Phase II Study of Crenolanib (CP-868,596), a Selective and Potent Inhibitor of PDGFR, for the Treatment of Patients With Advanced Gastrointestinal Stromal Tumors With the D842-related Mutations and Deletions, Including the D842V Mutation, in the PDGFRA Gene
Crenolanib (CP-868,596) is an orally bioavailable, selective inhibitor of PDGFR receptor
tyrosine kinase with IC50s of 0.4 ng/mL and 0.8 ng/mL for PDGFRα and PDGFRβ, respectively.
In preclinical models of cell lines with the D842V mutation in the PDGFRA gene, crenolanib
(CP-868,596) blocked phosphorylation of PDGFRα at nanomolar concentrations, suggesting that
it may provide a clinical benefit to patients with D842V mutant GIST.
In addition, crenolanib was also active in inhibiting phosphorylation of cell lines with two
point mutations (double mutants) PDGFRA V561D + D842V and PDGFRA T674I + D842V.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
The primary end-point is overall response rate
To determine the response rate of patients with advanced D842V mutant GIST, when treated with Crenolanib (CP-868,596). Response will primarily be determined by RECIST criteria
Margaret von Mehren, MD
Fox Chase Cancer Center
United States: Food and Drug Administration
|Fox Chase Cancer Center||Philadelphia, Pennsylvania 19111|
|Knight Cancer Institute, Oregon Health and Science University||Portland, Oregon 97239-3098|