JWCAR201 治疗自身免疫性疾病、狼疮：I 期临床试验

Inclusion Criteria:

For subjects with B cell driven malignancy (relapsed/refractory large B cell lymphoma)

1. aged \>= 18 years
2. willing to sign ICF
3. with histologically confirmed large B cell lymphoma and immunohistochemically positive CD20
4. The subject must have previously been treated with an anthracycline and rituximab (or another CD20-targeted therapy), and must have relapsed, not achieved remission, or experienced disease progression after receiving at least two lines of therapy, including autologous hematopoietic stem cell transplantation (autoHSCT)
5. The subject must have CT measurable lesions and PET evaluable lesions as determined by the Lugano criteria.
6. The subject must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

For subjects with SLE:

1. Voluntarily sign the informed consent form (ICF).
2. At the time of signing the ICF, be between 18 and 70 years old (inclusive of 18 and 70 years), with no restriction on gender.
3. Have been diagnosed with SLE (Systemic Lupus Erythematosus) for ≥ 6 months before screening, according to the 2019 EULAR/ACR revised criteria
4. Have previously required treatment with corticosteroids combined with immunosuppressants and biologics, with the treatment regimen stable for \>2 months and the dose stable for \>2 weeks before screening, yet the disease remains active.
5. At the time of screening, positive for antinuclear antibodies (ANA), and/or anti-dsDNA antibodies, and/or anti-Smith antibodies.
6. SLEDAI-2K score ≥ 7 points during the screening period.

   Exclusion Criteria:

   For subjects with B cell driven malignancy (relapsed/refractory large B cell lymphoma)

1\. Primary central nervous system (CNS) lymphoma (subjects with secondary CNS lymphoma are allowed to enroll).

2\. A history of another malignancy that has not been in complete remission for at least 2 years (the following conditions are exempt from the 2-year restriction: non-melanoma skin cancer, completely resected stage I tumors with a low likelihood of recurrence, treated localized prostate cancer, biopsy-confirmed in situ cervical cancer, or squamous intraepithelial lesions identified on a PAP smear).

3\. At the time of screening, the subject has:

1. Hepatitis B surface antigen (HBsAg) positivity (regardless of whether or not there is an increase in hepatitis B virus DNA copies).
2. Hepatitis B core antibody (HBcAb) positivity with an increase in hepatitis B virus DNA copies.
3. Hepatitis C, HIV, or syphilis infection. 4. The subject has had active deep vein thrombosis (DVT) (tumor thrombus or blood clot) or pulmonary embolism (PE) within 3 months prior to signing the informed consent form.

5\. The subject has been undergoing anticoagulant therapy for active DVT or PE within 3 months prior to signing the informed consent form (prophylactic treatment is excluded).

6\. Uncontrolled systemic fungal, bacterial, viral, or other infections. 7. Acute or chronic graft-versus-host disease (GvHD). 8. History of any of the following cardiovascular diseases within the past 6 months: New York Heart Association (NYHA) Class III or IV heart failure, cardiac angioplasty or stenting, myocardial infarction, unstable angina, or other clinically significant heart diseases.

9\. Clinically significant CNS diseases within the past 6 months or at the time of screening, such as epilepsy, seizures, paralysis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychiatric disorders.

10\. Pregnant or breastfeeding women. Women of childbearing potential must have a negative serum pregnancy test within 48 hours prior to the start of lymphodepleting chemotherapy.

11\. The investigator determines that the subject has any factors that could affect compliance with the protocol, including uncontrolled medical, psychological, familial, sociological, or geographical conditions; or the subject is unwilling or unable to comply with the procedures required by the study protocol.

12\. The subject has previously received CAR-T cell therapy or other gene-modified T cell therapy.

For subjects with SLE:

1. Severe lupus nephritis requiring hemodialysis within 2 months before screening, or treatment with prednisone ≥ 100 mg/day or equivalent corticosteroids for ≥ 14 days.
2. Lupus crisis within 1 month before screening, deemed unsuitable for participation in this study by the investigator.
3. Clinically significant central nervous system disease or pathological changes not caused by lupus before screening, including but not limited to: cerebrovascular accident, aneurysm, epilepsy, seizures/convulsions, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis. Central nervous system manifestations caused by lupus before screening, including but not limited to lupus headache, seizures, cognitive impairment, intellectual disability, visual impairment, etc.
4. Concurrent other autoimmune diseases requiring systemic treatment.
5. History of major organ transplantation (e.g., heart, lung, kidney, liver) or hematopoietic stem cell/bone marrow transplantation.
6. At the time of screening:

1)Active hepatitis B. 2)Hepatitis C, HIV, or syphilis infection. 7. History of any of the following cardiovascular diseases within 6 months before screening: New York Heart Association (NYHA) Class III or IV heart failure, myocardial infarction, unstable angina, uncontrolled or symptomatic atrial arrhythmias, any ventricular arrhythmias, or other clinically significant heart diseases.

8\. Use of any other investigational drug for SLE within 1 month before screening. However, if the investigational treatment was ineffective or the disease relapsed during the study treatment period, and at least 3 half-lives of the drug have passed before screening, the patient may be eligible for enrollment.

9\. Previous treatment with CAR-T cells or other gene-modified T cell therapies. 10. History of ≥ Grade 2 bleeding within 30 days before screening, or the need for long-term continuous use of anticoagulant medications (such as warfarin, low molecular weight heparin, or factor Xa inhibitors).

11\. Undergoing plasmapheresis, plasma exchange, or hemodialysis within 14 days before screening.

12\. Use of any live vaccines for infectious diseases within 1 month before screening.

13\. Known life-threatening allergic reaction, hypersensitivity, or intolerance to JWCAR201 cell product or its excipients (including dimethyl sulfoxide (DMSO)).

主要终点：the rate of Dose Limiting Toxicity events · Dose-Limiting Toxicity (DLT) refers to a specific type of adverse effect or toxic reaction caused by a drug or treatment that is severe enough to prevent an increase in dose or continuation of treatment. · 28 days；the rate of AE and SAE · any adverse event (AE) or serious adverse event (SAE) occurring after JWCAR201 administration · up to 2 years
次要终点：the change of number of JWCAR201 cells by measuring the cell number and the number of transgene copies over time；the change of numbers of B cell subtypes (e.g., CD19+, CD20+ B cells) in the blood；overall response rate (ORR) in subjects with hematology malignancy；complete response rate (CRR) in subjects with hematology malignancy；duration of response in subjects with hematology malignancy；progression free survival in subjects with hematology malignancy；Overall survival in subjects with hematology malignancy；the proportion of subjects achieving LLDAS in subjects with SLE

• JWCAR201 arm · EXPERIMENTAL · Subjects in this arm will receive intervention with JWCAR201

JWCAR201 is a CD19/CD20 CAR-T product. This trial is intended to evaluate the safety, PK/PD and efficacy of JWCAR201 in patients with B cell driven hematology malignancy and autoimmune diseases