Clinical Trial to Evaluate the Safety and Efficacy of IM92 CAR-T Cells Therapy in Patients With Advanced Gastric or Pancreatic Adenocarcinoma

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 IM92 CAR-T cells in Patients With advanced gastric/esophagogastric combination adenocarcinoma that has failed at least second-line therapy and advanced pancreatic cancer that has failed at least first-line therapy.

Official Title
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Clinical Trial to Evaluate the Safety and Efficacy of IM92 CAR-T Cells Therapy in Patients With Advanced Gastric or Pancreatic Adenocarcinoma

Conditions
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Advanced Solid Tumors, Gastric Cancer, Esophagogastric Junction Cancer, Pancreatic Cancer

Intervention / Treatment
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* Drug: IM92 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 gastric/ gastroesophageal junction adenocarcinoma who have failed second-line treatment at least; or patients with pathologically diagnosed advanced pancreatic cancer who have failed first-line treatment at least; Tumor tissue samples were positive for CLDN18.2 IHC staining(≥+，≥10%); Estimated life expectancy >12 weeks; 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; Adequate vascular access for leukapheresis procedure; 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 other malignancies with a higher risk of recurrence was assessed by the investigator; 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 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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IM92 CAR-T cells<br> | Drug: IM92 CAR-T cells<br>* 2.5×10^8 CAR-T cells<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events (AEs) | Incidence of treatment related AEs | 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 | 
| Disease Control Rate（DCR） | DCR,defined as the number of cases in which response are achieved from the start of cell infusion/the total number of evaluable cases (%). | 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 | 
| 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 | 
| Response rate of tumor markers (CEA, CA19-9) before and after CAR-T cells infusion |  | Up to 24 weeks after CAR-T cell infusion | 
| Anti-therapeutic IM92 CAR-T cells antibody |  | Up to 24 weeks after IM92 CAR-T cell infusion |