Overview

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 B-cell non-hodgkin lymphoma.

Eligibility

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 B-cell non-Hodgkin lymphoma (B-NHL) diagnosed according to the 2016 WHO classification, with priority given to the following pathological types: DLBCL (NOS; including DLBCL transformed from indolent NHL), PMBCL, FL3b, and HGBCL (including double-hit/triple-hit lymphomas).
7. CD19 positivity confirmed by flow cytometry and/or histopathology (Documented prior CD19 positivity confirmed by the investigator is acceptable). Subjects who have received prior anti-CD19 therapy must undergo a biopsy to confirm current CD19 positive expression.
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:
   1. Hepatic function: ALT ≤ 5 times the upper limit of normal (ULN) and total bilirubin \< 2.0 mg/dL (\< 3.0 mg/dL for patients with Gilbert's syndrome or documented lymphomatous infiltration of the liver);
   2. Renal function: Creatinine clearance (calculated by Cockcroft-Gault formula) ≥ 60 mL/min;
   3. Pulmonary function: Oxygen saturation (SaO₂) ≥ 92% on room air, and no active pulmonary infection;
   4. Cardiac function: Left ventricular ejection fraction (LVEF) ≥ 40% by echocardiography, absence of significant pericardial effusion, and no clinically significant electrocardiogram (ECG) abnormalities.
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 any of the following cardiovascular conditions within the past 6 months: Class III or IV heart failure as defined by the New York Heart Association (NYHA), cardiac angioplasty or stenting, myocardial infarction, unstable angina, or other clinically significant heart disease.
12. Presence of psychiatric illness.
13. History of drug abuse or addiction.
14. Use of the following medications or therapies:
    1. Corticosteroids: Therapeutic doses of corticosteroids (defined as prednisone or equivalent \>20 mg/day) within 72 hours prior to study drug infusion; physiologic replacement doses, and topical or inhaled steroids are permitted.
    2. Chemotherapy: Salvage chemotherapy within 2 weeks prior to study drug infusion.
    3. GvHD Therapy: Anti-graft-versus-host disease (GvHD) therapy within 4 weeks prior to study drug infusion.
    4. Allogeneic hematopoietic stem cell transplantation.
    5. Gene therapy.
    6. Adoptive cell therapy.
    7. Prior treatment with alemtuzumab within 6 months, or cladribine or clofarabine within 3 months prior to study drug infusion.
    8. Radiotherapy: Radiotherapy within 6 weeks prior to signing informed consent. To be eligible, lesions within the radiation field must have shown disease progression (PD), or the patient must have PET-positive lesions outside the radiation field. If PET-positive lesions exist outside the radiation field, radiotherapy to other lesions must have been completed at least 2 weeks prior to the first study drug dose.
15. Women who are breastfeeding.