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

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 ve...

Celý popis

Uloženo v:
Podrobná bibliografie
Vydáno v:British journal of cancer Ročník 129; číslo 6; s. 965 - 973
Hlavní autoři: Macaulay, Valentine M, Lord, Simon, Hussain, Syed, Maroto, José Pablo, Jones, Robert Hugh, Climent, Miguel Ángel, Cook, Natalie, Lin, Chia-Chi, Wang, Shian-Shiang, Bianchini, Diletta, Bailey, Mark, Schlieker, Laura, Bogenrieder, Thomas, de Bono, Johann
Médium: Journal Article
Jazyk:angličtina
Vydáno: England Nature Publishing Group 05.10.2023
Témata:
Antibodies, Neutralizing
Antineoplastic Combined Chemotherapy Protocols - adverse effects
Castration
Humans
Insulin-like growth factor I
Insulin-like growth factors
Male
Metastases
Metastasis
mRNA
Nitriles - therapeutic use
Prostate cancer
Prostate-specific antigen
Prostatic Neoplasms, Castration-Resistant - pathology
PTEN protein
Treatment Outcome
ISSN:0007-0920, 1532-1827, 1532-1827
On-line přístup:Získat plný text
Tagy: Přidat tag
Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!
Popis
Shrnutí: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. EudraCT number 2013-004011-41.
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
content type line 23
ObjectType-Undefined-3
ISSN:0007-0920
1532-1827
1532-1827
DOI:10.1038/s41416-023-02380-1