Actively Recruiting

Phase 1
Age: 18Years - 75Years
All Genders
NCT07021534

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

Led by Zhejiang University · Updated on 2025-06-15

12

Participants Needed

1

Research Sites

81 weeks

Total Duration

On this page

Sponsors

Z

Zhejiang University

Lead Sponsor

C

CNK Cell Therapeutics Co., Ltd.

Collaborating Sponsor

AI-Summary

What this Trial Is About

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.

CONDITIONS

Official Title

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

Who Can Participate

Age: 18Years - 75Years
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Age between 18 and 75 years, both males and females eligible
  • Advanced solid tumors with liver metastases that have failed prior standard treatments
  • Prior standard treatments for colorectal cancer include therapies with fluorouracil, oxaliplatin, irinotecan, and possibly bevacizumab, cetuximab, regorafenib, or fruquintinib
  • High expression of NKG2D ligands in tumor tissue prioritized
  • Expected survival of at least 12 weeks
  • At least one measurable target lesion suitable for assessment by RECIST v1.1 criteria via CT, MRI, or PET-CT, or assessable by PCI scoring via laparoscopy
  • ECOG performance status score of 0 or 1
  • Adequate organ and bone marrow function with stable laboratory values: WBC ≥1.5×10⁹/L; platelets ≥60×10⁹/L; hemoglobin ≥8.0 g/dL; lymphocytes ≥0.4×10⁹/L; serum creatinine ≤1.5×ULN or creatinine clearance >50 mL/min; bilirubin ≤1.5×ULN; ALT and AST ≤2×ULN (or ≤5×ULN for liver metastases); amylase and lipase ≤1.5×ULN; urine protein <2+
  • Echocardiogram within the past month showing left ventricular ejection fraction >45%
  • Women of childbearing potential and men with partners of childbearing potential agree to use effective contraception during and for 6 months after treatment
  • Signed informed consent and willingness to comply with study requirements
Not Eligible

You will not qualify if you...

  • Pregnant or breastfeeding women
  • Known HIV infection; active hepatitis B or C; positive syphilis antibody; EB virus DNA >500 copies; positive CMV IgM
  • Active or uncontrolled severe infections
  • Severe arterial embolism or unfavorable hepatic arterial vascular variations for treatment
  • Current cardiac disease requiring treatment or poorly controlled hypertension
  • History of unstable angina, recent myocardial infarction, significant ECG abnormalities, or risk factors for arrhythmias
  • Coagulation abnormalities, bleeding tendencies, or use of certain anticoagulants or high-dose antiplatelet therapy
  • Use of systemic corticosteroids or immunosuppressive drugs during treatment
  • Oxygen saturation below 95%
  • Recent systemic corticosteroid use exceeding 15 mg/day prednisone equivalent
  • Uncontrolled arrhythmias or infections requiring intravenous antibiotics prior to lymphodepletion conditioning
  • History or presence of hepatic encephalopathy or significant central nervous system disorders or metastases
  • Previous or concurrent other malignancies except adequately treated basal or squamous cell carcinoma, certain in situ carcinomas, or completely resected malignancies in remission for 5 years
  • Severe psychiatric disorders
  • Participation in another clinical study within the past month
  • Inability or unwillingness to comply with study protocol
  • Previous withdrawal from this study without ability to re-enroll

AI-Screening

AI-Powered Screening

Complete this quick 3-step screening to check your eligibility

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Trial Site Locations

Total: 1 location

1

The First Affiliated Hospital Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

Actively Recruiting

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Research Team

W

Weijia Fang

CONTACT

Z

Zhicheng DU

CONTACT

How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

NA

Model

SINGLE_GROUP

Primary Purpose

TREATMENT

Number of Arms

1

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