Solid Tumors, Adult
Conditions
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
Interventions
BIOLOGICALLCAR-C18S cells
Before treatment with LCAR-C18S cells, subjects will receive a conditioning regimen
Sponsors
Nanjing Legend Biotech Co.
Shanghai East Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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. |
Countries
China
Outcome results
None listed