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

Legend Biotech

Status and phase: Enrolling; Early Phase 1

Conditions: Relapsed/Refractory Autoimmune Diseases

Treatments: Biological: LUCAR-DKS1 NK cells

Study type: Interventional

Funder types: Industry

Identifiers

NCT07095075

LB2405-0001

Details and patient eligibility

About

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.

Full description

This is a prospective, single-arm, open-label clinical study to evaluate the safety, tolerability, pharmacokinetics and efficacy profiles of LUCAR-DKS1, a chimeric antigen receptor (CAR) -NK cell therapy in subjects with relapsed/refractory autoimmune diseases. Patients who meet the eligibility criteria will receive LUCAR-DKS1 infusion. The study will include the following sequential stages: screening, pre-treatment (lymphodepleting chemotherapy), treatment LUCAR-DKS1 infusion) and follow-up.

Enrollment: 36 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Sequential Assignment

Masking: None (Open label)

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36 participants in 1 patient group

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

Experimental group

Description:

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.

Treatment:

Biological: LUCAR-DKS1 NK cells