@article{641f449e8a4e497b848770da06a9843c,
title = "Personalized neoantigen vaccine NEO-PV-01 with chemotherapy and anti-PD-1 as first-line treatment for non-squamous non-small cell lung cancer",
abstract = "Neoantigens arising from mutations in tumor DNA provide targets for immune-based therapy. Here, we report the clinical and immune data from a Phase Ib clinical trial of a personalized neoantigen-vaccine NEO-PV-01 in combination with pemetrexed, carboplatin, and pembrolizumab as first-line therapy for advanced non-squamous non-small cell lung cancer (NSCLC). This analysis of 38 patients treated with the regimen demonstrated no treatment-related serious adverse events. Multiple parameters including baseline tumor immune infiltration and on-treatment circulating tumor DNA levels were highly correlated with clinical response. De novo neoantigen-specific CD4+ and CD8+ T cell responses were observed post-vaccination. Epitope spread to non-vaccinating neoantigens, including responses to KRAS G12C and G12V mutations, were detected post-vaccination. Neoantigen-specific CD4+ T cells generated post-vaccination revealed effector and cytotoxic phenotypes with increased CD4+ T cell infiltration in the post-vaccine tumor biopsy. Collectively, these data support the safety and immunogenicity of this regimen in advanced non-squamous NSCLC.",
keywords = "NEO-PV-01, cancer vaccine, immunotherapy, neoantigen vaccine, non-small cell lung cancer",
author = "Awad, {Mark M.} and Ramaswamy Govindan and Balogh, {Kristen N.} and Spigel, {David R.} and Garon, {Edward B.} and Bushway, {Meghan E.} and Asaf Poran and Sheen, {Joong Hyuk} and Victoria Kohler and Ekaterina Esaulova and John Srouji and Suchitra Ramesh and Rohit Vyasamneni and Binisha Karki and Sciuto, {Tracey E.} and Himanshu Sethi and Dong, {Jesse Z.} and Moles, {Melissa A.} and Kelledy Manson and Rooney, {Michael S.} and Khondker, {Zakaria S.} and Mark DeMario and Gaynor, {Richard B.} and Lakshmi Srinivasan",
note = "Funding Information: We thank all of the patients and their families who participated in the study. We are grateful to all of the members of BioNTech US for their support and assistance on the study. We thank April Lamb and Jennifer Tepper for clinical operations; Marc Wolfgang, Scott White, Stephen Crimlisk, and Yeimy Garcia for technical operations; Jonathan McGee, Heidi Jackson, Madeline Worob, Yuting Huang, Daniel Kallin, and Alyssa Kruithof for peptide synthesis and manufacturing process development; Janani Sridar and Paul Turcott for tetramer reagent generation; Riley Curran, Samantha Turnbull, Rana Besada, Ben Trapp, Julian Scherer, and Gauri Mahimkar for immune analysis study support; Miles Kirsch and Dewi Harjanto for bioinformatics support; Kerry Chios and Nidal El-Assi for lab operation support and biobank management; Zhengping Huang and Amy Wanamaker for informatics support and clinical data management; Mominul Islam for biostatistics support; Andrew Finlayson for careful review; and Hugh O{\textquoteright}Dowd for support and guidance on the study. We thank Merck for the pembrolizumab supply. The study was sponsored by Neon Therapeutics/BioNTech US. Funding Information: We thank all of the patients and their families who participated in the study. We are grateful to all of the members of BioNTech US for their support and assistance on the study. We thank April Lamb and Jennifer Tepper for clinical operations; Marc Wolfgang, Scott White, Stephen Crimlisk, and Yeimy Garcia for technical operations; Jonathan McGee, Heidi Jackson, Madeline Worob, Yuting Huang, Daniel Kallin, and Alyssa Kruithof for peptide synthesis and manufacturing process development; Janani Sridar and Paul Turcott for tetramer reagent generation; Riley Curran, Samantha Turnbull, Rana Besada, Ben Trapp, Julian Scherer, and Gauri Mahimkar for immune analysis study support; Miles Kirsch and Dewi Harjanto for bioinformatics support; Kerry Chios and Nidal El-Assi for lab operation support and biobank management; Zhengping Huang and Amy Wanamaker for informatics support and clinical data management; Mominul Islam for biostatistics support; Andrew Finlayson for careful review; and Hugh O'Dowd for support and guidance on the study. We thank Merck for the pembrolizumab supply. The study was sponsored by Neon Therapeutics/BioNTech US. M.M.A. L.S. and R.B.G. conceptualization and implementation of the study; M.M.A. R.G. D.R.S. and E.B.G. clinical investigators on the study; K.N.B. M.E.B. A.P. J.H.S. V.K. E.E. S.R. T.E.S. and M.S.R. biomarker and sequencing analysis; K.N.B. V.K. and S.R. patient immune analysis, J.Z.D. peptide synthesis and purification; J.S. and R.V. tetramer reagent generation; M.A.M. and K.M. clinical operations and program management; Z.S.K.:biostatistics support; M.mD.M. edical monitor on the study; M.M.A. K.N.B. M.D.M. L.S. and R.B.G. manuscript preparation, with inputs from all of the authors. M.M.A.research grants (to institution): Genentech, Lilly, Bristol-Myers Squibb, AstraZeneca; consulting/advisory board fees, Genentech, Bristol-Myers Squibb, Merck, AstraZeneca, AbbVie, Neon, Achilles, Maverick, Blueprint Medicine, Hengrui, Syndax, Ariad, Nektar, Gritstone, ArcherDX, Mirati, NextCure, Novartis, EMD Serono, Panvaxal/NovaRx, Foundation Medicine. R.G. advisory role, Precisca Lung, Merck, Jacobio. D.R.S. research grants (to institution), Aeglea, Agios, Apollomics, Arcus, Arrys, Astellas, AstraZeneca, Bayer, BeiGene, Therapeutics, BioNTech RNA Pharmaceuticals, Blueprint Medicine, Boehringer-Ingelheim, Bristol-Myers Squibb, Calithera, Celldex, Clovis, Cyteir, Daiichi Sankyo, Biopharma, Eisai, Elevation Oncology, EMD Serono, Evelo Biosciences, G1, Roche/Genentech, GlaxoSmithKline, GRAIL, Hutchison MediPharma, ImClone Systems, Incyte, ImmunoGen, Ipsen, Janssen, Kronos Bio, Loxo Oncology, MacroGenics, MedImmune, Merck, Molecular Partners, Molecular Template, Nektar, Novartis, Novocure, Oncologie, Pfizer, PTC, PureTech Health, Razor Genomics, Repare, Rgenix, Takeda, Tesaro, Tizona Therapeutics, Transgene, University of Texas Southwestern, Verastem; consulting/advisory board (to institution), Amgen, AstraZeneca, Bristol-Myers Squibb, Curio Science, EMD Serono, Evidera, Exelixis, GlaxoSmithKline, Intellisphere, Ipsen, Janssen, Jazz, Lilly, Mirati, Molecular Templates, Novartis, Novocure, Pfizer, Puma Biotechnology, Regeneron, Roche/Genentech, Sanofi-Aventis. EBG: Consulting or Advisory Role: ABL Bio, Boehringer Ingelheim, Bristol-Myers Squibb, Dracen, Eisai, Eli Lilly, EMD Serono, Gilead, GSK, Merck, Natera, Novartis, Personalis, Regeneron, Sanofi, Shionogi, Xilio; grant/research support, ABL Bio, AstraZeneca, Bristol-Myers Squibb, Dynavax Technologies, EMD Serono, Genentech, Iovance Biotherapeutics, Eli Lilly, Merck, Mirati, Neon, Novartis. R.B.G. Board of Directors, Alkermes plc, Infinity Pharmaceuticals, and Zai Laboratory, and Scientific Advisory Board, Leap Therapeutics; consultant Third Rock Ventures, stockholder and employee of BioNTech US. H.S. employee of Natera, with stock/options to own stock in the company. K.N.B. M.E.B. A.P. J.H.S. V.K. E.E. J.S. S.R. R.V. T.E.S. J.Z.D. M.A.M. K.M. M.S.R. Z.S.K. M.D.M. and L.S. stockholder and either current or past employees of Neon Therapeutics/BioNTech US. Publisher Copyright: {\textcopyright} 2022 Elsevier Inc.",
year = "2022",
month = sep,
day = "12",
doi = "10.1016/j.ccell.2022.08.003",
language = "English",
volume = "40",
pages = "1010--1026.e11",
journal = "Cancer Cell",
issn = "1535-6108",
number = "9",
}