{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T14:41:57Z","timestamp":1791729717946,"version":"4.3.4"},"reference-count":42,"publisher":"BMJ","issue":"9","license":[{"start":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T00:00:00Z","timestamp":1757289600000},"content-version":"unspecified","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"ISA Pharmaceuticals","award":["No grant\/ award number"],"award-info":[{"award-number":["No grant\/ award number"]}]},{"DOI":"10.13039\/100009857","name":"Regeneron Pharmaceuticals","doi-asserted-by":"publisher","award":["No Grant\/ Award number"],"award-info":[{"award-number":["No Grant\/ Award number"]}],"id":[{"id":"10.13039\/100009857","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2025,8,22]]},"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Peltopepimut-S is a therapeutic vaccine, which induces specific expansion of both CD4+helper\u2009and CD8+cytotoxic T-cells against human papillomavirus type 16 (HPV16) E6\/E7 oncoproteins.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and methods<\/jats:title>\n                    <jats:p>In a randomized phase 2 trial, we evaluated the efficacy and safety of peltopepimut-S plus cemiplimab compared with cemiplimab alone as first-line or second-line therapy in recurrent\/metastatic HPV16-positive head and neck cancer. The primary efficacy endpoint was the objective response rate (ORR) by an independent review (Response Evaluation Criteria in Solid Tumors version 1.1, RECIST v1.1), while the primary safety endpoint was frequency and severity of adverse events. Secondary endpoints included progression-free survival (PFS) and overall survival (OS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Overall, 198 anti-programmed cell death protein-1 therapy-na\u00efve patients with confirmed HPV16-positive recurrent\/metastatic oropharyngeal cancer were randomized to receive cemiplimab plus peltopepimut-S (n=100) or placebo (n=99). The trial did not meet its primary objective (ORR, 25.3% in peltopepimut-S arm vs 22.9% in placebo arm; p=0.735). The median OS (mOS) and PFS in the placebo arm were unexpectedly longer than in the peltopepimut-S arm (26.9 vs 15.8 months) and (20.3 vs 5.5 months), respectively. In predefined exploratory analyses this was associated with an excess death rate from progressive disease in patients with pre-treatment programmed death-ligand 1 (PD-L1) combined positive score (CPS) &lt;20. In contrast, patients with CPS \u226520 had a higher ORR of 51.7% (95% CI, 32.5% to 70.6%) vs 25.8% (95% CI, 11.9% to 44.6%) and a longer mOS in the peltopepimut-S arm (34.8 vs 28.8 months) compared with the placebo arm, respectively. If patients had received all three vaccine or placebo doses, the ORR in patients with CPS \u226520 was 70.0% (95% CI, 45.7% to 88.1%) vs 29.2% (95% CI, 12.6% to 51.1%) in the peltopepimut-S arm and placebo arms, respectively, associated with mOS not reached (after 42 months) versus 23.3 months. The addition of peltopepimut-S to cemiplimab did not increase cemiplimab\u2019s toxicity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Adding peltopepimut-S to cemiplimab did not improve ORR and worsened mOS in the primary analysis. Divergent outcomes were seen in patients with pretreatment PD-L1 CPS &lt;20 (worse ORR and mOS compared with placebo) and CPS \u226520 (higher ORR and longer mOS compared with placebo) values. Future drug development is justifiable in the CPS \u226520 patient population.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT03669718\">NCT03669718<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2025-012555","type":"journal-article","created":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T17:26:19Z","timestamp":1757352379000},"page":"e012555","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":7,"title":["Randomized clinical efficacy and safety study of peltopepimut-S plus cemiplimab compared to cemiplimab alone in patients with recurrent\/metastatic HPV16-positive head and neck cancer"],"prefix":"10.1136","volume":"13","clinical-trial-number":[{"clinical-trial-number":"nct03669718","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Caroline","family":"Even","sequence":"first","affiliation":[{"name":"Head and Neck Oncology, Gustave Roussy Institute, Villejuif, \u00cele-de-France, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6014-348X","authenticated-orcid":false,"given":"Kevin J","family":"Harrington","sequence":"additional","affiliation":[{"name":"Division of Radiotherapy and Imaging, The Institute of Cancer Research, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erminia","family":"Massarelli","sequence":"additional","affiliation":[{"name":"Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6732-7137","authenticated-orcid":false,"given":"Simon","family":"Laban","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology and Head and Neck Surgery, Universitatsklinikum Ulm, Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8126-7019","authenticated-orcid":false,"given":"J\u00e9r\u00f4me","family":"Fayette","sequence":"additional","affiliation":[{"name":"Centre L\u00e9on B\u00e9rard, Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Oliva","sequence":"additional","affiliation":[{"name":"Institut Catala d\u2019Oncologia, L\u2019Hospitalet de Llobregat, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marielle","family":"Klein Hesselink","sequence":"additional","affiliation":[{"name":"TargED Biopharmaceuticals, Leiden, The 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