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

Phase 1

Terminated

• Conditions: Solid Tumors, Adult
• Interventions: Biological: LCAR-C18S cells

• Registration Number: NCT04467853
• Lead Sponsor: Shanghai East Hospital

Brief Summary

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.

Detailed Description

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

Study Timeline

• Study First Submitted: 2020-07-01
• Study First Submitted QC: 2020-07-10
• Study First Posted: 2020-07-13
• Study Start: 2020-09-21
• Primary Completion: 2023-07-17
• Study Completion: 2023-07-17
• Status Verified: 2023-08
• Last Update Submitted: 2023-08-11
• Last Update Posted: 2023-08-15

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 34

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
LCAR-C18S Cells	LCAR-C18S cells	Each subject will receive LCAR-C18S Cells

Primary Outcome Measures

Name	Time	Method
Dose-limiting toxicity (DLT) and incidence, severity, and type of treatment-emergent adverse events (TEAEs),Safety	Minimum 2 years after LCAR-C18S infusion (Day 1)	Dose-limiting toxicity (DLT) and incidence, severity, and type of treatment-emergent adverse events (TEAEs),Safety
To determine the recommended dose of the phase Ⅱ trial of this cell therapy (RP2D)	90 days post infusion	To determine the recommended dose of the phase Ⅱ trial of this cell therapy (RP2D)
Pharmacokinetic (PK) parameters	Minimum 2 years after LCAR-C18S infusion (Day 1)	Blood samples will be collected for determination of cellular concentrations and transgenic levels of serum LCAR-C18S for pharmacokinetic analysis

Secondary Outcome Measures

Name	Time	Method
Overall response rate (ORR) after administration	Minimum 2 years after LCAR-C18S infusion (Day 1)	Objective Response Rate (ORR) is defined as the proportion of subjects who achieve CR or PR after treatment via LCAR-C18S cell infusion, and the objective tumor response rate will be calculated for patients with measurable disease per RECIST 1.1 only
Overall Survival (OS) after administration	Minimum 2 years after LCAR-C18S infusion (Day 1)	Overall Survival (OS) is defined as the time from the date of first infusion of LCAR-C18S to death of the subject.
Progress Free Survival (PFS) after administration	Minimum 2 years after LCAR-C18S infusion (Day 1)	Progression Free Survival (PFS) is defined as the time from the date of first infusion of the LCAR-C18S to the first documented disease progression (according to RECIST 1.1) or death (due to any cause), whichever occurs first

Trial Locations

Locations (3)

Anhui Provincial Hospital; 🇨🇳 Hefei, Anhui, China

Shanghai East Hospital; 🇨🇳 Shanghai, China/Shanghai, China

Shanghai Artemed Hospital; 🇨🇳 Shanghai, Shanghai, China