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.

Study Overview

• Status: Terminated
• Conditions: Solid Tumors, Adult
• Intervention / Treatment: Biological: LCAR-C18S cells

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 Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China
      • Anhui Provincial Hospital
  • China/Shanghai
    • Shanghai, China/Shanghai, China, 200126
      • Shanghai East Hospital
  • Shanghai
    • Shanghai, Shanghai, China
      • Shanghai Artemed Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LCAR-C18S Cells; Each subject will receive LCAR-C18S Cells	Biological: LCAR-C18S cells; Before treatment with LCAR-C18S cells, subjects will receive a conditioning regimen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
To determine the recommended dose of the phase Ⅱ trial of this cell therapy (RP2D)	To determine the recommended dose of the phase Ⅱ trial of this cell therapy (RP2D)	90 days post infusion
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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)
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)

Collaborators and Investigators

• Sponsor: Shanghai East Hospital
• Collaborators: Nanjing Legend Biotech Co.
• Investigators: Principal Investigator: Jin Li, MD, PhD, Shanghai East Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 21, 2020
• Primary Completion (Actual): July 17, 2023
• Study Completion (Actual): July 17, 2023

Study Registration Dates

• First Submitted: July 1, 2020
• First Submitted That Met QC Criteria: July 10, 2020
• First Posted (Actual): July 13, 2020

Study Record Updates

• Last Update Posted (Actual): August 15, 2023
• Last Update Submitted That Met QC Criteria: August 11, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: BM2L201910

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No