Personalized DNA and Peptide Vaccines Elicit Neoantigen-Driven T-Cell Responses in Pancreatic Cancer

This study provides data from two phase I clinical trials (NCT03122106, NCT03956056) that evaluated the safety and immunogenicity of DNA-based and synthetic long peptide personalized cancer vaccines. Exome and RNA sequence data were used to identify somatic mutations, predict neoantigens, and design personalized cancer vaccines. Immune monitoring was performed on each patient to assess neoantigen specific T-cell responses.]]>
Complete Inclusion and Exclusion can be found in the associated clinical trials records at clinicaltrials.gov for NCT03122106 and NCT03956056. Both trials involved adult pancreatic adenocarcinoma. A partial summary of the Inclusion/Exclusion criteria are as follows: InclusionAdults (≥18 years) with histologically or cytologically confirmed pancreatic adenocarcinoma (mixed histology allowed if adenocarcinoma predominates).Completed R0 or R1 surgical resection.Adequate tumor material available (≥30% tumor cellularity, sufficient FFPE tissue).ECOG performance status ≤2 and life expectancy >12 months.Adequate bone marrow, hepatic, renal, and coagulation function.Ability to provide written informed consent.ExclusionNon-adenocarcinoma pancreatic malignancies (neuroendocrine, duodenal, ampullary).Prior neoadjuvant chemotherapy.Evidence of recurrent or metastatic disease prior to first vaccination.Active or recent (≤3 years) malignancy, with limited exceptions.Clinically significant comorbidities or psychiatric/social conditions limiting compliance.Autoimmune disease requiring immunosuppression or immunosuppressive therapy beyond limited exceptions.Pregnancy or breastfeeding.Known HIV-positive status.History of severe allergic reactions to vaccines (or related agents).]]>
Overview of the aims of each clinical trial related to this data submission:NCT03122106. A phase 1 open-label study to evaluate the safety and immunogenicity of a neoantigen DNA vaccine strategy in pancreatic cancer patients following surgical resection and adjuvant chemotherapy. The neoantigen DNA vaccines will incorporate prioritized neoantigens and personalized mesothelin epitopes and will be administered with an electroporation device. The hypothesis of this study is that neoantigen DNA vaccines will be safe and capable of generating measurable neoantigen-specific CD4 and CD8 T cell responses.NCT03956056. 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.]]>