Date: 2016-04-19
Type of information: Presentation of results at a congress
phase: preclinical
Announcement: presentation of results at the American Association for Cancer Research (AACR) Annual Meeting
Company: Eisai (Japan)
Product: lenvatinib in combination with everolimus
Action
mechanism: tyrosine kinase inhibitor/kinase inhibitor/mTor inhibitor. Lenvatinib is an oral molecular targeted agent that selectively inhibits the activities of several different molecules including vascular endothelial growth factor receptors (VEGFR), fibroblast growth factor receptors (FGFR), RET, KIT and platelet-derived growth factor receptors (PDGFR). It simultaneously inhibits VEGFR, FGFR and also RET which are especially involved in tumour angiogenesis and proliferation of thyroid cancer. This potentially makes lenvatinib the first TKI that simultaneously inhibits the kinase activities of FGFR 1-4 as well as VEGFR 1-3. It is currently under investigation as a treatment for thyroid, hepatocellular carcinoma (Phase III), non-small cell lung cancer (Phase II) and other solid tumour types. Discovered and developed by Eisai, lenvatinib received accelerated European Medicines Agency (EMA) review on the 31 July and was filed in Europe and the U.S. on 18 August 2014. The FDA granted approval to Lenvima® (lenvatinib) to treat patients with progressive, differentiated thyroid cancer (DTC) whose disease progressed despite receiving radioactive iodine therapy (radioactive iodine refractory disease) on February 13, 2015. Lenvatinib was granted orphan drug designation (ODD) for the treatment of follicular and papillary thyroid cancer by the European Commission in April 2013. Lenvatinib is currently indicated for the treatment of adult patients with progressive locally advanced or metastatic, differentiated (papillary, follicular, Hürthle cell) thyroid carcinoma (DTC) refractory to radioactive iodine (RAI).
Everolimus is a signal transduction inhibitor. Signal transduction inhibitors stop some of the signals within cells that make them grow and divide. Everolimus stops a particular protein called mTOR from working properly. mTOR controls other proteins that trigger cancer cells to grow. So everolimus helps to stop the cancer growing or may slow it down.[8]
Disease: kidney cancer
Therapeutic area: Cancer - Oncology
Country:
Trial details:
Latest
news: * On April 19, 2016, Eisai announced that data presented at the American Association for Cancer Research annual meeting support significant combination effects and possible mechanisms of action of lenvatinib plus everolimus
A preclinical study of lenvatinib plus everolimus demonstrates enhanced inhibition of vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF)-induced angiogenesis than for either agent alone in human endothelial cell models. The combination also showed synergistic enhancement against bFGF- driven angiogenesis, distinguishing this from other VEGFR2 tyrosine kinase inhibitors.
The enhanced effect of the combination lenvatinib plus everolimus is also demonstrated in a second study presented at AACR in human renal cell carcinoma xenograft models (a graft of tissue or cells from one species to an unlike species). Results indicate that lenvatinib in combination with everolimus causes significant antitumour effects through the potent antiangiogenic activity of lenvatinib and direct antitumour activity of everolimus. Gene expression analysis also supports the mode of action in this model, i.e., lenvatinib alone upregulates hypoxia-related genes and everolimus decreases proliferation-related genes.
In January 2016, Eisai submitted a new Marketing Authorisation Application (MAA) to the European Medicines Agency (EMA) for the use of lenvatinib in combination with everolimus for advanced renal cell carcinoma in people who have received one prior VEGF-targeted therapy. A similar application has already been submitted to the FDA in the US. Lenvatinib was granted an accelerated assessment for advanced RCC in Europe by the EMA in October 2015.
