CDH17 CAR-T Therapy in Advanced Malignant Solid Tumors

Inclusion criteria

• 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.

Exclusion criteria

• 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.