Intraperitoneal SK-NK Cell Injection for Advanced Ovarian Cancer With Massive Ascites

A Single-Arm, Open-Label Phase I/II Clinical Trial of Intraperitoneal Perfusion of SK-NK Cell Injection for the Treatment of Advanced Ovarian Cancer Patients With Massive Ascites

This is a single-center, open-label, Phase I/II clinical study designed to evaluate the safety, tolerability, and preliminary efficacy of SK-NK Cell Injection administered via intraperitoneal (IP) perfusion in patients with advanced ovarian cancer complicated by massive ascites .

The study focuses on patients who have failed standard therapies and are suffering from severe ascites. The treatment involves the direct infusion of allogeneic, highly activated Natural Killer (NK) cells (SK-NK) into the abdominal cavity .

The study consists of two phases:

Phase I (Dose Escalation): To determine the safety profile and the Recommended Phase 2 Dose (RP2D) using a "3+3" design with three increasing dose levels.

Phase II (Dose Expansion): To further evaluate the efficacy of the treatment in controlling ascites and suppressing tumor growth at the determined RP2D.

Participants will receive the study treatment once weekly for 4 weeks.

Study Overview

• Status: Recruiting
• Conditions: Ascites; Ovarian Neoplasms Malignant
• Intervention / Treatment: Biological: SK-NK Cell Injection

Detailed Description

Background and Rationale:

Ovarian cancer often presents with malignant ascites in advanced stages, which is associated with poor prognosis and severely reduced quality of life. The peritoneal cavity in these patients is characterized by an immunosuppressive tumor microenvironment. Natural Killer (NK) cells are innate immune effector cells capable of recognizing and killing tumor cells without MHC restriction. "Super Kill-NK" (SK-NK) cells are highly activated allogeneic NK cells derived from healthy donors, characterized by high expression of activation markers (e.g., CD16, NKG2D) and enhanced cytotoxicity. Intraperitoneal delivery allows for direct contact between effector cells and tumor cells within the peritoneal cavity, potentially increasing local therapeutic concentration while minimizing systemic toxicity .

Study Design:

This is an open-label, single-arm, Phase I/II study. Phase I (Dose Escalation): Utilizing a standard "3+3" design to assess safety and identify the Dose-Limiting Toxicity (DLT). Three dose cohorts are planned: 3×10^8, 6×10^8, and 9×10^8 cells per dose. The DLT observation period is 28 days after the first infusion.

Phase II (Dose Expansion): Once the Recommended Phase 2 Dose (RP2D) is determined, additional patients will be enrolled to evaluate efficacy.

Intervention:

Eligible patients will receive SK-NK Cell Injection via intraperitoneal perfusion. The treatment schedule consists of one infusion every week for a total of 4 doses (Days 1, 8, 15, and 22).

Objectives:

Primary: To evaluate safety, tolerability, and determine the RP2D. Secondary: To assess the Ascites Response Rate, Objective Response Rate (ORR), Duration of Relief (DoR), and 1-year Overall Survival (OS). Pharmacokinetics (PK) and pharmacodynamics (PD) will also be evaluated by monitoring SK-NK cell persistence and cytokine levels in peripheral blood and ascites .

Exploratory: To investigate the mechanism of action of NK cell therapy in the malignant ascites microenvironment.

• Study Type: Interventional
• Enrollment (Estimated): 29
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Ning Li, MD; Phone Number: 8610-87787211; Email: liningnci@126.com

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100021
      • Recruiting
      • Cancer Hospital, Chinese Academy of Medical Sciences
      • Principal Investigator: Ning Li, MD
      • Contact: Ning Li, MD; Phone Number: 8610-87787210; Email: cancergcp@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Voluntarily sign the written Informed Consent Form (ICF) and be able to comply with study procedures and follow-up.

Female, aged 18 to 75 years. ECOG performance status of 0 to 2. Histologically or cytologically confirmed advanced ovarian cancer. Participants must have failed at least two lines of standard therapy (disease progression or intolerance), have no standard therapy available, or be unable to receive standard therapy for other reasons .

Complicated by massive malignant ascites, defined as a volume of ≥ 2000 mL indicated by Ultrasound or CT.

Expected survival time ≥ 3 months.

Adequate organ function (no blood transfusion, cell growth factors, etc., within 14 days prior to enrollment), defined as:

Neutrophils (ANC) ≥ 1.0×10^9/L Platelets (PLT) ≥ 80×10^9/L Hemoglobin (Hb) ≥ 80 g/L Total Bilirubin (TBIL) ≤ 1.5×ULN (≤ 3×ULN for Gilbert's syndrome or liver metastasis) ALT and AST ≤ 2.5×ULN (≤ 5×ULN if liver metastasis is present) INR ≤ 1.5×ULN and APTT ≤ 1.5×ULN (unless on anticoagulant therapy) Creatinine clearance ≥ 60 mL/min (calculated by Cockcroft-Gault formula) Toxicities from prior therapies must have recovered to ≤ Grade 1 (except for alopecia and ≤ Grade 2 neurotoxicity caused by chemotherapy) .

Exclusion Criteria:

Prior receipt of other cell therapies. Presence of loculated (septated) ascites indicated by CT or Ultrasound. Receipt of any systemic anti-tumor therapy (including chemotherapy, targeted therapy, etc.) within 3 weeks prior to intraperitoneal perfusion.

Receipt of Traditional Chinese Medicine (herbal) with anti-tumor indications within 3 weeks prior to intraperitoneal perfusion.

Receipt of systemic corticosteroids (≥ 10 mg/day prednisone or equivalent) or other immunosuppressive medications within 2 weeks prior to intraperitoneal perfusion (inhaled, topical, or physiologic replacement doses are allowed).

Major surgery within 4 weeks prior to screening or planned major surgery during the study period.

History of other malignancies within 5 years (except for cured local tumors with low risk of recurrence, such as non-melanoma skin cancer).

History of active or suspected autoimmune or inflammatory disease. History of organ transplantation or hematopoietic stem cell transplantation.

Presence of active infection, including:

Active Hepatitis B (HBsAg positive and HBV-DNA > 1000 copies/mL) Active Hepatitis C (HCV antibody positive and HCV-RNA detected) Systemic active infection requiring antibiotic treatment Congenital or acquired immunodeficiency (e.g., HIV infection) Vaccination with live or attenuated vaccines within 4 weeks prior to intraperitoneal perfusion.

Severe cardiovascular diseases, including:

Uncontrolled hypertension (SBP > 160 mmHg and/or DBP > 100 mmHg) History of hypertensive crisis or hypertensive encephalopathy Cardiovascular accident, TIA, myocardial infarction, unstable angina, or significant vascular disease within 6 months NYHA Class ≥ II heart failure or LVEF < 50% Severe arrhythmia uncontrolled by medication (QTc ≥ 450 ms for males, ≥ 470 ms for females), or congenital Long QT syndrome Severe respiratory disease (e.g., history of severe interstitial lung disease, severe COPD), FEV1 < 2L, or DLCO < 40%.

History of clear neurological or psychiatric disorders, including epilepsy or dementia.

Other conditions considered unsuitable for the study by the investigator (e.g., prior Grade ≥ 3 adverse events from immunotherapy).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: SK-NK Cell Injection; Participants receive SK-NK Cell Injection via intraperitoneal perfusion. Phase I follows a "3+3" dose-escalation design with three cohorts (3*10^8, 6*10^8, and 9*10^8 cells). Phase II operates at the Recommended Phase 2 Dose (RP2D). Treatment is administered once weekly for 4 weeks (Days 1, 8, 15, and 22).

Biological: SK-NK Cell Injection; Administered via intraperitoneal perfusion. Phase I involves a "3+3" dose escalation with three cohorts: 3x10^8, 6x10^8, and 9x10^8 cells. Phase II uses the Recommended Phase 2 Dose (RP2D). The treatment schedule consists of one infusion weekly for 4 weeks (Days 1, 8, 15, and 22). The product is characterized by high purity (>99%) and high expression of activation markers.; Other Names: Super Kill-NK Cell Injection; Allogeneic NK Cell Injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
RP2D	To determine the optimal dose for the Phase II expansion phase based on the evaluation of DLTs and the overall safety profile observed in the dose-escalation cohorts.	Up to approximately 28 days after the first dose of the last participant in the dose-escalation phase.
Incidence of Adverse Events and Dose-Limiting Toxicities	Number of participants experiencing TEAEs and DLTs. Safety is evaluated using NCI CTCAE v5.0 and ASTCT consensus for CRS.	From baseline up to 28 days post-infusion for DLT; safety follow-up through study completion (approx. 1 year)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ascites Response Rate	Defined as the proportion of participants who require no paracentesis (abdominal drainage) for at least 4 weeks and whose ascites volume (measured by ultrasound as average depth x 10 x abdominal circumference) is controlled at Day 29.	At Day 29 (±3 days) post-treatment initiation
Objective Response Rate (ORR)	Defined as the percentage of participants who achieve a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) after intraperitoneal perfusion.	Assessed periodically up to approximately 1 year
Ascites Symptom Improvement Rate	Defined as the proportion of participants whose malignant ascites symptom scale score decreases by ≥30% compared to baseline.	Assessed periodically up to approximately 1 year
Duration of Ascites Relief (DoR)	Defined as the time from the first documentation of objective response (CR or PR) to the first documented disease progression or death from any cause.	From date of first response until progression or death, assessed up to approx. 1 year
1-Year Overall Survival (OS) Rate	Defined as the percentage of participants who are alive at 1 year after the initiation of treatment.	1 year post-treatment initiation
Persistence of SK-NK Cells in Peripheral Blood	Measured by qPCR to detect specific DNA sequences in peripheral blood samples.	At Days 1, 8, 15, 22, and 29 during the treatment phase
Persistence of SK-NK Cells in Ascites	Measured by qPCR to detect specific DNA sequences in ascites samples.	At Days 1, 8, 15, 22, and 29 during the treatment phase

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Cytokine Levels in Peripheral Blood and Ascites	Evaluation of levels of IL-2, TNF-a, and IFN-y (measured in pg/mL) using flow cytometry.	At Baseline, Day 8, Day 15, Day 22, and End of Treatment (Day 29).
Changes in Immune Cell Subsets	Evaluation of the percentage of Tregs, Macrophages, and MDSCs relative to total CD45+ cells.	At Baseline, Day 8, Day 15, Day 22, and End of Treatment (Day 29).

Collaborators and Investigators

• Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
• Collaborators: Cells First Biotechnology (Beijing) Co., Ltd
• Investigators: Principal Investigator: Ning Li, MD, Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Actual): January 5, 2026
• Primary Completion (Actual): January 23, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: February 21, 2026
• First Submitted That Met QC Criteria: February 21, 2026
• First Posted (Actual): February 27, 2026

Study Record Updates

• Last Update Posted (Actual): March 17, 2026
• Last Update Submitted That Met QC Criteria: March 13, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Immunotherapy; Adoptive Immunotherapy; Natural Killer Cells; NK Cell Therapy; SK-NK Cell Injection; Intraperitoneal Perfusion; Massive Ascites
• Additional Relevant MeSH Terms: Pathologic Processes; Pathological Conditions, Signs and Symptoms; Ascites
• Other Study ID Numbers: NCC5843

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data that underlie the results reported in this study (text, tables, figures, and appendices) will be made available.
• IPD Sharing Time Frame: Data will be available beginning 6 months and ending 36 months following article publication.
• IPD Sharing Access Criteria: Data requests should be submitted to the corresponding author via email. Requesting researchers must provide a methodologically sound proposal and sign a data access agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No