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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Drug: CT041 autologous CAR T-cell injection


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: anti-claudin18.2 chimeric antigen receptor T-cell therapy<br>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<br>* Treatment with anti-claudin18.2 chimeric antigen receptor T-cell infusion. Up to 3 times CT041 autologous CAR T-cell injection infusion<br>* Other names: Single Group Assignment;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Adjuvant therapy, Pancreatic Cancer, Claudin18.2, CLDN18.2, CAR T cell