Originally published as JCO Early Release 10.1200/JCO.2007.15.9319 on May 12 2008

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lacy, M. Q. Articles by Gualberto, A. Search for Related Content PubMed PubMed Citation Articles by Lacy, M. Q. Articles by Gualberto, A. Social Bookmarking                            What's this?

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

Martha Q. Lacy, Melissa Alsina, Rafael Fonseca, M. Luisa Paccagnella, Carrie L. Melvin, Donghua Yin, Amarnath Sharma, M. Enriquez Sarano, Michael Pollak, Sundar Jagannath, Paul Richardson, Antonio Gualberto

From the Mayo Clinic, Divisions of Hematology and Cardiovascular Diseases, Rochester, MN; H. Lee Moffitt Cancer Center and Research Institute, University of South Florida, Tampa, FL; Mayo Clinic, Division of Hematology, Scottsdale, AZ; Pfizer Global Research & Development, New London, CT; St Vincent's Comprehensive Cancer Center, New York, NY; Dana Farber Cancer Institute Boston, MA; and the McGill University and Lady Davis Research Institute, Montreal, Quebec, Canada

Corresponding author: Antonio Gualberto, MD, PhD, Pfizer Global Research & Development, 50 Pequot Ave, MS6025-A3266, New London, CT 06320; e-mail: antonio.gualberto{at}pfizer.com

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.

published online ahead of print at www.jco.org on May 12, 2008.

Supported in part by Pfizer Inc (M.Q.L., M.A., R.F., M.M.P., S.J., P.R.).

Presented at the 49th Annual Meeting of the American Society of Hematology.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Clinical Trials repository link available on www.JCO.org.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				S. G. Holtan, D. J. Creedon, P. Haluska, and S. N. Markovic Cancer and Pregnancy: Parallels in Growth, Invasion, and Immune Modulation and Implications for Cancer Therapeutic Agents Mayo Clin. Proc., November 1, 2009; 84(11): 985 - 1000. [Abstract] [Full Text] [PDF]

				P. Sabbatini, S. Korenchuk, J. L. Rowand, A. Groy, Q. Liu, D. Leperi, C. Atkins, M. Dumble, J. Yang, K. Anderson, et al. GSK1838705A inhibits the insulin-like growth factor-1 receptor and anaplastic lymphoma kinase and shows antitumor activity in experimental models of human cancers Mol. Cancer Ther., October 1, 2009; 8(10): 2811 - 2820. [Abstract] [Full Text] [PDF]

				D. D. Karp, L. G. Paz-Ares, S. Novello, P. Haluska, L. Garland, F. Cardenal, L. J. Blakely, P. D. Eisenberg, C. J. Langer, G. Blumenschein Jr, et al. Phase II Study of the Anti-Insulin-Like Growth Factor Type 1 Receptor Antibody CP-751,871 in Combination With Paclitaxel and Carboplatin in Previously Untreated, Locally Advanced, or Metastatic Non-Small-Cell Lung Cancer J. Clin. Oncol., May 20, 2009; 27(15): 2516 - 2522. [Abstract] [Full Text] [PDF]

				A. C. Sprynski, D. Hose, L. Caillot, T. Reme, J. D. Shaughnessy Jr, B. Barlogie, A. Seckinger, J. Moreaux, M. Hundemer, M. Jourdan, et al. The role of IGF-1 as a major growth factor for myeloma cell lines and the prognostic relevance of the expression of its receptor Blood, May 7, 2009; 113(19): 4614 - 4626. [Abstract] [Full Text] [PDF]

				P. Sabbatini, J. L. Rowand, A. Groy, S. Korenchuk, Q. Liu, C. Atkins, M. Dumble, J. Yang, K. Anderson, B. J. Wilson, et al. Antitumor Activity of GSK1904529A, a Small-molecule Inhibitor of the Insulin-like Growth Factor-I Receptor Tyrosine Kinase Clin. Cancer Res., May 1, 2009; 15(9): 3058 - 3067. [Abstract] [Full Text] [PDF]

				D. L. Kleinberg, T. L. Wood, P. A. Furth, and A. V. Lee Growth Hormone and Insulin-Like Growth Factor-I in the Transition from Normal Mammary Development to Preneoplastic Mammary Lesions Endocr. Rev., February 1, 2009; 30(1): 51 - 74. [Abstract] [Full Text] [PDF]

				M. M. Chitnis, J. S.P. Yuen, A. S. Protheroe, M. Pollak, and V. M. Macaulay The Type 1 Insulin-Like Growth Factor Receptor Pathway Clin. Cancer Res., October 15, 2008; 14(20): 6364 - 6370. [Abstract] [Full Text] [PDF]