Clinical trial NCT05911217: A Study to Evaluate the Efficacy and Safety of CT041 After Adjuvant Chemotherapy for Pancreatic Cancer
Official title: 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 type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Pancreatic Cancer
Keywords: Adjuvant therapy
Pancreatic Cancer
Claudin18.2
CLDN18.2
CAR T cell
Lead sponsor: CARsgen Therapeutics Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Fudan University
First posted: 2023-06-20
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Disease free survival (DFS)
timeFrame: Up to 18 months
Secondary outcomes:
measure: Incidence of Treatment Related adverse events (AEs), treatment related AEs, AEs of special interest (AESI).
timeFrame: Up to 18 months
measure: 1 year DFS rate
timeFrame: Up to 18 months
measure: Metastasis free Survival (MFS)
timeFrame: Up to 18 months
measure: Overall Survival (OS)
timeFrame: Up to 18 months
measure: The phamacokinetics in subjects receiving CT041 infusion in this study
timeFrame: Up to 18 months
measure: The immunogenicity in subjects receiving CT041 infusion in this study
timeFrame: Up to 18 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Wuhan
country: China
facility: Union Hospital, Tongji Medical College, Hua zhong University of Science and Technology
state: Hubei
city: Changsha
country: China
facility: Hunan Provincial People's Hospital
state: Hunan
city: Shanghai
country: China
facility: Ruijin Hospital, affiliated to Shanghai Jiaotong University, school of medicine
state: Shanghai
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Hospital
state: Shanghai
city: Xian
country: China
facility: The First Affiliated Hospital of Xi'an Jiaotong University
state: Shanxi
city: Hangzhou
country: China
facility: Zhejiang Provincial People's Hospital
state: Zhejiang
Study officials:
affiliation: Fudan University
name: Xianjun Yu, Ph.D
role: PRINCIPAL_INVESTIGATOR
References: