D842-related Mutant GIST Clinical Trial
Official title:
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
This Phase II study is designed to evaluate the antitumor efficacy and pharmacokinetics of crenolanib (CP-868,596) in patients with D842-related mutant metastatic GIST.
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.
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