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

Solid Tumors, Adult Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04467853
• Other study ID #: BM2L201910
• Status: Terminated
• Phase: Phase 1
• Start date: September 21, 2020
• Est. completion date: July 17, 2023

Study information

• Verified date: August 2023
• Source: Shanghai East Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 34
• Est. completion date: July 17, 2023
• Est. primary completion date: July 17, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumors, Adult

Intervention

Biological:
• LCAR-C18S cells
Before treatment with LCAR-C18S cells, subjects will receive a conditioning regimen

Locations

Country	Name	City	State
China	Anhui Provincial Hospital	Hefei	Anhui
China	Shanghai Artemed Hospital	Shanghai	Shanghai
China	Shanghai East Hospital	Shanghai	China/Shanghai

Sponsors (2)

Lead Sponsor	Collaborator
Shanghai East Hospital	Nanjing Legend Biotech Co.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose-limiting toxicity (DLT) and incidence, severity, and type of treatment-emergent adverse events (TEAEs),Safety	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)
Primary	To determine the recommended dose of the phase ? trial of this cell therapy (RP2D)	To determine the recommended dose of the phase ? trial of this cell therapy (RP2D)	90 days post infusion
Primary	Pharmacokinetic (PK) parameters	Blood samples will be collected for determination of cellular concentrations and transgenic levels of serum LCAR-C18S for pharmacokinetic analysis	Minimum 2 years after LCAR-C18S infusion (Day 1)
Secondary	Overall response rate (ORR) after administration	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	Minimum 2 years after LCAR-C18S infusion (Day 1)
Secondary	Progress Free Survival (PFS) after administration	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	Minimum 2 years after LCAR-C18S infusion (Day 1)
Secondary	Overall Survival (OS) after administration	Overall Survival (OS) is defined as the time from the date of first infusion of LCAR-C18S to death of the subject.	Minimum 2 years after LCAR-C18S infusion (Day 1)