Claudin18.2 CAR-T (CT041) in Patients with Gastric, Pancreatic Cancer, or Other Specified Digestive Cancers

Inclusion Criteria

• Inclusion Criteria: Patients are eligible for screening for potential inclusion in the study (* indicates inclusion criteria at Baseline (for subjects to be eligible for preconditioning)): 1. Voluntarily signed the ICF; 2. Age ≥ 18 and < 76 years with pathologically/histologically confirmed diagnosis of adenocarcinoma of the stomach or gastroesophageal junction, referred to collectively as STAD, or pancreatic adenocarcinoma (PAAD);or biliary tract cancers (BTCs, including intrahepatic/extrahepatic cholangiocarcinoma and gallbladder cancer but not ampullary carcinoma); 3. Must have CLDN18.2-positive tumor expression as determined by the CLDN18.2 IHC assay; 4. Estimated life expectancy > 4 months*; 5. Failed or been intolerant of prior lines of systemic therapy: 1. For screening: - Leukapheresis can be performed for subjects with STAD who have progressed or were intolerant of at least 1 prior line of systemic therapy, or, - Leukapheresis can be performed for subjects with PAAD who are receiving first-line treatment, or, - Leukapheresis can be performed for subjects with BTC who are receiving first-line treatment. 2. Baseline*: - Subjects with STAD who have progressed or were intolerant of at least 2 prior lines of systemic therapy, or, - Subjects with PAAD who have progressed or were intolerant of at least 1 prior line of systemic therapy, or, - Subjects with BTC who have progressed or were intolerant of at least 1 prior line of systemic therapy. For subjects with CCA with who has FGFR2 fusions or rearrangements, or IDH1-mutant must have received FDA-approved target therapies. 6. At least 1 measurable lesion per RECIST 1.1*; 7. ECOG performance status of 0 or 1*; 8. Sufficient venous access for leukapheresis collection and no other contraindications to leukapheresis; 9. Patients should have adequate CBC counts, renal and hepatic functions*; 10. Women of childbearing age must undergo a serum pregnancy test with negative results before screening and infusion and be willing to use effective and reliable method of contraception*; 11. Men must be willing to use effective and reliable method of contraception for at least 12-months after T-cell infusion*; 12. Sufficient nutritional status. Exclusion Criteria for screening (* indicates exclusion criteria for baseline as well): 1. Pregnant or lactating women*; 2. HIV, active hepatitis C virus (HCV), active hepatitis B virus (HBV), or active syphilis infection; 3. Any active infection requiring systemic treatment*; 4. AEs from previous treatment that have not recovered*; 5. Patients who have clinically significant thyroid dysfunction; 6. Patients allergic to any drugs of the preconditioning regimen, tocilizumab, dimethyl sulfoxide (DMSO), or CT041 CAR-CLDN18.2 T-cell; 7. Patients who have received: 1. prior cellular therapy such as (CAR T, TCR, tumor-infiltrating lymphocytes) within one year. 2. organ transplantation. 3. previous anti-claudin18.2 CAR T-cell therapy, mRNA-based cancer immunotherapy, or bispecific T cell engager. 8. Untreated central nervous system (CNS) metastatic disease, leptomeningeal disease, or cord compression; 9. Patients with heavy tumor burdens; 10. Unstable/active ulcer, anastomotic recurrence with full-thickness tumor infiltration or tumor involving any major vessels, digestive tract bleeding, or recent digestive surgery that may have increased risk of bleeding*; 11. Patients who have a history of esophageal or gastric resection plus current evidence of locally recurrent tumor that involves any major blood vessels or that has evidence of recent bleeding or perforation*; 12. Patients requiring anticoagulant therapy such as warfarin or heparin; 13. Patients requiring long-term antiplatelet therapy; 14. Use of prednisone >/= 10mg daily or other equivalent steroids within 14 days before leukapheresis or preconditioning*; 15. Anticancer treatment within approximately 2 weeks prior to leukapheresis or preconditioning*; 16. Major surgery less than 1 week prior to leukapheresis or 3 weeks prior to preconditioning*; 17. Patients who have clinically significant cardiac conditions that researchers believe that participating in this clinical trial may endanger the health of the patients*; 18. Inadequate pulmonary function*; 19. Patients known to have active autoimmune diseases; 20. Patients with second malignancies; 21. Patients have significant neurologic disorders; 22. Patients are unable or unwilling to comply with the requirements of clinical trial. Additional exclusion criteria solely for baseline (prior to conditioning regimen): 23. Fever > 38.0°C; 24. Active illness or existing toxicity that would place the subject at undue risk; 25. Abrupt deterioration of clinical status or condition; 26. Subjects who have received a live attenuated vaccine 4 weeks before preconditioning. Inclusion Criteria Before Infusion: There are no inclusion criteria at this timepoint. Exclusion Criteria Before Infusion: 1. Patients who have clinically significant cardiac conditions that researchers believe that participating in this clinical trial may endanger the health of the patients; 2. Inadequate pulmonary function; 3. Active infection requiring systemic therapy or causing fever within 7 days prior to investigational infusion; 4. Active illness or toxicity that would place the subject at undue risk; 5. Abrupt deterioration of clinical status or condition; 6. New or worsening Grade ≥ 3 non-hematologic toxicities.