Cell
Volume 183, Issue 2, 15 October 2020, Pages 347-362.e24
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Article
A Phase Ib Trial of Personalized Neoantigen Therapy Plus Anti-PD-1 in Patients with Advanced Melanoma, Non-small Cell Lung Cancer, or Bladder Cancer

https://doi.org/10.1016/j.cell.2020.08.053Get rights and content
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Highlights

  • The personalized neoantigen vaccine Neo-PV-01 plus nivolumab is feasible and safe

  • NEO-PV-01 plus nivolumab stimulates durable neoantigen-specific T cell reactivity

  • NEO-PV-01-specific T cells have cytotoxic potential and can traffic to the tumor

  • NEO-PV-01 induces epitope spreading consistent with vaccine-mediated tumor cytotoxicity

Summary

Neoantigens arise from mutations in cancer cells and are important targets of T cell-mediated anti-tumor immunity. Here, we report the first open-label, phase Ib clinical trial of a personalized neoantigen-based vaccine, NEO-PV-01, in combination with PD-1 blockade in patients with advanced melanoma, non-small cell lung cancer, or bladder cancer. This analysis of 82 patients demonstrated that the regimen was safe, with no treatment-related serious adverse events observed. De novo neoantigen-specific CD4+ and CD8+ T cell responses were observed post-vaccination in all of the patients. The vaccine-induced T cells had a cytotoxic phenotype and were capable of trafficking to the tumor and mediating cell killing. In addition, epitope spread to neoantigens not included in the vaccine was detected post-vaccination. These data support the safety and immunogenicity of this regimen in patients with advanced solid tumors (Clinicaltrials.gov: NCT02897765).

Keywords

immunotherapy
epitope spread
metastatic cancer
NEO-PV-01
cancer vaccine
T cell
neoantigen
personalized vaccine
checkpoint inhibitor
anti-PD-1

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