Rheumatoid Arthritis (RA)Phase 1NCT07729995
BAFF CAR-T Cells (LMY-922) for Treatment of Refractory Autoimmune Disease
A Phase 1 study testing LMY-922 in people with Rheumatoid Arthritis (RA) and Systemic Lupus Erthematosus (SLE), run by Luminary Therapeutics at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 16 to 75 years
- Conditions the study is for
- Rheumatoid Arthritis (RA), Systemic Lupus Erthematosus (SLE), Dermatomyositis (DM)
- What is being tested?
- LMY-922
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 94 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2026to Mar 2030
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 to 75 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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:
- Rheumatoid Arthritis:
- 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
- Disease Activity Score DAS28-ESR>3.2 at screening.
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- 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.
- Inadequate response to at least one csDMARD and at least two tsDMARD/bDMARDs with two different mechanisms of action.
- Rheumatoid factor or ACPA positivity (cut off 20 mU/ml) at screening.
- Systemic Lupus Erythematosus:
- Meets European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) Classification Criteria for Systemic Lupus Erythematosus prior to screening
- 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
- An inadequate response to at least two immunomodulatory agents (cyclophosphamide, azathioprine, tacrolimus, cyclosporine, mycophenolate mofetil) and one biologic agent (e.g., belimumab, anifrolumab)
- 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.
- Dermatomyositis:
- 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.
- Positivity for at least one myositis-specific antibody (aminoacyl tRNA synthetases, Mi2, MDA5, SAE, SRP, ARS, HMGCR, MJ, TIF1gamma)
- 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.
- Failure of at least 2 standard-of-care therapies, including csDMARDs + corticosteroids and bDMARD or IVIG
- 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).
- Systemic Sclerosis:
- 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
- Participants must have adequate cardiac function as defined as left ventricular ejection fraction ≥ 45% on the most recent echocardiogram and no clinically significant arrhythmias, pericardial effusion, valvular, or ischemic heart disease.
- Adequate pulmonary function with pulse oximetry ≥92% on room air.
- Total Bilirubin < 1.5× the institutional upper limit of normal (except in participants with Gilbert's syndrome).
- ALT (SGPT) and AST (SGOT) < 1.5× the institutional upper limit of normal (except for participants with active myositis).
- Hemoglobin ≥ 8.5 g/dL, and no red blood cell transfusion within 60 days before the laboratory test.
- Platelets ≥ 100,000/μL, no transfusion support within 7 days before the laboratory test, and no associated bleeding.
- Absolute neutrophil count ≥1000.
- Participants (or legal guardians) must have the ability to understand and the willingness to sign a written informed consent document.
- For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use a contraceptive method with a failure rate of < 1% per year during the treatment period and for at least 1 year after the BAFF CAR-T cell infusion.
- A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (< 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus).
- Examples of contraceptive methods with a failure rate of < 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.
- For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as defined below: With female partners of childbearing potential, men must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of < 1% per year during the treatment period and for at least 1 year after the BAFF CART cell infusion. Men must refrain from donating sperm during this same period. With pregnant female partners, men must remain abstinent or use a condom during the treatment period and for at least 1 year after the BAFF CAR-T cell infusion to avoid potential embryonal or fetal exposure.
- The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.
- Body weight of at least 55kg for participants treated at Dose Level 3 (450 × 10^6 BAFF+ CAR cells) and at least 37kg for all other dose levels.
- Participants must be vaccinated per institutional guidelines at least four weeks prior to lymphodepletion.
Who cannot join
- The presence of any of the following will exclude a participant from study enrollment:
- Significant disease-related complications
- For Systemic Lupus Erythematosus participants:
- 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
- Active secondary hemophagocytic lymphohistiocytosis (sHLH)/macrophage activation syndrome (MAS)
- 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
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- For Systemic Sclerosis participants:
- Anticentromere antibody seropositivity
- SSc mimics (eg, scleromyxedema, eosinophilic fasciitis)
- 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.
- Steroid dose must be able to be weaned to 0.5 mg/kg/day or equivalent prior to CAR-T cell infusion.
- Immunosuppressive medications must be able to be stopped at least 5 halflives prior to CAR-T cell infusion.
- Treatment with rituximab or other B cell depleting agent within 6 months of planned CAR-T cell infusion, or treatment with agents such as etanercept, adalimumab, anakinra, infliximab, certolizumab pegol, belimumab, golimumab, abatacept, or tocilizumab within 4 weeks or 5 half-lives (whichever is shorter) prior to planned CAR-T cell infusion.
- Participants with IgG levels < 600mg/dL.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
Boston Children's Hospital
Boston, Massachusetts, 02115
Susan Prockop, MD, 617-355-3087, susan.prockop@childrens.harvard.edu
About this study
Official title: A Phase 1 Study of Allogeneic (γ/δ) BAFF CAR-T Cells (LMY-922) for Treatment of Refractory Autoimmune Disease
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.
Read the detailed description
LMY-922 is an allogeneic CAR-T cell therapy consisting of allogeneic cluster of differentiation 4 (CD4) positive and cluster of differentiation 8 (CD8) positive human T cells that are genetically engineered using the non-viral transposon system to express the BAFF-ligand CAR-T that target BAFF receptor family members to eliminate pathological B cells. BAFF receptor family includes B-cell activating factor receptor (BR3), B-cell maturation antigen (BCMA) and transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI). These receptors are present on the B cells of patients with refractory autoimmune disease. The goal of LMY-922-001 phase 1 study is to find the recommended phase 2 dose of LMY-922 for treatment of patients with refractory autoimmune disease.
- Conditions
- Rheumatoid Arthritis (RA), Systemic Lupus Erthematosus (SLE), Dermatomyositis (DM), Systemic Sclerosis (SSc)
- Being tested
- LMY-922
- Keywords
- Systemic Scleroderma, Lupus, Lupus Nephritis
- Medical subject headings
- Arthritis, Rheumatoid, Dermatomyositis, Scleroderma, Systemic, Lupus Nephritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LMY-922Biological
Also called BAFF CAR-T Cells
Allogeneic CAR-T cell therapy expressing the BAFF-ligand
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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. Receives: 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. Receives: Biological: LMY-922 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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)
Measured: 24 Months
Secondary outcomes (15)
Response in Rheumatoid Arthritis: Chage from Baseline DAS28-CRP Score
Change from baseline in DAS28-CRP score at 3 and 6 months.
Measured: 24 Months
Response in Systemic Lupus Erythematosus: Change in Systemic Lupus Erythematosus Disease Activity Index
Change from baseline in Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) at 3 and 6 months.
Measured: 24 Months
Response in Dermatomyositis: Core Set Measurement Total Improvement Score improvement rate.
Core Set Measurement Total Improvement Score (CSM TIS) 20/40/60 improvement rate.
Measured: 24 Months
Response in Systemic Sclerosis: Change in Modified Rodnan Skin Score
Change from baseline in the Modified Rodnan Skin Score (mRSS) at 3 and 6 months.
Measured: 24 Months
Response in Rheumatoid Arthritis: DAS28-CRP Remission
DAS28-CRP remission rate at 3 and 6 months.
Measured: 24 Months
Response in Rheumatoid Arthritis: ACR 20/50/70 Response Rate
ACR 20/50/70 response rate at 3 and 6 months.
Measured: 24 Months
Response in Rheumatoid Arthritis: Rheumatoid Factor levels
Change in Rheumatoid Factor (RF) levels (U/ml) over time.
Measured: 24 Months
Response in Rheumatoid Arthritis: Anti-Citrullinated Protein Antibody Levels
Change in anti-citrullinated protein antibody (ACPA) levels (mU/ml) over time.
Measured: 24 Months
Response in Rheumatoid Arthritis: Percentage of Participants with Conversion to Anti-Citrullinated Protein Antibody Seronegative Status
Percentage of participants with conversion to anti-citrullinated protein antibody (ACPA) seronegative status = ACPA level <20 mU/ml.
Measured: 24 Months
Response in Systemic Lupus Erythematosus: Change in British Isles Lupus Assessment Group (BILAG) Score
Change from baseline in British Isles Lupus Assessment Group of SLE clinics (BILAG-2004) at 3 and 6 months.
Measured: 24 Months
Response in Systemic Lupus Erythematosus: Change in Physician Global Assessment score
Change from baseline in Physician Global Assessment (PGA) scores at 3 and 6 months.
Measured: 24 Months
Response in Systemic Lupus Erythematosus: SLE Responder Index response
SLE Responder Index (SRI) response at 3 and 6 months.
Measured: 24 Months
Response in Systemic Lupus Erythematosus: Definitions of Remission in SLE rate
Definitions of Remission in SLE (DORIS) remission rate at 3 and 6 months.
Measured: 24 Months
Response in Dermatomyositis: Change in Cutaneous Dermatomyositis Disease Area and Severity Index
Change from baseline in Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) at 3 and 6 months.
Measured: 24 Months
Response in Systemic Sclerosis: American College of Rheumatology Combined Response Index in Systemic Sclerosis response rate
The American College of Rheumatology Combined Response Index in Systemic Sclerosis (ACR CRISS) response rate (calculated).
Measured: 24 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jul 2026
- Study startOct 2026 (estimated)
- Primary completionMar 2030 (estimated)
- Study completionMar 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rheumatoid Arthritis (RA)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 94 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Luminary Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07729995
- Sponsor's protocol ID
- LMY-922-001
- Status last verified
- Jul 2026
- First submitted
- 15 Jul 2026
- Last updated
- 28 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No