Summary
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.
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Acknowledgments
The investigators thank Karen Matijevich for research nursing support, Jeffrey Bozeman for data management, Yuanyuan Zha for help with correlative assays, Theodore Karrison for statistical assistance, and all the members of the University of Chicago Phase II clinical trial consortium. This work was supported by N01-CM-62201from the National Cancer Institute.
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This study was supported by the National Cancer Institute Early Therapeutics Development with Phase II emphasis [grant number N01-CM-62201]
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The authors do not have any relationships that they believe could be construed as resulting in an actual, potential, or perceived conflict of interest with regard to the manuscript submitted for review.
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Gangadhar, T.C., Clark, J.I., Karrison, T. et al. Phase II study of the Src kinase inhibitor saracatinib (AZD0530) in metastatic melanoma. Invest New Drugs 31, 769–773 (2013). https://doi.org/10.1007/s10637-012-9897-4
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DOI: https://doi.org/10.1007/s10637-012-9897-4