A Phase Ib/II study of IGF-neutralising antibody xentuzumab with enzalutamide in metastatic castration-resistant prostate cancer.
Date
2023-10-05ICR Author
Author
Macaulay, VM
Lord, S
Hussain, S
Maroto, JP
Jones, RH
Climent, MÁ
Cook, N
Lin, C-C
Wang, S-S
Bianchini, D
Bailey, M
Schlieker, L
Bogenrieder, T
de Bono, J
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
Male
Humans
Prostatic Neoplasms, Castration-Resistant
Treatment Outcome
Antibodies, Neutralizing
Nitriles
Antineoplastic Combined Chemotherapy Protocols
Research team
PrCa Targeted Therapy
Language
eng
Date accepted
2023-07-25
License start date
2023-10-05
Citation
British Journal of Cancer, 2023, 129 (6), pp. 965 - 973
Publisher
SPRINGERNATURE