TY - JOUR
T1 - Phase I, pharmacokinetic and pharmacodynamic study of the anti-insulinlike growth factor type 1 receptor monoclonal antibody CP-751,871 in patients with multiple myeloma
AU - Lacy, Martha Q.
AU - Alsina, Melissa
AU - Fonseca, Rafael
AU - Paccagnella, M. Luisa
AU - Melvin, Carrie L.
AU - Yin, Donghua
AU - Sharma, Amarnath
AU - Sarano, M. Enriquez
AU - Pollak, Michael
AU - Jagannath, Sundar
AU - Richardson, Paul
AU - Gualberto, Antonio
PY - 2008
Y1 - 2008
N2 - Purpose: A phase I first-in-human study was conducted to characterize the safety, tolerability, pharmacokinetic, and pharmacodynamic properties of the anti-insulinlike growth factor 1 receptor (IGF-IR) monoclonal antibody CP-751,871. Patients and Methods: After informed consent and screening, 47 patients with multiple myeloma in relapse or refractory phase were enrolled into 11 dose-escalation cohorts of CP-751,871 at doses from 0.025 to 20 mg/kg for 4 weeks. Patients with less than a partial response to CP-751,871 treatment were eligible to receive CP-751,871 in combination with oral dexamethasone at the discretion of the investigator. Treatment with CP-751,871 and rapamycin with or without dexamethasone was also offered to patients enrolled in the 10 and 20 mg/kg cohorts with less than a partial response to initial therapy with single-agent CP-751,871. Results: No CP-751,871-related dose-limiting toxicities were identified. Plasma CP-751,871 concentrations increased with dose and concentration-time profiles were consistent with those of antibodies with target-mediated disposition. Importantly, CP-751,871 administration led to a decrease in granulocyte IGF-IR expression and serum insulinlike growth factor 1 accumulation at high doses, suggesting systemic IGF-IR inhibition. Tumor response was assessed according to the European Group for Blood and Marrow Transplantation criteria. Nine responses were reported in 27 patients treated with CP-751,871 in combination with dexamethasone. Of interest, two of the patients with a partial response were progressing from dexamethasone treatment at study entry. Conclusion: These data indicate that CP-751,871 is well tolerated and may constitute a novel agent in the treatment of multiple myeloma.
AB - Purpose: A phase I first-in-human study was conducted to characterize the safety, tolerability, pharmacokinetic, and pharmacodynamic properties of the anti-insulinlike growth factor 1 receptor (IGF-IR) monoclonal antibody CP-751,871. Patients and Methods: After informed consent and screening, 47 patients with multiple myeloma in relapse or refractory phase were enrolled into 11 dose-escalation cohorts of CP-751,871 at doses from 0.025 to 20 mg/kg for 4 weeks. Patients with less than a partial response to CP-751,871 treatment were eligible to receive CP-751,871 in combination with oral dexamethasone at the discretion of the investigator. Treatment with CP-751,871 and rapamycin with or without dexamethasone was also offered to patients enrolled in the 10 and 20 mg/kg cohorts with less than a partial response to initial therapy with single-agent CP-751,871. Results: No CP-751,871-related dose-limiting toxicities were identified. Plasma CP-751,871 concentrations increased with dose and concentration-time profiles were consistent with those of antibodies with target-mediated disposition. Importantly, CP-751,871 administration led to a decrease in granulocyte IGF-IR expression and serum insulinlike growth factor 1 accumulation at high doses, suggesting systemic IGF-IR inhibition. Tumor response was assessed according to the European Group for Blood and Marrow Transplantation criteria. Nine responses were reported in 27 patients treated with CP-751,871 in combination with dexamethasone. Of interest, two of the patients with a partial response were progressing from dexamethasone treatment at study entry. Conclusion: These data indicate that CP-751,871 is well tolerated and may constitute a novel agent in the treatment of multiple myeloma.
UR - http://www.scopus.com/inward/record.url?scp=49249125421&partnerID=8YFLogxK
U2 - 10.1200/JCO.2007.15.9319
DO - 10.1200/JCO.2007.15.9319
M3 - Article
C2 - 18474873
AN - SCOPUS:49249125421
SN - 0732-183X
VL - 26
SP - 3196
EP - 3203
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 19
ER -