A Study of LUCAR-DKS1 in Subjects With Relapsed/Refractory Autoimmune Diseases

NCT07095075 | Recruiting Early Phase 1

• 1 other identifier: LB2405-0001
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 5

Brief Summary

This is a prospective, single-arm, open-label and dose-escalation Investigator Initialed study to evaluate LUCAR-DKS1 in adult subjects with relapsed/refractory autoimmune diseases.

Conditions

Relapsed/Refractory Autoimmune Diseases

Outcome Measures

Primary Outcomes (6)

• Incidence, severity, and type of treatment-emergent adverse events (TEAEs) .

  ≥Grade 1 clinical symptoms, laboratory test abnormalities, and clinical events that are possibly, likely, or definitely related to study treatment. Accessed by CTCAE5.0.

  About 2 years after LUCAR-DKS1infusion (Day 1)

• Incidence of dose-limiting toxicity (DLT)

  DLTs are severe adverse events that refers to any untoward medical occurred in a subject participated in a clinical investigation, which have a causal relationship with the treatment and will limit the dose escalation.

  About 2 years after LUCAR-DKS1 infusion (Day 1)

• Cmax

  CAR positive NK cells in peripheral blood after LUCAR-DKS1 infusion, maximum concentration (Cmax).

  About 2 years after LUCAR-DKS1 infusion (Day 1)

• Tmax

  CAR positive NK cells levels in peripheral blood after LUCAR-DKS1 infusion, time to Cmax (Tmax).

  About 2 years after LUCAR-DKS1 infusion (Day 1)

• AUC

  CAR positive NK cells levels in peripheral blood after LUCAR-DKS1 infusion， area under the concentration-time curve (AUC) .

  About 2 years after LUCAR-DKS1 infusion (Day 1)

• Recommended phase 2 dose regimen finding

  Recommended phase 2 dose regimen established through dose exploratoration finding.

  About 2 years after LUCAR-DKS1 infusion (Day 1)

Secondary Outcomes (5)

• SLE disease activity: Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K)

  About 2 years after LUCAR-DKS1infusion (Day 1)

• SSc disease activity :Modified rodnan skin score(mRSS)

  About 2 years after LUCAR-DKS1 infusion (Day 1)

• AAV disease activity： Birmingham vasculitis activity score (BVAS)

  About 2 years after LUCAR-DKS1 infusion (Day 1)

• IIM disease activity ：Manual muscle test-8

  About 2 years after LUCAR-DKS1 infusion (Day 1)

• SjS disease activity: Sjögren's Tool for Assessing(STAR)

  About 2 years after LUCAR-DKS1 infusion (Day 1)

Study Arms (1)

Chimeric antigen receptor NK cells (LUCAR-DKS1), single-dose for each subject.

EXPERIMENTAL

Experimental: chimeric antigen receptor NK cells (LUCAR-DKS1). Dose level1：25 millions /kg Dose level2：50 millions /kg Dose level3：100 millions /kg Dose level4：200 millions /kg Dose level5：400 millions /kg Totally 5 dose groups, each subject will be given a single-dose LUCAR-DKS1 cells infusion at a certain level, subject will be administered at day 1.

Biological: LUCAR-DKS1 NK cells

Interventions

LUCAR-DKS1 NK cells BIOLOGICAL

Prior to the infusion of the LUCAR-DKS1 cells, subjects will receive a conditioning premedication regimen consisting of cyclophosphamide and fludarabine.

Chimeric antigen receptor NK cells (LUCAR-DKS1), single-dose for each subject.

Eligibility Criteria

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

You may qualify if:

• Subjects voluntary agreement to provide written informed consent.
• Aged 18 to 70 years, either sex.
• Clinical laboratory values meet screening criteria.
• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Nanjing Legend Biotech Co.: lead

Study Sites (5)

The Third The People's Hospital of BengBu

Bengbu, Anhui, 233000, China

NOT YET RECRUITING

The First Affiliated Hospital of USTC (Anhui Provincial Hospital)

Hefei, Anhui, 230036, China

RECRUITING

Jiangsu Province Hospital

Nanjing, Jiangsu, 210029, China

RECRUITING

The First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, 215006, China

RECRUITING

The First Affiliated Hospital of Wenzhou Medical University

Wenzhou, Zhejiang, 325015, China

NOT YET RECRUITING

MeSH Terms

Conditions

Autoimmune Diseases

Condition Hierarchy (Ancestors)

Immune System Diseases

Study Officials

• Wenfeng Tan Principal Investigator

  The First Affiliated Hospital with Nanjing Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Wenbo Hu

CONTACT

13581888439; wenbo.hu@legendbiotech.cn

Liyuan Yu

CONTACT

18618406418; liyuan.yu@legendbiotech.cn

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This study is a dose exploration study that employs an accelerated titration design combined with BF-BOIN, planned to investigate 5 dose groups. Dose Level1 （25×10\^6 cells/kg) and Level 2(50×10\^6 cells/kg)belong to the accelerated titration method for dose assessment, three dosage levels of 100×10\^6 cells/kg, 200×10\^6 cells/kg, and 400×10\^6 cells/kg are assessed using the BOIN dose escalation and de-escalation rules.

Study Record Dates

• First Submitted: June 23, 2025
• First Posted: July 31, 2025
• Study Start: October 14, 2025
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2029
• Last Updated: December 10, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (5)