Phase I trial and pharmacokinetic study of lexatumumab in pediatric patients with solid tumors. Academic Article uri icon

Overview

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 ageā‰¤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.

publication date

  • October 15, 2012

Research

keywords

  • Antibodies, Monoclonal
  • Neoplasms

Identity

PubMed Central ID

  • PMC3494837

Scopus Document Identifier

  • 84869396787

Digital Object Identifier (DOI)

  • 10.1200/JCO.2012.44.1055

PubMed ID

  • 23071222

Additional Document Info

volume

  • 30

issue

  • 33