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

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 (NCT07021534) is a Phase 1 interventional studying Patients With Advanced Solid Tumors With Liver Metastases Who Have Failed Standard Treatments, sponsored by Zhejiang University. RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

About This Trial

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.

What Stage of Research Is This?

Phase 1 trials test a new treatment for the first time in humans, focusing on safety, dosing, and how the body processes the drug. For Patients With Advanced Solid Tumors With Liver Metastases Who Have Failed Standard Treatments, a Phase 1 study typically enrolls a small number of participants — often healthy volunteers or patients who have exhausted standard treatment options. Phase 1 results determine whether a treatment moves into larger Phase 2 efficacy studies.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

With a target enrollment of 12 participants, this is a small study — typical of early-phase research, rare-disease trials, or pilot studies designed to generate preliminary signal before a larger study is launched.

Who May Be Eligible (Plain English)

Who May Qualify: 1. Age between 18 and 75 years (inclusive of boundary values), both males and females are eligible. 2. Advanced solid tumors with liver metastasis that have failed prior standard treatment (including disease progression and intolerable adverse reactions). The colorectal cancer cohort will be enrolled first (prior standard treatment includes combination or sequential therapy with fluorouracil, oxaliplatin, and irinotecan, with or without bevacizumab and/or cetuximab and/or regorafenib and/or fruquintinib). 3. Patients with high expression of NKG2D ligands in tumor tissue sections will be prioritized for enrollment. 4. The expected survival of the subjects is ≥12 weeks. 5. Subjects must have at least one target lesion that can be stably assessed according to the RECIST v.1.1 criteria by CT, MRI, or PET-CT. The target lesion should have measurable dimensions (tumor lesion long diameter ≥10 mm on CT scan, lymph node lesion short diameter ≥15 mm on CT scan, and scan slice thickness no more than 5 mm). Alternatively, through laparoscopic exploration, there should be at least one target lesion that can be assessed according to the PCI scoring criteria. 6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0-1. 7. Subjects must have adequate organ and bone marrow function. Laboratory screening must meet all of the following criteria, with all laboratory test results within the specified stable range and without ongoing supportive therapy. 1. Hematology: White blood cell count (WBC) ≥1.5×10⁹/L; platelet count (PLT) ≥60×10⁹/L; hemoglobin (Hb) ≥8.0 g/dL; lymphocyte count (LYM) ≥0.4×10⁹/L. ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language

Inclusion Criteria: 1. Age between 18 and 75 years (inclusive of boundary values), both males and females are eligible. 2. Advanced solid tumors with liver metastasis that have failed prior standard treatment (including disease progression and intolerable adverse reactions). The colorectal cancer cohort will be enrolled first (prior standard treatment includes combination or sequential therapy with fluorouracil, oxaliplatin, and irinotecan, with or without bevacizumab and/or cetuximab and/or regorafenib and/or fruquintinib). 3. Patients with high expression of NKG2D ligands in tumor tissue sections will be prioritized for enrollment. 4. The expected survival of the subjects is ≥12 weeks. 5. Subjects must have at least one target lesion that can be stably assessed according to the RECIST v.1.1 criteria by CT, MRI, or PET-CT. The target lesion should have measurable dimensions (tumor lesion long diameter ≥10 mm on CT scan, lymph node lesion short diameter ≥15 mm on CT scan, and scan slice thickness no more than 5 mm). Alternatively, through laparoscopic exploration, there should be at least one target lesion that can be assessed according to the PCI scoring criteria. 6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0-1. 7. Subjects must have adequate organ and bone marrow function. Laboratory screening must meet all of the following criteria, with all laboratory test results within the specified stable range and without ongoing supportive therapy. 1. Hematology: White blood cell count (WBC) ≥1.5×10⁹/L; platelet count (PLT) ≥60×10⁹/L; hemoglobin (Hb) ≥8.0 g/dL; lymphocyte count (LYM) ≥0.4×10⁹/L. 2. Biochemistry: Serum creatinine ≤1.5×ULN. If serum creatinine \>1.5×ULN, creatinine clearance rate must be \>50 mL/min (calculated by the Cockcroft-Gault formula); serum total bilirubin ≤1.5×ULN; alanine aminotransferase (ALT) ≤2×ULN; aspartate aminotransferase (AST) ≤2×ULN (for patients with liver metastasis or primary liver cancer, ALT ≤5×ULN and AST ≤5×ULN); amylase and lipase ≤1.5×ULN. 3. Urinalysis: Urine protein \<2+. 8. Echocardiogram within the past month showing left ventricular ejection fraction (LVEF) \>45%. 9. Fertility status: Women of childbearing potential or men whose sexual partners are women of childbearing potential must agree to use effective contraception from the time of signing the informed consent form until 6 months after the last cell infusion (women of childbearing potential include premenopausal women and women within 2 years after menopause). 10. Subjects must sign a written informed consent form and date it. 11. Subjects must be willing and able to comply with the prescribed treatment plan, laboratory tests, follow-up visits, and other study requirements. Exclusion Criteria: 1. Pregnant or breastfeeding women. 2. Known history of human immunodeficiency virus (HIV) infection; acute or chronic active hepatitis B (HBsAg positive); acute or chronic active hepatitis C (HCV antibody positive). Positive syphilis antibody; EB virus DNA quantitative \>500 copies; cytomegalovirus (CMV) infection (IgM positive). 3. Active or poorly controlled severe infections. 4. Presence of severe arterial embolism identified by CT angiography or hepatic arterial vascular variations that are unfavorable for HAI treatment. 5. Current presence of cardiac disease requiring treatment or poorly controlled hypertension as judged by the investigator (defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure \>90 mmHg after standardized antihypertensive drug treatment). 6. Presence of any of the following cardiac clinical symptoms or diseases: 1. Unstable angina. 2. Myocardial infarction within the past year. 3. Resting electrocardiogram (ECG) showing QTc \>450 ms (male) or QTc \>470 ms (female). 4. Resting ECG revealing clinically significant abnormalities (such as abnormal heart rate, conduction, or morphological features) or complete left bundle branch block or third-degree heart block or second-degree heart block or PR interval \>250 ms. 5. Presence of factors that increase the risk of QTc prolongation or arrhythmias, such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or sudden unexplained death in first-degree relatives under the age of 40, or use of drugs that prolong the QT interval. 7. Coagulation abnormalities (INR \>1.5×ULN), tendency to bleed, or undergoing thrombolytic or routine anticoagulant therapy (e.g., warfarin or heparin). Patients requiring long-term antiplatelet therapy (aspirin, dose \>300 mg/day; clopidogrel, dose \>75 mg/day). 8. Subjects who require systemic treatment with corticosteroids or other immunosuppressive drugs during the treatment period. 9. Oxygen saturation ≤95% (measured by pulse oximetry) before treatment. 10. Systemic corticosteroid use equivalent to \>15 mg/day prednisone within 4 weeks before treatment (excluding inhaled corticosteroids). 11. Development of new arrhythmias in the subject before lymphodepletion conditioning, including but not limited to uncontrolled arrhythmias with medication, hypotension requiring vasopressors, bacterial, fungal, or viral infections requiring intravenous antibiotics. Subjects receiving prophylactic antibiotics for infection will be assessed by the investigator for continued eligibility. 12. Known history of or current need for treatment of hepatic encephalopathy; subjects with current or history of central nervous system disorders, such as seizures, cerebral ischemia/infarction, dementia, cerebellar disease, or any autoimmune diseases involving the central nervous system; subjects with clinically symptomatic central nervous system metastases or leptomeningeal metastases, or other evidence indicating that the central nervous system metastases or leptomeningeal metastases are not controlled, and deemed unsuitable for enrollment by the investigator. 13. Subjects with previous or concurrent other malignancies, with the following exceptions: a) Adequately treated basal cell or squamous cell carcinoma (with sufficient wound healing required before enrollment in the study). b) Cervical carcinoma in situ or ductal carcinoma in situ of the breast, treated with curative intent, with no signs of recurrence for at least 3 years before the study. c) Primary malignancy that has been completely resected and in complete remission for ≥5 years. 14. Subjects with severe psychiatric disorders. 15. Participation in another clinical study within the past month. 16. Subjects assessed by the investigator as unable or unwilling to comply with the requirements of the study protocol. 17. Subjects who have withdrawn from the study for any reason and cannot re-enroll.

Treatments Being Tested

BIOLOGICAL

NKG2D 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)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

The First Affiliated Hospital Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT07021534), the sponsor (Zhejiang University), and the key eligibility criteria — to your next appointment. Your doctor can review the inclusion and exclusion criteria against your medical history, lab values, and current treatments to assess whether you are likely to qualify. They can also help you weigh whether trial participation makes sense alongside your existing care plan.

Useful questions to walk through together: What does the trial protocol require beyond standard care? How long is the active treatment phase, and how long is follow-up? Are there study visits at sites I can reach? Who pays for the trial-specific procedures, and who pays for standard-of-care portions? See our 25 questions to ask about clinical trials guide for a more complete checklist.

Authoritative Sources

The official record for this trial lives on ClinicalTrials.gov — the federal registry maintained by the National Library of Medicine at NIH. For background on how this trial fits into the FDA approval pathway, see the FDA drug approval process. For oncology-specific guidance for patients considering trials, the National Cancer Institute publishes patient-oriented overviews. International trial registries are aggregated by the WHO ICTRP.

Frequently Asked Questions

What is the NCT07021534 clinical trial studying?

Who can participate in NCT07021534?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

How do I contact the trial site for NCT07021534?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

How This Page Is Built

Every field on this page is pulled directly from the ClinicalTrials.gov API v2 — no estimates, no proxies. The plain-English eligibility translation is generated from the original protocol text and reviewed for fidelity to the underlying clinical criteria. The original clinical text remains visible in the collapsible section above so users and clinicians can verify the translation. Read the full methodology for the data pipeline and known limitations.

Source: ClinicalTrials.gov API v2 record for NCT07021534. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT07021534. Data: ClinicalTrials.gov."

Medical disclaimer: This page is informational, not medical advice. Talk to your doctor about whether a clinical trial is right for you.

Last updated 2026-06-07 · Data from ClinicalTrials.gov.