Show simple item record

dc.contributor.authorChoudhury, AD
dc.contributor.authorHigano, CS
dc.contributor.authorde Bono, JS
dc.contributor.authorCook, N
dc.contributor.authorRathkopf, DE
dc.contributor.authorWisinski, KB
dc.contributor.authorMartin-Liberal, J
dc.contributor.authorLinch, M
dc.contributor.authorHeath, EI
dc.contributor.authorBaird, RD
dc.contributor.authorGarcia-Corbacho, J
dc.contributor.authorQuintela-Fandino, M
dc.contributor.authorBarry, ST
dc.contributor.authorde Bruin, EC
dc.contributor.authorColebrook, S
dc.contributor.authorHawkins, G
dc.contributor.authorKlinowska, T
dc.contributor.authorMaroj, B
dc.contributor.authorMoorthy, G
dc.contributor.authorMortimer, PG
dc.contributor.authorMoschetta, M
dc.contributor.authorNikolaou, M
dc.contributor.authorSainsbury, L
dc.contributor.authorShapiro, GI
dc.contributor.authorSiu, LL
dc.contributor.authorHansen, AR
dc.date.accessioned2022-05-24T14:24:12Z
dc.date.available2022-05-24T14:24:12Z
dc.date.issued2022-03-04
dc.identifier.citationClinical cancer research : an official journal of the American Association for Cancer Research, 2022, pp. clincanres.3087.2021 - ?en
dc.identifier.issn1078-0432
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/5141
dc.identifier.eissn1557-3265en_US
dc.identifier.eissn1557-3265
dc.identifier.doi10.1158/1078-0432.ccr-21-3087en_US
dc.identifier.doi10.1158/1078-0432.ccr-21-3087
dc.description.abstractTo characterize safety and tolerability of the selective PI3Kβ inhibitor AZD8186, identify a recommended phase II dose (RP2D), and assess preliminary efficacy in combination with abiraterone acetate or vistusertib. This phase I open-label study included patients with advanced solid tumors, particularly prostate cancer, triple-negative breast cancer, and squamous non-small-cell lung cancer. The study comprised four arms: 1) AZD8186 monotherapy dose-finding; 2) monotherapy dose-expansion; 3) AZD8186/abiraterone acetate (with prednisone); and 4) AZD8186/vistusertib. The primary endpoints were safety, tolerability, and identification of the RP2D of AZD8186 monotherapy and in combination. Secondary endpoints included pharmacokinetics, pharmacodynamics, and tumor and prostate-specific antigen (PSA) responses. In total, 161 patients were enrolled. AZD8186 was well tolerated across all study arms, the most common adverse events being gastrointestinal symptoms. In the monotherapy dose-finding arm, four patients experienced dose-limiting toxicities (mainly rash). AZD8186 doses of 60 mg twice daily (BID; 5 days on, 2 days off [5:2]) and 120 mg BID (continuous and 5:2 dosing) were taken into subsequent arms. The pharmacokinetics of AZD8186 were dose proportional, without interactions with abiraterone acetate or vistusertib, and target inhibition was observed in plasma and tumor tissue. Monotherapy and combination therapy showed preliminary evidence of limited anti-tumor activity by imaging and, in prostate cancer, PSA reduction. AZD8186 monotherapy had an acceptable safety and tolerability profile, and combination with abiraterone acetate/prednisone or vistusertib was also tolerated. There was preliminary evidence of anti-tumor activity, meriting further exploration of AZD8186 in subsequent studies in PI3Kb-pathway-dependent cancers.en_US
dc.formatPrint-Electronicen_US
dc.format.extentclincanres.3087.2021 - ?en_US
dc.languageengen_US
dc.language.isoengen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.titleA phase I study investigating AZD8186, a potent and selective inhibitor of PI3Kβ/δ, in patients with advanced solid tumors.en
dc.typeJournal Article
dcterms.dateAccepted2022-03-01
rioxxterms.versionVoRen
rioxxterms.versionofrecord10.1158/1078-0432.ccr-21-3087en
rioxxterms.licenseref.startdate2022-03-04
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, Johannen_US


Files in this item

Thumbnail

This item appears in the following collection(s)

Show simple item record

http://creativecommons.org/licenses/by/4.0/
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by/4.0/