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Phase 1\/2 studies suggest tolerability and anti-tumor activity in various types of cancer; a Phase 3 study of napabucasin plus standard therapy in colorectal cancer is ongoing. This is a Phase 1 dose-escalation study in patients with advanced solid tumors, and the first study of napabucasin in Japanese patients.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>Patients received napabucasin 480, 960, or 1440\u00a0mg daily in 28-day cycles until disease progression or intolerable toxicity. Primary objectives were to determine dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), and the pharmacokinetic (PK) profile of napabucasin. Blood samples were taken for PK analysis on Days 1, 2, 8, and 15 of Cycle 1, and Days 29 and 30 of Cycle 2. Secondary objectives were to assess napabucasin antitumor activity, and the relationship between biomarkers and antitumor activity. JapicCTI-No: JapicCTI-132152.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>Enrolled were 14 patients (480\u00a0mg [<jats:italic>n<\/jats:italic>\u2009=\u20093], 960\u00a0mg [<jats:italic>n<\/jats:italic>\u2009=\u20094], 1440\u00a0mg [<jats:italic>n<\/jats:italic>\u2009=\u20097]). One patient experienced a DLT (Grade 3, anorexia). MTD was 1440\u00a0mg\/day. Most common drug-related adverse events were diarrhea (<jats:italic>n<\/jats:italic>\u2009=\u20099), nausea (<jats:italic>n<\/jats:italic>\u2009=\u20094), vomiting (<jats:italic>n<\/jats:italic>\u2009=\u20093), and anorexia (<jats:italic>n<\/jats:italic>\u2009=\u20093). Napabucasin showed a similar PK profile to previous studies and no abnormal accumulation was observed. Following treatment, two patients had stable disease; the remaining 12 had progressive disease.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusion<\/jats:title>\n<jats:p>Napabucasin was well-tolerated at doses up to 1440\u00a0mg\/day in Japanese patients with advanced solid tumors; the PK profile was comparable to that reported previously.<\/jats:p>\n<\/jats:sec>","DOI":"10.1007\/s00280-020-04059-3","type":"journal-article","created":{"date-parts":[[2020,3,31]],"date-time":"2020-03-31T07:03:10Z","timestamp":1585638190000},"page":"855-862","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Phase 1 study of napabucasin, a cancer stemness inhibitor, in patients with advanced solid tumors"],"prefix":"10.1007","volume":"85","author":[{"given":"Akihito","family":"Kawazoe","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasutoshi","family":"Kuboki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideaki","family":"Bando","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shota","family":"Fukuoka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Kojima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8490-9064","authenticated-orcid":false,"given":"Yoichi","family":"Naito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuichi","family":"Iino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhide","family":"Yodo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihiko","family":"Doi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kohei","family":"Shitara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Yoshino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,3,31]]},"reference":[{"key":"4059_CR1","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1146\/annurev.cellbio.22.010305.104154","volume":"23","author":"NA Lobo","year":"2007","unstructured":"Lobo NA, Shimono Y, Qian D, Clarke MF (2007) The biology of cancer stem cells. 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Y.K. received research funding from Sumitomo Dainippon Pharma and honoraria from MSD. H.B. received lecture fees from and Eli Lilly Japan and Taiho and research funding from, AstraZeneca, Sysmex and Taiho. S.F. and T.K. have no conflict of interest to declare. Y.N. has served on speakers\u2019 bureau from Chigai Pharma, Eisai, Novartis and Pfizer, and research funding from Roche. S.I. and Y.Y. are employees of Sumitomo Dainippon Pharma. T.D. has held a consulting\/advisory role for Abbvie, Amgen, Bayer, Boeringer Ingelheim, Daiichi Sankyo, Kyowa Hakko Kirin, MSD, Novartis, Rakuten Medical, Sumitomo Dainippon Pharma, Taiho, and Takeda and has received research funding from Abbvie, Boeringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Eisai, Eli Lilly, Kyowa Hakko Kirin, Merck Serono, MSD, Novartis, Pfizer, Sumitomo Dainippon Pharma and Taiho Pharmaceutical. K.S. received personal fees from AbbVie, Astellas Pharma, Bristol Myers Squibb, Eli Lilly, MSD, Ono Pharmaceutical, Novartis, Pfizer, Takeda and Yakult and grants from Astellas Pharma, Chugai Pharma, Daiichi Sankyo, Eli Lilly, Medi Science, MSD, Ono Pharmaceutical, Sumitomo Dainippon Pharma and Taiho Pharmaceutical. T.Y. has received research funding from Chugai Pharma Co., Ltd., Daiichi Sankyo Co., Ltd., GlaxoSmithKline K.K., MSD K.K., Novartis, K.K., Ono Pharmaceutical Co., Ltd., Parexel International Inc., Sanofi K.K. and Sumitomo Dainippon Pharma Co., Ltd.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}