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

Starting soon · Phase 1

Conditions studied: Rheumatoid Arthritis (RA), Systemic Lupus Erthematosus (SLE), Dermatomyositis (DM), Systemic Sclerosis (SSc)

In brief

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.

Key facts

Study ID

NCT07729995

Run by

Luminary Therapeutics

People needed

94

Starts

2026-10-01

Expected to finish

2030-03-01

Last updated by the study team

2026-07-28

Who can join

Age: 16 and older, up to 75. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Participants must meet all the following inclusion criteria to be eligible for enrollment:
• 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.
• ii. Positivity for at least one myositis-specific antibody (aminoacyl tRNA synthetases, Mi2, MDA5, SAE, SRP, ARS, HMGCR, MJ, TIF1gamma)
• iii. Active DM as defined by at least one of the following: Active skin disease as defined by a CDASI-A score of at least 14, or active muscle disease as defined as Manual Muscle Testing (MMT-8) score <142/150 and creatine kinase, aldolase, LDH, AST, or ALT ≥2×ULN (if deemed due to muscle inflammation by investigator) and MRI evidence of active myositis within last 3 months.
• iv. Failure of at least 2 standard-of-care therapies, including csDMARDs + corticosteroids and bDMARD or IVIG
• v. Inadequate response to intravenous immunoglobulin (IVIG) and at least two immunomodulator agents: cyclophosphamide, azathioprine, tacrolimus, cyclosporine, mycophenolate mofetil and one biologic agent (e.g., rituximab, belimumab).
• d. Systemic Sclerosis:
• i. Per 2013 ACR/EULAR classification criteria and all of the following: 1. Disease duration of ≤ 3 years (time from the first non-Raynaud phenomenon manifestation); 2. mRSS > 10 at screening with early disease or rapid progression, or mRSS ≥ 15 with disease duration ≥ 18 month.; 3. Positivity for at least one SSc-specific parameter (Scl70, RNA polymerase, Th/To, RP11/12, U3RNP autoantibodies); 4. Failure of treatment with at least 2 standard-of-care therapies, including ≥2 csDMARDs (including mycophenolate or cyclophosphamide) and ≥1 bDMARD (including rituximab); 5. Diffuse SSc with or without interstitial lung disease (ILD)
• Stable doses of corticosteroids for at least 4 weeks and other immunosuppressives for 8 weeks.
• Adequate organ function as defined by each of the following:
• Creatinine clearance more than or equal to 45 ml/min calculated per the 2021 CKD-EPI Creatinine Equation

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)
• iii. History of antiphospholipid syndrome diagnosed by ACR/EULAR criteria (isolated obstetric antiphospholipid syndrome is allowed) b. For Dermatomyositis participants: i. Overlap myositis/connective tissue disease (except for overlap with Sjögren's syndrome) ii. Participants with other types of myositis or myopathies: polymyositis, paraneoplastic myositis, inclusion body myositis, metabolic or drug induced myopathy, dystrophies
• 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.
• Cardiovascular disorders including unstable angina pectoris, clinically significant cardiac arrhythmias, myocardial infarction or stroke (including transient ischemic attack, or other ischemic event) within 6 months prior to registration.
• Active infection requiring intravenous systemic treatment.
• HIV seropositivity.
• Pregnant or breastfeeding women are excluded from this study (breastfeeding should be discontinued), because there is an unknown, but potential risk for adverse events in fetuses and nursing infants secondary to treatment of the mother with LMY-922 and lymphodepleting chemotherapy. Women of childbearing potential must have a negative serum pregnancy test
• Serologic status reflecting active hepatitis B or C infection. Participants that are positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), or hepatitis C antibody must have a negative polymerase chain reaction (PCR) prior to enrollment. (PCR positive participants will be excluded.)
• Participants with history of clinically relevant CNS pathology such as uncontrolled epilepsy, paresis, aphasia, uncontrolled cerebrovascular disease, severe brain injuries, dementia, and Parkinson's disease.
• Participants with uncontrolled intercurrent illness including, but not limited to symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, pulmonary abnormalities, or psychiatric illness/social situations that would limit compliance with study requirements.
• Participants receiving a live vaccine within 2 weeks prior to screening.
• Concurrent use of high dose systemic steroids and/or immunosuppressive therapies.

Where it is running

• Boston Children's Hospital — Boston, Massachusetts, United States

Full record on ClinicalTrials.gov

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