(MET and VEGFR2 inhibitor, activity on variety of solid tumors and bone metastasis)
Cabozantinib pharma web site:
http://www.exelixis.com/cabozantinib
Link to trials
http://www.rttnews.com/Content/Quick...d=1639120&SM=1
Exelixis Reports Interim Data Of Ongoing Phase 2 Trial Of Cabozantinib
Sunday reported interim data from its ongoing phase 2 trial of cabozantinib in patients with advanced solid tumors.
Cabozantinib is an investigational agent that provides coordinated inhibition of metastasis and angiogenesis to kill tumor cells while blocking their escape pathways.
As of the February 11, 490 patients had been enrolled in the randomized discontinuation trial. Evidence of soft tissue tumor regression was observed in all tumor types.
Rates of overall disease control at Week 12 of 40 percent or higher were observed in HCC, castration-resistant prostate cancer, ovarian cancer, melanoma, breast cancer, and NSCLC.
Twenty patients were enrolled in the breast cancer cohort, of which
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tumor regression was observed in 15 of 16 or 94 percent
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of evaluable patients.
Cancer Res. 2011 Jun 1. [Epub ahead of print]
VEGF and c-Met blockade amplify angiogenesis inhibition in pancreatic islet cancer.
You WK,
Sennino B,
Williamson CW,
Falcon B,
Hashizume H,
Yao LC,
Aftab DT,
McDonald DM.
Source
Comprehensive Cancer Center and Dept of Anatomy, Univ of California, San Francisco.
LINK
Abstract
Angiogenesis inhibitors that block vascular endothelial growth factor receptor (VEGFR) signaling slow the growth of many types of tumors, but eventually the disease progresses. Multiple strategies are being explored to improve efficacy by concurrent inhibition of other functionally relevant receptor tyrosine kinases (RTKs).
XL880 (foretinib, GSK1363089) and XL184 (cabozantinib) are small molecule inhibitors that potently block multiple RTKs including VEGFR and the receptor of hepatocyte growth factor c-Met, which can drive tumor invasion and metastasis. This study compared the cellular effects of XL880 and XL184 to those of an RTK inhibitor (XL999) that blocks VEGFR but not c-Met. Treatment of RIP-Tag2 mice with XL999 resulted in 43% reduction in vascularity of spontaneous pancreatic islet tumors over 7 days, but
treatment with XL880 or XL184 eliminated ~ 80% of the tumor vasculature, reduced pericytes and empty basement membrane sleeves, caused widespread intratumoral hypoxia and tumor cell apoptosis, and slowed regrowth of the tumor vasculature after drug withdrawal. Importantly, XL880 and XL184 also decreased invasiveness of primary tumors and reduced metastasis. Overall, these findings indicate that
inhibition of c-Met and functionally related kinases amplifies the effects of VEGFR blockade and leads to rapid, robust, and progressive regression of tumor vasculature, increased intratumoral hypoxia and apoptosis, and reduced tumor invasiveness and metastasis.
- PMID:
- 21613405
- [PubMed - as supplied by publisher]
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