Study Population: Adult subjects aged 18-75 years with relapsed/refractory advanced solid tumors (including liver, gastric, colorectal, ovarian cancer, etc.) and malignant ascites confirmed by cytology, who have failed at least 2 lines of standard systemic therapy. Study Design: This is a dose-escalation, single-center, open-label, prospective Phase 1 study. A total of 18 subjects will be enrolled and assigned to 2 administration groups (9 subjects each): Group A (Intravenous infusion): For subjects with small-volume malignant ascites. Group B (Intraperitoneal perfusion): For subjects with large-volume symptomatic malignant ascites. Each group will follow a conventional "3+3" dose-escalation design with 3 dose levels (1×10⁹, 3×10⁹, 6×10⁹ NK cells per dose), administered once weekly, 3 weeks per cycle, for 2 consecutive cycles. Primary Objectives: To evaluate the safety and tolerability, and to determine the dose-limiting toxicity (DLT) of NK521 administered intravenously and intraperitoneally. Secondary Objectives: To assess the preliminary anti-tumor efficacy including objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), duration of response (DOR), puncture-free survival (PuFS), and changes in tumor markers, as well as health-related quality of life (HRQoL).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
18
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.
Cancer Hospital, Chinese Academy of Medical Sciences
Beijing, Beijing Municipality, China
RECRUITINGIncidence of Treatment-Emergent Adverse Events and dose-limiting toxicities [Safety and Tolerability]
The incidence and severity of treatment-emergent adverse events, the occurrence of dose-limiting toxicities, and clinically significant laboratory abnormalities, to evaluate the safety and tolerability of the study treatment.
Time frame: 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.
Objective Response Rate (ORR)
The proportion of subjects achieving complete response (CR) or partial response (PR) as assessed by the investigator using RECIST v1.1 criteria.
Time frame: From the first administration, assessed every 6 weeks until disease progression or death, whichever comes first, up to 24 months.
Progression-Free Survival (PFS)
Time from first administration to documented disease progression (per RECIST v1.1) or death from any cause, whichever occurs first.
Time frame: From the first administration, assessed every 6 weeks until progression or death, up to 24 months.
Overall Survival (OS)
Time from first administration to death from any cause.
Time frame: From the first administration, followed up every 3-6 months until death or study closure, up to 24 months.
Malignant Ascites Control Rate
The proportion of subjects with reduction in ascites volume (≥50%) and decreased need for paracentesis, assessed using clinical and imaging criteria.
Time frame: From the first intraperitoneal administration, assessed every 3 weeks until the end of treatment, up to 24 months.
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