The Exelixis pipeline includes our lead compounds, cabozantinib and cobimetinib, as well as other programs that are the subject of partnerships and collaborations. An additional wholly-owned compound, XL888, is the subject of ongoing clinical research through our Investigator-Sponsored Trial program. Safety and efficacy for these compounds in the unapproved uses or indications described below has not yet been established.
Exelixis’ internal development efforts are primarily focused on cabozantinib, a targeted agent that inhibits the activity of receptor tyrosine kinases including MET, VEGF receptors, AXL, and RET. These receptor tyrosine kinases are involved in both normal cellular function and in pathologic processes such as oncogenesis, metastasis, tumor angiogenesis, and maintenance of the tumor microenvironment. Exelixis has worldwide rights to cabozantinib, which we believe could have the potential to treat a wide variety of cancers.
Cabozantinib is the subject of a broad, global clinical development program that includes approximately 45 ongoing or planned clinical trials. Exelixis is sponsoring multiple randomized phase 3 trials, including METEOR in metastatic renal cell carcinoma and CELESTIAL in advanced hepatocellular carcinoma.
METEOR Clinical Trial Update
In July 2015, Exelixis announced that METEOR met its primary endpoint, demonstrating a statistically significant improvement in progression-free survival (PFS) for cabozantinib versus everolimus in a population of patients with metastatic renal cell carcinoma who have experienced disease progression following treatment with at least one prior VEGFR tyrosine kinase inhibitor. The primary analysis was conducted on the first 375 patients enrolled, and the hazard ratio was 0.58 (95% CI 0.45-0.75, p<0.0001), equating to a 42% decrease in the risk of disease progression or death for the cabozantinib arm. As expected, data pertaining to overall survival (OS) for the entire 658-patient study population were not mature at the data cut-off, but a pre-planned interim analysis showed a trend favoring cabozantinib (HR=0.67, unadjusted 95 percent CI 0.51-0.89; p=0.005); the trial will continue to the final OS analysis anticipated in 2016. The frequency of serious adverse events of any grade, regardless of causality, was approximately balanced between study arms, and the rate of discontinuations for adverse events was low (10%) in both arms.
Based on the METEOR results, Exelixis plans to complete regulatory filings in the United States and EU in early 2016. For more information on the trial, please view the press release and accompanying webcast replay.
Additional Clinical Development
For more information on cabozantinib clinical trials, including additional trials conducted as part of our Investigator-Sponsored Trial program and collaboration with the National Cancer Institute’s Cancer Therapy Evaluation Program, please visit the Clinical Trials section of our site.
Cabozantinib is commercially available in the U.S. and EU for a single indication, and it is marketed as COMETRIQ® for that use. For more information, including important safety information and boxed warnings, please visit www.cometriq.com.
Cobimetinib (formerly GDC-0973/XL518)
Cobimetinib, an Exelixis-discovered compound, is a selective inhibitor of MEK, part of the RAS/RAF/MEK/ERK pathway that is frequently dysregulated in human tumors. Cobimetinib is being developed by Roche and Genentech (a member of the Roche Group) under a collaboration agreement with Exelixis. More information on cobimetinib is available here.
XL888 is a highly potent, orally bioavailable ATP-competitive inhibitor of HSP90, a molecular chaperone protein that affects the activity and stability of a range of key regulatory proteins, including kinases such as BRAF, MET, and VEGFR2. We discovered XL888 and own the compound exclusively. More information on XL888 is available here.
We have established multiple partnerships and collaborations with other leading pharmaceutical and biopharmaceutical companies. These partnerships are designed to advance the development of a variety of potential therapies for cancer and other serious diseases. More information on our partnered compounds is available here.