Ignite Creation Date:
2024-05-06 @ 6:40 PM
Last Modification Date:
2024-10-26 @ 2:52 PM
Study NCT ID:
NCT05743595
Status:
RECRUITING
Last Update Posted:
2024-07-05
First Post:
2023-02-14
Brief Title:
Neoantigen-based Personalized DNA Vaccine With Retifanlimab PD-1 Blockade Therapy in Patients With Newly Diagnosed Unmethylated Glioblastoma
Sponsor:
Washington University School of Medicine
Organization:
Washington University School of Medicine
Study Overview
Official Title:
A Pilot Study to Assess the Safety and Immunogenicity of a Neoantigen-based Personalized DNA Vaccine With Retifanlimab PD-1 Blockade Therapy in Patients With Newly Diagnosed Unmethylated Glioblastoma
Status:
RECRUITING
Status Verified Date:
2024-07
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:
This is a single institution open-label multi-arm phase I study assessing the safety and immunogenicity of a personalized neoantigen-based personalized DNA vaccine combined with PD-1 blockade therapy in subjects with newly diagnosed MGMT promoter unmethylated glioblastoma GBM
Immune checkpoint blockade specifically those targeting the PD-1PD-L1 pathways has shown efficacy in multiple solid and hematologic malignancies Furthermore as has been demonstrated in metastatic melanoma combining PD-1PD-L1 blockade with other immune checkpoint inhibitors has shown improved objective response rates though there is a significant increase in serious immune-related adverse events As such current trials are exploring different doses administration schedules and immune checkpoint agents One alternative approach however is to introduce a tumor-directed therapy such as a personalized neoantigen vaccine combined with these immune modulating agents ie immune checkpoint blocking antibodies to maximize the tumor-specific response but minimize the toxicity associated with increasing non-specific systemic immune activation by generating a potent and focused neoantigen specific immune response
This study will test the hypothesis that a personalized neoantigen DNA vaccine in combination with concurrent administration of immune checkpoint blockade therapy will enhance the magnitude and breadth of neoantigen-specific T cell responses while maintaining an acceptable safety profile The overall goal of this study is to identify the optimal vaccine plus adjuvant platform that can be tested in a subsequent phase II study to determine the efficacy of a personalized neoantigen vaccine approach in patients with GBM
Immune checkpoint blockade specifically those targeting the PD-1PD-L1 pathways has shown efficacy in multiple solid and hematologic malignancies Furthermore as has been demonstrated in metastatic melanoma combining PD-1PD-L1 blockade with other immune checkpoint inhibitors has shown improved objective response rates though there is a significant increase in serious immune-related adverse events As such current trials are exploring different doses administration schedules and immune checkpoint agents One alternative approach however is to introduce a tumor-directed therapy such as a personalized neoantigen vaccine combined with these immune modulating agents ie immune checkpoint blocking antibodies to maximize the tumor-specific response but minimize the toxicity associated with increasing non-specific systemic immune activation by generating a potent and focused neoantigen specific immune response
This study will test the hypothesis that a personalized neoantigen DNA vaccine in combination with concurrent administration of immune checkpoint blockade therapy will enhance the magnitude and breadth of neoantigen-specific T cell responses while maintaining an acceptable safety profile The overall goal of this study is to identify the optimal vaccine plus adjuvant platform that can be tested in a subsequent phase II study to determine the efficacy of a personalized neoantigen vaccine approach in patients with GBM
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
True
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None