A Phase Ib/II study of IGF-neutralising antibody xentuzumab with enzalutamide in metastatic castration-resistant prostate cancer
Macaulay, Valentine M. (University of Oxford)
Lord, Simon (University of Oxford)
Hussain, Syed (University of Sheffield)
Maroto Rey, Pablo (Institut d'Investigació Biomèdica Sant Pau)
Jones, Robert Hugh (Velindre Cancer Centre and Cardiff University)
Climent, Miguel Ángel (Instituto Valenciano de Oncología (IVO))
Cook, Natalie (The Christie NHS Foundation Trust and the University of Manchester)
Lin, Chia-Chi (National Taiwan University Hospital)
Wang, Shiang-Shiang (Taichung Veterans General Hospital)
Bianchini, Diletta (The Royal Marsden NHS Foundation Trust)
Bailey, Mark (Boehringer Ingelheim Ltd. Bracknell)
Schlieker, Laura (Boehringer Ingelheim)
Bogenrieder, Thomas (University Hospital of Tübingen (Alemanya))
de Bono, Johann S (The Royal Marsden NHS Foundation Trust)
Universitat Autònoma de Barcelona

Date:	2023
Abstract:	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). 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. 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. Xentuzumab plus enzalutamide was tolerable but lacked antitumour activity in unselected patients with mCRPC. Clinical trial registration: EudraCT number 2013-004011-41.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Prostate cancer ; Drug discovery
Published in:	British journal of cancer, Vol. 129 Núm. 6 (may 2023) , p. 965-973, ISSN 1532-1827

DOI: 10.1038/s41416-023-02380-1
PMID: 37537253

9 p, 666.6 KB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
Articles > Published articles