{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T19:20:06Z","timestamp":1794338406065,"version":"4.9.0"},"reference-count":30,"publisher":"American Medical Association (AMA)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Oncol"],"published-print":{"date-parts":[[2025,4,1]]},"abstract":"IMPORTANCE<\/jats:title>Patients who experience progression of advanced human papillomavirus (HPV)\u2013associated cancers and who have previously received first-line systemic treatment have a poor prognosis and limited therapeutic options.<\/jats:p><\/jats:sec>OBJECTIVE<\/jats:title>To assess the clinical activity of the combination of the HPV type 16 therapeutic vaccine PDS0101, the tumor-targeting interleukin 12 antibody-drug conjugate PDS01ADC, and the bifunctional anti\u2013programmed cell death ligand 1 (PD-L1)\/transforming growth factor \u03b2 (TGF-\u03b2) bintrafusp alfa in advanced HPV-associated cancers.<\/jats:p><\/jats:sec>DESIGN, Setting, and Participants<\/jats:title>This nonrandomized clinical trial was phase 1\/2 and investigator initiated, and was conducted at a single US cancer research center between June 2020 and July 2022. Patients with advanced or metastatic HPV-associated cancers were eligible, including patients who were both immune checkpoint blockade (ICB) naive and ICB resistant. The cutoff date for data analysis was May 13, 2024.<\/jats:p><\/jats:sec>INTERVENTION<\/jats:title>Patients received 1 mL of PDS0101 subcutaneously every 4 weeks for 6 doses then every 12 weeks for 2 additional doses, PDS01ADC, 16.8 \u00b5g\/kg, subcutaneously every 4 weeks or PDS01ADC, 8 \u00b5g\/kg, subcutaneously every 2 weeks, and bintrafusp alfa, 1200 mg, intravenously every 2 weeks.<\/jats:p><\/jats:sec>MAIN OUTCOMES AND MEASURES<\/jats:title>Objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors version 1.1 in ICB-naive patients.<\/jats:p><\/jats:sec>RESULTS<\/jats:title>Of the 50 eligible patients, 26 (52%) were men and the median age was 56 years (range, 28-80 years). The median (IQR) follow-up was 37.7 (30.6-42.0) months. Fourteen patients (28%) were ICB naive, with an ORR of 35.7% (95% CI, 12.8%-64.9%), and median overall survival (OS) 42.4 months (95% CI, 8.3 months-not estimable); in ICB-resistant patients, the ORR was 16.7% (6 of 36 patients; 95% CI, 6.4%-32.8%) and median OS was 15.8 months (95% CI, 9.0-21.3 months). Among patients with HPV-16\u2013positive tumors (37 patients [74%]), in the ICB-naive group (8 patients [21.6%]) the ORR was 62.5% (95% CI, 24.5%-91.5%) and a median OS measure was not reached. Grade 3 and 4 treatment-related adverse events occurred in 26 of 50 patients (52%). There were no treatment-related deaths.<\/jats:p><\/jats:sec>CONCLUSIONS AND RELEVANCE<\/jats:title>In this trial, the combination of PDS0101, PDS01ADC, and bintrafusp alfa showed an acceptable safety profile and promising antitumor activity and improved OS in patients with HPV-16\u2013positive cancers, in both ICB-naive and ICB-resistant patients, warranting further evaluation of the combination of PDS0101 and PDS01ADC with simultaneous PD-L1\/TGF-\u03b2 inhibition in these populations.<\/jats:p><\/jats:sec>Trial Registration<\/jats:title>ClinicalTrials.gov Identifier: NCT04287868<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1001\/jamaoncol.2024.6998","type":"journal-article","created":{"date-parts":[[2025,2,20]],"date-time":"2025-02-20T16:01:16Z","timestamp":1740067276000},"page":"394","source":"Crossref","is-referenced-by-count":42,"title":["Novel Combination Immunotherapy and Clinical Activity in Patients With HPV-Associated 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