ACKNOWLEDGMENTS 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 assis-tance on the study. We thank April Lamb and Jennifer Tepper for clinical oper- ations; Marc Wolfgang, Scott White, Stephen Crimlisk, and Yeimy Garcia for technical operations; Jonathan McGee, Heidi Jackson, Madeline Worob, Yut-ing Huang, Daniel Kallin, and Alyssa Kruithof for peptide synthesis andmanufacturing process development; Janani Sridar and Paul Turcott fortetramer reagent generation; Riley Curran, Samantha Turnbull, Rana Besada,Ben Trapp, Julian Scherer, and Gauri Mahimkar for immune analysis studysupport; Miles Kirsch and Dewi Harjanto for bioinformatics support; KerryChios and Nidal El-Assi for lab operation support and biobank management;Zhengping Huang and Amy Wanamaker for informatics support and clinicaldata management; Mominul Islam for biostatistics support; Andrew Finlaysonfor careful review; and Hugh O’Dowd for support and guidance on the study.We thank Merck for the pembrolizumab supply. The study was sponsored byNeon Therapeutics/BioNTech US. AUTHOR CONTRIBUTIONS 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 andsequencing 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.,:bios-tatistics 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 theauthors. DECLARATION OF INTERESTS M.M.A.,research grants (to institution): Genentech, Lilly, Bristol-Myers Squibb, AstraZeneca; consulting/advisory board fees, Genentech, Bristol-MyersSquibb, Merck, AstraZeneca, AbbVie, Neon, Achilles, Maverick, BlueprintMedicine, 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 Pharmaceuti- cals, Blueprint Medicine, Boehringer-Ingelheim, Bristol-Myers Squibb, Cali-thera, Celldex, Clovis, Cyteir, Daiichi Sankyo, Biopharma, Eisai, ElevationOncology, 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, Novar-tis, Novocure, Oncologie, Pﬁzer, PTC, PureTech Health, Razor Genomics,Repare, Rgenix, Takeda, Tesaro, Tizona Therapeutics, Transgene, Universityof Texas Southwestern, Verastem; consulting/advisory board (to institution),Amgen, AstraZeneca, Bristol-Myers Squibb, Curio Science, EMD Serono, Evi-dera, Exelixis, GlaxoSmithKline, Intellisphere, Ipsen, Janssen, Jazz, Lilly, Mir-ati, 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, Re-generon, 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; consultantThird 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 currentor past employees of Neon Therapeutics/BioNTech US. Received: February 14, 2022 Revised: June 6, 2022Accepted: August 2, 2022Published: August 25, 2022 REFERENCES Abbosh, C., Birkbak, N.J., Wilson, G.A., Jamal-Hanjani, M., Constantin, T., Salari, R., Le Quesne, J., Moore, D.A., Veeriah, S., Rosenthal, R., et al.(2017). Phylogenetic ctDNA analysis depicts early-stage lung cancer evolu-tion. Nature 545, 446–451.