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

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

doi:10.1016/j.cell.2020.08.053

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.

Authors

Patrick A Ott¹, Siwen Hu-Lieskovan², Bartosz Chmielowski², Ramaswamy Govindan³, Aung Naing⁴, Nina Bhardwaj⁵, Kim Margolin⁶, Mark M Awad⁷, Matthew D Hellmann⁸, Jessica J Lin⁹, Terence Friedlander¹⁰, Meghan E Bushway¹¹, Kristen N Balogh¹¹, Tracey E Sciuto¹¹, Victoria Kohler¹¹, Samantha J Turnbull¹¹, Rana Besada¹¹, Riley R Curran¹¹, Benjamin Trapp¹¹, Julian Scherer¹¹, Asaf Poran¹¹, Dewi Harjanto¹¹, Dominik Barthelme¹¹, Ying Sonia Ting¹¹, Jesse Z Dong¹¹, Yvonne Ware¹¹, Yuting Huang¹¹, Zhengping Huang¹¹, Amy Wanamaker¹¹, Lisa D Cleary¹¹, Melissa A Moles¹¹, Kelledy Manson¹¹, Joel Greshock¹¹, Zakaria S Khondker¹¹, Ed Fritsch¹¹, Michael S Rooney¹¹, Mark DeMario¹¹, Richard B Gaynor¹¹, Lakshmi Srinivasan¹²

Affiliations

¹ Dana Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA. Electronic address: patrick_ott@dfci.harvard.edu.
² Department of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
³ Washington University School of Medicine, St. Louis, MO, USA.
⁴ Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁵ Tisch Cancer Institute, Icahn School of Medicine, New York, NY, USA.
⁶ Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, CA, USA.
⁷ Dana Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA.
⁸ Memorial Sloan Kettering Cancer Center, New York, NY, USA.
⁹ Cancer Center, Massachusetts General Hospital, and Harvard Medical School, Boston, MA, USA.
¹⁰ Department of Medicine, Division of Hematology and Oncology, University of California, San Francisco, San Francisco, CA, USA.
¹¹ Neon Therapeutics/BioNTech US, Cambridge, MA, USA.
¹² Neon Therapeutics/BioNTech US, Cambridge, MA, USA. Electronic address: lakshmi.srinivasan@biontech.us.

PMID: 33064988
DOI: 10.1016/j.cell.2020.08.053

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).

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

Substances

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

Associated data

ClinicalTrials.gov/NCT02897765