Background: Mutation-derived tumor antigens (MTAs) arise as a result of somatic mutations, such as nucleotide substitutions and small insertions/deletions. MTAs can serve as specific targets for antitumor therapy, including neoantigen vaccines. The goal of neoantigen vaccination is to help prime T cells to recognize such tumor-specific mutations. Here we describe a phase I trial testing a personalized genomic vaccine (PGV-001) in multiple histologies in the adjuvant setting (NCT02721043).

Methods: This trial included patients with histologic diagnosis of solid malignancies or multiple myeloma with a >30% risk of recurrence but no measurable disease at the time of first vaccination. For each patient, HLA typing was performed, and the patient's tumor and germline DNA and tumor RNA were sequenced. Mutated peptides containing predicted neoantigens were selected using the OpenVax computational pipeline, which prioritizes somatic mutations by expression of the mutant allele in the tumor RNA and predicted MHC class I epitope binding for the patient's HLA type. A maximum of 10 peptides was included in each patient's personalized vaccine. The vaccine was administered over the course of 6 months, given in combination with poly-ICLC as the adjuvant. The primary objectives were to determine safety and tolerability, feasibility, and immunogenicity of the PGV-001 neoantigen vaccine.

Results: The neoantigen vaccine was successfully administered to 13 patients, spanning 5 different tumor types. For each patient, an average of 1730 somatic mutations were identified (range 521-5106), of which 349 were coding variants (range 68-1493), 88 were coding and expressed in the tumor RNA (range 9-233), and 71 were coding, expressed and resulted in predicted MHC class I ligands (range 8-193). The urothelial, head & neck, and lung tumors resulted in larger numbers of predicted neoantigens than in the cases of multiple myeloma or breast tumors. Despite this difference, each of the 13 patient tumor samples showed enough of a neoantigen load to enable vaccination. We have also initiated analysis of immunogenicity, and early reports demonstrate neoantigen-specific CD4 and CD8 T-cell responses.

Conclusions: The PGV-001 personalized neoantigen vaccine was successfully administered to 13 patients, where each patient's neoantigen load was adequate for vaccine synthesis. While we have demonstrated the computational feasibility of identification of neoantigens for inclusion in the PGV-001 genomic vaccine, clinical outcomes will be reported separately.

Citation Format: Julia Kodysh, Thomas Marron, Alex Rubinsteyn, Tim O'Donnell, John Finnigan, Ana Blazquez, Mansi Saxena, Marcia Meseck, Philip Friedlander, Nina Bhardwaj. PGV-001: A phase I trial of a multipeptide personalized neoantigen vaccine in the adjuvant setting [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT173.