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

Journal article

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

Authors: Macaulay, VM; Lord, S; Hussain, S; Maroto, JP; Jones, RH

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Springer Nature [academic journals on nature.com]
• Journal: British Journal of Cancer
• Volume: 129
• Issue: 6
• Pages: 965-973
• Publication date: 2023-08-03
• DOI: 10.1038/s41416-023-02380-1
• EISSN: 1532-1827
• ISSN: 0007-0920
• Language: English
• Keywords: Medicine; Clinical trial; Docetaxel; Androgen receptor; Phases of clinical research; Enzalutamide; Internal medicine; Prostate cancer; Oncology; Cancer