Publications Repository

Publications Repository

View item 
  •   Home
  • ICR Divisions
  • Clinical Studies
  • View item
  • Home
  • ICR Divisions
  • Clinical Studies
  • View item
JavaScript is disabled for your browser. Some features of this site may not work without it.

Phase I Study of MEDI3726: A Prostate-Specific Membrane Antigen-Targeted Antibody-Drug Conjugate, in Patients with mCRPC after Failure of Abiraterone or Enzalutamide.

Thumbnail
View/Open
Accepted version (1.062Mb)
ICR Author
De Bono, Johann
Author
de Bono, JS
Fleming, MT
Wang, JS
Cathomas, R
Miralles, MS
Bothos, J
Hinrichs, MJ
Zhang, Q
He, P
Williams, M
Rosenbaum, AI
Liang, M
Vashisht, K
Cho, S
Martinez, P
Petrylak, DP
Show allShow less
Type
Journal Article
Metadata
Show full item record
Abstract
Purpose MEDI3726 is an antibody-drug conjugate targeting the prostate-specific membrane antigen and carrying a pyrrolobenzodiazepine warhead. This phase I study evaluated MEDI3726 monotherapy in patients with metastatic castration-resistant prostate cancer after disease progression on abiraterone and/or enzalutamide and taxane-based chemotherapy.Patients and methods MEDI3726 was administered at 0.015-0.3 mg/kg intravenously every 3 weeks until disease progression/unacceptable toxicity. The primary objective was to assess safety, dose-limiting toxicities (DLT), and MTD/maximum administered dose (MAD). Secondary objectives included assessment of antitumor activity, pharmacokinetics, and immunogenicity. The main efficacy endpoint was composite response, defined as confirmed response by RECIST v1.1, and/or PSA decrease of ≥50% after ≥12 weeks, and/or decrease from ≥5 to <5 circulating tumor cells/7.5 mL blood.Results Between February 1, 2017 and November 13, 2019, 33 patients received MEDI3726. By the data cutoff (January 17, 2020), treatment-related adverse events (TRAE) occurred in 30 patients (90.9%), primarily skin toxicities and effusions. Grade 3/4 TRAEs occurred in 15 patients (45.5%). Eleven patients (33.3%) discontinued because of TRAEs. There were no treatment-related deaths. One patient receiving 0.3 mg/kg had a DLT of grade 3 thrombocytopenia. The MTD was not identified; the MAD was 0.3 mg/kg. The composite response rate was 4/33 (12.1%). MEDI3726 had nonlinear pharmacokinetics with a short half-life (0.3-1.8 days). The prevalence of antidrug antibodies was 3/32 (9.4%), and the incidence was 13/32 (40.6%).Conclusions Following dose escalation, no MTD was identified. Clinical responses occurred at higher doses, but were not durable as patients had to discontinue treatment due to TRAEs.
URI
https://repository.icr.ac.uk/handle/internal/4624
DOI
https://doi.org/10.1158/1078-0432.ccr-20-4528
Collections
  • Clinical Studies
Research team
Prostate Cancer Targeted Therapy Group
Prostate Cancer Targeted Therapy Group
Language
eng
Date accepted
2021-03-29
Citation
Clinical cancer research : an official journal of the American Association for Cancer Research, 2021

Browse

All of ICR repositoryICR DivisionsBy issue dateAuthorsTitlesPublication TypesThis collectionBy issue dateAuthorsTitlesPublication Types
  • Login
  • Registered office: The Institute of Cancer Research, 123 Old Brompton Road, London, SW7 3RP
    A Charity, Not for Profit. Company Limited by Guarantee.
    Registered in England No. 534147. VAT Registration No. GB 849 0581 02.