This is a phase 1 open-label study to evaluate the safety and immunogenicity of a neoantigen peptide vaccine strategy in pancreatic cancer patients following surgical resection and adjuvant chemotherapy. The neoantigen peptide vaccines will incorporate prioritized neoantigens and personalized mesothelin epitopes and will be co-administered with poly-ICLC. The hypothesis of this study is that neoantigen peptide vaccines will be safe and capable of generating measurable neoantigen-specific CD4 and CD8 T cell responses.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
12
• Each pool of vaccine study drug + poly IC:LC will be administered to one of the four limbs (A - Right Arm, B - Left Arm, C - Right Leg, D - Left Leg) by subcutaneous (SC) injection.
• Each pool of vaccine study drug + poly IC:LC will be administered to one of the four limbs (A - Right Arm, B - Left Arm, C - Right Leg, D - Left Leg) by subcutaneous (SC) injection.
-Baseline, day 1, day 22, day 50, day 78, week 25, and week 73
Washington University School of Medicine
St Louis, Missouri, United States
Safety of Neoantigen Peptide Vaccine as Measured by the Number of Serious Adverse Events
-Toxicity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events v5.0.
Time frame: Through 30 days following completion of treatment (median follow-up of 107 days, full range of 88-157 days)
Number of Participants With Immune Response as Measured by ELISPOT Analysis
The ELISpot assay was performed after in vitro culture of patient PBMC with neoantigen peptide for \~12 days. The number of spot-forming T cells, a surrogate for the number of neoantigen-specific T cells, was determined after neoantigen peptide re-stimulation for the duration of the assay (48 hours) and compared to that of control cells that were not re-stimulated with neoantigen during the assay. Independent t tests between pre- and post-vaccination PBMCs were performed.
Time frame: Baseline through week 52
Number of Participants With Immune Response as Measured by Multiparametric Flow Cytometry (CD4)
Multiparametric flow cytometry was performed as a second readout to characterize the neoantigen-specific T cell response. Markers included CD4, CD8, IFNγ, and a viability marker. After culture, as described above, T cells were stimulated overnight with/without neoantigen and stained with fluorescent antibodies specific for the various markers. Data were analyzed by comparing, between pre- and post-vaccination PBMCs, the percent ratio of IFNγ+ CD4/CD8 cells with neoantigen stimulation over those without stimulation; a \>2-fold increase in response after vaccination was considered positive.
Time frame: Baseline through week 52
Number of Participants With Immune Response as Measured by Multiparametric Flow Cytometry (CD8)
Multiparametric flow cytometry was performed as a second readout to characterize the neoantigen-specific T cell response. Markers included CD4, CD8, IFNγ, and a viability marker. After culture, as described above, T cells were stimulated overnight with/without neoantigen and stained with fluorescent antibodies specific for the various markers. Data were analyzed by comparing, between pre- and post-vaccination PBMCs, the percent ratio of IFNγ+ CD4/CD8 cells with neoantigen stimulation over those without stimulation; a \>2-fold increase in response after vaccination was considered positive.
Time frame: Baseline through week 52
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