Phase 1 study of CP-868,596 an oral, highly specific PDGFR inhibitor

3524 Background: CP-868,596 is an orally available, highly specific inhibitor of platelet-derived growth factor receptors (PDGFR). PDGF and its receptor play an important role in angiogenesis, modulation of tumor interstitial fluid pressure (IFP), and influence cell growth, migration, and survival through signal-transduction pathways. Methods: The safety, tolerability and pharmacokinetics (PK) of daily oral CP-868,596 administered in 4-week cycles were assessed in patients with advanced solid malignancies. Original dose escalation cohorts were 100, 200, 280 and 340 mg QD administered on an empty stomach. Prevalence of persistent Grade 1 nausea and vomiting led to amendments that include “with food” cohorts. Safety assessments included adverse events (AEs), clinical laboratories, and ECG monitoring. PK blood samples were collected after a single dose and at steady state. PK parameters were estimated by non compartmental techniques. Results: Data is available for all 59 patients enrolled in the trial [(29 M...