Pancreatic Cancer
Conditions
Keywords
Adjuvant therapy, Pancreatic Cancer, Claudin18.2, CLDN18.2, CAR T cell
Brief summary
An open-label, single-arm, multicenter, Phase Ib clinical trial to evaluate the efficacy and safety of CT041 Autologous CAR T Cell Injection after adjuvant chemotherapy in subjects with pancreatic cancer.
Detailed description
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.
Interventions
Treatment with anti-claudin18.2 chimeric antigen receptor T-cell infusion. Up to 3 times CT041 autologous CAR T-cell injection infusion
Sponsors
Fudan University
CARsgen Therapeutics Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 79 Years
Healthy volunteers
No
Inclusion criteria
1. 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; 2. Aged 18 to 79 years; 3. Histologically confirmed pancreatic ductal adenocarcinoma; 4. Macroscopic complete tumor removal (R0 or R1 resection); 5. Postoperative pathological stage (pTNM): T1-3, N0-2, M0; 6. Immunohistochemistry (IHC) staining of subject's tumor tissue sample is CLDN18.2-positive; 7. Subjects had recovered from surgery and had received 3 months of standard adjuvant therapy; 8. Abnormal CA19-9 level; 9. With sufficient venous access for leukapheresis collection; 10. ECOG performance status score 0-1; 11. Adequate organ function; 12. Men and women of childbearing potential must be willing to use effective methods of contraception to prevent pregnancy;
Exclusion criteria
1. Prior neoadjuvant therapy for pancreatic cancer; 2. Subjects with borderline resectable pancreatic cancer; 3. Present or past history of metastatic or locally recurrent pancreatic cancer; 4. Evidence of malignant ascites; 5. Subjects had diseases that may interfere with CA19-9 level, including but not limited to cholangitis, pancreatitis, obstructive jaundice, etc. 6. 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; 7. Pregnant or lactating women; 8. Positive serology for HIV, Treponema pallidum or HCV; 9. Any active infections, including but not limited to active tuberculosis, HBV, EBV, CMV, COVID-19 infections; 10. Clinically significant thyroid dysfunction; 11. Previous allergy to immunotherapy and related drugs, allergy to CT041 ingredients and other serious allergic history; 12. Subjects who may be at high risk for potential digestive tract bleeding or perforation; 13. Known active autoimmune disease, including but not limited to, psoriasis or rheumatoid arthritis, or other conditions requiring long-term immunosuppressive therapy; 14. Subjects who have a history of organ transplantation or are awaiting organ transplantation; 15. Subjects who require anticoagulant therapy; 16. Subjects who are receiving or are expected to require long-term antiplatelet therapy during the study; 17. 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; 18. Previously received any gene-modified cell therapies (including CAR T, TCR T); 19. Subjects who have other serious diseases that may restrict them from participating in the study assessed by investigators; 20. Subjects with oxygen saturation ≤ 95%; 21. Subjects who have signs of central nervous system diseases or clinically significant neurological examination abnormalities; 22. 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; 23. Vaccination with live attenuated vaccines within 4 weeks prior to apheresis or planned during the study; 24. Subjects who are unable to or unwilling to comply with the requirements of the study protocol as assessed by investigators.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease free survival (DFS) | Up to 18 months | The time from the first infusion to the occurrence of local recurrence/distant metastasis or death from any cause, whichever occurred first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 1 year DFS rate | Up to 18 months | Proportion of patients alive without local recurrence/distant metastasis 1 year after the first infusion. |
| Metastasis free Survival (MFS) | Up to 18 months | The time from the first infusion to the occurrence of any pancreatic cancer distant metastases or death from any cause, whichever occurred first. |
| Incidence of Treatment Related adverse events (AEs), treatment related AEs, AEs of special interest (AESI). | Up to 18 months | An assessment of severity grade will be made according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) |
| The phamacokinetics in subjects receiving CT041 infusion in this study | Up to 18 months | Peak cell expansion, peak expansion, area under the curve (AUC), and duration of cell survival after infusion of CT041 cells. |
| The immunogenicity in subjects receiving CT041 infusion in this study | Up to 18 months | Drug antibody (ADA) positive rate after infusion of CT041 cells. |
| Overall Survival (OS) | Up to 18 months | The time from the first infusion to death of the subject from any cause. |
Countries
China
Contacts
Primary ContactLifeng Zhang
Backup ContactNing Wang
Outcome results
None listed