Awad et al. demonstrated that a personalized neoantigen vaccine, NEO-PV-01, in combination with anti-PD-1 and chemo as first-line therapy for advanced non-squamous NSCLC was well tolerated, without any serious treatment-related adverse events. Pre-treatment T cell infiltration into the TME, HLA class-II gene expression, and TCR diversity correlated with clinical response. Post-vaccine tumor biopsies showed increase in CD4+ T cell infiltration with effector and cytotoxic phenotypes. NEO-PV-01 combination therapy induced neoepitope-specific, persistent, and cytotoxic T cell responses, along with non-vaccinated epitope spread to KRAS and other mutations.
Contributed by Shishir Pant
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.