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
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Solid Tumors, Adult
- Sponsor
- Shanghai East Hospital
- Enrollment
- 34
- Locations
- 3
- Primary Endpoint
- Dose-limiting toxicity (DLT) and incidence, severity, and type of treatment-emergent adverse events (TEAEs),Safety
- Status
- Terminated
- Last Updated
- 2 years ago
Overview
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
Investigators
Jin Li
Director
Shanghai East Hospital
Eligibility Criteria
Inclusion Criteria
- •The subjects have been fully informed of the possible risks and benefits of participating in the study and have signed the informed consent form;
- •Age 18-70 years;
- •Immunohistochemistry of tumor tissue samples indicates Claudin18.2 positive ;
- •Recurrent or metastatic advanced solid tumors (including advanced gastric cancers and non-gastric cancers) and have been failed to prior lines of systemic treatment
- •According to the RECIST v1.1, at least one measuable tumor lesion;
- •ECOG performance status score of 0-1;
- •Expected survival ≥ 3 months;
- •Subjects should have adequate organ functions before screening and treatment.
- •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
- •Previous CAR-T cell therapy or other cell therapies or therapeutic tumor vaccination against any target;
- •Any previous therapy targeting Claudin18.2;
- •Prior antitumor therapy with insufficient washout period;
- •Pregnant or lactating women;
- •Brain metastases with central nervous system symptoms;
- •Uncontrolled diabetes;
- •Oxygen is required to maintain adequate blood oxygen saturation;
- •Gastric perforation, pyloric obstruction, complete biliary obstruction, complete or incomplete intestinal obstruction requiring clinical intervention, or pleural effusion or peritoneal effusion requiring clinical intervention;
- •Clinically significant liver disorders (including liver cirrhosis, active viral hepatitis or other hepatitis);
- •HIV, Treponema pallidum or HCV serologically positive;
Outcomes
Primary Outcomes
Dose-limiting toxicity (DLT) and incidence, severity, and type of treatment-emergent adverse events (TEAEs),Safety
Time Frame: 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)
Time Frame: 90 days post infusion
To determine the recommended dose of the phase Ⅱ trial of this cell therapy (RP2D)
Pharmacokinetic (PK) parameters
Time Frame: 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 Outcomes
- Overall response rate (ORR) after administration(Minimum 2 years after LCAR-C18S infusion (Day 1))
- Overall Survival (OS) after administration(Minimum 2 years after LCAR-C18S infusion (Day 1))
- Progress Free Survival (PFS) after administration(Minimum 2 years after LCAR-C18S infusion (Day 1))