The goal of this exploratory clinical trial is to evaluate the safety and efficacy of human anti-human epidermal growth factor receptor 2(HER2) Chimeric antigen receptor macrophage cells (CAR-M) in advanced HER2+ gastric cancer. Participants will mobilize bone marrow stem cells and engineer autologous macrophages to express Chimeric antigen receptor (CAR), and CAR-M will be infused intraperitoneally back into the patient for systemic anti-tumor effects.
The standard approach for managing advanced peritoneal metastatic gastric cancer typically involves systemic administration of antitumor drugs. In the case of HER2-positive gastric cancer patients, a combination of trastuzumab, platinum, and fluorouracil chemotherapeutic agents is commonly employed. Nevertheless, conventional therapy encounters obstacles stemming from tumor heterogeneity and the intricate microenvironment. The self-developed humanized anti-HER2 chimeric antigen receptor macrophage (human anti-HER2 CAR-M) uses an adenoviral vector system to genetically engineer autologous macrophages to express CAR molecules containing single-chain antibodies, which specifically bind to human HER2 antigens to recognize and kill tumor cells. Cell and animal experiments as well as preclinical trials showed that anti-human HER2 CAR M cells have significant anti-tumor efficacy and good safety. This study can provide abundant clinical data for the safety and feasibility of CAR macrophage therapy for solid tumors, and promote the progress of CAR macrophage therapy for solid tumors.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
9
The human anti-HER2 chimeric antigen receptor macrophages (anti-HER2 CAR-M cells) independently developed use adenoviral vector system to genetically engineer autologous macrophages to express CAR molecules containing single-chain antibodies, which specifically bind to the human HER2 antigen to recognize and kill tumor cells.
Affiliated Hangzhou Cancer Hospital, Zhejiang University School of Medicine
Hangzhou, Zhejiang, China
Adverse effects
Collect information on the type, frequency, and severity of adverse events.Identify and grade adverse events following CTCAE 5.0 criteria.
Time frame: The evaluation was conducted within 28 days of administration, with a total of 30 recording points
Time to Sustained Remission (DOR)
Solid tumor efficacy was assessed following the RECIST 1.1 criteria, calculating the time from first onset of efficacy (i.e., complete remission (CR) or partial remission (PR)), to earliest disease progression or death.
Time frame: 1 month, 2 months, 3 months, 6 months, 9 months, 12 months, 18 months, 24 months post-infusion.
Overall response rate (ORR)
Solid tumor efficacy was assessed following RECIST 1.1 criteria, and the proportion of subjects in complete or partial remission was calculated.
Time frame: Initiation of the first evaluation of the tumor as CR or PR to the beginning of the -th evaluation as progressive disease (PD) or death from any cause.
Disease Control Rate (DCR)
The RECIST 1.1 criteria were followed to assess the efficacy of solid tumors, and DCR was defined as the number of cases that achieved remission (CR+PR) and stable disease (SD) after treatment as a percentage of the number of evaluable cases.
Time frame: Assessed every month, up to 3 months.
Progression-free survival (PFS)
Solid tumor efficacy was assessed following the RECIST 1.1 criteria by calculating the time between infusion and the first record of disease progression or death.
Time frame: From date of administration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
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Overall Survival (OS)
Calculation of time from infusion to death from any cause.
Time frame: From date of randomization until the date of death from any cause, assessed up to 100 months