A Clinical Study to Evaluate CAR-T Cell-based Medicinal Product in the Treatment of Advanced Solid Tumors

A Phase 1, Open-Label Study Evaluating the Safety, Tolerability and Efficacy of LCAR-C18S, an CAR-T Cell Therapy Targeting Claudin18.2 in Patients With Advanced Solid Tumors

This is a prospective, single-arm, open-label Phase 1 dose-finding and expansion study to evaluate the safety, tolerability, pharmacokinetics, and anti-tumor efficacy profiles of the cell-based LCAR-C18S (hereinafter "LCAR-C18S") in subjects with Claudin18.2-positive advanced solid Tumors.

This is a prospective, single-arm, open-label Phase 1 dose-finding and expansion study to evaluate the safety, tolerability, pharmacokinetics, and anti-tumor efficacy profiles of the cell-based LCAR-C18S (hereinafter "LCAR-C18S") in subjects with Claudin18.2-positive advanced solid Tumors. Patients who meet the eligibility criteria will receive LCAR-C18S infusion. The study will include the following sequential phases: screening, pre-treatment , treatment and follow up

Inclusion Criteria:

1. The subjects have been fully informed of the possible risks and benefits of participating in the study and have signed the informed consent form;
2. Age 18-70 years;
3. Immunohistochemistry of tumor tissue samples indicates Claudin18.2 positive ;
4. Recurrent or metastatic advanced solid tumors (including advanced gastric cancers and non-gastric cancers) and have been failed to prior lines of systemic treatment
5. According to the RECIST v1.1, at least one measuable tumor lesion;
6. ECOG performance status score of 0-1;
7. Expected survival ≥ 3 months;
8. Subjects should have adequate organ functions before screening and treatment.
9. Women of childbearing age must have a negative blood pregnancy test; subjects of childbearing potential must use effective contraception for ≥ 1 year after the final study treatment.

Exclusion Criteria:

1. Previous CAR-T cell therapy or other cell therapies or therapeutic tumor vaccination against any target;
2. Any previous therapy targeting Claudin18.2;
3. Prior antitumor therapy with insufficient washout period;
4. Pregnant or lactating women;
5. Brain metastases with central nervous system symptoms;
6. Uncontrolled diabetes;
7. Oxygen is required to maintain adequate blood oxygen saturation;
8. Gastric perforation, pyloric obstruction, complete biliary obstruction, complete or incomplete intestinal obstruction requiring clinical intervention, or pleural effusion or peritoneal effusion requiring clinical intervention;
9. Clinically significant liver disorders (including liver cirrhosis, active viral hepatitis or other hepatitis);
10. HIV, Treponema pallidum or HCV serologically positive;
11. Severe underlying disease
12. New York Heart Association (NYHA) Class III or IV congestive heart failure or left ventricular ejection fraction (LVEF) < 50%; unstable angina, myocardial infarction or coronary artery bypass grafting (CABG) in the past 6 months; history of severe non-ischemic cardiomyopathy; or severe uncontrolled arrhythmia;
13. Any condition that, in the opinion of the investigator, will make the subject unsuitable for participation in this study.