CDH17 CAR-T Therapy in Advanced Malignant Solid Tumors

NCT06937567 | Recruiting Early Phase 1

• 1 other identifier: UCLH801-II
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

The investigational product used in this study, UCLH801 cells, is a CAR-T cell therapy specifically targeting CDH17. The proposed indication includes CDH17-positive advanced solid tumors, such as but not limited to colorectal cancer, gastric cancer, pancreatic cancer, biliary tract tumors, neuroendocrine tumors, ovarian cancer, and lung cancer. The primary objective of this study is to evaluate the safety and tolerability of UCLH801 cells in patients with CDH17-positive advanced malignant solid tumors. The secondary objectives include assessing the preliminary efficacy of UCLH801 cells, their pharmacokinetics and pharmacodynamics in the body, and their immunogenicity. This study aims to observe how the infusion of UCLH801 cells affects patients 's body, including any discomfort or changes in laboratory test results. Additionally, it will evaluate whether UCLH801 cells have any effect on tumor. Furthermore, the study will investigate how UCLH801 cells are metabolized; the mechanisms through which they exert their effects, and how to develops any immune response or rejection against UCLH801 cells.

Conditions

Biliary Tract Cancer; Colorectal Carcinoma; Gastric Cancer, Metastatic; Pancreatic Adenocarcinoma (Ductal Adenocarcinoma); Multiple Cancer

Keywords

CAR-T; CDH17

Outcome Measures

Primary Outcomes (1)

• The safety of UCLH801 cells in patients with advanced malignant solid tumors with positive expression of CDH17

  The number and severity of dose-limiting toxicity (DLT) events and all adverse events occurring in subjects following the infusion of UCLH801 cells; The determination of the recommended Phase II dose (RP2D). Periodic analysis may be conducted during the dose esclation stage, including subgroup analysis, such as CDH17 expression strength, prior therapy lines and tumor burden.

  28 days after the CAR-T cells infusion

Secondary Outcomes (7)

• Evaluate the preliminary response rate of UCLH801 cells in patients with advanced malignant solid tumors expressing CDH17.

  64 days

• Evaluate the pharmacodynamic (PD) characteristics of UCLH801 cells in subjects

  28 days

• Evaluate the concentration of anti-UCLH801 cell antibodies in serum

  28 days

• Evaluate the preliminary response rate of UCLH801 cells in patients with advanced malignant solid tumors expressing CDH17.

  2 years

• Evaluate the peak plasma concentration (Cmax) of UCLH801 cells

  28 days

Other Outcomes (10)

• Explore the changes in T cell infiltration and tumor microenvironment components in tumor tissues before and after UCLH801 cell infusion.

  64 days

• Explore the changes in T cell phenotype, function, persistence, and gene expression profile, and their correlation with clinical response.

  64days

• Subgroup evaluation of the preliminary response rate of UCLH801 cells in patients with different expressing level of CDH17.

  64 days

Study Arms (1)

CDH17 CAR-T treatment arm

EXPERIMENTAL

In this study, patients with advanced malignant solid tumors with positive CDH17 expression will be enrolled in a traditional "3+3 design" dose climb test. The initial dose of cell therapy in this clinical study was set at 1.0×106/Kg and the maximum dose was set at 6.0×106/Kg.

Biological: CDH17 CAR-T

Interventions

CDH17 CAR-T BIOLOGICAL

The initial dose of cell therapy in this clinical study was set at 1.0×106/Kg and the maximum dose was set at 6.0×106/Kg.

CDH17 CAR-T treatment arm

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histopathologically confirmed malignant solid tumors, including but not limited to colorectal cancer, gastric cancer, pancreatic cancer, and biliary tract tumors.
• Patients must have failed standard treatments, be intolerant to standard treatments, or lack effective treatment options.
• At least one measurable lesion as defined by RECIST v1.1 criteria.
• Tumor tissue must be available either from prior tumor biopsy or by providing new tumor specimens.
• Tumor specimens must be confirmed as CDH17-positive by immunohistochemistry (IHC) or immunocytochemistry (ICC) staining.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Expected survival time ≥ 3 months.
• Appropriate organ function: hematological: Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L; Absolute lymphocyte count (ALC) ≥ 0.5 × 10⁹/L. Hemoglobin (HGB) ≥ 80 g/L; Platelet count (PLT) ≥ 75 × 10⁹/L. Liver Function: aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤ 3.0 × ULN (≤ 5.0 × ULN for patients with primary liver tumors or liver metastases); total bilirubin ≤ 1.5 × ULN (≤ 3.0 × ULN for patients with primary liver tumors or liver metastases; ≤ 3 × ULN for Gilbert's syndrome with direct bilirubin ≤ 1.5 × ULN). Coagulation: international normalized ratio (INR) ≤ 1.5 × ULN (unless on therapeutic anticoagulants); activated partial thromboplastin time (APTT) ≤ 1.5 × ULN (unless on therapeutic anticoagulants). Renal Function: serum creatinine (Cr) ≤ 1.5 × ULN or creatinine clearance rate ≥ 60 mL/min (based on Cockcroft-Gault formula). Cardiac Function: left ventricular ejection fraction (LVEF) ≥ 50% (confirmed by echocardiography). Pulmonary Function: resting oxygen saturation (SpO₂) \> 92% without supplemental oxygen.
• Female participants of childbearing potential must have a negative pregnancy test.
• Female participants of childbearing potential or male participants with partners of childbearing potential must agree to use effective contraception during the study and for 1 year after the final cell infusion.
• Willingness to sign the informed consent form, demonstrating understanding of the study and agreement to comply with study procedures.

You may not qualify if:

• Women who are pregnant or breastfeeding.
• Positive hepatitis B surface antigen (HBsAg), or hepatitis B core antibody (HBcAb) with peripheral HBV DNA levels above the lower limit of detection.
• Positive hepatitis C virus (HCV) antibody with peripheral HCV RNA levels above the lower limit of detection.
• Positive HIV antibody.
• Positive syphilis-specific and non-specific antibody tests.
• Non-hematological toxicity from prior treatment (surgery, chemotherapy, radiotherapy, targeted therapy, immunotherapy, etc.) has not resolved to ≤ CTCAE grade 1 (except for hair loss and peripheral sensory neuropathy).
• Prior allogeneic tissue or organ transplant (including bone marrow, stem cell, liver, kidney, etc.), except for transplants not requiring immunosuppression (e.g., corneal or hair transplantation).
• Patients who have previously received CDH17 CAR-T therapy, except those who received CAR-T infusion within this study.
• Underwent major surgery within 4 weeks prior to signing informed consent and has not fully recovered, or has a history of serious unresolved trauma.
• Known central nervous system (CNS) metastases (with exceptions for asymptomatic brain metastases or stable clinical symptoms).
• Severe active infections or pulmonary diseases requiring systemic corticosteroid treatment within 6 months prior to signing informed consent.
• Symptomatic congestive heart failure (NYHA class II-IV), severe aortic stenosis, or symptomatic mitral stenosis.
• ECG showing QTc \> 450 ms or QTc \> 480 ms with bundle branch block.
• Uncontrolled hypertension (SBP ≥ 160 mmHg and/or DBP ≥ 100 mmHg).
• Cerebrovascular accidents within 6 months prior to signing informed consent.

Sponsors & Collaborators

• Zhejiang University: lead
• UTC Therapeutics Inc.: collaborator

Study Sites (1)

The First Affiliated Hospital Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

RECRUITING

MeSH Terms

Conditions

Biliary Tract Neoplasms; Colorectal Neoplasms; Stomach Neoplasms; Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Stomach Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Weijia Fang, Doctor

CONTACT

+86-0571-87235147; weijiafang@zju.edu.cn

Hangyu Zhang

CONTACT

+86-0571-87235149; zhanghangyu@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief doctor

Study Record Dates

• First Submitted: December 24, 2024
• First Posted: April 22, 2025
• Study Start: December 26, 2024
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): January 31, 2027
• Last Updated: April 22, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)