{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T11:31:14Z","timestamp":1790422274365,"version":"4.1.0"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2021,10,2]],"date-time":"2021-10-02T00:00:00Z","timestamp":1633132800000},"content-version":"vor","delay-in-days":274,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006436","name":"Celgene","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006436","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Bristol-Myers Squibb Company, Summit"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>This phase I\/II trial in patients with recurrent glioblastoma (GBM) evaluates the safety and preliminary efficacy of marizomib, an irreversible pan-proteasome inhibitor that crosses the blood\u2013brain barrier.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Part A assessed the safety and efficacy of marizomib monotherapy. In Part B, escalating doses of marizomib (0.5\u20130.8 mg\/m2) in combination with bevacizumab were evaluated. Part C explored intra-patient dose escalation of marizomib (0.8\u20131.0 mg\/m2) for the combination.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In Part A, 30 patients received marizomib monotherapy. The most common AEs were fatigue (66.7%), headache (46.7%), hallucination (43.3%), and insomnia (43.3%). One patient (3.3%) achieved a partial response. In Part B, the recommended phase II dose of marizomib was 0.8 mg\/m2 when combined with bevacizumab 10 mg\/kg. In Part C, dose escalation to 1.0 mg\/m2 was not tolerated. Pooled analysis of 67 patients treated with marizomib \u22640.8 mg\/m2 and bevacizumab showed a nonoverlapping safety profile consistent with the known safety profile of each agent: the most common grade \u22653 AEs were hypertension (16.4%), confusion (13.4%), headache (10.4%), and fatigue (10.4%). The overall response rate was 34.3%, including 2 patients with complete response. Six-month progression-free survival was 29.8%; median overall survival was 9.1 months.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The safety profile of marizomib as monotherapy and in combination with bevacizumab was consistent with previous observations that marizomib crosses the blood\u2013brain barrier. Preliminary efficacy did not demonstrate a meaningful benefit of the addition of marizomib to bevacizumab for the treatment of recurrent GBM.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/noajnl\/vdab142","type":"journal-article","created":{"date-parts":[[2021,10,2]],"date-time":"2021-10-02T18:01:57Z","timestamp":1633197717000},"source":"Crossref","is-referenced-by-count":21,"title":["Marizomib alone or in combination with bevacizumab in patients with recurrent glioblastoma: Phase I\/II clinical trial data"],"prefix":"10.1093","volume":"3","author":[{"given":"Daniela A","family":"Bota","sequence":"first","affiliation":[{"name":"Chao Family Comprehensive Cancer Center and Departments of Neurology and Neurological Surgery, University of California, Irvine, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Warren","family":"Mason","sequence":"additional","affiliation":[{"name":"Princess Margaret Cancer Centre, Toronto, Ontario, 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