BAFF CAR-T Cells (LMY-922) for Treatment of Refractory Autoimmune Disease

NCT07729995 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: LMY-922-001
• Study Type: interventional
• Target: 94
• Locations: 1 country
• Sites: 1

Brief Summary

Therapy with chimeric antigen receptor T (CAR-T) cells has demonstrated activity against refractory autoimmune disease, however not all disease responds or remains in response to CD19 targeted CAR-T cells. We posit that CAR-T cells expressing BAFF (BAFF CAR-T cells) can become another strategy to treat refractory autoimmune disease, even after relapse following other treatments. This phase 1 study will evaluate safe dose and provide initial signal of the activity of BAFF CAR-T cells against refractory autoimmune disease using a BAFF CAR-T cell manufacturing process with or without lymphodepletion regimen.

Conditions

Rheumatoid Arthritis (RA); Dermatomyositis (DM); Systemic Sclerosis (SSc); Systemic Lupus Erthematosus (SLE)

Keywords

Systemic Scleroderma; Lupus; Lupus Nephritis

Outcome Measures

Primary Outcomes (2)

• To evaluate the Incidence and Severity of Treatment-Emergent Adverse Events (Safety) of LMY-922 in Patients ≥16 Years of Age with Refractory Autoimmune Disease

  Incidence and severity of treatment-emergent adverse events

  24 Months

• To determine the recommended Phase II dose of LMY-922 based on Incidence of dose limiting toxicities in patients with refractory autoimmune disease.

  Incidence of dose limiting toxicities (DLT)

  24 Months

Secondary Outcomes (15)

• Response in Rheumatoid Arthritis: Chage from Baseline DAS28-CRP Score

  24 Months

• Response in Systemic Lupus Erythematosus: Change in Systemic Lupus Erythematosus Disease Activity Index

  24 Months

• Response in Dermatomyositis: Core Set Measurement Total Improvement Score improvement rate.

  24 Months

• Response in Systemic Sclerosis: Change in Modified Rodnan Skin Score

  24 Months

• Response in Rheumatoid Arthritis: DAS28-CRP Remission

  24 Months

Other Outcomes (12)

• Drug-free remission and response

  24 Months

• Serum soluble BR3

  24 Months

• Serum soluble TACI

  24 Months

Study Arms (3)

Part A: Standard Dose Escalation Assessment

EXPERIMENTAL

Open label, dose escalation study with up to four dose levels of LMY-922. The maximum tolerated dose (MTD) of LMY-922 will be determined using dose-escalation 3+3 design. Dose Level -1: 75×10\^6 CAR-T cells Dose Level 1: 150×10\^6 CAR-T cells Dose Level 2: 300×10\^6 CAR-T cells Dose Level 3: 450×10\^6 CAR-T cells

Biological: LMY-922

Part B: Conditioning Assessment

EXPERIMENTAL

Evaluation of LMY-922 without lymphodepletion in Part B will be initiated only after safety, tolerability, and dose parameters are established in Part A.

Biological: LMY-922

Part C: Scheduling Assessment

EXPERIMENTAL

Evaluation of LMY-922 fractionated dosing with or without lymphodepletion in Part C will be initiated only after safety, tolerability, lymphodepletion regimen parameters and dose parameters are established in Part A and Part B. Participants will receive three equal fractionated doses of LMY-922 administered approximately 3 weeks apart (Days 0, 21, and 42). The total cumulative dose will be equivalent to the dose selected in Parts A and B.

Biological: LMY-922

Interventions

LMY-922 BIOLOGICAL

Allogeneic CAR-T cell therapy expressing the BAFF-ligand

Also known as: BAFF CAR-T Cells

Part A: Standard Dose Escalation Assessment; Part B: Conditioning Assessment; Part C: Scheduling Assessment

Eligibility Criteria

• Age: 16 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female 16-75 years of age, inclusive.
• For participants with:
• a. Rheumatoid Arthritis:
• i. Meets criteria for seropositive, adult-onset RA as defined by the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria, or seropositive (rheumatoid factor positive) polyarticular juvenile arthritis as defined by the International League of Associations for Rheumatology (ILAR) classification criteria for at least 3 months prior to screening
• ii. Disease Activity Score DAS28-ESR\>3.2 at screening.
• iii. At least one swollen joint with Power Doppler activity of at least grade 1 or B-mode activity of at least grade 2 at screening.
• iv. Inadequate response to at least one csDMARD and at least two tsDMARD/bDMARDs with two different mechanisms of action.
• v. Rheumatoid factor or ACPA positivity (cut off 20 mU/ml) at screening.
• b. Systemic Lupus Erythematosus:
• i. Meets European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) Classification Criteria for Systemic Lupus Erythematosus prior to screening
• ii. Participant must be positive for at least one of the following at screening: Anti-dsDNA (above the upper limit of normal \[ULN\]); or anti-Sm (above the ULN); or anti-chromatin
• iii. An inadequate response to at least two immunomodulatory agents (cyclophosphamide, azathioprine, tacrolimus, cyclosporine, mycophenolate mofetil) and one biologic agent (e.g., belimumab, anifrolumab)
• iv. Diagnosed with active SLE based on at least one of the following: 1. Active non-renal SLE with SLEDAI score ≥6 at screening; 2. Biopsy proven lupus nephritis (LN) with a urine protein creatinine ratio of ≥1 mg/mg on a first morning void. A biopsy must be performed in the 6 months prior to the screening showing active LN class III or IV, with or without class V, in accordance with the 2018 International Society of Nephrology/Renal Pathology Society classification.
• c. Dermatomyositis:
• i. Meets 2017 EULAR/ACR Classification Criteria for Adult and Juvenile Idiopathic Inflammatory Myopathies for definite or probable diagnosis of DM or juvenile DM at least 6 months before screening.

You may not qualify if:

• The presence of any of the following will exclude a participant from study enrollment:
• Significant disease-related complications
• a. For Systemic Lupus Erythematosus participants:
• i. Features of severe neuropsychiatric lupus, including seizures, psychosis, stroke, lupus cerebritis or lupus meningitis. Prior history of severe neuropsychiatric lupus with active features should be discussed with the medical monitor
• ii. Active secondary hemophagocytic lymphohistiocytosis (sHLH)/macrophage activation syndrome (MAS)
• c. For Systemic Sclerosis participants:
• i. Anticentromere antibody seropositivity
• ii. SSc mimics (eg, scleromyxedema, eosinophilic fasciitis)
• iii. Pulmonary arterial hypertension (PAH) as determined by right heart catheterization or on PAH approved medications for PAH. It is acceptable to use PDFE-5 inhibitors for Raynaud's and digital ulcers
• Active thrombotic thrombocytopenic purpura (TTP)/microthrombotic vasculopathy (TMA)
• Current or prior malignancy, unless the malignancy was treated with curative intent and the participant has no known active malignant disease present for ≥ 5 years prior to enrollment.
• Symptomatic congestive heart failure.
• Renal failure requiring regular dialysis.
• Uncontrolled pulmonary disease.
• Ongoing infection, whether controlled or uncontrolled.

Sponsors & Collaborators

• Luminary Therapeutics: lead

Study Sites (1)

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid; Dermatomyositis; Scleroderma, Systemic; Lupus Nephritis

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Polymyositis; Myositis; Muscular Diseases; Neuromuscular Diseases; Nervous System Diseases; Skin Diseases; Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Lupus Erythematosus, Systemic

Central Study Contacts

Susan Prockop, MD

CONTACT

617-355-3087; susan.prockop@childrens.harvard.edu

Study Design

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

Study Record Dates

• First Submitted: July 15, 2026
• First Posted: July 28, 2026
• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): March 1, 2030
• Study Completion (Estimated): March 1, 2030
• Last Updated: July 28, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)