E7820 Shows Promise in Tumor Growth Inhibition through a2-Integrin Inhibition

Strategic Insights -

Researchers from the Netherlands Cancer Institute in Amsterdam, Netherlands, have found that the investigational integrin inhibitor E7820, currently in phases I and II clinical trials, demonstrates potential in suppressing tumor growth through the inhibition of a2-integrin expression. In a preclinical and clinical study, the researchers aimed to evaluate the levels of inhibition needed to achieve tumor stasis in mice and compare this to the level of inhibition achieved in humans.

Key Takeaways:

  • The study found that moderate inhibition of a2-integrin expression corresponded to tumor stasis in mice, with levels of inhibition as low as 14.7% (RSE 7%) and 17.9% (RSE 8%) being sufficient to achieve tumor stasis in 50% and 90% of the mice, respectively.
  • In clinical trials, the daily administration of E7820 at a dose of 100 mg qd led to a stronger inhibition of a2-integrin expression in greater than 95% and greater than 50% of patients, respectively, compared to the levels needed to achieve tumor stasis in mice.
  • The researchers developed PK-PD models to predict the relationship between the plasma concentration of E7820 and a2-integrin expression, which was subsequently linked to an exponential tumor growth model.
  • The study provides valuable insights into the potential of E7820 as a treatment for various types of cancer, including pancreatic cancer, and highlights the importance of a2-integrin expression as a biomarker for tumor growth inhibition.
  • The study was conducted with the support of the Netherlands Cancer Institute and the researchers plan to continue exploring the potential of E7820 in future clinical trials.

Statistics:

  • 119 a2-integrin measurements and 210 tumor size measurements were available from the mice used in the preclinical study.
  • The study included 100 mg qd (MTD) as the dose level for E7820 administration in the clinical trial.
  • The researchers found that a2-integrin expression was inhibited in greater than 95% of patients when administered E7820 at a dose of 100 mg qd.
  • The study used NONMEM to develop PK-PD models to predict the relationship between the plasma concentration of E7820 and a2-integrin expression.
  • The study was published in The AAPS Journal [electronic Resource] in 2011.

Sources:

  • Keizer, R.J., et al. "Evaluation of a2-integrin expression as a biomarker for tumor growth inhibition for the investigational integrin inhibitor E7820 in preclinical and clinical studies." The AAPS Journal [electronic Resource] 13.2 (2011): 230-9.
  • The AAPS Journal [electronic Resource] is published by Springer, 233 Spring Street, New York, NY 10013, USA.