Safety and Preliminary Efficacy of Anti-CDH17 CAR-T Cell Therapy in Patients with CDH17-positive Advanced Solid Tumors

A Phase I Clinical Study to Evaluate the Safety and Preliminary Efficacy of CDH17 CAR-T in Patients with CDH17-positive Advanced Solid Tumors

This is a single-center, open-label, single-arm study to evaluate the safety and preliminary efficacy of anti-CDH17 CAR-T cells in patients with CDH17-positive advanced solid tumors.

Study Overview

• Status: Recruiting
• Conditions: CDH17-positive Advanced Solid Tumors
• Intervention / Treatment: Biological: Anti-CDH17 CAR-T cells infusion

Detailed Description

This is a single-center, open-label, single-arm study to evaluate the safety and preliminary efficacy of anti-CDH17 CAR-T cells in patients with CDH17-positive advanced solid tumors.A leukapheresis procedure will be performed to manufacture Anti-CDH17 chimeric antigen receptor (CAR) modified T cells. Prior to Anti-CDH17 CAR-T cells infusion subjects will receive lymphodepleting therapy with fludarabine and cyclophosphamide. After infusion, the safety and efficacy of CAR-T therapy was evaluated by investigators.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Sanbin Wang, MD; Phone Number: 13187424131; Email: Sanbin1011@163.com

Study Locations

• China
  • Yunnan
    • Kunming, Yunnan, China, 650100
      • Recruiting
      • Sanbin Wang
      • Contact: Sanbin Wang Wang, MD; Phone Number: 13187424131; Email: Sanbin1011@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. The patient understands and voluntarily signs the informed consent form, and is expected to complete the follow-up examination and treatment of the study procedures;
2. Age 18-75 years old, gender unlimited;
3. Tumor patients who have positive expression of CDH17 target in tumor tissues measured by immunohistochemistry (IHC) in a laboratory approved by the partner, and have no standard therapy or are ineffective or not suitable for standard treatment;
4. Have at least one extracranial measurable lesion according to RECIST 1.1 criteria;
5. Estimated survival ≥ 12 weeks;
6. Baseline ECOG (Eastern Cooperative Oncology Group) score ≤ 1 point;
7. The patient has recovered from the toxicity of the prior treatment, i.e., CTCAE toxicity grade < 2 (unless the abnormality is related to the tumor or is stable as judged by the investigator and has little impact on safety or efficacy);
8. Venous access could be established; without contraindications of apheresis.

Exclusion Criteria:

1. Patients with prior or current other malignancies;
2. Presence of brain metastases and clinically significant central nervous system disease;
3. Prior antitumor therapy (prior to blood collection for CAR-T preparation) : targeted therapy, epigenetic therapy, or investigational drug therapy within 14 days or at least 5 half-lives, whichever is shorter;
4. Subjects with positive HBsAg or HBcAb positive and peripheral blood HBV DNA titer is higher than the lower limit of detection of the research institution; HCV antibody positive; HIV antibody positive; CMV DNA titer is higher than the lower limit of detection of the research institution; EBV DNA titer is higher than the lower limit of detection of the research institution
5. Those who have a positive sputum smear and T-cell test for tuberculosis infection;
6. Patients with objective evidence of a history of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonia, and severe impairment of lung function, both past and present;
7. Patients have a severe allergic history;
8. Patients with severe heart disease or uncontrollable refractory hypertension;
9. Patients with severe liver and kidney dysfunction or consciousness disorders;
10. Active autoimmune or inflammatory diseases of the nervous system;
11. Uncontrolled infections that need antibiotics treatment;
12. Live attenuated vaccine within 4 weeks before screening;
13. Alcoholics or persons with a history of drug abuse;
14. Pregnant or Lactating Women; Patients and his or her spouse have a fertility plan within two years after CAR-T cell infusion;
15. Any unsuitable to participate in this trial judged by the investigator.

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: Anti-CDH17 CAR-T cells; CDH17 CAR-T is a novel CAR cell therapy for the treatment of advanced solid tumors.	Biological: Anti-CDH17 CAR-T cells infusion; Subiects who meet the enrollment conditions will receive intravenous infusion of anti-CDH17 CAR-T Cells after lymphodepleting therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events(AE) after infusion	The frequency, severity, and laboratory findings of all adverse events/serious adverse events are included.Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome are graded by American Society for Transplantation and Cellular Therapy (ASTCT) criteria.	within 52 weeks post-infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	The Objective Response Rate (ORR) is the percentage of participants who achieved Complete Response (CR) or Partial Response (PR) based on RECIST version 1.1.	within 52 weeks post-infusion
Concentration of CAR-T cells	Concentration of CAR-T cells measured by Flow cytometry after CAR-T infusion	Days 2, 5, 8, 11, 14, 21, 28, 35 and weeks 6, 12, 18, 26, 34, 42, 52 after infusion
Progression-free survival(PFS)	Progression-free survival(PFS) refers to the time from cell reinfusion to the first assessment of tumor progression or death from any cause.	within 52 weeks post-infusion
Overall survival(OS)	Overall survival (OS) refers to the time from the time the patient received an infusion of CAR-T cells until death (from any cause).	within 52 weeks post-infusion

Collaborators and Investigators

• Sponsor: 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China
• Collaborators: Guangzhou Bio-gene Technology Co., Ltd
• Investigators: Principal Investigator: Sanbin Wang, MD, Principal Investigator Sanbin Wang 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2025
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): June 1, 2028

Study Registration Dates

• First Submitted: February 6, 2025
• First Submitted That Met QC Criteria: February 6, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 6, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: CDH17 CAR-T
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: BG-CT-22-013

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