Neoantigen-based Personalized DNA Vaccine With Retifanlimab PD-1 Blockade Therapy in Patients With Newly Diagnosed, Unmethylated Glioblastoma

Conditions

• Unmethylated Glioblastoma

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Personalized Neoantigen DNA vaccine — BIOLOGICAL
  The sites of immunization may be rotated for each of the immunizations.
• Retifanlimab — BIOLOGICAL
  Retifanlimab will be supplied by Incyte.
• TDS-IM v 2.0 electroporation device — DEVICE
  Each DNA vaccination will be 1 mL vaccine administered intramuscularly using an integrated electroporation administration system

Study Details

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-1/PD-L1 pathways, has shown efficacy in multiple solid and hematologic malignancies. Furthermore, as has been demonstrated in metastatic melanoma, combining PD-1/PD-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 (i.e. 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.

Key Dates

Start date

Oct 27, 2023

Status verified

May 2026

Primary completion

Apr 7, 2026

Completion

Mar 9, 2029

Study Design

Enrollment

27 participants (actual)

Allocation

NON_RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Arms

• Experimental: Cohort A: Personalized neoantigen DNA vaccine + retifanlimab
  * Cohort A will receive the personalized neoantigen DNA vaccine via electroporation mediated IM injection alone during the first two priming doses, then concurrently with retifanlimab during the subsequent boosting doses (Doses 3 through 6) * The personalized neoantigen DNA vaccine will be given once every 28 days for up to 6 doses. Retifanlimab is given at a fixed dose of 500 mg every 28 days. * Patients may receive up to 6 doses of personalized neoantigen DNA vaccine and up to 12 months total of retifanlimab
• Experimental: Cohort B: Personalized neoantigen DNA vaccine + retifanlimab
  * Cohort B will receive the personalized neoantigen DNA vaccine via electroporation mediated IM injection plus concurrent retifanlimab beginning with Dose 1 and continuing for a total of 6 doses. * The personalized neoantigen DNA vaccine will be given once every 28 days for up to 6 doses. Retifanlimab is given at a fixed dose of 500 mg every 28 days. * Patients may receive up to 6 doses of personalized neoantigen DNA vaccine and up to 12 months total of retifanlimab

Primary Outcome Measure

Safety as measured by treatment-related dose-limiting toxicity (DLT) rate related to vaccination [ Time Frame: Through completion of DLT observation period for all enrolled subjects (estimated to be up to 12 months and 87 days) ]

Locations (1)

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