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 Journal Article
| Authors: | Ott, P. A.; Hu-Lieskovan, S.; Chmielowski, B.; Govindan, R.; Naing, A.; Bhardwaj, N.; Margolin, K.; Awad, M. M.; Hellmann, M. D.; Lin, J. J.; Friedlander, T.; Bushway, M. E.; Balogh, K. N.; Sciuto, T. E.; Kohler, V.; Turnbull, S. J.; Besada, R.; Curran, R. R.; Trapp, B.; Scherer, J.; Poran, A.; Harjanto, D.; Barthelme, D.; Ting, Y. S.; Dong, J. Z.; Ware, Y.; Huang, Y.; Huang, Z.; Wanamaker, A.; Cleary, L. D.; Moles, M. A.; Manson, K.; Greshock, J.; Khondker, Z. S.; Fritsch, E.; Rooney, M. S.; DeMario, M.; Gaynor, R. B.; Srinivasan, L. |
| Article Title: | 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: | In a phase Ib clinical trial, Ott et al. demonstrate feasibility, safety, and immunogenicity of the combination of personalized neoantigen vaccines and PD-1 inhibition in patients with advanced solid tumors. Vaccine-induced T cells persist over time, exhibit cytotoxic potential, and can migrate to tumors. Epitope spread and major pathologic tumor responses were detected following vaccination. © 2020 Elsevier Inc. 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). © 2020 Elsevier Inc. |
| Keywords: | adult; aged; middle aged; unclassified drug; major clinical study; advanced cancer; drug safety; cd8+ t lymphocyte; melanoma; bladder cancer; immunotherapy; cancer vaccine; cd4+ t lymphocyte; vaccination; cytotoxic t lymphocyte; open study; phase 1 clinical trial; cancer control; cell transport; vaccine; cell killing; personalized medicine; non small cell lung cancer; t cell; metastatic cancer; nivolumab; human; male; female; priority journal; article; anti-pd-1; checkpoint inhibitor; neoantigen; epitope spread; neo-pv-01; personalized vaccine; neo pv 01 |
| Journal Title: | Cell |
| Volume: | 183 |
| Issue: | 2 |
| ISSN: | 0092-8674 |
| Publisher: | Cell Press |
| Date Published: | 2020-10-15 |
| Start Page: | 347 |
| End Page: | 362.e24 |
| Language: | English |
| DOI: | 10.1016/j.cell.2020.08.053 |
| PUBMED: | 33064988 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 November 2020 -- Source: Scopus |
