Phase I trial and pharmacokinetic study of lexatumumab in pediatric patients with solid tumors.
J Clin Oncol
; 30(33): 4141-7, 2012 Nov 20.
Article
em En
| MEDLINE
| ID: mdl-23071222
ABSTRACT
PURPOSE:
Lexatumumab is an agonistic, fully human monoclonal antibody against tumor necrosis factor-related apoptosis-inducing ligand receptor 2 with preclinical evidence of activity in pediatric solid tumors. PATIENTS ANDMETHODS:
This phase I dose-escalation study examined the safety, tolerability, pharmacokinetics, and immunogenicity of lexatumumab at doses up to, but not exceeding, the adult maximum-tolerated dose (3, 5, 8, and 10 mg/kg), administered once every 2 weeks to patients age≤21 years with recurrent or progressive solid tumors.RESULTS:
Twenty-four patients received a total of 56 cycles of lexatumumab over all four planned dose levels. One patient had grade 2 pericarditis consistent with radiation recall, and one patient developed grade 3 pneumonia with hypoxia during the second cycle. Five patients experienced stable disease for three to 24 cycles. No patients experienced complete or partial response, but several showed evidence of antitumor activity, including one patient with recurrent progressive osteosarcoma who experienced resolution of clinical symptoms and positron emission tomography activity, ongoing more than 1 year off therapy. One patient with hepatoblastoma showed a dramatic biomarker response.CONCLUSION:
Pediatric patients tolerate 10 mg/kg of lexatumumab administered once every 14 days, the maximum-tolerated dose identified in adults. The drug seems to mediate some clinical activity in pediatric solid tumors and may work with radiation to enhance antitumor effects.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Anticorpos Monoclonais
/
Neoplasias
Tipo de estudo:
Prognostic_studies
Limite:
Adolescent
/
Adult
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Child
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Child, preschool
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Female
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Humans
/
Male
Idioma:
En
Revista:
J Clin Oncol
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Estados Unidos