NCT07274449

Exploratory Clinical Study on Memory NK Cell Therapy for Advanced Metastatic Solid Tumors

• Status: Active Not Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 6 (estimated)
• Sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

This study is a single-center, prospective, Phase Ib/II clinical trial designed to evaluate the safety and efficacy of cell membrane-modified memory NK cells in treating patients with advanced metastatic solid tumors. The primary objective of this study is to evaluate the safety and tolerability profile of memory NK cells administered in combination with standard therapy in the Intent-to-Treat (ITT) population. The assessment will be based on the following endpoints: 1）Incidence of dose-limiting toxicities (DLTs)； 2) Frequency and severity of adverse events; 3) Occurrence of clinically significant abnormalities in laboratory parameters, physical examinations, and vital signs. The secondary Study Objectives: 1) To evaluate the preliminary efficacy of the combination regimen by assessing the objective response rate (ORR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and serial changes in tumor markers; 2) To characterize the pharmacokinetic profile of memory NK cells when used in combination with standard therapy within the ITT population. A pilot cohort of 6 patients will first be enrolled to assess the safety of NK cell therapy, with dose-limiting toxicities (DLT) evaluated over a 21-day observation period following the last NK cell infusion. If safety is confirmed, a protocol amendment for cohort expansion will be submitted to the Ethics Committee.

Detailed description

After passing screening, eligible subjects will have haploidentical mononuclear cells collected for memory NK cell culture. When the cell count reaches the specified 5×10\^9/L after approximately 2-3 weeks of culture, cell reinfusion will be initiated. Each cycle consists of three reinfusions (on Days 1, 8, and 15). Standard guideline-recommended therapy will be administered 3-5 days before the first reinfusion of each cycle. One day prior to each reinfusion, a 2Gy low-dose immunotherapeutic radiation may be administered to tumor-involved lesions based on the patient's performance status. Efficacy will be evaluated after two cycles of reinfusion. For patients with rapid tumor progression or high tumor burden, investigators may administer standard chemotherapy during the cell culture phase based on the patient's condition. Subsequently, subjects will continue maintenance therapy according to the original standard treatment until any of the following occurs: disease progression, intolerable toxicity, initiation of new antitumor therapy, withdrawal of informed consent, loss to follow-up, death, or other protocol-specified conditions for treatment discontinuation, whichever comes first.

Conditions

• Advanced Solid Cancers

Interventions

Type	Name	Description
BIOLOGICAL	Memory-Like NK Cells	The study employs iRGD-modified cytokine-induced memory-like NK cells. These memory NK cells-primed with IL-12, IL-15, and IL-18-exhibit enhanced antitumor functionality, characterized by ↓KIR expression, ↑NKP30 expression, increased IFN-γ/TNF-α secretion, and significantly improved in vitro cytotoxicity. The iRGD modification, applied to cell membranes using our proprietary tumor-penetrating peptide technology, confers active tumor-targeting and tissue-penetrating capabilities to the NK cells.

Timeline

• Start date: 2025-05-08
• Primary completion: 2027-12-31
• Completion: 2028-12-31
• First posted: 2025-12-10
• Last updated: 2025-12-10

Locations

1 site across 1 country: China