Neoantigen peptide vaccine(Washington University School of Medicine)

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.

This is a randomized phase 1 clinical trial to evaluate the safety of an optimized neoantigen synthetic long peptide (SLP) vaccines in pancreatic cancer patients following neoadjuvant chemotherapy. The neoantigen SLP vaccines will incorporate prioritized neoantigens and will be co-administered with poly-ICLC. Patients will be randomized to one of two arms: Arm 1 (neoantigen vaccine following neoadjuvant chemotherapy and surgery) or Arm 2 (neoantigen vaccine following neoadjuvant chemotherapy in the window prior to surgery).
Those who are ineligible for vaccine administration including those whose disease progresses or recurs during neoadjuvant chemo or who are otherwise unable to complete surgical resection but who had a personalized neoantigen vaccine manufactured, or significant progress has been made as determined by treating physician, are permitted to receive vaccine injections on study.