Lacy MQ et al. - In a trial to assess safety, tolerability, pharmacokinetic, and pharmacodynamic properties of the anti–insulinlike growth factor 1 receptor (IGF-IR) monoclonal antibody CP-751,871, it was shown that CP-751,871 is well tolerated and may constitute a novel agent for multiple myeloma Methods
47 pts 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
Pts with less than a partial response to CP-751,871 treatment were eligible to receive CP-751,871 in combination with oral dexamethasone at investigator's discretion
Treatment with CP-751,871 and rapamycin with or without dexamethasone was also offered to pts 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
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
9 responses were reported in 27 pts treated with CP-751,871 in combination with dexamethasone
2 pts with a partial response were progressing from dexamethasone treatment at study entry
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