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

Neoantigens arising from mutations in tumor DNA provide targets for immune-based therapy. Here, we report the clinical and immune data from a Phase lb 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.

Automated summary

Neoantigens derived from tumor DNA mutations can be targeted for immune-based therapy. This study presents the clinical and immune data from a Phase lb clinical trial investigating a personalized neoantigen vaccine NEO-PV-01 in combination with other drugs for first-line treatment of advanced non-squamous non-small cell lung cancer (NSCLC). The analysis of 38 patients showed that this regimen is safe and has immunogenicity.