CDH17 CAR-T Therapy In Advanced Malignant Solid Tumors

Study Overview

CDH17 CAR-T Therapy in Advanced Malignant Solid Tumors

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.

The trial progresses through sequential Phase Ia (dose-finding) and Phase Ib (dose-expansion) stages. Phase Ia cessation triggers include either confirmation of Recommended Phase II Dose (RP2D) or investigator-verified favorable therapeutic index at any dose level. Post-Phase Ia completion, protocol amendment submission to the Institutional Review Board precedes Phase Ib initiation, featuring multi-cohort expansion (n=9-18/cohort) across specified malignancies: colorectal adenocarcinoma (CRC), gastric carcinoma (GC), high-grade serous ovarian carcinoma (HGSOC), breast cancer (BC), non-small cell lung cancer (NSCLC), SCLC, metastatic castration-resistant prostate cancer (mCRPC), clear cell renal cell carcinoma (ccRCC), and cervical squamous cell carcinoma (CSCC), etc. This study has 3 dose levels and follows a ȣ+3 design," with an estimated enrollment of 9 to 18 subjects. The final sample size will depend on the occurrence of dose-limiting toxicities (DLTs), the number of dose escalation groups before observing DLTs, and the maximum tolerated dose (MTD). Considering the possibility of cell production preparation failure or other reasons (such as rapid disease progression during cell preparation) leading to subjects ultimately being unable to receive cell infusion therapy, the number of participants in the cell collection and preparation process may be greater than the planned number of cases. The observation period for dose-limiting toxicity (DLT) is set from the start of cell infusion to 4 weeks after the completion of cell infusion (D0 to D28). The starting dose of cell infusion therapy in this clinical study is set at 1.0×10^6/Kg, and the maximum dose is set at 6.0×10^6/Kg.

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

BIOLOGICAL: CDH17 CAR-T

UCLH801-II

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2024-12-24	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2025-04-13
First Submitted that Met QC Criteria 2025-04-13	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2025-04-22
First Posted (ACTUAL) 2025-04-22	Results First Posted N/A	Last Verified 2025-04

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: CDH17 CAR-T treatment arm 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	BIOLOGICAL: CDH17 CAR-T 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.

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: CDH17 CAR-T treatment arm

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

BIOLOGICAL: CDH17 CAR-T

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.

Primary Outcome Measures	Measure Description	Time Frame
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 Outcome Measures	Measure Description	Time Frame
Evaluate the preliminary response rate of UCLH801 cells in patients with advanced malignant solid tumors expressing CDH17.	Efficacy: Evaluated based on objective response rate (ORR) and disease control rate (DCR)	64 days
Evaluate the pharmacodynamic (PD) characteristics of UCLH801 cells in subjects	Pharmacodynamics: Cytokine levels in blood/serum at various time points, including IL-2, IL-6, IL-8, IL-10, TNF-α, and IFN-γ.	28 days
Evaluate the concentration of anti-UCLH801 cell antibodies in serum	The production 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.	Evaluate the PFS and OS of all enrolled patients	2 years
Evaluate the peak plasma concentration (Cmax) of UCLH801 cells	After cell infusion, the peak concentration (Cmax), time to reach peak concentration (Tmax)	28 days
Evaluate the long-time area under the curve (AUC) of UCLH801 cells.	Pharmacokinetics: After cell infusion, the area under the curve (AUC) from 0 to 90 days (AUC0-90) of UCLH801 cells in peripheral blood.	90 days
Evaluate the area under the plasma concentration versus time curve (AUC) of UCLH801 cells	After cell infusion, evaluate the area under the curve (AUC) from 0 to 28 days (AUC0-28)	28 days

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: Weijia Fang, Doctor

Phone Number: +86-0571-87235147

Email: weijiafang@zju.edu.cn

Study Contact Backup

Name: Hangyu Zhang

Phone Number: +86-0571-87235149

Email: zhanghangyu@zju.edu.cn

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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.

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.
Active, chronic, or recurrent severe autoimmune diseases requiring immunosuppressive treatment (with exceptions).
Any form of primary or secondary immunodeficiency.
Risk of organ perforation or bleeding as judged by the investigator.
Severe systemic hypersensitivity reactions to study drugs/components. - Received live attenuated vaccines within 4 weeks prior to signing informed consent.
Participated in another clinical study within 4 weeks prior to signing informed consent.
History of another malignancy within the past 5 years, except for adequately treated non-melanoma skin cancer or in situ cancers.
Diagnosed with neuropsychiatric disorders or any condition deemed by the investigator as unsuitable for participation.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

UTC Therapeutics Inc.

Investigators

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