Pharmaprojects R&D Pipeline News Feed
Nexavar fails Phase III melanoma trial
30 Apr 2009
The multi-targeted kidney and liver cancer drug Nexavar (sorafenib tosylate), under joint development by Bayer and Onyx Pharmaceuticals, has failed the first Phase III trial conducted in melanoma patients where it was administered as a first-line therapy.
A planned interim analysis of the trial (ECOG 2603), sponsored by the US NCI and led by the Eastern Cooperative Oncology Group, concluded that it would not meet the primary endpoint of improved overall survival in 800 patients with stage III or IV melanoma, receiving either Nexavar, in combination with the chemotherapeutic agents carboplatin and paclitaxel, or placebo plus the chemotherapeutic agents.
Nexavar is an orally-active ras signalling pathway inhibitor with Raf kinase inhibitor activity; however this may not be sufficiently potent to target BRAF (a component of the Ras signalling pathway) in melanoma. It also blocks angiogenesis by inhibiting VEGFR-2, with greater potency, and is likely to be the reason for its activity in renal cell carcinoma and hepatocellular carcinoma.
Several drugs have previously failed in Phase III metastatic melanoma trials, including a second-line trial of Nexavar in 270 advanced melanoma patients after progression on dacarbazine or temozolomide regimens. Bayer and Onyx do not plan to conduct further melanoma trials with Nexavar.
Nexavar is currently approved in over 70 countries for the treatment of patients with liver cancer, and in more than 80 countries for the treatment of renal cell carcinoma. Approval for the treatment of breast cancer is expected in 2012. It is also in ongoing Phase III trials for non-small cell lung cancer and in Phase II development for various other tumour types.
