Personalized neoantigen vaccine NEO-PV-01 with chemotherapy and anti-PD-1 as first-line treatment for non-squamous non-small cell lung cancer

Mark M. Awad, Ramaswamy Govindan, Kristen N. Balogh, David R. Spigel, Edward B. Garon, Meghan E. Bushway, Asaf Poran, Joong Hyuk Sheen, Victoria Kohler, Ekaterina Esaulova, John Srouji, Suchitra Ramesh, Rohit Vyasamneni, Binisha Karki, Tracey E. Sciuto, Himanshu Sethi, Jesse Z. Dong, Melissa A. Moles, Kelledy Manson, Michael S. RooneyZakaria S. Khondker, Mark DeMario, Richard B. Gaynor, Lakshmi Srinivasan

Research output: Contribution to journalArticlepeer-review

58 Scopus citations

Abstract

Neoantigens arising from mutations in tumor DNA provide targets for immune-based therapy. Here, we report the clinical and immune data from a Phase Ib clinical trial of a personalized neoantigen-vaccine NEO-PV-01 in combination with pemetrexed, carboplatin, and pembrolizumab as first-line therapy for advanced non-squamous non-small cell lung cancer (NSCLC). This analysis of 38 patients treated with the regimen demonstrated no treatment-related serious adverse events. Multiple parameters including baseline tumor immune infiltration and on-treatment circulating tumor DNA levels were highly correlated with clinical response. De novo neoantigen-specific CD4+ and CD8+ T cell responses were observed post-vaccination. Epitope spread to non-vaccinating neoantigens, including responses to KRAS G12C and G12V mutations, were detected post-vaccination. Neoantigen-specific CD4+ T cells generated post-vaccination revealed effector and cytotoxic phenotypes with increased CD4+ T cell infiltration in the post-vaccine tumor biopsy. Collectively, these data support the safety and immunogenicity of this regimen in advanced non-squamous NSCLC.

Original languageEnglish
Pages (from-to)1010-1026.e11
JournalCancer Cell
Volume40
Issue number9
DOIs
StatePublished - Sep 12 2022

Keywords

  • NEO-PV-01
  • cancer vaccine
  • immunotherapy
  • neoantigen vaccine
  • non-small cell lung cancer

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