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dc.contributor.authorSarker, D
dc.contributor.authorDawson, NA
dc.contributor.authorAparicio, AM
dc.contributor.authorDorff, TB
dc.contributor.authorPantuck, AJ
dc.contributor.authorVaishampayan, UN
dc.contributor.authorHenson, L
dc.contributor.authorVasist, L
dc.contributor.authorRoy-Ghanta, S
dc.contributor.authorGorczyca, M
dc.contributor.authorYork, W
dc.contributor.authorGanji, G
dc.contributor.authorTolson, J
dc.contributor.authorde Bono, JS
dc.date.accessioned2021-10-20T09:40:35Z
dc.date.available2021-10-20T09:40:35Z
dc.date.issued2021-07-19
dc.identifier.citationClinical cancer research : an official journal of the American Association for Cancer Research, 2021
dc.identifier.issn1078-0432
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/4835
dc.identifier.eissn1557-3265
dc.identifier.eissn1557-3265
dc.identifier.doi10.1158/1078-0432.ccr-21-1115
dc.identifier.doi10.1158/1078-0432.ccr-21-1115
dc.description.abstract<h4>Purpose</h4>In patients with metastatic castration-resistant prostate cancer (mCRPC), resistance to androgen receptor (AR) targeted therapies, such as enzalutamide, remains an issue. Inactivation of inhibitory phosphatase and tensin homolog (PTEN) activates phosphoinositide 3-kinase (PI3K)/AKT signaling and contributes to resistance to androgen-deprivation therapy and poor outcomes. Therefore, dual targeting of AR and PI3K/AKT pathways may limit tumor growth and reverse resistance.<h4>Patients and methods</h4>In this Phase I study (NCT02215096), patients with PTEN-deficient mCRPC, who progressed on prior enzalutamide, received once-daily enzalutamide 160 mg plus PI3Kβ inhibitor GSK2636771 at 300 mg initial dose, with escalation or de-escalation in 100 mg increments, followed by dose expansion. Primary objectives were to evaluate safety/tolerability, determine the recommended Phase II dose (RP2D), and assess the 12-week non-progressive disease (PD) rate.<h4>Results</h4>Overall, 37 patients were enrolled; 36 received {greater than or equal to}1 dose of GSK2636771 (200 mg: n=22, 300 mg: n=12; 400 mg: n=2) plus 160 mg enzalutamide. Dose-limiting toxicities occurred in 5 patients (200 mg: n=1; 300 mg: n=2, 400 mg: n=2). No new or unexpected adverse events nor evidence of drug-drug interaction were observed. At the recommended dose of GSK2636771 (200 mg) plus enzalutamide, the 12-week non-PD rate was 50% (95% CI: 28.2-71.8%, n=22); 1 (3%) patient achieved a radiographic partial response lasting 36 weeks. 4/34 (12%) patients had prostate-specific antigen reduction of {greater than or equal to}50%.<h4>Conclusions</h4>Although there was acceptable safety and tolerability with GSK2636771 plus enzalutamide in patients with PTEN-deficient mCRPC after failing enzalutamide, limited antitumor activity was observed.
dc.formatPrint-Electronic
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://www.rioxx.net/licenses/all-rights-reserveden_US
dc.titleA Phase I, Open-Label, Dose-Finding Study of GSK2636771, a PI3Kβ inhibitor, Administered with Enzalutamide in Patients with Metastatic Castration-Resistant Prostate Cancer.en_US
dc.typeJournal Article
dcterms.dateAccepted2021-07-14
rioxxterms.versionAMen_US
rioxxterms.versionofrecord10.1158/1078-0432.ccr-21-1115en_US
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden_US
rioxxterms.licenseref.startdate2022-07-19
dc.relation.isPartOfClinical cancer research : an official journal of the American Association for Cancer Researchen_US
pubs.notesNot knownen_US
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Prostate Cancer Targeted Therapy Group
pubs.publication-statusPublisheden_US
pubs.embargo.termsNot knownen_US
icr.researchteamProstate Cancer Targeted Therapy Group
dc.contributor.icrauthorDe Bono, Johann


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