Phase II study of the Src kinase inhibitor saracatinib (AZD0530) in metastatic melanoma

Invest New Drugs. 2013 Jun;31(3):769-73. doi: 10.1007/s10637-012-9897-4. Epub 2012 Nov 15.


Background: Src kinases are activated in melanoma, and inhibition of Src kinase activity has pre-clinical anti-tumor effects. Targeting this pathway could therefore have therapeutic activity in patients with metastatic melanoma.

Patients and methods: We conducted a multi-center, open-label study of the Src kinase inhibitor saracatanib (AZD0530) in patients with metastatic melanoma. Twenty-three patients received saracatanib at a dose of 175 mg daily. The primary objectives were to determine whether this agent had clinical activity in patients with advanced melanoma and whether it increased progression free survival. Functional effects on circulating T cells were also assessed.

Results: Twenty-three patients received oral saracatanib on a continuous daily dosing regimen. There were no objective clinical responses. Saracatanib was generally well tolerated with few grade 3-4 adverse events. T cell function was inhibited in most patients, based on decreased superantigen-induced IL-2 production in post- versus pre-treatment samples.

Conclusions: Saracatanib has minimal clinical activity as a single agent in an unselected population of patients with advanced melanoma, as evidenced by a lack of objective responses in this study. Reduced T cell cytokine production in most treated patients suggests potential immune suppressive activity by this agent.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Benzodioxoles / pharmacology
  • Benzodioxoles / therapeutic use*
  • Female
  • Humans
  • Interleukin-2 / immunology
  • Male
  • Melanoma / drug therapy*
  • Melanoma / immunology
  • Melanoma / pathology
  • Middle Aged
  • Neoplasm Metastasis
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use*
  • Quinazolines / pharmacology
  • Quinazolines / therapeutic use*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • Treatment Outcome
  • src-Family Kinases / antagonists & inhibitors*


  • Antineoplastic Agents
  • Benzodioxoles
  • Interleukin-2
  • Protein Kinase Inhibitors
  • Quinazolines
  • saracatinib
  • src-Family Kinases