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

David Olmos, Sophie Postel-Vinay, L. Rhoda Molife, Scott Heitaka Okuno, Scott M. Schuetze, M. Luisa Paccagnella, Gretchen N. Batzel, Donghua Yin, Kathryn Pritchard-Jones, Ian Judson, Francis P. Worden, Antonio Gualberto, Michelle Scurr, Johann S. de Bono, Paul Haluska

Research output: Contribution to journalArticle

240 Citations (Scopus)

Abstract

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. 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. 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. Interpretation: Figitumumab is well tolerated and has antitumour activity in Ewing's sarcoma, warranting further investigation in this disease. Funding: Pfizer Global Research and Development.

Original languageEnglish (US)
Pages (from-to)129-135
Number of pages7
JournalThe Lancet Oncology
Volume11
Issue number2
DOIs
StatePublished - Feb 2010

Fingerprint

Somatomedin Receptors
Ewing's Sarcoma
Sarcoma
Cohort Studies
Pharmacokinetics
Safety
Antibodies
figitumumab
Synovial Sarcoma
gamma-Glutamyltransferase
Fibrosarcoma
Somatomedins
Back Pain
Drug Delivery Systems
Aspartate Aminotransferases
Uric Acid
Alanine Transaminase
Venous Thrombosis
Vomiting

ASJC Scopus subject areas

  • Oncology

Cite this

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. / Olmos, David; Postel-Vinay, Sophie; Molife, L. Rhoda; Okuno, Scott Heitaka; Schuetze, Scott M.; Paccagnella, M. Luisa; Batzel, Gretchen N.; Yin, Donghua; Pritchard-Jones, Kathryn; Judson, Ian; Worden, Francis P.; Gualberto, Antonio; Scurr, Michelle; de Bono, Johann S.; Haluska, Paul.

In: The Lancet Oncology, Vol. 11, No. 2, 02.2010, p. 129-135.

Research output: Contribution to journalArticle

Olmos, D, Postel-Vinay, S, Molife, LR, Okuno, SH, Schuetze, SM, Paccagnella, ML, Batzel, GN, Yin, D, Pritchard-Jones, K, Judson, I, Worden, FP, Gualberto, A, Scurr, M, de Bono, JS & Haluska, P 2010, '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', The Lancet Oncology, vol. 11, no. 2, pp. 129-135. https://doi.org/10.1016/S1470-2045(09)70354-7
Olmos, David ; Postel-Vinay, Sophie ; Molife, L. Rhoda ; Okuno, Scott Heitaka ; Schuetze, Scott M. ; Paccagnella, M. Luisa ; Batzel, Gretchen N. ; Yin, Donghua ; Pritchard-Jones, Kathryn ; Judson, Ian ; Worden, Francis P. ; Gualberto, Antonio ; Scurr, Michelle ; de Bono, Johann S. ; Haluska, Paul. / 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. In: The Lancet Oncology. 2010 ; Vol. 11, No. 2. pp. 129-135.
@article{8c0b269ff6384ce9bf136c5232a49e70,
title = "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",
abstract = "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. 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. 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. Interpretation: Figitumumab is well tolerated and has antitumour activity in Ewing's sarcoma, warranting further investigation in this disease. Funding: Pfizer Global Research and Development.",
author = "David Olmos and Sophie Postel-Vinay and Molife, {L. Rhoda} and Okuno, {Scott Heitaka} and Schuetze, {Scott M.} and Paccagnella, {M. Luisa} and Batzel, {Gretchen N.} and Donghua Yin and Kathryn Pritchard-Jones and Ian Judson and Worden, {Francis P.} and Antonio Gualberto and Michelle Scurr and {de Bono}, {Johann S.} and Paul Haluska",
year = "2010",
month = "2",
doi = "10.1016/S1470-2045(09)70354-7",
language = "English (US)",
volume = "11",
pages = "129--135",
journal = "The Lancet Oncology",
issn = "1470-2045",
publisher = "Lancet Publishing Group",
number = "2",

}

TY - JOUR

T1 - Safety, pharmacokinetics, and preliminary activity of the anti-IGF-1R antibody figitumumab (CP-751,871) in patients with sarcoma and Ewing's sarcoma

T2 - a phase 1 expansion cohort study

AU - Olmos, David

AU - Postel-Vinay, Sophie

AU - Molife, L. Rhoda

AU - Okuno, Scott Heitaka

AU - Schuetze, Scott M.

AU - Paccagnella, M. Luisa

AU - Batzel, Gretchen N.

AU - Yin, Donghua

AU - Pritchard-Jones, Kathryn

AU - Judson, Ian

AU - Worden, Francis P.

AU - Gualberto, Antonio

AU - Scurr, Michelle

AU - de Bono, Johann S.

AU - Haluska, Paul

PY - 2010/2

Y1 - 2010/2

N2 - 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. 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. 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. Interpretation: Figitumumab is well tolerated and has antitumour activity in Ewing's sarcoma, warranting further investigation in this disease. Funding: Pfizer Global Research and Development.

AB - 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. 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. 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. Interpretation: Figitumumab is well tolerated and has antitumour activity in Ewing's sarcoma, warranting further investigation in this disease. Funding: Pfizer Global Research and Development.

UR - http://www.scopus.com/inward/record.url?scp=75249097799&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=75249097799&partnerID=8YFLogxK

U2 - 10.1016/S1470-2045(09)70354-7

DO - 10.1016/S1470-2045(09)70354-7

M3 - Article

VL - 11

SP - 129

EP - 135

JO - The Lancet Oncology

JF - The Lancet Oncology

SN - 1470-2045

IS - 2

ER -