JY231(JY231) Injection for the Treatment of Relapsed or Refractory B-Cell Lymphoma

An Early Exploratory Clinical Study on the Safety, Tolerability, and Preliminary Efficacy of JY231 Injection in the Treatment of Relapsed or Refractory B-Cell Lymphoma

This study is an investigator-initiated single center, single arm clinical study with a target population of patients with relapsed or refractory B cell lymphoma. It is an early exploratory clinical study of the safety, tolerability and initial efficacy of JY231 injection in the treatment of relapsed or refractory B cell lymphoma.

This study included the screening period (Day -18 to Day -7), the baseline period (Day -1), the treatment and observation period (Day 0 to 28), and the follow-up period (Month 2[from Day 29] to Year 15). Participants eligible for the screening period will be admitted to the study center for a single JY231 treatment and a follow-up period after the end of the treatment and observation period.

After completing the follow-up for the first five years, methods such as telephone or written questionnaires can be used, and relevant samples should be collected as much as possible. The subjects should be followed up at least once a year until the end of the follow-up period. The maximum monitoring time can be extended to 15 years, and all monitoring data during the extension process need to be recorded.

Inclusion Criteria:

1. Subjects voluntarily signed an informed consent form and were willing and able to comply with all study requirements;

2. Age 18~75 years old, gender is not limited;

3. Malignant tumor cells positive for Cluster of Differentiation 19(CD19);

4. Meet the criteria for relapsed or refractory B-cell lymphoma. Relapsed: the subject's tumor reappears after achieving complete remission of the disease; refractory: the subject is ineffective or in only partial remission on standard treatment regimens. Subjects must have relapsed or become refractory after receiving at least two lines of systemic therapy or autologous hematopoietic stem cell transplantation.

5. The presence of at least one measurable lesion on imaging of relapsed or refractory B-cell lymphoma, i.e., a lymph node lesion >15 mm in length or an extranodal lesion >10 mm in length based on CT cross-sectional images, along with a positive Fluorodeoxyglucose Computed Tomography(FDG-PET).

6. Expected survival ≥12 weeks;

7. Eastern Cooperative Oncology Group(ECOG) score of 0 to 1 at baseline;

8. Good organ function (the standard can be appropriately relaxed for indicators involving liver and kidney function)

   1. Albuminous aminotransferase (ALT) ≤ 3 times the upper limit of normal (ULN);
   2. Albumin transaminase (AST) ≤ 3 times the ULN;
   3. Total bilirubin ≤ 1.5 times the ULN;
   4. Serum creatinine ≤1.5 times ULN or creatinine clearance ≥30 mL/min;
   5. Room oxygen saturation ≥92% without oxygen;
   6. left ventricular ejection fraction (LVEF) ≥50%;

9. Men of childbearing potential to ensure effective contraception for sexual partners; women of childbearing potential to use effective contraception and agree to use contraception throughout the study period.

Exclusion Criteria:

1. Subjects with active central nervous system (CNS) lymphoma;

2. Subjects with a history of active CNS disease such as seizures, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement;

3. Subjects who have been treated with another investigational drug within 30 days prior to screening or are still in the washout period;

4. Subjects who have had radiation therapy within 2 weeks prior to infusion;

5. Subjects with uncontrolled acute life-threatening bacterial, viral, or fungal infections (e.g., positive blood cultures ≤ 72 hours prior to infusion);

6. Subjects with unstable angina and/or myocardial infarction within 6 months prior to Screening;

7. Subjects with other prior or concurrent malignancies, with the following exceptions:

   1. Adequately treated basal cell, papillary thyroid, or squamous cell carcinoma (adequate wound healing is required prior to enrollment in the study);
   2. Carcinoma in situ of the cervix or breast, curatively treated, with no sign of recurrence for at least 3 years prior to study entry;
   3. Primary malignant tumor that has been completely resected and in complete remission for ≥ 5 years.

8. Presence of subjects with arrhythmias not controlled by medical management;

9. Subjects with active neurologic autoimmune or inflammatory conditions (e.g. Guillain-Barre syndrome, amyotrophic lateral sclerosis);

10. Women who are pregnant or breastfeeding, and female subjects who plan to become pregnant within 2 years of their JY231 injection infusion or male subjects whose partners plan to become pregnant within 2 years of their JY231 injection infusion;

11. Subjects who, in the investigator's judgment and/or clinical criteria, have a contraindication to any of the study procedures or have other medical conditions that may place them at unacceptable risk.

12. Other conditions that, in the opinion of the investigator, should not be enrolled in this clinical study, such as poor compliance.