Phase I trial and pharmacokinetic study of lexatumumab in pediatric patients with solid tumors Journal Article


Authors: Merchant, M. S.; Geller, J. I.; Baird, K.; Chou, A. J.; Galli, S.; Charles, A.; Amaoko, M.; Rhee, E. H.; Price, A.; Wexler, L. H.; Meyers, P. A.; Widemann, B. C.; Tsokos, M.; Mackall, C. L.
Article Title: Phase I trial and pharmacokinetic study of lexatumumab in pediatric patients with solid tumors
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 and Methods: 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. © 2012 by American Society of Clinical Oncology.
Keywords: immunohistochemistry; osteosarcoma; adolescent; adult; child; clinical article; controlled study; preschool child; school child; treatment outcome; treatment response; child, preschool; young adult; unclassified drug; drug tolerability; fatigue; area under the curve; drug efficacy; drug safety; solid tumor; treatment duration; cancer patient; cancer radiotherapy; positron emission tomography; antineoplastic agent; neoplasms; biological marker; liver toxicity; multiple cycle treatment; drug administration schedule; antineoplastic activity; dose-response relationship, drug; drug dose escalation; pneumonia; hypoxia; hypokalemia; symptom; antibodies, monoclonal; disease severity; drug accumulation; drug distribution; multicenter study; vein thrombosis; tumor recurrence; immunogenicity; drug clearance; pleura effusion; maximum plasma concentration; drug blood level; maximum tolerated dose; phase 1 clinical trial; drug half life; tumor growth; synovial sarcoma; drug determination; nephroblastoma; pediatrics; pericarditis; drug elimination; lexatumumab; hypertransaminasemia; hepatoblastoma; hgs etr 2
Journal Title: Journal of Clinical Oncology
Volume: 30
Issue: 33
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2012-11-20
Start Page: 4141
End Page: 4147
Language: English
DOI: 10.1200/jco.2012.44.1055
PROVIDER: scopus
PMCID: PMC3494837
PUBMED: 23071222
DOI/URL:
Notes: --- - "Export Date: 3 December 2012" - "CODEN: JCOND" - "Source: Scopus"
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MSK Authors
  1. Anita P Price
    34 Price
  2. Leonard H Wexler
    129 Wexler
  3. Alexander Ja-Ho Chou
    55 Chou
  4. Paul Meyers
    239 Meyers