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

Phase 1

Recruiting

• Conditions: Pancreatic Cancer
• Interventions: Drug: CT041 autologous CAR T-cell injection

• Registration Number: NCT05911217
• Lead Sponsor: CARsgen Therapeutics Co., Ltd.

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.

Study Timeline

• Study First Submitted: 2023-06-12
• Study First Submitted QC: 2023-06-12
• Study First Posted: 2023-06-20
• Study Start: 2023-07-11
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-24
• Last Update Posted: 2024-05-28
• Primary Completion: 2026-12-31
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 20

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
anti-claudin18.2 chimeric antigen receptor T-cell therapy	CT041 autologous CAR T-cell injection	Experimental: anti-claudin18.2 chimeric antigen receptor T-cell therapy Phase 1b: Evaluate the efficacy and safety of CT041

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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)
1 year DFS rate	Up to 18 months	Proportion of patients alive without local recurrence/distant metastasis 1 year after the first infusion.
Overall Survival (OS)	Up to 18 months	The time from the first infusion to death of the subject from any cause.
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.
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.
The immunogenicity in subjects receiving CT041 infusion in this study	Up to 18 months	Drug antibody (ADA) positive rate after infusion of CT041 cells.

Trial Locations

Locations (8)

Fudan University Shanghai Cancer Hospital; 🇨🇳 Shanghai, Shanghai, China

Hunan Provincial People's Hospital; 🇨🇳 Changsha, Hunan, China

Ruijin Hospital, affiliated to Shanghai Jiaotong University, school of medicine; 🇨🇳 Shanghai, Shanghai, China

Zhejiang Provincial People's Hospital; 🇨🇳 Hangzhou, Zhejiang, China

Henan Cancer Hospital; 🇨🇳 Zhengzhou, Henan, China

Beijing Cancer Hospital; 🇨🇳 Beijing, Beijing, China

Union Hospital, Tongji Medical College, Hua zhong University of Science and Technology; 🇨🇳 Wuhan, Hubei, China

The First Affiliated Hospital of Xi'an Jiaotong University; 🇨🇳 Xian, Shanxi, China