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.

Abstract

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).

• Authors: Patrick A Ott, Siwen Hu-Lieskovan, Bartosz Chmielowski, Ramaswamy Govindan, Aung Naing, Nina Bhardwaj, Kim Margolin, Mark M Awad, Matthew D Hellmann, Jessica J Lin, Terence Friedlander, Meghan E Bushway, Kristen N Balogh, Tracey E Sciuto, Victoria Kohler, Samantha J Turnbull, Rana Besada, Riley R Curran, Benjamin Trapp, Julian Scherer, Asaf Poran, Dewi Harjanto, Dominik Barthelme, Ying Sonia Ting, Jesse Z Dong, Yvonne Ware, Yuting Huang, Zhengping Huang, Amy Wanamaker, Lisa D Cleary, Melissa A Moles, Kelledy Manson, Joel Greshock, Zakaria S Khondker, Ed Fritsch, Michael S Rooney, Mark DeMario, Richard B Gaynor, Lakshmi Srinivasan
• Journal: Cell (Cell) Vol. 183 Issue 2 Pg. 347-362.e24 (10 15 2020) ISSN: 1097-4172 [Electronic] United States
• PMID: 33064988 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Elsevier Inc. All rights reserved.

Chemical References

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

Topics

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