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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Drug: CT041 autologous CAR T-cell injection

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 Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Lifeng Zhang; Phone Number: 86-21-54489928; Email: lifengzhang@carsgen.com
• Study Contact Backup: Name: Ning Wang; Phone Number: 86-21-54489926; Email: ningwang@carsgen.com

Study Locations

• China
  • Henan
    • Zhengzhou, Henan, China
      • Not yet recruiting
      • Henan Cancer Hospital
      • Contact: Xiaobing Chen, Ph.D; Email: zlyychenxb0807@zzu.edu.cn
  • Hubei
    • Wuhan, Hubei, China
      • Not yet recruiting
      • Union Hospital, Tongji Medical College, Hua zhong University of Science and Technology
      • Contact: Heshui Wu, Ph.D; Email: heshuiwu@hust.edc.cn
  • Hunan
    • Changsha, Hunan, China
      • Recruiting
      • Hunan Provincial People's Hospital
      • Contact: Wei Cheng, Ph.D; Email: 13974866177@163.com
  • Shanghai
    • Shanghai, Shanghai, China, 200025
      • Not yet recruiting
      • Ruijin Hospital, affiliated to Shanghai Jiaotong University, school of medicine
      • Contact: Jun Zhang, Ph.D; Email: junzhang@188.com
    • Shanghai, Shanghai, China, 201321
      • Recruiting
      • Fudan University Shanghai Cancer Hospital
      • Contact: Xianjun Yu, Ph.D; Phone Number: 02164175590; Email: yuxianjun@fudanpci.org
      • Contact: Jian Zhang, Ph.D; Phone Number: 02164175590; Email: Syner2000@163.com
  • Shanxi
    • Xian, Shanxi, China
      • Recruiting
      • The First Affiliated Hospital of Xi'An JiaoTong University
      • Contact: Zheng Wu; Email: woozheng@xjtu.edu.cn
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Recruiting
      • Zhejiang Provincial People's Hospital
      • Contact: Yiping Mou, Ph.D; Email: yipingmou@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: anti-claudin18.2 chimeric antigen receptor T-cell therapy; Experimental: anti-claudin18.2 chimeric antigen receptor T-cell therapy Phase 1b: Evaluate the efficacy and safety of CT041	Drug: CT041 autologous CAR T-cell injection; Treatment with anti-claudin18.2 chimeric antigen receptor T-cell infusion. Up to 3 times CT041 autologous CAR T-cell injection infusion; Other Names: Single Group Assignment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease free survival (DFS)	The time from the first infusion to the occurrence of local recurrence/distant metastasis or death from any cause, whichever occurred first.	Up to 18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment Related adverse events (AEs), treatment related AEs, AEs of special interest (AESI).	An assessment of severity grade will be made according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)	Up to 18 months
1 year DFS rate	Proportion of patients alive without local recurrence/distant metastasis 1 year after the first infusion.	Up to 18 months
Metastasis free Survival (MFS)	The time from the first infusion to the occurrence of any pancreatic cancer distant metastases or death from any cause, whichever occurred first.	Up to 18 months
Overall Survival (OS)	The time from the first infusion to death of the subject from any cause.	Up to 18 months
The phamacokinetics in subjects receiving CT041 infusion in this study	Peak cell expansion, peak expansion, area under the curve (AUC), and duration of cell survival after infusion of CT041 cells.	Up to 18 months
The immunogenicity in subjects receiving CT041 infusion in this study	Drug antibody (ADA) positive rate after infusion of CT041 cells.	Up to 18 months

Collaborators and Investigators

• Sponsor: CARsgen Therapeutics Co., Ltd.
• Collaborators: Fudan University
• Investigators: Principal Investigator: Xianjun Yu, Ph.D, Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): July 11, 2023
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: June 12, 2023
• First Submitted That Met QC Criteria: June 12, 2023
• First Posted (Actual): June 20, 2023

Study Record Updates

• Last Update Posted (Actual): August 16, 2023
• Last Update Submitted That Met QC Criteria: August 14, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: CAR T cell; Pancreatic Cancer; Adjuvant therapy; Claudin18.2; CLDN18.2
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms
• Other Study ID Numbers: CT041-ST-05

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No