A Study to Evaluate the Efficacy and Safety of CT041 After Adjuvant Chemotherapy for Pancreatic Cancer

This study is an open, multicenter, Phase Ib clinical trial evaluating chimeric antigen receptor-modified autologous T cells targeting Claudin18.2 (CLDN18.2) (CT041 autologous CAR T) in subjects with CLDN18.2 expression-positive pancreatic cancer who has undergone adjuvant chemotherapy. The aim of this study is to evaluate the efficacy, safety of CT041 treatment.

Inclusion criteria

• Voluntary participation in the clinical trial; fully understand, be informed about this study and have signed the ICF; willing to follow and able to complete all study procedures;
• Aged 18 to 79 years;
• Histologically confirmed pancreatic ductal adenocarcinoma;
• Macroscopic complete tumor removal (R0 or R1 resection);
• Postoperative pathological stage (pTNM): T1-3, N0-2, M0;
• Immunohistochemistry (IHC) staining of subject's tumor tissue sample is CLDN18.2-positive;
• Subjects had recovered from surgery and had received 3 months of standard adjuvant therapy;
• Abnormal CA19-9 level;
• With sufficient venous access for leukapheresis collection;
• ECOG performance status score 0-1;
• Adequate organ function;
• Men and women of childbearing potential must be willing to use effective methods of contraception to prevent pregnancy;

Exclusion criteria

• Prior neoadjuvant therapy for pancreatic cancer;
• Subjects with borderline resectable pancreatic cancer;
• Present or past history of metastatic or locally recurrent pancreatic cancer;
• Evidence of malignant ascites;
• Subjects had diseases that may interfere with CA19-9 level, including but not limited to cholangitis, pancreatitis, obstructive jaundice, etc.
• Toxicities caused by previous treatment have not recovered to CTCAE ≤ grade 2, except alopecia and other tolerable events as judged by the investigator or laboratory abnormalities allowed in this study;
• Pregnant or lactating women;
• Positive serology for HIV, Treponema pallidum or HCV;
• Any active infections, including but not limited to active tuberculosis, HBV, EBV, CMV, COVID-19 infections;
• Clinically significant thyroid dysfunction;
• Previous allergy to immunotherapy and related drugs, allergy to CT041 ingredients and other serious allergic history;
• Subjects who may be at high risk for potential digestive tract bleeding or perforation;
• Known active autoimmune disease, including but not limited to, psoriasis or rheumatoid arthritis, or other conditions requiring long-term immunosuppressive therapy;
• Subjects who have a history of organ transplantation or are awaiting organ transplantation;
• Subjects who require anticoagulant therapy;
• Subjects who are receiving or are expected to require long-term antiplatelet therapy during the study;
• Subjects who have experienced major surgery or have significant trauma within 4 weeks before apheresis, or who are expected to undergo major surgery during the study period;
• Previously received any gene-modified cell therapies (including CAR T, TCR T);
• Subjects who have other serious diseases that may restrict them from participating in the study assessed by investigators;
• Subjects with oxygen saturation ≤ 95%;
• Subjects who have signs of central nervous system diseases or clinically significant neurological examination abnormalities;
• Subjects who have other uncured malignant tumors in the past 3 years or at the same time, except those with very low degree of malignancy such as cervical cancer in situ and basal cell carcinoma of skin;
• Vaccination with live attenuated vaccines within 4 weeks prior to apheresis or planned during the study;
• Subjects who are unable to or unwilling to comply with the requirements of the study protocol as assessed by investigators.