Nilotinib Tasigna AMN107 Sorafenib (Nexavar) Dasatinib (Sprycel) MLN518 Vatalanib (PTK787) OSI-930 AZD2171 Amuvatinib (MP470) TKI258 Pazopanib (Votrient) Masitinib (AB1010) Regorafenib Crenolanib (CP-868,596) DCC-2618

Regorafenib (BAY 73-4506)

Regorafenib, also known as BAY 73-4506 and as fluro-sorafenib, is under development by Bayer.  Regorafenib is structurally similar to sorafenib, with a change in a single atom that gives it an additional mechanism of action: a second blockade of angiogenesis via inhibition of Tie-2.  For an image showing how regorafenib is related to sorafenib, see this link.

Definition from NCI Drug Dictionary: An orally bioavailable small molecule with potential antiangiogenic and antineoplastic activities. Multikinase inhibitor BAY 73-4506 binds to and inhibits vascular endothelial growth factor receptors (VEGFRs) 2 and 3, and Ret, Kit, PDGFR and Raf kinases, which may result in the inhibition of tumor angiogenesis and tumor cell proliferation. VEGFRs are receptor tyrosine kinases that play important roles in tumor angiogenesis; the receptor tyrosine kinases RET, KIT, and PDGFR, and the serine/threonine-specific Raf kinase are involved in tumor cell signaling.

Mode of action: inhibitor of vascular endothelial growth factor receptors (VEGFRs) 2 and 3, and Ret, Kit, PDGFR and Raf kinases, plus the angiogenesis-related Tie2 kinase.

Information at manufacturer website:

http://www.bayerhealthcare.com/html/pdf/DAST_190607_EN.pdf

Clinical trials relevant to GIST:

Open Label Regorafenib Study to Evaluate Cardiovascular Safety Parameters, Tolerability, and Anti-tumor Activity.  NCT01339104.

Study of Regorafenib as a 3rd-line or Greater Treatment for Gastrointestinal Stromal Tumors (GIST) (GRID)  a Phase III trial, NCT 01271712.  This trial is no longer recruiting but is ongoing.

Regorafenib in Patients With Metastatic and/or Unresectable Gastrointestinal Stromal Tumor, NCT01068769  This trial is no longer recruiting but is ongoing.

Other sources of information about regorafenib:

A multicenter phase II study of regorafenib in patients (pts) with advanced gastrointestinal stromal tumor (GIST), after therapy with imatinib (IM) and sunitinib (SU).
Authors: S. George, M. von Mehren, M. C. Heinrich, Q. Wang, C. L. Corless, J. E.
    Butrynski, J. A. Morgan, A. J. Wagner, E. Choy, W. D. Tap, J. Manola,
    J. T. Yap, A. D. Van Den Abbeele, S. Solomon, J. A. Fletcher, and G. D. Demetri
ASCO Meeting Abstracts. 2011;  29(15_suppl): p. 10007

http://en.wikipedia.org/wiki/Regorafenib

http://www.medicalnewstoday.com/articles/164835.php

http://prod2.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=47&abstractID=33859