{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T07:35:51Z","timestamp":1776411351554,"version":"3.51.2"},"reference-count":32,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T00:00:00Z","timestamp":1739404800000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007136","name":"Karyopharm Therapeutics","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007136","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Selinexor (SEL) is a nuclear exportin 1 inhibitor that blocks the transport of nuclear proteins, including tumor suppressors, to the cytoplasm. Preclinical data suggest that the combination of SEL with checkpoint blockade may result in improved response to immunotherapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>NCT02419495 was a multiarm phase IB study of SEL in combination with other standard regimens in patients with advanced malignancies. Arm M utilized twice weekly oral SEL and intravenous nivolumab (NIVO). Arm N utilized weekly oral SEL with NIVO plus ipilimumab (IPI). The primary objective of this study was to evaluate the safety of SEL\u2009+\u2009NIVO and SEL\u2009+\u2009NIVO+IPI. Secondary objectives included determining the objective response rate (ORR) and progression\u2010free survival (PFS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Twenty\u2010nine patients were enrolled in the study, of which 26 (90%) had clear cell RCC (ccRCC). Most patients (72%, <jats:italic>n<\/jats:italic>\u2009=\u200921) had prior systemic therapies. All patients (100%) developed at least one treatment\u2010emergent adverse event, and 93% had a treatment\u2010related adverse event (TRAE). Grade \u2265\u20093 TRAE occurred in 31% of patients, including 10% with hyponatremia, 7% with neutropenia, and 7% with thromboembolic events. At a median follow\u2010up of 12.4\u2009months, the ORR in 27 patients evaluable for response was 19% (<jats:italic>n<\/jats:italic>\u2009=\u20095). An additional 17 patients (63%) had stable disease (SD) as the best response. The median PFS for the overall cohort was 14.5\u2009months (95% CI 5.2\u201317.4\u2009months; SEL\u2009+\u2009NIVO+IPI: 12.2\u2009months, SEL\u2009+\u2009NIVO: 14.5\u2009months). The median overall survival was 27.8\u2009months (95% CI 15.3\u201332.5; SEL\u2009+\u2009NIVO+IPI: unreached, SEL\u2009+\u2009NIVO: 21.3\u2009months).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>SEL in combination with NIVO or NIVO+IPI had a potentially favorable safety profile and showed modest clinical activity in patients with advanced renal cell carcinoma.<\/jats:p><jats:p><jats:bold>Trial Registration:<\/jats:bold> This clinical trial was registered on <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">clinicaltrials.gov<\/jats:ext-link> (NCT02419495)<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.70280","type":"journal-article","created":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T12:06:07Z","timestamp":1739448367000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A Phase IB Trial of Selinexor in Combination With Immune Checkpoint Blockade in Patients With Advanced Renal Cell Carcinoma"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9658-2206","authenticated-orcid":false,"given":"Omar","family":"Alhalabi","sequence":"first","affiliation":[{"name":"Department of Genitourinary Medical Oncology, Division of Cancer Medicine The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4829-6739","authenticated-orcid":false,"given":"Mohamed A.","family":"Gouda","sequence":"additional","affiliation":[{"name":"Department of Investigational Cancer Therapeutics, Division of Cancer Medicine The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Den\u00e1i R.","family":"Milton","sequence":"additional","affiliation":[{"name":"Department of Biostatistics The University of Texas MD Anderson 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