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Drugs bound to albumin selectively target cancer cells with upregulated macropinocytosis, a process driven by constitutively hyper\u2010activated EGFR\/RAS\/PIK3CA signaling, which is common in HNSCC. Nanoparticle albumin\u2010bound (\n                      <jats:italic>nab<\/jats:italic>\n                      )\u2010paclitaxel is active in PD\u20101 inhibitor\u2010na\u00efve RM\u2010HNSCC and alters immune cells to potentially prime tumor response and reverse resistance to PD\u20101 inhibitors.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In a single\u2010arm phase 2 trial, patients with PD\u20101 inhibitor\u2010refractory RM\u2010HNSCC received\n                      <jats:italic>nab\u2010<\/jats:italic>\n                      paclitaxel and nivolumab given in 28\u2010day cycles. The primary endpoint was objective response rate (ORR), using RECIST1.1. Key secondary endpoints were duration of response (DoR), progression\u2010free survival (PFS), and overall survival (OS). At least one tumor response assessment was required to be evaluable for ORR and PFS. A Simon optimal two\u2010stage design tested the primary hypothesis (ORR: H\n                      <jats:sub>1<\/jats:sub>\n                      \u2009\u2265\u200950 vs. H\n                      <jats:sub>0<\/jats:sub>\n                      \u2009\u2264\u200930%, type I error 0.05; power 0.80). H\n                      <jats:sub>0<\/jats:sub>\n                      was rejected if \u2265\u200919 responses were observed in 46 patients. This sample size had a power of 80% to detect the difference in the key secondary hypothesis (median PFS: H\n                      <jats:sub>1<\/jats:sub>\n                      6.0 vs. H\n                      <jats:sub>0<\/jats:sub>\n                      3.6\u2009months, two\u2010sided, one\u2010sample log rank test; type I error 0.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      From 9\/28\/2021\u20131\/4\/2024, 46 patients enrolled into the trial. One patient was not evaluable for ORR and PFS. Tumor response occurred in 21 of 45 evaluable patients (ORR 46.7%, 95% CI: 33.8\u201359.9; vs. H\n                      <jats:sub>0<\/jats:sub>\n                      ,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0073) and included confirmed response in 20 and unconfirmed response in 1. The best tumor response was complete (4), partial (17), stable (18), and progression (6). The median DoR was 6.1\u2009months (95% CI: 2.8\u20139.4). With a median follow\u2010up of 14.1\u2009months (IQR: 7.6\u201320.1), the median PFS was 5.5\u2009months (95% CI: 3.9\u20137.8) and the median OS was 13.9\u2009months (95% CI: 9.0\u201318.9). Treatment\u2010related deaths did not occur.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Among patients with PD\u20101 inhibitor\u2010refractory RM\u2010HNSCC,\n                      <jats:italic>nab<\/jats:italic>\n                      \u2010paclitaxel and nivolumab resulted in an ORR and median PFS that were better than historically reported with standard therapy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>Trial registered on www.clinicaltrials.gov, National Clinical Trial (NCT) 04831320<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.71533","type":"journal-article","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T05:49:34Z","timestamp":1768196974000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Nanoparticle Albumin\u2010Bound Paclitaxel and Nivolumab for\n                    <scp>PD<\/scp>\n                    \u20101 Inhibitor\u2010Refractory Recurrent or Metastatic Head and Neck Squamous\u2010Cell Carcinoma"],"prefix":"10.1002","volume":"15","author":[{"given":"Douglas","family":"Adkins","sequence":"first","affiliation":[{"name":"Alvin J. 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Siteman Cancer Center Washington University School of Medicine  St. Louis Missouri USA"},{"name":"Division of Medical Oncology Washington University School of Medicine  St. Louis Missouri USA"},{"name":"Robert Ebert and Greg Stubblefield Head and Neck Tumor Center Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brendan","family":"Knapp","sequence":"additional","affiliation":[{"name":"Alvin J. Siteman Cancer Center Washington University School of Medicine  St. Louis Missouri USA"},{"name":"Division of Medical Oncology Washington University School of Medicine  St. Louis Missouri USA"},{"name":"Robert Ebert and Greg Stubblefield Head and Neck Tumor Center Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesse","family":"Zaretsky","sequence":"additional","affiliation":[{"name":"Alvin J. 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