This study is a single-center exploratory clinical trial. It is estimated that 9-24 subjects will be enrolled. The "3+3" dose escalation design is adopted. The main purpose is to evaluate the safety of RD133 in the treatment of subjects with relapsed or refractory MSLN-positive solid tumors and explore the Recommend phase II dose of RD133 in the treatment of patients with relapsed/refractory MSLN-positive solid tumors.
Leukapheresis procedure will be performed to manufacture RD133 chimeric antigen receptor (CAR) modified T cells. Bridging therapy is allowed between PBMC collection and lymphodepletion. Lymphodepletion with fludarabine and cyclophosphamide was performed for three consecutive days. After 1-day rest, subjects will receive a single dose infusion of RD133 at 1.0, 3.0, or 6.0x 10\^6 CAR+ T cells/Kg. Subjects will be followed in the study for a minimum of 2 years after RD133 infusion. Long-term follow-up for lentiviral vector safety will be followed for up to 15 years after RD133 infusion.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
24
The enhanced MSLN-CAR-T cell design of this study is obtained by co-infecting T cells with two lentiviral vectors. One lentiviral vector expresses CD19-CAR and tEGFR molecular safety switch, and the other lentiviral vector expresses MSLN- CAR and dnTGFβRII receptors. dnTGFβRII receptor without intracellular signal is used to resist the inhibition of T cell function by the immune microenvironment of tumor tissue. In addition, for the safety of CAR-T cell application in vivo, tEGFR is used in the CAR design as a molecular safety switch for CAR-T cells.
The First Affiliated Hospital with Nanjing Medical University
Nanjing, Jiangsu, China
RECRUITINGType and incidence of dose-limiting toxicity (DLT) by dose group
The number and percentage of DLT in each dose group
Time frame: 2 years post infusion
Type and incidence of adverse events (AEs) and serious adverse events (SAEs) by dose group
Calculate type and incidence of adverse events (AE), serious adverse event (SAE), including those happened after lymphodepletion and after infusion, those related to study drug and lymphodepletion, or those that led to withdrawal from the study. They will also be aggregated by systematic organ classification (SOC), preferred term (PT), and severity.
Time frame: 2 years post infusion
Number of Participants With Adverse Events
An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product
Time frame: 2 years post infusion
Objective response rate (ORR)
The proportion of subjects who have achieved best response of partial response (PR) or complete response (CR) according to the RECIST V1.1 evaluation criteria 3 months after RD133 cell infusion.
Time frame: 2 years post infusion
Duration of response (DoR)
The time from the date of initial documentation of CR/PR after RD133 cell infusion to the date of progressive disease or death due to the disease studied
Time frame: 2 years post infusion
Time to response (TTR)
The time from the date of RD133 cell infusion to the first efficacy evaluation of partial response (PR) or complete response (CR)
Time frame: 2 years post infusion
Disease control rate (DCR)
The proportion of subjects with best efficacy assessment of complete response (CR), partial response (PR) or stable disease (SD)
Time frame: 2 years post infusion
Progression-free survival (PFS)
The time from the date of RD133 cell infusion to the date of initial documentation of progressive disease/relapse or death from any cause
Time frame: 2 years post infusion
Overall survival (OS)
The time from the date of RD133 cell infusion to the date of death
Time frame: 2 years post infusion
Transgene Levels of RD133
Changes of virus vector copy number (VCN) in peripheral blood and tumor tissue (if any) after RD133 infusion
Time frame: 2 years post infusion
Chimeric Antigen Receptor T (CAR-T) Positive Cell Concentration
Changes of CAR T cell concentration in peripheral blood and tumor tissue (if any) after RD133 infusion
Time frame: 2 years post infusion
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