteria for SjS.
* Positive test for anti-SSA and/or anti-SSB antibodies at screening.
* Fulfill relapsed/refractory SjS conditions.

Exclusion Criteria:

1. Active infections such as hepatitis and tuberculosis.
2. Other autoimmune diseases.
3. Serious underlying diseases such as tumor, uncontrolled diabetes.
4. Female subjects who were pregnant, breastfeeding.
5. Those with a history of major organ transplantation.
6. Have received autologous cell therapy of any target before.

Where this trial is running

Bengbu, Anhui and 4 other locations

• The Third The People's Hospital of BengBu — Bengbu, Anhui, China (Not_yet_recruiting)
• The First Affiliated Hospital of USTC (Anhui Provincial Hospital) — Hefei, Anhui, China (Recruiting)
• Jiangsu Province Hospital — Nanjing, Jiangsu, China (Recruiting)
• The First Affiliated Hospital of Soochow University — Suzhou, Jiangsu, China (Recruiting)
• The First Affiliated Hospital of Wenzhou Medical University — Wenzhou, Zhejiang, China (Not_yet_recruiting)

Study contacts

• Principal investigator: Wenfeng Tan Principal Investigator — The First Affiliated Hospital with Nanjing Medical University
• Study coordinator: Wenbo Hu

Conditions Relapsed/Refractory Autoimmune Diseases