KSV01 Injection for the Treatment of Relapsed/Refractory Diffuse Large B-Cell Lymphoma

A Phase I Clinical Study on the Safety, Tolerability, and Efficacy of KSV01 Injection in Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma

This is a single center, single arm, open-label, dose escalation, phase 1 study to evaluate the safety, tolerability and preliminary efficacy of KSV01 Injection for patients with diffuse large B-cell lymphoma.

Inclusion Criteria:

1. Patients or their legal guardians voluntarily participate in the study and provide written informed consent.
2. Aged 18 to 80 years (inclusive), male or female.
3. ECOG performance status score of ≤ 1.
4. Life expectancy > 3 months.
5. KPS score ≥ 70.
6. Patients with diffuse large B-cell lymphoma (DLBCL) diagnosed according to the 2016 WHO classification. Patients with DLBCL should have been diagnosed as relapsed or refractory after at least one prior line of systemic therapy.
7. CD19 positivity confirmed by flow cytometry and/or histopathology.
8. According to the Lugano 2014 criteria, the presence of PET-positive target lesions for tumor assessment is required (Deauville 5-Point Scale [5-PS] ≥ 4).
9. Adequate organ function.
10. Female patients of childbearing potential must have a negative urine/blood pregnancy test during the screening period and agree to use effective contraception for at least 1 year after infusion; male subjects with partners of childbearing potential must agree to use effective barrier contraception for at least 1 year after infusion.

Exclusion Criteria:

1. History of another primary malignancy that has not been in continuous remission for at least 2 years, except for the following conditions which are exempt from the 2-year limit: non-melanoma skin cancer, Stage I solid tumors treated with curative intent and low risk of recurrence, cured localized prostate cancer, biopsy-confirmed carcinoma in situ of the cervix, or squamous intraepithelial lesion identified on Pap smear.

2. Uncontrolled infectious disease within 4 weeks prior to enrollment.

3. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.

4. HIV infection.

5. Positive for Treponema pallidum(syphilis).

6. Severe autoimmune disease or immunodeficiency, with the exception of well-controlled Type I diabetes and thyroid disorders.

7. History of severe allergy or hypersensitivity to macromolecular biologic agents (e.g., antibodies, cytokines).

8. Participation in any other clinical trial within 4 weeks prior to enrollment.

9. History of clinically significant central nervous system (CNS) diseases, including but not limited to epilepsy, paresis, aphasia, stroke, severe head injury, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome.

10. Presence of isolated CNS involvement by lymphoma, or any ongoing CNS condition that precludes accurate neurological evaluation.

11. History of severe cardiovascular conditions within the past 6 months.

12. Presence of psychiatric illness.

13. History of drug abuse or addiction.

14. Use of the following medications or therapies:

    1. Corticosteroids (physiologic replacement doses, and topical or inhaled steroids are permitted).
    2. Chemotherapy.
    3. GvHD Therapy.
    4. Allogeneic hematopoietic stem cell transplantation.
    5. Gene therapy.

15. Women who are breastfeeding.

16. In the investigator's judgment, the subject is unlikely to complete all protocol-required study visits or procedures (including follow-up visits) or unlikely to comply with the requirements for participation in this study.