Endoscopic Ultrasound (EUS) Intratumoral Injection of CAR-NK Cells in the Treatment of Advanced Pancreatic Cancer

A Single-center, Single-arm, Open-label, Dose-escalation Clinical Study to Evaluate the Safety and Anti-tumor Efficacy of Intratumoral NKG2D CAR-NK Cell Injection Guided by EUS in the Treatment of Locally Advanced Pancreatic Cancer.

This is a single-center, single-arm, open-label, dose-escalation clinical study to evaluate the safety and anti-tumor efficacy of intratumoral NKG2D CAR-NK cell injection guided by endoscopic ultrasound in the treatment of locally advanced pancreatic cancer.

Study Overview

• Status: Recruiting
• Conditions: Pancreatic Cancer Non-resectable
• Intervention / Treatment: Biological: CAR-NK

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Qi Zhang, M.D.; Phone Number: 8613858108798; Email: qi.zhang@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310009
      • Recruiting
      • the first affiliated hospital of Zhejiang University，school of medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 18~75 years old (including boundary value), both male and female.
2. Histologically or cytologically confirmed pancreatic ductal adenocarcinoma or IPMN carcinogenesis.
3. Recurrent or unresectable locally advanced pancreatic cancer. Patients with technically resectable tumors but are considered as unable to undergo surgical treatment due to medical comorbidities or the patient's refusal of surgery are also eligible for enrollment.
4. ECOG PS score of 0-1.
5. At least 3 months of life expectancy at screening, as judged by the investigator.
6. Subject has adequate organ and bone marrow function. Laboratory screening results should be within the stable range described below, and there should be no ongoing supportive care ("jaundice relieve" therapy such as PTCD, ENBD, or bile duct stenting is allowed when pancreatic cancer invades the common bile duct). a) Blood biochemistry: serum creatinine ≤ 1.5×ULN, serum total bilirubin ≤ 2.0×ULN, and serum liver aminotransferase ≤ 3 ×ULN b) Blood tests: neutrophil count ≥ 1.5×109/L, platelet count ≥ 60×109/L, hemoglobin ≥ 8.0g/dL, lymphocyte count ≥ 0.4×109/L;
7. Childbearing status: not pregnant and, if of childbearing potential, willing 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 of postmenopausal time).
8. Subjects must sign a written informed consent form.
9. Subjects must be voluntary and able to comply with the scheduled treatment regimen, laboratory tests, follow-up, and other study requirements.

Exclusion Criteria:

1. Pregnant and lactating females.
2. Received any anti-tumor therapy (including but not limited to radiotherapy, chemotherapy, or immunotherapy) for pancreatic cancer within 28 days prior to enrollment.
3. In the opinion of the investigator, the EUS technique poses undue risks to the subject, including but not limited to: - Previous EUS-FNA was technically deemed too difficult to perform; - Imaging showing multiple collateral vessels around or near the target tumor within the pancreas; - Presence of varicose veins near the target tumor. - If any of the above risk profiles become apparent after subject screening and/or enrollment, consideration should be given to withdrawal from the study prior to treatment.
4. History of malignancy within 5 years, with the exception of basal cell carcinoma of the skin and carcinoma in situ of the cervix.
5. Any other health condition by the judgment of the investigator would preclude participation in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CAR-NK：intratumoral injection combined with intravenous infusion	Biological: CAR-NK; Endoscopic ultrasound-guided intratumoral CAR-NK injection once at day 0, combined with intravenous CAR-NK infusion twice at day 4 and 5

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum tolerated dose	Determine the optimal agent for NKG2D CAR-NK at maximum tolerated dose	within 28 days after NKG2D CAR-NK treatment
Dose limiting toxicity	Describe the adverse events of limiting further increases in the dose of NKG2D CAR-NK	From enrollment of the first subject to completion of follow-up of the last subject（up to 2 years））

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effectiveness evaluation	Objective Response Rate (ORR) According to Response Evaluation Criteria In Solid Tumors Version 1.1	At weeks 4，8 and months 3，6，9，12，16，20 and 24 after treatment
Cell continued survival time in vivo	Detect the copy number of NKG2D CAR DNA in peripheral blood at each visit point after the end of the infusion, until any 2 consecutive test results were negative	At weeks 4，8 and months 3，6，9，12，16，20 and 24 after treatment

Collaborators and Investigators

• Sponsor: Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): June 9, 2024
• Primary Completion (Estimated): June 30, 2025
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: June 9, 2024
• First Submitted That Met QC Criteria: June 22, 2024
• First Posted (Actual): June 27, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 21, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms
• Other Study ID Numbers: IIT-C1/22A1-08

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No