Abstract LB196: NOUS-PEV, a personalized cancer immunotherapy targeting neoantigens, induces long lasting, tumor infiltrating memory T cells
Authors: Bechter Oliver , D'Alise Anna Morena , Leoni Guido , Cotugno Gabriella , Siani Loredana , Vitale Rosa , Ruzza Valentino , Garzia Irene , Antonucci Laura , Micarelli Elisa , Gogov Sven , Capone Alessia , Martin-Liberal Juan , Calvo Emiliano , Moreno Victor , Symeonides Stefan , Scarselli Elisa 
Published: April 2023

Abstract
Personalized vaccines hold great promise to exert meaningful clinical efficacy, with durable tumor control maintained by a vaccine–induced memory response. NOUS–PEV is a personalized viral prime–boost cancer vaccine that expresses 60 patient–specific neoantigens identified by next generation sequencing (NGS) and selected with a proprietary algorithm VENUS (Leoni & D’Alise et al, Vaccines, 9, 2021). Administration is intramuscular, with a priming Great Ape Adenovirus (GAd) vaccination, followed by Modified Vaccinia Ankara (MVA) “boosts”, administered in combination with the PD–1 blocking antibody pembrolizumab in patients with metastatic malignant melanoma and non–small cell lung cancer. Data from the Part 1 dose–confirmation cohort of 3 patients demonstrated the combination of NOUS–PEV and pembrolizumab to be safe and well–tolerated, with early indications of efficacy and immunogenicity (Bechter, et al SITC 2022 Poster number: 706). Now in Part 2 extension–expansion cohorts, we present extended safety, immunogenicity and clinical data at 11 months median follow–up for 6 vaccinated melanoma patients. Tolerability remains good with no grade 3 or 4 vaccine related adverse events and activity encouraging, with 4 PRs, 1 SD and only 1 PD as best response. Immune responses were evaluated by ex–vivo interferon–gamma ELISpot on PBMC collected at baseline, post pembrolizumab, and post vaccination. Vaccine immunogenicity was demonstrated in all evaluable patients receiving the prime/boost regimen (n=4), with a mean of T cell response of ~ 650 IFN–γ spot forming cells (SFC) per million of PBMC (range 380–1,250 SFC/106) and with observed induction of both CD4 and CD8 T cell responses which lasted for at least 6 months. By analyzing the intratumoral TCR repertoire, we found increase of T cells by ~3 fold on average post treatment with NOUS–PEV in all evaluable patients (n=3), with expansion and diversification of intratumoral T cell clones. Vaccine–induced TCR clonotypes were found in on–treatment tumor biopsies of 2 vaccinated patients, providing the proof–of–concept for neoantigen induced T cells homing and infiltrating into the tumor. Overall, these data show that NOUS–PEV continues to be safe, and elicits a robust long lasting immune response and clinical activity.
Citation Format: Oliver Bechter, Anna Morena D'Alise, Guido Leoni, Gabriella Cotugno, Loredana Siani, Rosa Vitale, Valentino Ruzza, Irene Garzia, Laura Antonucci, Elisa Micarelli, Sven Gogov, Alessia Capone, Juan Martin-Liberal, Emiliano Calvo, Victor Moreno, Stefan Symeonides, Elisa Scarselli. NOUS-PEV, a personalized cancer immunotherapy targeting neoantigens, induces long lasting, tumor infiltrating memory T cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB196.