An open label, single/multiple dose exploratory clinical study to evaluate the safety, efficacy, and pharmacokinetics of autologous humanized anti-claudin18.2 chimeric antigen receptor T cell in advanced solid tumor.
This study is an open, single/multiple infusion, dose escalation/dose regimen finding study to assess the safety and pharmacokinetics of CAR-CLDN18.2 T cell therapy, and to obtain the preliminary efficacy results in subjects who have been diagnosed with advanced solid tumor with positive claudin 18.2 expression and failed to standard systemic treatment.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
134
Preconditioning with fludarabine, cyclophosphamide, based chemotherapy regimen at sub-clinical doses • Chimeric Antigen Receptor T Cells Targeting Claudin18.2
Chimeric Antigen Receptor T Cells Targeting Claudin18.2 with PD-1
First-line systemic therapy according to physician's choice
Department of GI Oncology, Peking University Cancer Hospital
Beijing, Beijing Municipality, China
The First Affiliated Hospital of Zhengzhou University
Zhengzhou, Henan, China
The First Affiliated Hospital , Zhejiang University School of Medicine
Hangzhou, Zhejiang, China
Dose-limiting toxicity (DLT)
Safety
Time frame: 28 days of single infusion
Maximum tolerated dose (MTD)
tolerability
Time frame: 28 days of single infusion
Pharmacokinetics (the number of cell copies and cell persistence duration in peripheral blood)
CAR-CLDN18.2 DNA in peripheral blood detected by q-PCR at each visit after infusion
Time frame: 26 weeks
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Adverse events occurring through 26 weeks and 12 months post infusion of CAR-CLDN18.2 T-Cell infusion, such as abnormalities or changes in laboratory examinations, physical examinations, vital signs, etc.
Time frame: 1 year
Antitumor efficacy-Progression-free survival (PFS)
The period from the day when the subject receives the infusion of cells to the first recorded tumor progression (whether treated or not) or death of any cause, which occurs first.
Time frame: 1 year
Antitumor efficacy-Duration of response (DOR)
The period from the first evaluation of CR or PR to the first evaluation of PD or death of any cause
Time frame: 1 year
Antitumor efficacy-Duration of disease control (DDC)
The period from the first evaluation of clinical benefit to the first evaluation of PD or any cause of death.
Time frame: 1 year
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Antitumor efficacy-Overall survival (OS)
The period from the first infusion to any cause of death
Time frame: 1 years
Antitumor efficacy-Objective response rate (ORR)
The number of cases in which tumor size is reduced to PR or CR / the total number of evaluable cases (%). In the event of PR or CR, the subjects should confirm it no less than 4 weeks after the first evaluation
Time frame: 1 year
Antitumor efficacy-Disease control rate (DCR)
The number of cases in which response are achieved from the start of cell infusion/the total number of evaluable cases (%).
Time frame: 1 year
Long term survival follow up
The period from the first infusion to any cause of death
Time frame: 15 years