NK521 in the Treatment of Advanced Solid Tumors

Prior treatment

• Received radical radiotherapy within 4 weeks before enrollment; received local palliative radiotherapy within 2 weeks before enrollment.
• Received cellular antineoplastic therapy within 1 year before dosing; received other antineoplastic therapy outside this protocol within 4 weeks before dosing, including but not limited to chemotherapy, molecular targeted therapy, hormonal therapy, immunotherapy, biotherapy, or Chinese herbal patent medicine with antineoplastic indications.
• Received blood transfusion, erythropoietin, granulocyte colony-stimulating factor (G-CSF), or granulocyte-macrophage colony-stimulating factor therapy within 2 weeks before enrollment.
• Received systemic therapy with corticosteroids (prednisone \>10 mg/day or equivalent) or other immunomodulatory agents (e.g., thymosin, interleukin-2, interferon) within 2 weeks before enrollment. Inhaled or topical corticosteroids are allowed in subjects without active autoimmune disease.

Other illness

• History of immunodeficiency, including positive HIV test, other acquired or congenital immunodeficiency diseases, or organ transplantation.

Lab values

• History of severe cardiovascular and cerebrovascular diseases, including but not limited to: severe cardiac arrhythmia or conduction abnormality requiring clinical intervention (e.g., ventricular arrhythmia, third-degree atrioventricular block); QTc interval \>480 ms on 12-lead ECG at rest; acute coronary syndrome, congestive heart failure, aortic dissection, stroke, or other Grade ≥3 cardiovascular/cerebrovascular events within 6 months before enrollment; NYHA Class ≥II heart failure or left ventricular ejection fraction (LVEF) \<50%; uncontrolled hypertension.
• Positive virology test for hepatitis B or hepatitis C at screening, meeting any of the following:
  • HBsAg positive with positive HBV-DNA titer or above upper limit of normal (ULN); b. HCV antibody positive.
• Meeting any of the following laboratory criteria:a. Hematology: Absolute neutrophil count \<1.5×10⁹/L; platelet count \<75×10⁹/L; hemoglobin \<90 g/L.b. Hepatic function: ALT \>3×ULN (≥5×ULN for liver metastasis); AST \>3×ULN (≥5×ULN for liver metastasis); TBIL \>1.5×ULN, or TBIL \>2.5×ULN (3.0 mg/dL) for subjects with Gilbert syndrome.c. Renal function: Serum creatinine \>1.5×ULN or creatinine clearance \<50 mL/min.
• Any other severe or uncontrolled medical disease, active infection, abnormal physical examination, abnormal laboratory test, altered mental status, or psychiatric disease that, in the investigator's opinion, increases subject risk or affects study results.

Other

• Symptomatic central nervous system (CNS) metastasis and/or carcinomatous meningitis.

• Patients with pathologically confirmed relapsed/refractory advanced solid tumors, including hepatocellular carcinoma and ovarian cancer. Patients enrolled in the intraperitoneal perfusion group (Group B) must have malignant ascites with tumor cells identified in the ascitic fluid.
• Patients with advanced solid tumors who have received ≥ 1 line of standard therapy.
• At least one measurable lesion on CT or MRI per RECIST v1.1.
• ECOG performance status 0-2.
• Life expectancy ≥3 months.
• Women of childbearing potential must be non-lactating with a negative serum pregnancy test within 1 week before enrollment; all subjects must agree to use contraception from signing informed consent until 6 months after the last NK521 infusion.
• Able to comply with the study protocol and follow-up procedures.
• Voluntarily signed and provided written informed consent.