MB-CART19.1 in Refractory SLE

Inclusion Criteria:

1. Patients at least 18 years of age.

2. Signed and dated informed consent before the conduct of any trial-specificprocedure.

3. SLE fulfilling the 2019 ACR/EULAR classification criteria (refer to Appendix 8).

4. One BILAG A or two BILAG B despite treatment with at least two of the followingtreatment options: MMF, cyclophosphamide, rituximab belimumab, anifrolumab,methotrexate, azathioprine.

5. SLE with major organ involvement defined as either:

6. Presence of active lupus nephritis according to the following criteria:

• Histology proven class III or IV lupus nephritis according to ISN/RPS 2003classification
• Urine protein-to-creatinine ratio (UPCR) >1 in 24-hour urine collection
• Glomerular filtration rate (eGFR) of ≥30 mL/min/1.73 m2
• No history of kidney transplantation.

2. Lupus with heart involvement (e.g., myocarditis, pericarditis, endocarditis) asmeasured by MRI or echocardiography/ultrasound.

3. Lupus with pulmonary involvement (Lupus pleuritis, pulmonary arterialhypertension (PAH)) or lung disease defined as:

• Forced Vital Capacity (FVC) ≥ 60 % OR
• Forced Expiratory Volume (FEV1) ≥ 60 %,Total Lung Capacity (TLC) ≥ 60 %,DLCO (diffusion capacity) ≥ 60 % (according to ATS/ERS guidelines).

6. Absolute CD3+ T cell count ≥ 100/µl.

7. No childbearing potential or negative pregnancy test at screening and beforechemotherapy in women with childbearing potential. Subjects must agree to use acontraceptive method from screening until 12 months after the administration of theIMP.

8. Fully vaccinated against SARS-CoV-2 according to the recommendations of RKI orconfirmed SARS-CoV-2 infection within the last 6 months.

Exclusion Criteria:

1. Active clinically significant central nervous system (CNS) dysfunction (includingbut not limited to uncontrolled seizure disorders, cerebrovascular ischemia orhemorrhage, dementia, paralysis).

2. Uncontrolled diabetes mellitus.

3. Therapy induced lung disease and tuberculosis.

4. Forced Vital Capacity (FVC) < 60 %, FEV1 < 60 %, Total Lung Capacity (TLC) < 60 %and DLCO (diffusion capacity) < 60 %.

5. BILAG A or BILAG B for neuropsychiatric SLE.

6. History of a malignancy unless disease free for ≥ 5 years with the exception ofbasal or squamous cell skin cancer.

7. Cardiac function: Unstable coronary heart disease; left ventricular ejectionfraction (LVEF) < 50 %; no active myocarditis.

8. Renal function: eGFR < 30 ml/min/1.73 m2.

9. Liver function: Severe hepatic insufficiency defined as a Child-Pugh score > 10(C) (Appendix 10).

10. Known history of infection with human immunodeficiency virus or active infectionwith hepatitis B (hepatitis B surface antigen positive).

11. Known history of infection with hepatitis C virus unless treated and confirmed to bepolymerase chain reaction (PCR) negative.

12. Any active, uncontrolled bacterial, viral or fungal infection including SARS-CoV-2.

13. History of hematopoietic stem cell or solid organ transplantation.

14. Irreversible organ damage.

15. Medications:

• Systemic corticosteroids >10 mg within 7 days prior to leukapheresis;

• T cell targeting drugs (e.g., mycophenolate mofetil, calcineurin inhibitors)within 21 days prior to leukapheresis;

• Prior treatment with anti-CD19 therapy;

• Previous adoptive T cell therapy or any gene therapy including CAR T celltherapy;

• Live vaccines within 30 days prior to leukapheresis;

• Current cytotoxic drugs.

16. Hypersensitivity against any drug or its ingredients/impurities that is scheduled orlikely to be given during trial participation, e.g., as part of the mandatorypreparative chemotherapy or rescue medication/salvage therapies for treatmentrelated toxicities.

17. Contraindication of trial related procedures as judged by the investigator.

18. Women of childbearing potential (WOCBP) who do not agree to use highly effectivecontraceptive measures (Pearl index < 1) or practice true sexual abstinence from anyheterosexual intercourse (true abstinence is only acceptable if it is in line withthe preferred and usual life style of the participant) or have a vasectomisedpartner as the sole sexual partner (the vasectomised partner must have receivedmedical assessment of the surgical success) for at least 1 month before the studystart, during the study and in the 12 months following the last dose of studytreatment. A woman is considered a WOCBP, i.e. fertile, following menarche and until becomingpost-menopausal unless permanently sterile. WOCBP who want to become pregnant aftercompleting treatment should seek advice about oocyte cryoconservation prior totreatment because of possible irreversible infertility. WOCBP must refrain from eggdonation throughout the study until 12 months after the last dose of studytreatment. Highly effective methods of contraception include hormonal contraceptives associatedwith inhibition of ovulation (oral, intravaginal, transdermal, injectable,implantable) and intrauterine devices or systems (e.g. hormonal and non-hormonal)and bilateral tubal occlusion. Permanent sterilization methods include hysterectomy, bilateral salpingectomy andbilateral oophorectomy. A post-menopausal state is defined as no menses for 12 months without an alternativemedical cause.

19. Men with non-pregnant WOCBP partners who do not agree to use highly effectivecontraceptive measures (Pearl index < 1, e.g. spermicide and condom or other highlyeffective contraceptive measures (Pearl index < 1) taken by their WOCBP partner) orpractice true sexual abstinence from any heterosexual intercourse (true abstinenceis only acceptable if it is in line with the preferred and usual life style of theparticipant.), unless they are surgically sterile (meaning at least 2 consecutiveanalyses following vasectomy demonstrate absence of sperms in the ejaculate), duringthe study and in the 12 months following the last dose of study treatment. Men should seek advice about sperm conservation prior to treatment because ofpossible irreversible infertility. Men must furthermore refrain from sperm donationthroughout the study until 12 months after the last administration of studytreatment.

20. Concurrent participation in any other interventional trial.

21. Inability to understand the procedures and risks associated with the trial.