Figitumumab is a fully human IgG2 monoclonal antibody targeting the insulin-like growth-factor-1
receptor (IGF-1R). Preclinical data suggest a dependence on insulin-like growth-factor
signalling for sarcoma subtypes, including Ewing's sarcoma, and early reports show
antitumour activity of IGF-1R-targeting drugs in these diseases.
Between January, 2006, and August, 2008, patients with refractory, advanced sarcomas
received figitumumab (20 mg/kg) in two single-stage expansion cohorts within a solid-tumour
phase 1 trial. The first cohort (n=15) included patients with multiple sarcoma subtypes,
age 18 years or older, and the second cohort (n=14) consisted of patients with refractory
Ewing's sarcoma, age 9 years or older. The primary endpoint was to assess the safety
and tolerability of figitumumab. Secondary endpoints included pharmacokinetic profiling
and preliminary antitumour activity (best response by Response Evaluation Criteria
in Solid Tumours [RECIST]) in evaluable patients who received at least one dose of
medication. This study is registered with ClinicalTrials.gov, number NCT00474760.
29 patients, 16 of whom had Ewing's sarcoma, were enrolled and received a total of
177 cycles of treatment (median 2, mean 6.1, range 1-24). Grade 3 deep venous thrombosis,
grade 3 back pain, and grade 3 vomiting were each noted once in individual patients;
one patient had grade 3 increases in aspartate aminotransferase and gammaglutamyltransferase
concentrations. This patient also had grade 4 increases in alanine aminotransferase
concentrations. The only other grade 4 adverse event was raised concentrations of
uric acid, noted in one patient. Pharmacokinetics were comparable between patients
with sarcoma and those with other solid tumours. 28 patients were assessed for response;
two patients, both with Ewing's sarcoma, had objective responses (one complete response
and one partial response) and eight patients had disease stabilisation (six with Ewing's
sarcoma, one with synovial sarcoma, and one with fibrosarcoma) lasting 4 months or
longer.
Figitumumab is well tolerated and has antitumour activity in Ewing's sarcoma, warranting
further investigation in this disease.
Pfizer Global Research and Development.
Copyright 2010 Elsevier Ltd. All rights reserved.