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

Prior treatment

• AEs from previous treatment that have not recovered\*;
• Patients requiring anticoagulant therapy such as warfarin or heparin;
• Patients requiring long-term antiplatelet therapy;
• Use of prednisone \>/= 10mg daily or other equivalent steroids within 14 days before leukapheresis or preconditioning\*;
• Anticancer treatment within approximately 2 weeks prior to leukapheresis or preconditioning\*;
• Major surgery less than 1 week prior to leukapheresis or 3 weeks prior to preconditioning\*;
• Patients are unable or unwilling to comply with the requirements of clinical trial.
  • Additional exclusion criteria solely for baseline (prior to conditioning regimen):
• Subjects who have received a live attenuated vaccine 4 weeks before preconditioning.
• Active infection requiring systemic therapy or causing fever within 7 days prior to investigational infusion;

Other illness

• HIV, active hepatitis C virus (HCV), active hepatitis B virus (HBV), or active syphilis infection;
• Any active infection requiring systemic treatment\*;
• Patients allergic to any drugs of the preconditioning regimen, tocilizumab, dimethyl sulfoxide (DMSO), or CT041 CAR-CLDN18.2 T-cell;
• Untreated central nervous system (CNS) metastatic disease, leptomeningeal disease, or cord compression;
• 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\*;
• 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\*;
• Patients who have clinically significant cardiac conditions that researchers believe that participating in this clinical trial may endanger the health of the patients\*;
• Patients known to have active autoimmune diseases;
• Patients with second malignancies;
• Patients have significant neurologic disorders;
• Active illness or existing toxicity that would place the subject at undue risk;
• Abrupt deterioration of clinical status or condition;
• Patients who have clinically significant cardiac conditions that researchers believe that participating in this clinical trial may endanger the health of the patients;
• Active illness or toxicity that would place the subject at undue risk;
• Abrupt deterioration of clinical status or condition;

Lab values

• Patients who have received:
  • prior cellular therapy such as (CAR T, TCR, tumor-infiltrating lymphocytes) within one year.
  • organ transplantation.
  • previous anti-claudin18.2 CAR T-cell therapy, mRNA-based cancer immunotherapy, or bispecific T cell engager.

Other

• Pregnant or lactating women\*;
• Patients who have clinically significant thyroid dysfunction;
• Patients with heavy tumor burdens;
• Inadequate pulmonary function\*;
• Fever \> 38.0°C;
• Inadequate pulmonary function;
• New or worsening Grade ≥ 3 non-hematologic toxicities.

• Patients are eligible for screening for potential inclusion in the study (\* indicates inclusion criteria at Baseline (for subjects to be eligible for preconditioning)):
• Voluntarily signed the ICF;
• 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);
• Must have CLDN18.2-positive tumor expression as determined by the CLDN18.2 IHC assay;
• Estimated life expectancy \> 4 months\*;
• Failed or been intolerant of prior lines of systemic therapy:
  • 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.
  • 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.
• At least 1 measurable lesion per RECIST 1.1\*;
• ECOG performance status of 0 or 1\*;
• Sufficient venous access for leukapheresis collection and no other contraindications to leukapheresis;
• Patients should have adequate CBC counts, renal and hepatic functions\*;
• 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\*;
• Men must be willing to use effective and reliable method of contraception for at least 12-months after T-cell infusion\*;
• Sufficient nutritional status.