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.
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
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
29
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.
Cancer Hospital, Chinese Academy of Medical Sciences
Beijing, Beijing Municipality, China
RECRUITINGIncidence 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.
Time frame: From baseline up to 28 days post-infusion for DLT; safety follow-up through study completion (approx. 1 year)
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.
Time frame: Up to approximately 28 days after the first dose of the last participant in the dose-escalation phase.
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: At Days 1, 8, 15, 22, and 29 during the treatment phase
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