Crenolanib (ARO-002 or CP-868,596)
NCI drug dictionary definition:
PDGFR inhibitor CP-868,596 is an orally bioavailable small molecule, targeting the platelet-derived growth factor receptor (PDGFR), with potential antineoplastic activity. PDGFR inhibitor CP-868596 binds to and inhibits PDGFR, which may result in the inhibition of PDGFR-related signal transduction pathways, and, so, the inhibition of tumor angiogenesis and tumor cell proliferation. PDGFR, up-regulated in many tumor cell types, is a receptor tyrosine kinase essential to cell migration and the development of the microvasculature.
Mode of action:
oral inhibitor of both receptors for platelet derived growth factor: PDGFR alpha and PDGFR beta
Crenolanib (ARO-002 or CP-868,596) is under development by AROG Pharmaceuticals LLC.
It was originally under development by Pfizer, but AROG obtained the license to continue development.
For information at the AROG website see this link: http://arogpharma.com/index%205-1.html
Please link here for a detailed explanation of PDGF, its receptors, the role of mutant PDGFRA in GIST, and the potential treatments of PDGFRA-mutant GIST.
Poster from 2011 AACR meeting:
Please link here to view a poster describing the success of crenolanib in controlling GIST cell lines.
Poster from 2011 ASCO meeting:
Please link here to view the latest poster presentation from the June 2011 ASCO meeting.
GIST Trial of Crenolanib Opened in April 2011
AROG opened a Phase II trial for GIST patients with the D842V mutation in PDGFRA exon 18 in April 2011 at Fox Chase Cancer Center in Pennsylvania and in June 2011 at Oregon Health & Science University's Knight Cancer Center in Portland.
The trial is listed by clinicaltrials.gov at THIS LINK (NCT01243346).
For more information, contact Arog as shown on this page:
You can view a pdf of the Study Schedule to review the requirements in each drug cycle.
Past Clinical Trial Results
Published papers are available from a Phase I trial with Crenolanib (CP-868,596) used as a single agent in a variety of solid tumors, and from a Phase IB trial with Crenolanib (CP-868,596) used in combination treatment with other drugs. Neither of these trials identifies GIST patients among the trial subjects. The most common side effects reported were nausea, vomiting, and diarrhea, but these were reduced when the drug was taken with food.
Michael M, Vlahovic G, Khamly K, Pierce KJ, Guo F, Olszanski AJ.
Phase Ib study of CP-868,596, a PDGFR inhibitor, combined with docetaxel with or without
axitinib, a VEGFR inhibitor.
Br J Cancer. 2010 Oct 19. [Epub ahead of print]
PubMed PMID: 20959830.
Lewis NL, Lewis LD, Eder JP, Reddy NJ, Guo F, Pierce KJ, Olszanski AJ, Cohen RB.
Phase I study of the safety, tolerability, and pharmacokinetics of oral CP-868,596, a highly specificplatelet-derived growth factor receptor tyrosine kinase inhibitor in patients with advanced cancers.
J Clin Oncol. 2009 Nov 1;27(31):5262-9.
PubMed PMID: 19738123; PubMed Central PMCID: PMC2773478 (free access).