Clinical Trial to Evaluate the Safety and Efficacy of IM96 CAR-T Cells Therapy in Patients With Advanced Digestive System Neoplasms

Study Overview
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Brief Summary
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This is a open-label, single center to determine the efficacy and safety of IM96 CAR-T cells in Patients With Advanced Digestive System Neoplasms

Official Title
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Clinical Trial to Evaluate the Safety and Efficacy of IM96 CAR-T Cells Therapy in Patients With Advanced Digestive System Neoplasms

Conditions
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Pancreatic Cancer Resectable, Advanced Solid Tumors, Digestive System Neoplasms, Colorectal (Colon or Rectal) Cancer

Intervention / Treatment
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* Drug: IM96 CAR-T cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18 to 75 years, either sex; Patients with pathologically diagnosed advanced gastrointestinal cancer:Patients with metastatic colorectal cancer who have failed or cannot tolerate second-line or above standard treatment;Patients with unresectable locally advanced or metastatic pancreatic cancer who have failed or cannot tolerate first-line or above standard treatment; Patients with unresectable locally advanced or metastatic other gastrointestinal cancer (gastric cancer, esophageal cancer, small intestinal cancer, etc.) who have failed or cannot tolerate standard treatment, or have no standard treatment regimen; At least one measurable lesion meeting RECIST 1.1 criteria; Tumor tissue samples were positive for GUCY2C IHC staining; Estimated life expectancy >3 months; Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; Women of childbearing age who had a negative blood pregnancy test before the start of the trial and agreed to take effective contraceptive measures during the trial period until the last follow-up; male subjects with fertility partners agreed to take effective contraceptive measures during the trial period until the last follow-up; Adequate organ function; Volunteer to participate in this trial and sign on the informed consent. Exclusion Criteria: Patients have brain metastasis； Patients with a history of organ transplantation or awaiting organ transplantation; The side effects caused by the previous treatment of the subjects did not return to CTCAE ≤1; other tolerable events determined by investigator; There is a large amount of serous effusion that cannot be controlled by treatment (such as pleural effusion, peritoneal effusion and pericardial effusion); History of autoimmune disease (eg Crohn's disease, rheumatoid arthritis, systemic lupus) within the last 2 years; Presence of acute or chronic graft-versus-host disease (GVHD); Use prohibited drugs or treatments within a specified period of time before cell collection； History or presence of CNS disorder, such as epilepsy, epileptic seizures, cerebrovascular disease (ischemia / hemorrhage / cerebral infarction), brain edema, reversible posterior white matter encephalopathy, paralysis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, cerebral organic syndrome or mental disease; Chronic or active infections requiring systemic treatment, and a history of symptomatic viral infection that has not been completely cured； Live vaccine received within 6 weeks before the start of screening; Cardiac dysfunction includes: long QTc syndrome or QTc interval > 480 MS; Complete left bundle branch block, grade II / III atrioventricular block; Serious and uncontrolled arrhythmias requiring drug treatment; A history of chronic congestive heart failure with NYHA ≥ 3, and the cardiac ejection fraction was less than 50% within 6 months before screening; Cardiac valvular disease with CTC AE ≥ 3; Myocardial infarction, cardiac angioplasty or stenting, unstable angina pectoris, history of severe pericardial disease or other clinically significant heart diseases within 6 months before screening; Patients requiring anticoagulant therapy; Patients requiring continuous anti-platelet therapy; History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months of enrollment; A history of malignancy other than non melanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast), unless it has been disease-free for at least 3 years; Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring intravenous (IV) antimicrobials for management. Simple urinary tract infection (UTI) and bacterial pharyngitis are permitted if the investigator evaluates that it can be controlled by treatment, they can be included in the group; Patients with gastrointestinal obstruction; Patients at high risk of hemorrhage or perforation; Patients were enrolled in another clinical study at the same time, unless it was an observational (non intervention) clinical study; In the investigator's judgment, the subject is unlikely to complete all protocol-required study visits or procedures, including follow-up visits, or comply with the study requirements for participation.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IM96 CAR-T cells<br> | Drug: IM96 CAR-T cells<br>* treatment with anti-GUCY2C chimeric antigen receptor T-cell infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment Related adverse events (AEs) | Incidence of treatment related AE. | Up to 28 days after CAR-T cell infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) | ORR, defined as the proportion of participants with a complete response or partial response, as determined by the investigator according to RECIST v1.1 | Up to 24 weeks after CAR-T cell infusion | 
| Progression-free survival (PFS) | PFS, defined as the time from CAR-T cell infusion to the first occurrence of disease progression or death from any cause (whichever occurs first) , as determined by the investigator according to RECIST v1.1 | Up to 24 weeks after CAR-T cell infusion | 
| Duration of Response (DOR) | DOR, defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first) in Stage 1, as determined by the investigator according to RECIST v1.1 | Up to 24 weeks after CAR-T cell infusion | 
| Overall survival (OS) | OS , defined as the time from CAR-T cell infusion to death from any cause | Up to 24 weeks after CAR-T cell infusion | 
| Persistence of CAR-T cells (cell counts and cell percentage in peripheral blood) | The persistence over time of CAR T cells in the peripheral blood as determined by flow cytometry and qPCR. | Up to 24 weeks after CAR-T cell infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Digestive System Neoplasms, Pancreatic Cancer Resectable, Colorectal (Colon or Rectal) Cancer