A Phase Ib/II study of IGF-neutralising antibody xentuzumab with enzalutamide in metastatic castration-resistant prostate cancer

Macaulay, Valentine M., Lord, Simon, Hussain, Syed, Maroto, José Pablo, Jones, Robert Hugh ORCID: https://orcid.org/0000-0003-3576-9496, Climent, Miguel Ángel, Cook, Natalie, Lin, Chia-Chi, Wang, Shian-Shiang, Bianchini, Diletta, Bailey, Mark, Schlieker, Laura, Bogenrieder, Thomas and de Bono, Johann 2023. A Phase Ib/II study of IGF-neutralising antibody xentuzumab with enzalutamide in metastatic castration-resistant prostate cancer. British Journal of Cancer 129 , pp. 965-973. 10.1038/s41416-023-02380-1

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Publisher:	Springer Nature [academic journals on nature.com]
ISSN:	0007-0920
Date of First Compliant Deposit:	14 August 2023
Date of Acceptance:	25 July 2023
Last Modified:	09 Oct 2023 08:12
URI:	https://orca.cardiff.ac.uk/id/eprint/161708

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