This is a single arm, open-label, dose escalation clinical study to evaluate the safety and tolerability of fast autologous mesothelin (MSLN)-targeted chimeric antigen receptor (MSLN-CAR) T cells secreting PD-1 nanobodies in patients with solid tumors.
The main aim of this study is to determin the safety and efficacy of BZT2312 in patients with solid tumors. BZT2312 is an autologous mesothelin (MSLN)-targeted chimeric antigen receptor (MSLN-CAR) T cells secreting PD-1 nanobodies. This study comprises of a screening phase(less than or equal to 28 days prior to apheresis) followed by apheresis(will occur upon enroiiment); Apheresis phase(less than or equal to 10 days prior to infusion ) followed by lymphodepletion. lymphodepletion phase (from day -5 to day -3) followed by infusion.Treatment Phase including infusion of BZT2312 on Day0 and then post-infusion assessments from Day1 to Day 28; and a Post-treatment Phase(Day 29 and up to end of the study). Efficacy will be explored to assessed and safety will be closely monitored during the study.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
12
Subjects will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) for the production of Fast CAR T cells. During Fast CAR T cells production, subjects will receive cyclophosphamide and fludarabine for the purpose of lymphocytes depletion. After lymphodepletion, subjects will receive one dose treatment with Fast CAR T cells by intravenous (IV) injection.
Shanghai Mengchao Cancer Hospital
Shanghai, Shanghai Municipality, China
RECRUITINGDose-limiting toxicity(DLT)
Safety
Time frame: 28 days
Maximum tolerated dose (MTD)
Tolerability
Time frame: 28 days
Objective response rate (ORR)
Clinical response will be assessed by RECIST 1.1
Time frame: Month 12
Progression-free survival (PFS)
PFS of patients receiving Fast CAR T cells
Time frame: Month 12
Overall survival (OS)
OS of patients receiving Fast CAR T cells
Time frame: Month 12
Peak Plasma Concentration (Cmax)
Pharmacokinetics (PK)
Time frame: Month 12
AUC
Pharmacokinetics (PK)
Time frame: Month 12
Pharmacodynamics (PD)
D of IL-2, IL-4, IL-6, IL-8, IL-10, IL-15, IFN-γ, TNF-α and MCP1 will be analysed after CAR T cell infusion
Time frame: Day 28
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