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

Cell. 2020 Oct 15;183(2):347-362.e24. doi: 10.1016/j.cell.2020.08.053.


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

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cancer Vaccines / genetics
  • Cancer Vaccines / immunology*
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / immunology
  • Female
  • Humans
  • Immunotherapy / methods*
  • Kaplan-Meier Estimate
  • Male
  • Melanoma / drug therapy
  • Melanoma / immunology
  • Middle Aged
  • Mutation
  • Nivolumab / therapeutic use
  • Precision Medicine / methods*
  • Programmed Cell Death 1 Receptor / immunology
  • Programmed Cell Death 1 Receptor / metabolism
  • Urinary Bladder Neoplasms / drug therapy
  • Urinary Bladder Neoplasms / immunology


  • Antigens, Neoplasm
  • Cancer Vaccines
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Nivolumab

Associated data

  • ClinicalTrials.gov/NCT02897765