A Study of IMC008 for Advanced Solid Tumors

Study Overview
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Brief Summary
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An open label, multi-center, dose-escalating study to evaluate the safety and preliminary efficacy of IMC008 in CLDN18.2 positive advanced solid tumors.

Detailed Description
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This study is an open label, multi-center, dose-escalating clinical study to evaluate the safety and preliminary efficacy of IMC008 in the treatment of CLDN18.2 positive advanced solid tumors. DLTs observations will be performed 28 days after IMC008 administration. During the study, regular safety meetings will be held according to the progress of the study, and recommendations will be made on dose escalation, safety of subjects and possible study change.

Official Title
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A Clinical Study on the Safety and Preliminary Efficacy of IMC008 in the Treatment of CLDN18.2- Positive Advanced Solid Tumors

Conditions
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Advanced Solid Tumor

Intervention / Treatment
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* Drug: IMC008


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Advanced gastric cancer /esophagogastric junction adenocarcinoma advanced pancreatic cancer. Tumor tissue samples of subjects expected to be available with positive for CLDN18.2 immunohistochemistry. The expected survival period of the subject is ≥12 weeks. The subject needs to have at least one target lesion that can be stably evaluated. The ECOG score is 0-1. Subject has adequate organ and bone marrow function All toxic reactions caused by previous anti-tumor therapy were relieved to grade 0-1. Fertility status : Women of childbearing age or men whose sexual partners are women of childbearing age are willing to take medically approved high-efficiency contraceptive measures. Subjects must sign and date written informed consent. Exclusion Criteria: Pregnant and lactating women. Known history of human immunodeficiency virus infection; acute or chronic active hepatitis B; acute or chronic active hepatitis C. Syphilis antibody positive; Epstein-Barr virus infection; CMV infection. Serious infection that is active or poorly controlled clinically. Uncontrollable pleural effusion, pericardial effusion, peritoneal effusion existed before enrollment. Extensive or diffuse lung metastases or extensive or diffuse liver metastases. Oxygen saturation ≤ 95% without oxygen inhalation. Suffering from other research diseases that may limit their participation in this study. Known past or current hepatic encephalopathy requiring treatment; patients with current or history of central nervous system disease. There are heart diseases that need to be treated or hypertension that is poorly controlled by the investigator, poorly controlled after standard treatment type 2 diabetes mellitus. Presence of any cardiac clinical symptoms or disorders. Evidence of significant coagulopathy or other significant bleeding risk. Received systemic steroids equivalent to >15 mg/ day prednisone cumulatively for more than 3 days within 2 weeks prior to apheresis , excluding inhaled steroids. Prior or concurrent occurrence of other malignancies, with the following exceptions. Subjects who have previously received other gene therapy. Allergic/ intolerance to lymphodepletion regimen or CRS treatment drugs or IMC008. Subjects with severe mental disorders. The investigator assessed the subject's inability or unwillingness to comply with the requirements of the study protocol .

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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
Interventional Model Description: Dose escalation of 3 dosage groups
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IMC008 dose 1-3<br>a certain number of IMC008 cell per kg will be infused | Drug: IMC008<br>* allowing 10% dose error<br>* Other names: NKG2D receptor-modified autologous CAR -T cells targeting CLDN18.2;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DLT | To observe the incidence of dose-limiting toxicity (DLT) after IMC008 infusion | within 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| TRAE | To treatment-related adverse events (TRAE) and severity | up to 96 weeks | 
| PFS | To evaluate the progression-free survival of IMC008 in patients with CLDN18.2 positive advanced solid tumor | upto 96 weeks | 
| Objective response rate (ORR) | The ORR is defined as the proportion of subjects with confirmed CR or confirmed PR, based on RECIST Version 1.1 | upto 96 weeks | 
| Tmax | Tmax of CAR-T cells in the blood. | upto 96 weeks | 
| Lymphocyte subsets | CAR-T cell lymphocyte subsets/phenotype, etc. | upto 96 weeks | 
| OS | To evaluate the overall survival of of IMC008 in patients with CLDN18.2 positive advanced solid tumor | upto 96 weeks |