The open-label, dose-escalation study conducted at two major cancer treatment centers is designed to evaluate the safety and tolerability of the small molecule Aurora kinases inhibitor VX-680 when administered in multiple cycles to patients with solid tumors refractory to prior chemotherapy treatment.
The initiation of this clinical study is supported by VX-680’s activity in both in vitro and in vivo cancer models and Merck and Vertex plan to initiate additional phase I studies of VX-680 this year.
Aurora kinases are implicated in the onset of many human cancers, and Aurora kinase inhibitors such as VX-680 have the potential to play an important role in the treatment and management of a wide range of tumor types.
In June 2004, Vertex and Merck entered into a global collaboration to develop and commercialize VX-680. Along with clinical development, Vertex and Merck are conducting a joint research program to characterize VX-680’s activity across a broad range of cancer types and will seek to identify additional drug candidates targeting the Aurora kinases.
“The Aurora kinases represent a target of high interest for the development of novel anticancer drugs because of the multiple roles Aurora kinases play in the development and progression of tumors,” said Dr Stephen Friend, senior vice president for molecular profiling and cancer research at Merck Research Laboratories.
“Oncology represents a key area of focus for Merck, and compounds such as VX-680 could potentially create a foundation for new types of chemotherapy regimens in the future treatment of cancer.”
VX-680 was discovered by scientists at Vertex’s Oxford, UK research site as part of a broad research effort targeting the kinase gene family. It was advanced to pre-clinical development in 2002, and, in studies published early in 2004, Vertex demonstrated that VX-680 induced tumor regression in xenograft models of human pancreatic and colon cancer.
In addition, Vertex has presented data that shows that VX-680 prolonged survival and induced sustained remission in an oncogene driven model of human acute myelocytic leukemia (AML).