{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T15:10:36Z","timestamp":1789657836350,"version":"4.0.1"},"reference-count":35,"publisher":"American Medical Association (AMA)","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Oncol"],"abstract":"\n Importance<\/jats:title>\n The incidence of human papillomavirus type 16 (HPV16\u2013positive) recurrent\/metastatic (R\/M) head and neck squamous cell carcinoma (HNSCC) is rising. Approved therapies offer a durable response to a minority of patients.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To determine the efficacy and safety of a therapeutic HPV16-targeted immunotherapy, PDS0101, in combination with pembrolizumab in participants with HPV16-positive R\/M HNSCC, with separate evaluation of immune checkpoint inhibitor (ICI)\u2013naive and ICI-resistant cohorts.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n VERSATILE-002 was a phase 2, open-label, multicenter nonrandomized clinical trial conducted at 26 oncology centers from March 29, 2021, to May 15, 2025, across the US, UK, and Ireland using the Simon 2-stage optimal design. Efficacy analyses were performed on modified intent-to-treat (mITT) population; safety analyses included all participants who received 1 or more doses. Eighty-eight participants with histologically confirmed R\/M HPV16-positive HNSCC were enrolled, of whom 87 (98.9%) received treatment and composed the safety population. Seventy five (85.2%) were in the mITT population used for efficacy analyses, of whom 53 (70.7%) were ICI-naive with a programmed cell death ligand 1 combined positive score of 1 or greater and 22 (29.3%) were ICI-resistant.<\/jats:p>\n <\/jats:sec>\n \n Exposures<\/jats:title>\n Pembrolizumab (200 mg, intravenously, every 3 weeks for up to 35 cycles) plus subcutaneous PDS0101 (5 scheduled doses per protocol).<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n \n The primary end point was objective response rate (ORR) per the\n Response Evaluation Criteria in Solid Tumors<\/jats:italic>\n , version 1.1, by a masked independent central reviewer. Secondary end points included progression-free survival (PFS), median overall survival (mOS), and safety, with exploratory end points of duration of response, disease control rate, and response rates by programmed cell death ligand 1 status.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Of the 75 patients in the mITT population, the mean (SD) age was 64.0 (8.3) years; 4 individuals (5%) were female and 71 (95%) were male; and 2 individuals (3%) were Asian, 1 (1%) was Black, 5 (7%) were Hispanic, and 71 (95%) were White. Among 53 ICI-naive participants in the mITT cohort, ORR by the central reviewer was 34.0%, median PFS was 5.3 months (95% CI, 2.10-9.00), and mOS was 39.3 months (95% CI, 23.90 to not evaluable). Among 22 ICI-resistant patients in the mITT cohort, no objective responses were observed and the primary end point (ORR by central reviewer) was not met, but mOS was 14.8 months (95% CI, 8.50-26.00). The treatment was well tolerated, with 13.8% experiencing grade 3 or higher treatment-related adverse events.<\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n The results of this nonrandomized clinical trial suggest that PDS0101 plus pembrolizumab showed antitumor activity in ICI-naive HPV16-positive R\/M HNSCC, with favorable safety, response rates, and survival outcomes. The findings support further evaluation in a first-line setting.<\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n \n ClinicalTrials.gov Identifier:\n NCT04260126<\/jats:ext-link>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamaoncol.2026.3492","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T15:00:25Z","timestamp":1789657225000},"source":"Crossref","is-referenced-by-count":0,"title":["PDS0101 With Pembrolizumab in HPV16-Positive Recurrent\/Metastatic Head and Neck Squamous Cell Carcinoma"],"prefix":"10.1001","author":[{"given":"Jared","family":"Weiss","sequence":"first","affiliation":[{"name":"Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Kaczmar","sequence":"additional","affiliation":[{"name":"Hollings Cancer Center, Medical University of South Carolina, 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