{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:28:24Z","timestamp":1792787304242,"version":"4.5.0"},"reference-count":20,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T00:00:00Z","timestamp":1736208000000},"content-version":"unspecified","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Norwegian Skattefunn R&D tax deduction program","award":["322860"],"award-info":[{"award-number":["322860"]}]},{"DOI":"10.13039\/100007013","name":"F. Hoffmann-La Roche","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100007013","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Nykode Therapeutics","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2024,12,23]]},"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Second-line treatment options for persistent, recurrent or metastatic (r\/m) cervical cancer are limited. We investigated the safety, efficacy, and immunogenicity of the therapeutic DNA-based vaccine VB10.16 combined with the immune checkpoint inhibitor atezolizumab in patients with human papillomavirus (HPV)16-positive r\/m cervical cancer.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and methods<\/jats:title>\n                    <jats:p>\n                      This multicenter, single-arm, phase 2a study (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT04405349\">NCT04405349<\/jats:ext-link>\n                      , registered 26 May 2020) enrolled adult patients with persistent, r\/m HPV16-positive cervical cancer. Patients received 3\u2009mg VB10.16 (every 3 weeks (Q3W) for 12 weeks, hereafter every 6 weeks) combined with 1,200\u2009mg atezolizumab (Q3W) for 48 weeks in total with a 12-month follow-up. The primary endpoints were incidence and severity of adverse events (AEs) and objective response rate (ORR; Response Evaluation Criteria in Solid Tumor V.1.1). ORR was assessed in the efficacy population, being all response-evaluable patients who received any administration of VB10.16 and atezolizumab and had at least one post-baseline imaging assessment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Between June 16, 2020, and January 25, 2022, 52 patients received at least one administration of study treatment. Of these, 47 patients had a minimum of one post-baseline tumor assessment. The median follow-up time for survival was 11.7 months. AEs related to VB10.16 were non-serious and mainly mild injection site reactions (9 of 52 patients). There were no signs of new toxicities other than what was already described with atezolizumab. ORR was 19.1% (95% CI 9.1% to 33.3%). Median duration of response was not reached (n.r.) (95%\u2009CI 2.2 to n.r.), median progression-free survival was 4.1 months (95%\u2009CI 2.1 to 6.2), and median overall survival was 21.3 months (95%\u2009CI 8.5 to n.r.). In programmed death-ligand 1 (PD-L1)-positive patients (n=24), ORR was 29.2% (95% CI 12.6 to 51.1). HPV16-specific T-cell responses were analyzed in 36 of 47 patients with an increase observed in 22\/36 (61%).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The therapeutic DNA-based vaccine VB10.16 combined with atezolizumab was safe and well tolerated showing a promising clinically meaningful efficacy with durable responses in patients with persistent, r\/m HPV16-positive cervical cancer, especially if PD-L1-positive.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2024-010827","type":"journal-article","created":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T14:20:48Z","timestamp":1736259648000},"page":"e010827","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":24,"title":["Safety and efficacy of the therapeutic DNA-based vaccine VB10.16 in combination with atezolizumab in persistent, recurrent or metastatic HPV16-positive cervical cancer: a multicenter, single-arm phase 2a study"],"prefix":"10.1136","volume":"13","clinical-trial-number":[{"clinical-trial-number":"nct04405349","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct02529930","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct04405349","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct04405349","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct04405349","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Peter","family":"Hillemanns","sequence":"first","affiliation":[{"name":"Department of Gynecology and Obstetrics, Hannover Medical School, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michal","family":"Zikan","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Bulovka University Hospital Na Bulovce Budinova 67\/2, Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Forget","sequence":"additional","affiliation":[{"name":"Center hospital de l\u2019Ardenne, Libramont, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannelore G","family":"Denys","sequence":"additional","affiliation":[{"name":"Medical Oncology, University Hospital Ghent, Gent, Flanders, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Francois","family":"Baurain","sequence":"additional","affiliation":[{"name":"University Clinic Saint-Luc, Bruxelles, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukas","family":"Rob","sequence":"additional","affiliation":[{"name":"University Hospital Kralovske Vinohrady, Praha, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linn","family":"Woelber","sequence":"additional","affiliation":[{"name":"Department of Gynecology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pawel","family":"Blecharz","sequence":"additional","affiliation":[{"name":"Gynecologic Oncology Department, Maria Sklodowska-Curie National Research Institute of Oncology in Warsaw Krakow Branch, Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariusz","family":"Bidzinski","sequence":"additional","affiliation":[{"name":"Gynecologic Oncology Department, Maria Sklodowska-Curie National Research Institute of Oncology, Warzawa, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josef","family":"Chovanec","sequence":"additional","affiliation":[{"name":"Masaryk Memorial Cancer Institute, Brno, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederik","family":"Marm\u00e9","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, University Hospital Mannheim, Mannheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa","family":"Link","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Medical Faculty, Dresden, Germany"},{"name":"Department of Gynecology and Obstetrics, Technische Universit\u00e4t Dresden, Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Dannecker","sequence":"additional","affiliation":[{"name":"Gynecology and Obstetrics, Faculty of Medicine, University of Augsburg, Augsburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders","family":"Rosholm","sequence":"additional","affiliation":[{"name":"Nykode Therapeutics ASA, Oslo, Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaja C G","family":"Berg","sequence":"additional","affiliation":[{"name":"Nykode Therapeutics ASA, Oslo, Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto S","family":"Oliveri","sequence":"additional","affiliation":[{"name":"Nykode Therapeutics ASA, Oslo, Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2162-0175","authenticated-orcid":false,"given":"Kristina","family":"Lindemann","sequence":"additional","affiliation":[{"name":"Department of gynecological oncology, Oslo University Hospital, Oslo, Norway"},{"name":"Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2025,1,7]]},"reference":[{"key":"2025100304531128000_13.1.e010827.1","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(22)00501-0"},{"key":"2025100304531128000_13.1.e010827.2","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21492"},{"key":"2025100304531128000_13.1.e010827.3","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1038\/488S2a","article-title":"HPV: The global burden","volume":"488","author":"Crow","year":"2012","journal-title":"Nature New Biol"},{"key":"2025100304531128000_13.1.e010827.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.pvr.2017.12.006"},{"key":"2025100304531128000_13.1.e010827.5","doi-asserted-by":"crossref","first-page":"1654","DOI":"10.1016\/S0140-6736(17)31607-0","article-title":"Bevacizumab for advanced cervical cancer: final overall survival and adverse event analysis of a randomised, controlled, open-label, phase 3 trial (Gynecologic Oncology Group 240)","volume":"390","author":"Tewari","year":"2017","journal-title":"The Lancet"},{"key":"2025100304531128000_13.1.e010827.6","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.18.01265"},{"key":"2025100304531128000_13.1.e010827.7","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2112435"},{"key":"2025100304531128000_13.1.e010827.8","doi-asserted-by":"crossref","first-page":"5505","DOI":"10.1200\/JCO.23.00914","article-title":"First-Line Pembrolizumab + Chemotherapy Versus Placebo + Chemotherapy for Persistent, Recurrent, or Metastatic Cervical Cancer: Final Overall Survival Results of KEYNOTE-826","volume":"41","author":"Monk","year":"2023","journal-title":"J Clin Oncol"},{"key":"2025100304531128000_13.1.e010827.9","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2112187"},{"key":"2025100304531128000_13.1.e010827.10","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/S0140-6736(23)02405-4","article-title":"Atezolizumab plus bevacizumab and chemotherapy for metastatic, persistent, or recurrent cervical cancer (BEATcc): a randomised, open-label, phase 3 trial","volume":"403","author":"Oaknin","year":"2024","journal-title":"Lancet"},{"key":"2025100304531128000_13.1.e010827.11","doi-asserted-by":"publisher","DOI":"10.1136\/ijgc-2024-005588"},{"key":"2025100304531128000_13.1.e010827.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2012.03.047"},{"key":"2025100304531128000_13.1.e010827.13","doi-asserted-by":"crossref","first-page":"4885","DOI":"10.1158\/1078-0432.CCR-22-1927","article-title":"A Therapeutic Antigen-Presenting Cell-Targeting DNA Vaccine VB10.16 in HPV16-Positive High-Grade Cervical Intraepithelial Neoplasia: Results from a Phase I\/IIa Trial","volume":"28","author":"Hillemanns","year":"2022","journal-title":"Clin Cancer Res"},{"key":"2025100304531128000_13.1.e010827.14","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/32588","article-title":"Dendritic cells and the control of immunity","volume":"392","author":"Banchereau","year":"1998","journal-title":"Nature New Biol"},{"key":"2025100304531128000_13.1.e010827.15","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00449-4"},{"key":"2025100304531128000_13.1.e010827.16","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1001\/jamaoncol.2018.4051","article-title":"Combining Immune Checkpoint Blockade and Tumor-Specific Vaccine for Patients With Incurable Human Papillomavirus 16-Related Cancer: A Phase 2 Clinical Trial","volume":"5","author":"Massarelli","year":"2019","journal-title":"JAMA Oncol"},{"key":"2025100304531128000_13.1.e010827.17","doi-asserted-by":"crossref","DOI":"10.1016\/j.annonc.2022.08.028","article-title":"LBA32 Efficacy and safety of GX-188E, a therapeutic DNA vaccine, combined with pembrolizumab in HPV 16- and\/or 18- positive advanced cervical cancer (phase II): Safe and effective in both PD-L1 positive and negative","volume":"33","author":"Lee","year":"2022","journal-title":"Ann Oncol"},{"key":"2025100304531128000_13.1.e010827.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2008.10.026"},{"key":"2025100304531128000_13.1.e010827.19","doi-asserted-by":"publisher","DOI":"10.1186\/s13000-023-01318-8"},{"key":"2025100304531128000_13.1.e010827.20","doi-asserted-by":"crossref","DOI":"10.1016\/S0090-8258(21)00696-X","article-title":"Pembrolizumab treatment of advanced cervical cancer: updated results from the phase II KEYNOTE-158 study","volume":"162","author":"Chung","year":"2021","journal-title":"Gynecol Oncol"}],"container-title":["Journal for ImmunoTherapy of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jitc-2024-010827","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T11:53:18Z","timestamp":1759492398000},"score":1,"resource":{"primary":{"URL":"https:\/\/jitc.bmj.com\/lookup\/doi\/10.1136\/jitc-2024-010827"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1]]},"references-count":20,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,1,7]]},"published-print":{"date-parts":[[2025,1]]}},"alternative-id":["10.1136\/jitc-2024-010827"],"URL":"https:\/\/doi.org\/10.1136\/jitc-2024-010827","relation":{},"ISSN":["2051-1426"],"issn-type":[{"value":"2051-1426","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1]]}}}