NK521 in the Treatment of Advanced Solid Tumors

Обзор

Eligible subjects with advanced hepatocellular carcinoma and ovarian cancer will be divided into two treatment groups based on the volume of ascites. Group A consists of patients with mild ascites, who will receive NK521 via intravenous infusion. Group B includes patients with moderate to severe ascites, who will be treated with investigator-selected systemic regimens combined with intraperitoneal perfusion of NK521. Systemic and local medications will be administered in accordance with the treatment regimens of respective groups, and the safety of the study drug will be monitored. Preliminary anti-tumor efficacy will be assessed using the RECIST 1.1 criteria at Week 6 after the first infusion of NK521. Catheter placement and ascites drainage will be performed 3 days prior to the first intraperitoneal perfusion of NK521. After the initial intraperitoneal perfusion treatment, the therapeutic effect on ascites will be evaluated per the WHO criteria for ascites assessment.

Вмешательства

• Биопрепарат NK521 Cell Injection
  Gene-edited natural killer (NK) cell product with knockout of TIGIT, NKG2A, and TGF-β, administered via intravenous infusion or intraperitoneal perfusion for the treatment of malignant ascites associated with advanced solid tumors.
• Биопрепарат NK521 Cell Injection
  Gene-edited natural killer (NK) cell product with knockout of TIGIT, NKG2A, and TGF-β, administered via intravenous infusion or intraperitoneal perfusion for the treatment of malignant ascites associated with advanced solid tumors.

Первичные конечные точки

• Incidence of Treatment-Emergent Adverse Events and dose-limiting toxicities [Safety and Tolerability] [Срок оценки: Treatment-emergent adverse events are recorded from the first administration until the final follow-up visit, up to 24 months, and dose-limiting toxicities are monitored within the 28-day period after the last administration.]

Вторичные конечные точки (4)

• Objective Response Rate (ORR) [Срок оценки: From the first administration, assessed every 6 weeks until disease progression or death, whichever comes first, up to 24 months.]
• Progression-Free Survival (PFS) [Срок оценки: From the first administration, assessed every 6 weeks until progression or death, up to 24 months.]
• Overall Survival (OS) [Срок оценки: From the first administration, followed up every 3-6 months until death or study closure, up to 24 months.]
• Malignant Ascites Control Rate [Срок оценки: From the first intraperitoneal administration, assessed every 3 weeks until the end of treatment, up to 24 months.]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• Symptomatic central nervous system (CNS) metastasis and/or carcinomatous meningitis.
• History of immunodeficiency, including positive HIV test, other acquired or congenital immunodeficiency diseases, or organ transplantation.
• 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.
• 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.
• Positive virology test for hepatitis B or hepatitis C at screening, meeting any of the following:

a. 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• 1st affiliated hospital of Anhui Medical University — Хэфэй

Идентификаторы

NCT: NCT07657416 · NK521-02

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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