{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T01:50:31Z","timestamp":1791942631605,"version":"4.3.4"},"reference-count":36,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,3,27]],"date-time":"2025-03-27T00:00:00Z","timestamp":1743033600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["1R21 CA213977"],"award-info":[{"award-number":["1R21 CA213977"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Immunosuppressive factors such as regulatory T cells and myeloid\u2010derived suppressive cells (MDSCs) limit the efficacy of immunotherapies. Histone deacetylase (HDAC) inhibitors have been shown to have immunomodulatory effects. Thus, we conducted a Phase Ib clinical study with the HDAC inhibitor vorinostat and the PD\u20101 inhibitor pembrolizumab in patients (pts) with metastatic urothelial (UC), renal (RCC) and prostate (PCA) carcinoma.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The phase I portion consisted of two dose levels of vorinostat (100 and 200\u2009mg, PO daily 2\u2009weeks ON and 1\u2009week OFF) and a fixed dose of pembrolizumab (200\u2009mg IV every 21\u2009days). Patients (pts) were assigned to three cohorts: Cohort A (previously treated, anti\u2010PD1\/PD\u2010L1 na\u00efve UC and RCC), Cohort B (previously treated, anti\u2010PD1\/PD\u2010L1 resistant UC and RCC pts), and Cohort C (PCA pts).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Dose levels 1 and 2 were completed without DLTs. We have enrolled 44 pts. (36 evaluable) in the dose expansion cohorts, and the most common resolved grade 3\/4 toxicities were diarrhea, hypophosphatemia, acute kidney injury, anemia, and hypothyroidism. For Cohort A (13 pts), B (11 pts), and C (12 pts) the objective response rate was 8%, 0%, and 17%, and the median progression\u2010free survival was 2.9, 3.5, and 3.5\u2009months, respectively. Four partial responses were observed, and two PCA pts. had a complete biochemical response with undetectable PSA. Persistent lower levels of peripheral CD11<jats:sup>+<\/jats:sup>, CD14<jats:sup>+<\/jats:sup> HLA\u2010DR<jats:sup>\u2212<\/jats:sup> monocytic MDSCs were associated with clinical benefit.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The combination of vorinostat and pembrolizumab is relatively well tolerated and may be active in a subset of immune checkpoint\u2010resistant UC\/RCC pts. and immune checkpoint\u2010na\u00efve PCA pts.<\/jats:p><jats:p><jats:bold>Trial Registration:<\/jats:bold> NCT02619253<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.70725","type":"journal-article","created":{"date-parts":[[2025,3,30]],"date-time":"2025-03-30T04:47:30Z","timestamp":1743310050000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["A Phase I\/<scp>IB<\/scp>, Open Label, Dose Finding Study to Evaluate Safety, Pharmacodynamics and Efficacy of Pembrolizumab in Combination With Vorinostat in Patients With Advanced Prostate, Renal or Urothelial Carcinoma"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-9993-9911","authenticated-orcid":false,"given":"Roberto","family":"Pili","sequence":"first","affiliation":[{"name":"University at Buffalo  Buffalo New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David I.","family":"Quinn","sequence":"additional","affiliation":[{"name":"USC Norris Comprehensive Cancer Center  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8905-8329","authenticated-orcid":false,"given":"Nabil","family":"Adra","sequence":"additional","affiliation":[{"name":"Indiana University Melvin and Bren Simon Comprehensive Cancer Center  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodore","family":"Logan","sequence":"additional","affiliation":[{"name":"Indiana University Melvin and Bren 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