Cited 103 times in
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 | 라선영 | - |
dc.contributor.author | 정현철 | - |
dc.date.accessioned | 2018-07-20T08:48:32Z | - |
dc.date.available | 2018-07-20T08:48:32Z | - |
dc.date.issued | 2017 | - |
dc.identifier.issn | 1078-0432 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/161400 | - |
dc.description.abstract | Background: The PI3K/protein kinase B (AKT) pathway is commonly activated in several tumor types. Selective targeting of p110β 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 PI3Kβ.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 type-specific 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. | - |
dc.description.statementOfResponsibility | restriction | - |
dc.language | English | - |
dc.publisher | American Association for Cancer Research | - |
dc.relation.isPartOf | CLINICAL CANCER RESEARCH | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
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.college | College of Medicine | - |
dc.contributor.department | Dept. of Internal Medicine | - |
dc.contributor.googleauthor | Joaquin Mateo | - |
dc.contributor.googleauthor | Gopinath Ganji | - |
dc.contributor.googleauthor | Charlotte Lemech | - |
dc.contributor.googleauthor | Howard A. Burris | - |
dc.contributor.googleauthor | Sae-Won Han | - |
dc.contributor.googleauthor | Karen Swales | - |
dc.contributor.googleauthor | Shaun Decordova | - |
dc.contributor.googleauthor | M. Phillip DeYoung | - |
dc.contributor.googleauthor | Deborah A. Smith | - |
dc.contributor.googleauthor | Shanker Kalyana-Sundaram | - |
dc.contributor.googleauthor | Jiuhua Wu | - |
dc.contributor.googleauthor | Monica Motwani | - |
dc.contributor.googleauthor | Rakesh Kumar | - |
dc.contributor.googleauthor | Jerry M. Tolson | - |
dc.contributor.googleauthor | Sun Young Rha | - |
dc.contributor.googleauthor | Hyun Cheol Chung | - |
dc.contributor.googleauthor | Joseph P. Eder | - |
dc.contributor.googleauthor | Sunil Sharma | - |
dc.contributor.googleauthor | Yung-Jue Bang | - |
dc.contributor.googleauthor | Jeffrey R. Infante | - |
dc.contributor.googleauthor | Li Yan | - |
dc.contributor.googleauthor | Johann S. de Bono | - |
dc.contributor.googleauthor | Hendrik-Tobias Arkenau | - |
dc.identifier.doi | 10.1158/1078-0432.CCR-17-0725 | - |
dc.contributor.localId | A01316 | - |
dc.contributor.localId | A03773 | - |
dc.relation.journalcode | J00564 | - |
dc.identifier.pmid | 28645941 | - |
dc.identifier.url | http://clincancerres.aacrjournals.org/content/23/19/5981.long | - |
dc.contributor.alternativeName | Rha, Sun Young | - |
dc.contributor.alternativeName | Chung, Hyun Cheol | - |
dc.contributor.affiliatedAuthor | Rha, Sun Young | - |
dc.contributor.affiliatedAuthor | Chung, Hyun Cheol | - |
dc.citation.volume | 23 | - |
dc.citation.number | 19 | - |
dc.citation.startPage | 5981 | - |
dc.citation.endPage | 5992 | - |
dc.identifier.bibliographicCitation | CLINICAL CANCER RESEARCH, Vol.23(19) : 5981-5992, 2017 | - |
dc.identifier.rimsid | 61318 | - |
dc.type.rims | ART | - |
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