http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(09)70354-7/abstract
The Lancet Oncology, Volume 11, Issue 2, Pages 129 –
135, February 2010
doi:10.1016/S1470-2045(09)70354-7
Safety, pharmacokinetics, and
preliminary activity of the anti-IGF-1R
antibody figitumumab
(CP-751,871) in
patients with sarcoma and Ewing's
sarcoma: a
phase 1 expansion cohort
study
Summary
Background
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.
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.
Methods
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.
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.
Findings
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.
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.
Interpretation
Figitumumab is well tolerated and has antitumour
activity in Ewing's sarcoma, warranting further
investigation in this disease.
activity in Ewing's sarcoma, warranting further
investigation in this disease.
Funding
Pfizer Global Research and Development.