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dc.contributor.authorde Bono, JS
dc.contributor.authorFleming, MT
dc.contributor.authorWang, JS
dc.contributor.authorCathomas, R
dc.contributor.authorMiralles, MS
dc.contributor.authorBothos, J
dc.contributor.authorHinrichs, MJ
dc.contributor.authorZhang, Q
dc.contributor.authorHe, P
dc.contributor.authorWilliams, M
dc.contributor.authorRosenbaum, AI
dc.contributor.authorLiang, M
dc.contributor.authorVashisht, K
dc.contributor.authorCho, S
dc.contributor.authorMartinez, P
dc.contributor.authorPetrylak, DP
dc.date.accessioned2021-06-11T11:43:03Z
dc.date.available2021-06-11T11:43:03Z
dc.identifier.citationClinical cancer research : an official journal of the American Association for Cancer Research, 2021
dc.identifier.issn1078-0432
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/4624
dc.identifier.eissn1557-3265
dc.identifier.eissn1557-3265en_US
dc.identifier.doi10.1158/1078-0432.ccr-20-4528
dc.identifier.doi10.1158/1078-0432.ccr-20-4528en_US
dc.description.abstractPurpose 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.
dc.formatPrint-Electronic
dc.languageeng
dc.language.isoeng
dc.titlePhase I Study of MEDI3726: A Prostate-Specific Membrane Antigen-Targeted Antibody-Drug Conjugate, in Patients with mCRPC after Failure of Abiraterone or Enzalutamide.
dc.typeJournal Article
dcterms.dateAccepted2021-03-29
rioxxterms.versionAM
rioxxterms.versionofrecord10.1158/1078-0432.ccr-20-4528
dc.relation.isPartOfClinical cancer research : an official journal of the American Association for Cancer Research
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Prostate Cancer Targeted Therapy Group
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Prostate Cancer Targeted Therapy Group
pubs.publication-statusPublished
pubs.embargo.termsNot known
icr.researchteamProstate Cancer Targeted Therapy Group
icr.researchteamProstate Cancer Targeted Therapy Groupen_US
dc.contributor.icrauthorDe Bono, Johannen


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