RecruitingPhase 1NCT07021534

Hepatic Artery Transfusion of NKG2D CAR-NK Cells Followed by Intravenous Infusion of NKG2D CAR-T Cells to Treat Patients With Advanced Solid Tumors With Liver Metastases Who Have Failed Standard Treatments: a Phase I Exploratory Clinical Trial


Sponsor

Zhejiang University

Enrollment

12 participants

Start Date

Jun 10, 2025

Study Type

INTERVENTIONAL

Conditions

Summary

This is a single-center, single-arm, open-label, dose-escalation clinical study to evaluate the safety and preliminary efficacy of NKG2D CAR-NK cells followed by NKG2D CAR-T cells in patients with advanced solid tumors (e.g.,colorectal cancer) with liver metastases who have failed standard treatments. The study primarily focuses on determining the maximum tolerated dose and recommended phase II dose through sequential cohort dose escalation, while secondarily characterizing the pharmacokinetic parameters and collecting initial efficacy data regarding tumor response. This investigation comprehensively evaluates the pharmacodynamic and pharmacokinetic profile of NKG2D CAR cellular therapy through three primary objectives: (1) systematic monitoring of treatment-emergent adverse events and clinically significant laboratory parameter deviations; (2) assessment of antitumor activity with correlative biomarker analysis; and (3) characterization of cellular kinetics including biodistribution patterns, and mechanistic pathways of therapeutic activity. The protocol clarifies cellular persistence and functional regulation within the tumor microenvironment by longitudinal monitoring of cytokine release and using advanced molecular tracking methods.


Eligibility

Min Age: 18 YearsMax Age: 75 Years

Plain Language Summary

Simplified for easier understanding

This Phase I study is testing an experimental cell therapy — using genetically modified immune cells (CAR-NK and CAR-T cells) that are designed to attack cancer — delivered directly to the liver via a blood vessel, in patients with advanced solid tumors that have spread to the liver and have failed all standard treatments. **You may be eligible if...** - You are between 18 and 75 years old - You have advanced solid cancer with liver metastases that has progressed on all standard treatments (colorectal cancer patients are enrolled first) - Your tumor tissue shows high expression of targets called NKG2D ligands - You have at least one measurable liver tumor - Your expected survival is at least 12 weeks **You may NOT be eligible if...** - You have active serious infections or uncontrolled other cancers - Your organ function does not meet study requirements - You are pregnant or breastfeeding - You have severe autoimmune disease Talk to your doctor to see if this trial is right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

Interested in this trial?

Get notified about updates and connect with the research team.

Interventions

BIOLOGICALNKG2D CAR NK and NKG2D CAR T cells

* NKG2D CAR-NK cells (hepatic artery infusion, D0 dose: 1×10⁹ cells,D1 dose: 1×10⁹ cells) * NKG2D CAR-T cells (Over a two-day period, CAR-T cells are administered via intravenous infusion on two consecutive occasions.In the initial phase, rapid titration dose escalation was performed with 1 case per group.The initial dose is set at 1.5×10⁷/kg. If grade 2 or higher cytokine release syndrome (CRS) or related adverse events (AEs) occur, the 3+3 dose escalation protocol will be initiated. If not, the starting dose for escalation will be set at 3×10⁷/kg per administration of-T CAR cells, with subsequent escalations to 5×10⁷/kg per administration and 7×10⁷/kg per administration.) Chemotherapy: If you are treated with autologous CAR-NK cells, lymphodepleting chemotherapy with FC is usually not required. If you are treated with allogeneic NKG2D CAR-NK cells derived from umbilical cord blood of a healthy donor, the researchers will adjust the FC chemotherapy dosage or choose another appropriate


Locations(1)

The First Affiliated Hospital Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

View Full Details on ClinicalTrials.gov

For the most up-to-date information, visit the official listing.

Visit

NCT07021534