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

Research output: Contribution to journalArticle

140 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3196-3203
Number of pages8
JournalJournal of Clinical Oncology
Volume26
Issue number19
DOIs
StatePublished - Sep 15 2008

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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