Ignite Creation Date:
2024-05-06 @ 6:31 PM
Last Modification Date:
2024-10-26 @ 2:49 PM
Study NCT ID:
NCT05693844
Status:
RECRUITING
Last Update Posted:
2024-05-10
First Post:
2022-12-27
Brief Title:
Pan-T Booster Co-expressing MSLN CAR T Cell Therapy in AdvancedMetastatic Solid Tumors
Sponsor:
Chinese PLA General Hospital
Organization:
Chinese PLA General Hospital
Study Overview
Official Title:
Phase III Study of Pan-T Booster Co-expressing MSLN CAR T Cell Therapy in AdvancedMetastatic Solid Tumors
Status:
RECRUITING
Status Verified Date:
2024-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
In preclinical study investigators have demonstrated that the newly developed pan-T booster harbouring CD40 agonist and one T cell costimulator agonist co-expressing MSLN CAR T cell possess more powerful antitumor activity than previously reported MSLN-CAR T cells In this clinical trial enrolled patients receive an initial dose of pan-T booster co-expressing MSLN CAR T cells at 1106 cellskg based on the basic principle of dose escalation design in order to evaluate the safety feasibility pharmacokineticspharmacodynamics and efficacy of pan-T booster co-expressing MSLN CAR T cell in vivo
Detailed Description:
In this study investigators have developed a novel CAR T cell system targeting mesothelin MSLN antigen termed as Pan-T booster harbouring CD40 agonist and one T cell costimulator agonist co-expressing MSLN CAR T cell Preclinical study demonstrated that this novel pan-T booster co-expressing MSLN CAR T cell possess more powerful antitumor activity than previously reported MSLN-CAR T cells In this clinical trial enrolled patients receive an initial dose of pan-T booster co-expressing MSLN CAR T cells at 1106 cellskg based on the basic principle of dose escalation design in order to evaluate the safety feasibility pharmacokineticspharmacodynamics and efficacy of pan-T booster co-expressing MSLN CAR T cell in vivo The level of CAR-T cell expansion and the duration of expansion are important determining factors for subsequent dose escalation infusions 3106 cellskg and 6106 cellskg Repeated infusion immune checkpoint inhibitor such as anti-PD1PD-L1 or local therapy radiotherapy are allowed when patients achieve clinical benefit and the level of CAR-T cell expansion declines to low level
In the 3 patients receiving the first dose treatment we observed high levels of expansion of both total T cells and CAR T cells in the PB after CAR T cell infusion CAR T 300 per microliter total T cells reaching 10 times the number of CAR T cells one patient experienced a grade 2 pulmonary toxicity and transient liver dysfunction during the CAR T cell expansion period infusion 14 days later transient marked enlargement of the spleen and required to be treated with glucocorticoids and ruxolitinib to control T cell toxicity Efficacy monitoring showed that some target lesion clearance or reduction could be achieved within 2-4 weeks after CAR T infusion Based on these observations it was concluded that low-dose CAR T infusion CART cells 1106 cellskg could achieve the sufficient level of CAR T cell expansion and the initially planned CAR T dose escalation was dispensable Subsequent patients after May 10th 2024 will all be treated using 1106 cellskg dose
In the 3 patients receiving the first dose treatment we observed high levels of expansion of both total T cells and CAR T cells in the PB after CAR T cell infusion CAR T 300 per microliter total T cells reaching 10 times the number of CAR T cells one patient experienced a grade 2 pulmonary toxicity and transient liver dysfunction during the CAR T cell expansion period infusion 14 days later transient marked enlargement of the spleen and required to be treated with glucocorticoids and ruxolitinib to control T cell toxicity Efficacy monitoring showed that some target lesion clearance or reduction could be achieved within 2-4 weeks after CAR T infusion Based on these observations it was concluded that low-dose CAR T infusion CART cells 1106 cellskg could achieve the sufficient level of CAR T cell expansion and the initially planned CAR T dose escalation was dispensable Subsequent patients after May 10th 2024 will all be treated using 1106 cellskg dose
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None