dc.contributor.author | Macaulay, VM | |
dc.contributor.author | Lord, S | |
dc.contributor.author | Hussain, S | |
dc.contributor.author | Maroto, JP | |
dc.contributor.author | Jones, RH | |
dc.contributor.author | Climent, MÁ | |
dc.contributor.author | Cook, N | |
dc.contributor.author | Lin, C-C | |
dc.contributor.author | Wang, S-S | |
dc.contributor.author | Bianchini, D | |
dc.contributor.author | Bailey, M | |
dc.contributor.author | Schlieker, L | |
dc.contributor.author | Bogenrieder, T | |
dc.contributor.author | de Bono, J | |
dc.coverage.spatial | England | |
dc.date.accessioned | 2023-09-22T12:38:37Z | |
dc.date.available | 2023-09-22T12:38:37Z | |
dc.date.issued | 2023-10-05 | |
dc.identifier | 10.1038/s41416-023-02380-1 | |
dc.identifier.citation | British Journal of Cancer, 2023, 129 (6), pp. 965 - 973 | en_US |
dc.identifier.issn | 0007-0920 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/5980 | |
dc.identifier.eissn | 1532-1827 | |
dc.identifier.eissn | 1532-1827 | |
dc.identifier.doi | 10.1038/s41416-023-02380-1 | |
dc.description.abstract | BACKGROUND: This multicentre, open-label, Phase Ib/II trial evaluated the insulin-like growth factor (IGF) 1/2 neutralising antibody xentuzumab plus enzalutamide in metastatic castrate-resistant prostate cancer (mCRPC). METHODS: The trial included Phase Ib escalation and expansion parts and a randomised Phase II part versus enzalutamide alone. Primary endpoints in the Phase Ib escalation, Phase Ib expansion and Phase II parts were maximum tolerated dose (MTD), prostate-specific antigen response and investigator-assessed progression-free survival (PFS), respectively. Patients in the Phase Ib escalation and Phase II parts had progressed on/after docetaxel/abiraterone. RESULTS: In the Phase Ib escalation (n = 10), no dose-limiting toxicities were reported, and xentuzumab 1000 mg weekly plus enzalutamide 160 mg daily (Xe1000 + En160) was defined as the MTD and recommended Phase 2 dose. In the Phase Ib expansion (n = 24), median PFS was 8.2 months, and one patient had a confirmed, long-term response. In Phase II (n = 86), median PFS for the Xe1000 + En160 and En160 arms was 7.4 and 6.2 months, respectively. Subgroup analysis suggested trends towards benefit with Xe1000 + En160 in patients whose tumours had high levels of IGF1 mRNA or PTEN protein. Overall, the combination was well tolerated. CONCLUSIONS: Xentuzumab plus enzalutamide was tolerable but lacked antitumour activity in unselected patients with mCRPC. CLINICAL TRIAL REGISTRATION: EudraCT number 2013-004011-41. | |
dc.format | Print-Electronic | |
dc.format.extent | 965 - 973 | |
dc.language | eng | |
dc.language.iso | eng | en_US |
dc.publisher | SPRINGERNATURE | en_US |
dc.relation.ispartof | British Journal of Cancer | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en_US |
dc.subject | Male | |
dc.subject | Humans | |
dc.subject | Prostatic Neoplasms, Castration-Resistant | |
dc.subject | Treatment Outcome | |
dc.subject | Antibodies, Neutralizing | |
dc.subject | Nitriles | |
dc.subject | Antineoplastic Combined Chemotherapy Protocols | |
dc.title | A Phase Ib/II study of IGF-neutralising antibody xentuzumab with enzalutamide in metastatic castration-resistant prostate cancer. | en_US |
dc.type | Journal Article | |
dcterms.dateAccepted | 2023-07-25 | |
dc.date.updated | 2023-09-22T12:37:53Z | |
rioxxterms.version | VoR | en_US |
rioxxterms.versionofrecord | 10.1038/s41416-023-02380-1 | en_US |
rioxxterms.licenseref.startdate | 2023-10-05 | |
rioxxterms.type | Journal Article/Review | en_US |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/37537253 | |
pubs.issue | 6 | |
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-status | Published | |
pubs.publisher-url | http://dx.doi.org/10.1038/s41416-023-02380-1 | |
pubs.volume | 129 | |
icr.researchteam | PrCa Targeted Therapy | en_US |
dc.contributor.icrauthor | De Bono, Johann | |
icr.provenance | Deposited by Mr Arek Surman (impersonating Prof Johann De Bono) on 2023-09-22. Deposit type is initial. No. of files: 1. Files: A Phase IbII study of IGF-neutralising antibody xentuzumab with enzalutamide in metastatic castration-resistant prostate can.pdf | |