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A first-time-in-human study of GSK2636771, a phosphoinositide 3 kinase beta-selective inhibitor, in patients with advanced solid tumors
DC Field | Value | Language |
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dc.contributor.author | Mateo, Joaquin | - |
dc.contributor.author | Ganji, Gopinath | - |
dc.contributor.author | Lemech, Charlotte | - |
dc.contributor.author | Burris, Howard A. | - |
dc.contributor.author | Han, Sae-Won | - |
dc.contributor.author | Swales, Karen | - |
dc.contributor.author | Decordova, Shaun | - |
dc.contributor.author | DeYoung, M. Phillip | - |
dc.contributor.author | Smith, Deborah A. | - |
dc.contributor.author | Kalyana-Sundaram, Shanker | - |
dc.contributor.author | Wu, Jiuhua | - |
dc.contributor.author | Motwani, Monica | - |
dc.contributor.author | Kumar, Rakesh | - |
dc.contributor.author | Tolson, Jerry M. | - |
dc.contributor.author | Rha, Sun Young | - |
dc.contributor.author | Chung, Hyun Cheol | - |
dc.contributor.author | Eder, Joseph P. | - |
dc.contributor.author | Sharma, Sunil | - |
dc.contributor.author | Bang, Yung-Jue | - |
dc.contributor.author | Infante, Jeffrey R. | - |
dc.contributor.author | Yan, Li | - |
dc.contributor.author | de Bono, Johann S. | - |
dc.contributor.author | Arkenau, Hendrik-Tobias | - |
dc.date.accessioned | 2021-01-31T11:08:07Z | - |
dc.date.available | 2021-01-31T11:08:07Z | - |
dc.date.created | 2018-01-10 | - |
dc.date.issued | 2017-10 | - |
dc.identifier.citation | Clinical Cancer Research, Vol.23 No.19, pp.5981-5992 | - |
dc.identifier.issn | 1078-0432 | - |
dc.identifier.other | 15021 | - |
dc.identifier.uri | https://hdl.handle.net/10371/173046 | - |
dc.description.abstract | Background: The PI3K/protein kinase B (AKT) pathway is commonly activated in several tumor types. Selective targeting of p110 beta could result in successful pathway inhibition while avoiding the on- and off-target effects of pan-PI3K inhibitors. GSK2636771 is a potent, orally bioavailable, adenosine triphosphate-competitive, selective inhibitor of PI3K beta. Methods: We evaluated the safety, pharmacokinetics, pharmacodynamics and antitumor activity of GSK2636771 to define the recommended phase II dose (RP2D). During the dose-selection and dose-escalation stages (parts 1 and 2), patients with PTEN-deficient advanced solid tumors received escalating doses of GSK2636771 (25-500 mg once daily) using a modified 3-3 design to determine the RP2D; tumor typespecific expansion cohorts (part 3) were implemented to further assess tumor responses at the RP2D. Results: A total of 65 patients were enrolled; dose-limiting toxicities were hypophosphatemia and hypocalcemia. Adverse events included diarrhea (48%), nausea (40%), and vomiting (31%). Single-and repeat-dose exposure increased generally dose proportionally. GSK2636771 400 mg once daily was the RP2D. Phospho/total AKT ratio decreased with GSK2636771 in tumor and surrogate tissue. A castrate-resistant prostate cancer (CRPC) patient harboring PIK3CB amplification had a partial response for over a year; an additional 10 patients derived durable (>= 24 weeks) clinical benefit, including two other patients with CRPC with PIK3CB alterations (>= 34 weeks). GSK2636771 400 mg once daily orally induced sufficient exposure and target inhibition with a manageable safety profile. Conclusions: Genomic aberrations of PIK3CB may be associated with clinical benefit from GSK2636771. (C) 2017 AACR. | - |
dc.language | 영어 | - |
dc.publisher | American Association for Cancer Research | - |
dc.title | A first-time-in-human study of GSK2636771, a phosphoinositide 3 kinase beta-selective inhibitor, in patients with advanced solid tumors | - |
dc.type | Article | - |
dc.contributor.AlternativeAuthor | 방영주 | - |
dc.identifier.doi | 10.1158/1078-0432.CCR-17-0725 | - |
dc.citation.journaltitle | Clinical Cancer Research | - |
dc.identifier.wosid | 000412160500032 | - |
dc.identifier.scopusid | 2-s2.0-85032305458 | - |
dc.citation.endpage | 5992 | - |
dc.citation.number | 19 | - |
dc.citation.startpage | 5981 | - |
dc.citation.volume | 23 | - |
dc.identifier.sci | 000412160500032 | - |
dc.description.isOpenAccess | Y | - |
dc.contributor.affiliatedAuthor | Bang, Yung-Jue | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.subject.keywordPlus | COMPREHENSIVE GENOMIC CHARACTERIZATION | - |
dc.subject.keywordPlus | RESISTANT PROSTATE-CANCER | - |
dc.subject.keywordPlus | CLINICAL-TRIALS | - |
dc.subject.keywordPlus | BREAST-CANCER | - |
dc.subject.keywordPlus | MOLECULAR PORTRAITS | - |
dc.subject.keywordPlus | ABIRATERONE ACETATE | - |
dc.subject.keywordPlus | PATHWAY INHIBITORS | - |
dc.subject.keywordPlus | ANTITUMOR-ACTIVITY | - |
dc.subject.keywordPlus | PI3K INHIBITION | - |
dc.subject.keywordPlus | PTEN | - |
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