A phase I study of the safety and immunogenicity of a multi-peptide personalized genomic vaccine in the adjuvant treatment of solid tumors and hematological malignancies.

person Ana Blazquez Icahn School of Medicine at Mount Sinai, New York, NY info_outline Ana Blazquez, Alex Rubinsteyn, Julia Kodysh, John Patrick Finnigan, Thomas Urban Marron, Marcia Meseck, Timothy O'Donnell, Jeffrey Hammerbacher, Michael J. Donovan, Milind Mahajan, Brett A. Miles, Hanna Irie, Amy Tiersten, Ashutosh Tewari, Samir S. Parekh, Sujit Nair, Matt D. Galsky, Eric E. Schadt, Philip Adam Friedlander, Nina Bhardwaj

Authors person Ana Blazquez Icahn School of Medicine at Mount Sinai, New York, NY info_outline Ana Blazquez, Alex Rubinsteyn, Julia Kodysh, John Patrick Finnigan, Thomas Urban Marron, Marcia Meseck, Timothy O'Donnell, Jeffrey Hammerbacher, Michael J. Donovan, Milind Mahajan, Brett A. Miles, Hanna Irie, Amy Tiersten, Ashutosh Tewari, Samir S. Parekh, Sujit Nair, Matt D. Galsky, Eric E. Schadt, Philip Adam Friedlander, Nina Bhardwaj Organizations Icahn School of Medicine at Mount Sinai, New York, NY, Icah School of Medicine at Mount Sinai, New York, NY, Mount Sinai Hospital, New York, NY, Mount Sinai, New York, NY, Department of Otolaryngology, Mount Sinai Medical Center, New York, NY, Albert Einstein College of Medicine, Bronx, NY, Department of Medicine, Icahn School of Medicine at Mount Sinai, Tisch Cancer Institute, New York, NY, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY Abstract Disclosures Research Funding Other Background: Mutation-derived tumor antigens (MTAs) arise as a direct result of somatic variations that occur during carcinogenesis and can be characterized via genetic sequencing and used to identify MTAs. We developed a platform for a fully-personalized MTA-based vaccine in the adjuvant treatment of solid and hematological malignancies. Methods: This is a single-arm, open label, proof-of-concept phase I study designed to test the safety and immunogenicity of Personalized Genomic Vaccine 001 (PGV001) that targets up to 10 predicted personal tumor neoantigens based on patient’s HLA profile (ClinicalTrials.gov: NCT02721043). Results: Patients who completed vaccination with PGV001_002 (head and neck squamous cell cancer) received 10 doses of vaccine comprising 10 long peptides (LP) combined with poly-ICLC (toll-like receptor-3 agonist) intradermally. Vaccine-induced T-cell responses were determined at weeks 0 and 27 (before and after treatment, respectively), ex vivo by interferon (IFN)-g enzyme-linked immunospot assay and after expansion by intracellular cytokine staining. Overlapping 15-mer peptides (OLPs) spanning the entirety of each LP and 9-10-mer peptides corresponding to each predicted class I epitope (Min) were pooled. Ex vivo responses to these peptide pools were undetectable at week 0 but were evident at week 27 against 2 OLPs out of 10 (20%) and in 5 Min out of 10 (50%). After in vitro expansion, neoantigen-specific CD4 + and CD8 + T-cell responses were found in 5 out of 10 pooled peptides (50%). 7 out of 10 (70%) epitopes elicited polyfunctional T-cell responses (secretion of INF-g, TNF-a, and/or IL-2) from either CD4 + or CD8 + T cells. Conclusions: The PGV001 vaccine in our first patient showed both safety and immunogenicity, eliciting CD4 + and CD8 + responses to the vaccine peptides. As we enroll additional patients in this clinical trial, and perform deeper phenotyping of their tumor-reactive T cells, we will learn the determinants necessary for the successful generation of MTA-based vaccines, while informing future immunotherapeutic approaches and rational combinations. Clinical trial information: NCT02721043