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.
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.
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.
Single group
CDH17 CAR-T
Biological/VaccineThe 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.
FAST LACO-Stim CDH17 CAR-T
Biological/VaccineThe initial dose of LACO-Stim CDH17 CAR-T cell therapy in this clinical study was set at 3.0×104/kg and the maximum dose was set at 1.0×105/kg. Subjects will be treated with Fludarabine and Cyclophosphamide based lymphodepleting chemotherapy before CAR-T cell infusion.
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.
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)
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.
Evaluate the concentration of anti-UCLH801 cell antibodies in serum
The production of anti-UCLH801 cell antibodies in serum
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
Explore the changes in T cell infiltration and tumor microenvironment components in tumor tissues before and after UCLH801 cell infusion.
The distribution, quantity, and proportion of Anti-CDH17 CAR+ T cells, Treg cells, MDSCs, TAMs, TAFs, etc., in tumor tissues before and after UCLH801 cell infusion.
Explore the changes in T cell phenotype, function, persistence, and gene expression profile, and their correlation with clinical response.
The expression and proportion of T cell surface markers (CD3, CD4, CD8, CD45RA, CD95, IL-2Rβ, CCR7, CD62L, PD1, TIM-3, LAG-3, etc.) in peripheral blood, tumor tissue, and pleural/ascitic fluid. Single-cell transcriptomic analysis of T cells in peripheral blood, tumor tissue, and pleural/ascitic fluid.
Subgroup evaluation of the preliminary response rate of UCLH801 cells in patients with different expressing level of CDH17.
Subgroup evaluation of the ORR and DCR of UCLH801 cells in patients with different expressing level of CDH17
Subgroup evaluation of the survival time of UCLH801 cells in patients with different expressing level of CDH17.
Subgroup evaluation of the PFS and OS of UCLH801 cells in patients with different expressing level of CDH17
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Zhejiang University
Lead sponsor
UTC Therapeutics Inc.
Collaborator
