Clinical trial NCT04467853: A Clinical Study to Evaluate CAR-T Cell-based Medicinal Product in the Treatment of Advanced Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Solid Tumors, Adult
Lead sponsor: Shanghai East Hospital
Sponsor class: OTHER
Collaborators: name: Nanjing Legend Biotech Co.
First posted: 2020-07-13
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Eligibility criteria: 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.

Primary outcomes:
measure: Dose-limiting toxicity (DLT) and incidence, severity, and type of treatment-emergent adverse events (TEAEs),Safety
timeFrame: Minimum 2 years after LCAR-C18S infusion (Day 1)
measure: To determine the recommended dose of the phase Ⅱ trial of this cell therapy (RP2D)
timeFrame: 90 days post infusion
measure: Pharmacokinetic (PK) parameters
timeFrame: Minimum 2 years after LCAR-C18S infusion (Day 1)
Secondary outcomes:
measure: Overall response rate (ORR) after administration
timeFrame: Minimum 2 years after LCAR-C18S infusion (Day 1)
measure: Progress Free Survival (PFS) after administration
timeFrame: Minimum 2 years after LCAR-C18S infusion (Day 1)
measure: Overall Survival (OS) after administration
timeFrame: Minimum 2 years after LCAR-C18S infusion (Day 1)
Other outcomes:
Locations:
city: Hefei
country: China
facility: Anhui Provincial Hospital
state: Anhui
city: Shanghai
country: China
facility: Shanghai East Hospital
state: China/Shanghai
city: Shanghai
country: China
facility: Shanghai Artemed Hospital
state: Shanghai
Study officials:
affiliation: Shanghai East Hospital
name: Jin Li, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: