NK521 for malignant ascites from advanced solid tumors

NK521 in the Treatment of Malignant Ascites Associated With Advanced Solid Tumors

This trial will test NK521, an NK-cell therapy, in adults (18–75) with relapsed or refractory advanced solid tumors and cytology-confirmed malignant ascites who have failed at least two standard treatments.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 18 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Base Therapeutics (Shanghai) Co., Ltd. (Industry-sponsored)
• Drugs / interventions: chemotherapy, immunotherapy, prednisone
• Locations: 1 site (Beijing, Beijing Municipality)
• Trial ID: NCT07561437 on ClinicalTrials.gov

What this trial studies

This is a single-center, open-label Phase 1 dose-escalation trial using a conventional 3+3 design to evaluate safety and dose-limiting toxicities of NK521. Eighteen participants will be enrolled into two administration groups (intravenous for small-volume ascites and intraperitoneal perfusion for large symptomatic ascites), with nine subjects per group. Three dose levels (1×10^9, 3×10^9, 6×10^9 NK cells per dose) will be given once weekly for three weeks per cycle for two consecutive cycles. The primary aim is to determine tolerability and the recommended dose for further study in this patient population.

Who should consider this trial

Good fit: Adults aged 18–75 with relapsed or refractory advanced solid tumors, cytology-confirmed malignant ascites, at least one measurable lesion, ECOG 0–2, life expectancy ≥3 months, and who have failed at least two lines of standard systemic therapy.

Not a fit: Patients without cytology-confirmed malignant ascites, those with poor performance status or life expectancy under three months, or those who can be managed effectively with standard therapies are unlikely to benefit from this early-phase safety trial.

Why it matters

Potential benefit: If successful, NK521 could reduce malignant ascites and related symptoms and offer a new therapeutic option for patients with advanced solid tumors.

How similar studies have performed: Other adoptive NK-cell therapies have shown safety signals and occasional responses in solid tumors and peritoneal disease, but intraperitoneal administration of NK521 for malignant ascites is a relatively novel approach with limited prior data.

Eligibility criteria

Inclusion Criteria:

* Pathologically diagnosed with relapsed/refractory advanced solid tumors, including but not limited to liver cancer, gastric cancer, colorectal cancer, ovarian cancer, etc.
* Complicated with malignant ascites with identifiable tumor cells in ascites. Patients with advanced solid tumors who have failed at least 2 lines 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.
* All toxicities from prior antineoplastic therapy have resolved to Grade 1 (CTCAE v5.0) or baseline except alopecia and fatigue; subjects with long-term stable sequelae from prior therapy (e.g., platinum-induced neuropathy) are allowed.
* 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.

Exclusion Criteria:

* Symptomatic central nervous system (CNS) metastasis and/or carcinomatous meningitis.
* History of other malignancies within the past 3 years.
* Active, known or suspected autoimmune disease, excluding hypothyroidism requiring only hormone replacement therapy, skin diseases not requiring systemic therapy (e.g., vitiligo, psoriasis, alopecia), or diseases not expected to relapse without external triggers.
* 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.

Not fully recovered from major surgery or trauma within 2 weeks before enrollment.

-Participated in another investigational drug trial and received investigational therapy or used an investigational device within 4 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:

  1. HBsAg positive with positive HBV-DNA titer or above upper limit of normal (ULN);
  2. HCV antibody positive.
* Known hypersensitivity or intolerance to PD-1 monoclonal antibody.

Meeting any of the following laboratory criteria:

1. Hematology: Absolute neutrophil count \<1.5×10⁹/L; platelet count \<75×10⁹/L; hemoglobin \<90 g/L.
2. 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.
3. Renal function: Serum creatinine \>1.5×ULN or creatinine clearance \<50 mL/min.

   * Any uncertain factors affecting subject safety or compliance.
   * 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.

Where this trial is running

Beijing, Beijing Municipality

• Cancer Hospital, Chinese Academy of Medical Sciences — Beijing, Beijing Municipality, China (Recruiting)

Conditions Advanced Solid Tumors