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Clinical Trial
. 2020 Oct 15;183(2):347-362.e24.
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

Patrick A Ott  1 , Siwen Hu-Lieskovan  2 , Bartosz Chmielowski  2 , Ramaswamy Govindan  3 , Aung Naing  4 , Nina Bhardwaj  5 , Kim Margolin  6 , Mark M Awad  7 , Matthew D Hellmann  8 , Jessica J Lin  9 , Terence Friedlander  10 , Meghan E Bushway  11 , Kristen N Balogh  11 , Tracey E Sciuto  11 , Victoria Kohler  11 , Samantha J Turnbull  11 , Rana Besada  11 , Riley R Curran  11 , Benjamin Trapp  11 , Julian Scherer  11 , Asaf Poran  11 , Dewi Harjanto  11 , Dominik Barthelme  11 , Ying Sonia Ting  11 , Jesse Z Dong  11 , Yvonne Ware  11 , Yuting Huang  11 , Zhengping Huang  11 , Amy Wanamaker  11 , Lisa D Cleary  11 , Melissa A Moles  11 , Kelledy Manson  11 , Joel Greshock  11 , Zakaria S Khondker  11 , Ed Fritsch  11 , Michael S Rooney  11 , Mark DeMario  11 , Richard B Gaynor  11 , Lakshmi Srinivasan  12
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Free article
Clinical Trial

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 et al. Cell. .
Free article

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.

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Conflict of interest statement

Declaration of Interests P.A.O.: research funding paid to the institution—Bristol-Myers Squibb, Merck, AstraZeneca, Celldex, CytomX, GlaxoSmithKline, ARMO Biosciences, Neon Therapeutics; consultant—Array, Bristol-Myers Squibb, Merck, Genentech, Pfizer, Novartis, Neon Therapeutics, CytomX, Celldex. S.H.-L.: consultant—Amgen, Bristol-Myers Squibb, Genmab, Xencor; research support—Bristol-Myers Squibb, Merck, and Vaccinex. B.C.: member of the speakers’ bureaus for Regeneron and Sanofi. R.G.: advisory board member—Achilles; consultant—Horizon Pharma (spouse), GenePlus. A.N.: research funding from NCI, EMD Serono, MedImmune, Healios Oncology Nutrition, Atterocor, Amplimmune, ARMO BioSciences, Eli Lilly, Karyopharm Therapeutics, Incyte, Novartis, Regeneron, Merck, Bristol-Myers Squibb, Pfizer, CytomX Therapeutics, Neon Therapeutics, Calithera Biosciences, TopAlliance Biosciences, Kymab, PsiOxus, and Immune Deficiency Foundation (spouse); advisory board member—CytomX Therapeutics, Novartis, Kymab, and Genome; travel and accommodation expense—ARMO BioSciences. N.B.: scientific advisory board member—Checkpoint Sciences, Curevac, Primevax, Novartis, Avidea, BI, Rome Therapeutics, Neon Therapeutics, Roche, and Genentech. Extramural member of the Parker Institute for Cancer Immunotherapy K.M.: advisory boards or consultant—Nektar, ImaginAb, Neoleukin, and Akrevia; DSMB—IOvance. M.M.A.: research grants—Genentech, Bristol-Myers Squibb, AstraZeneca, Lilly; consultant—Genentech, Bristol-Myers Squibb, AstraZeneca, Merck, Maverick, Blueprint Medicine, Syndax, Ariad, Nektar, Gritstone, and Neon Therapeutics M.D.H.: research funding—Bristol-Myers Squibb; consultant—Merck, Bristol-Myers Squibb, AstraZeneca, Genentech/Roche, Nektar, Syndax, Mirati, Blueprint, Immunai, and Shattuck Labs; travel support/honoraria—AstraZeneca, Eli Lilly, Merck, and Bristol-Myers Squibb; and a patent has been filed by MSK related to the use of tumor mutation burden to predict the response to immunotherapy (PCT/US2015/062208), which has received licensing fees from PGDx. J.J.L.: honoraria/consultant—Pfizer, C4 Therapeutics, Nuvalent, and Genentech; institutional research funding—Neon, Hengrui Therapeutics, Turning Point Therapeutics, and Novartis; travel fees—Pfizer; CME funding—OncLive. T.F.: research funding—Janssen; research funding to the institute—Seattle Genetics, Incyte, Bristol-Myers Squibb, Neon Therapeutics, and Roche/Genentech. R.B.G.: board of directors—Alkermes plc and Infinity Pharmaceuticals; scientific advisory board—Leap Therapeutics; stockholder and employee—Neon Therapeutics/BioNTech US. Stockholder and either current or past employees of Neon Therapeutics/BioNTech US: M.E.B., K.N.B., T.E.S., V.K., S.J.T., R.B., R.R.C., B.T., J.S., A.P., D.H., D.B., Y.S.T., J.Z.D., Y.W., Y.H., Z.H., A.W., L.D.C., M.A.M., K.M., J.G., Z.S.K., M.S.R., M.D., E.F., and L.S.

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