Phase II trial of the glycoprotein non-metastatic B-targeted antibody-drug conjugate, glembatumumab vedotin (CDX-011), in recurrent osteosarcoma AOST1521: A report from the Children's Oncology Group.
Adolescent
Clinical trial
Molecular targeted therapy
Osteosarcoma
Paediatrics
Young adult
Journal
European journal of cancer (Oxford, England : 1990)
ISSN: 1879-0852
Titre abrégé: Eur J Cancer
Pays: England
ID NLM: 9005373
Informations de publication
Date de publication:
11 2019
11 2019
Historique:
received:
22
02
2019
revised:
21
07
2019
accepted:
22
08
2019
pubmed:
7
10
2019
medline:
9
6
2020
entrez:
7
10
2019
Statut:
ppublish
Résumé
The prognosis is poor for children and adolescents with recurrent osteosarcoma (OS). Glycoprotein non-metastatic B (gpNMB) is a glycoprotein highly expressed in OS cells. We conducted a phase II study of glembatumumab vedotin (GV), a fully human IgG2 monoclonal antibody (CR011) against gpNMB conjugated to the microtubule inhibitor, monomethyl auristatin E. Patients aged ≥12 years and <50 years with relapsed or refractory OS were eligible. GV 1.9 mg/kg/dose was administered on day 1 of each 21 day cycle. Pharmacokinetics were mandatory in patients aged <15 years. gpNMB expression was measured by immunohistochemistry. The primary end-point was disease control at 4 months and Response Evaluation Criteria in Solid Tumours response. A 2-stage design was used to determine efficacy. Twenty-two patients were enrolled, and all were evaluable for response. Antibody-drug conjugate levels were detectable in patients, although small numbers limit comparison to adult data. The toxicities observed were similar to the previous studies with GV. The most common grade III adverse event was rash. One death from end organ failure occurred possibly related to GV. Of the 22 patients, one patient had a partial response, and two had stable disease. There was no correlation between gpNMB expression and response to GV. GV was well tolerated in this population. Although there was some antitumour activity, the extent of disease control in stage I did not meet the level required to proceed to stage II. NCT02487979.
Sections du résumé
BACKGROUND
The prognosis is poor for children and adolescents with recurrent osteosarcoma (OS). Glycoprotein non-metastatic B (gpNMB) is a glycoprotein highly expressed in OS cells. We conducted a phase II study of glembatumumab vedotin (GV), a fully human IgG2 monoclonal antibody (CR011) against gpNMB conjugated to the microtubule inhibitor, monomethyl auristatin E.
PATIENTS AND METHODS
Patients aged ≥12 years and <50 years with relapsed or refractory OS were eligible. GV 1.9 mg/kg/dose was administered on day 1 of each 21 day cycle. Pharmacokinetics were mandatory in patients aged <15 years. gpNMB expression was measured by immunohistochemistry. The primary end-point was disease control at 4 months and Response Evaluation Criteria in Solid Tumours response. A 2-stage design was used to determine efficacy.
RESULTS
Twenty-two patients were enrolled, and all were evaluable for response. Antibody-drug conjugate levels were detectable in patients, although small numbers limit comparison to adult data. The toxicities observed were similar to the previous studies with GV. The most common grade III adverse event was rash. One death from end organ failure occurred possibly related to GV. Of the 22 patients, one patient had a partial response, and two had stable disease. There was no correlation between gpNMB expression and response to GV.
CONCLUSIONS
GV was well tolerated in this population. Although there was some antitumour activity, the extent of disease control in stage I did not meet the level required to proceed to stage II.
TRIAL REGISTRATION NUMBERS
NCT02487979.
Identifiants
pubmed: 31586757
pii: S0959-8049(19)30475-7
doi: 10.1016/j.ejca.2019.08.015
pmc: PMC6952063
mid: NIHMS1547420
pii:
doi:
Substances chimiques
Antibodies, Monoclonal
0
Immunoconjugates
0
glembatumumab vedotin
1568H6A58U
Banques de données
ClinicalTrials.gov
['NCT02487979']
Types de publication
Clinical Trial, Phase II
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
177-183Subventions
Organisme : NCI NIH HHS
ID : U10 CA180886
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA180899
Pays : United States
Organisme : NCI NIH HHS
ID : UG1 CA233324
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier Ltd. All rights reserved.
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