Embryo-fetal developmental toxicity of figitumumab, an anti-insulin-like growth factor-1 receptor (IGF-1R) monoclonal antibody, in cynomolgus monkeys

Birth Defects Res B Dev Reprod Toxicol. 2010 Aug;89(4):326-38. doi: 10.1002/bdrb.20248.


Background: Insulin-like growth factor (IGF) signaling has been linked to tumor cell survival and tumorigenesis. The anti-IGF-1 receptor monoclonal antibody, figitumumab, has been developed as an anti-cancer therapeutic. As part of the safety evaluation, an embryo-fetal developmental toxicity study was conducted in the cynomolgus monkey.

Methods: Figitumumab was administered once weekly intravenously at a dose of 5, 15, or 100 mg/kg during the period of major organogenesis (gestation days [GD] 20-48) with scheduled cesarean section around GD100. Maternal endpoints included clinical observations, food consumption, body weights, hematology, placental weights, toxicokinetics, and immunogenicity. Fetal evaluations included viability; body weights; external, visceral, and skeletal examination (and measurements); drug exposure; and immunogenicity.

Results: There was a dose-dependent increase in embryo-fetal loss in the presence of decreased maternal food consumption and slight reduction in body weight. Figitumumab-related embryo-fetal developmental toxicity was observed as growth retardation exhibited by reduced fetal body weights at all doses with corresponding developmental delays in morphology. Treatment-related fetal structural malformations were also observed in the mid- and high-dose groups.

Conclusions: Maternal figitumumab dosing only during the period of organogenesis was associated with pregnancy loss and fetal growth deficits; both considered consistent with inhibition of IGF signaling. Fetal malformations were also observed, and were considered secondary to altered placental function and/or reduced fetal growth; however, direct inhibition of IGF signaling in the conceptus cannot be ruled out. This appears to be the first report of treatment-related fetal anomalies with a monoclonal antibody when administered only during the period of major organogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Drug-Induced / embryology*
  • Animals
  • Antibodies, Monoclonal / toxicity*
  • Anticarcinogenic Agents / toxicity*
  • Dose-Response Relationship, Drug
  • Embryonic Development
  • Female
  • Fetal Development
  • Immunoglobulins, Intravenous
  • Insulin-Like Growth Factor I / physiology
  • Macaca fascicularis / embryology
  • Macaca fascicularis / metabolism
  • Maternal-Fetal Exchange
  • Organogenesis
  • Pregnancy
  • Receptor, IGF Type 1 / antagonists & inhibitors*
  • Toxicity Tests


  • Antibodies, Monoclonal
  • Anticarcinogenic Agents
  • Immunoglobulins, Intravenous
  • Insulin-Like Growth Factor I
  • Receptor, IGF Type 1
  • figitumumab