A Phase I Study (Ca180021-Segment 2) of Dasatinib in Patients (pts) with Advanced Solid Tumors

14042 Background: SPRYCEL™ is a potent, orally active, multi-targeted kinase inhibitor, active against BCR-ABL and SRC family kinases. We report the results of a Phase I dose-escalation study evaluating safety, tolerability, pharmacokinetics, and biomarkers of dasatinib in pts with advanced solid tumors. Methods: Pts with adequate hematologic, renal, cardiac and liver function received oral dasatinib once daily for 7 days per week. Three doses and schedules were examined: 90 mg BID; 140 mg QD; and 180 mg QD. Pharmacokinetics and pharmacodynamic biomarkers were collected on Days 1 and 26 of Cycle 1. Tissue biomarkers were assessed at screening. CT was performed at least every 8 weeks, and FDG-PET at weeks 4, and 8. Results: 26 pts [M=15, F=11] ECOG PS ≤ 2 with epithelial tumors (n=14) or other solid tumors (n=12) have been treated in escalating dose levels. Toxicity was generally mild; most patients came off study for progressive disease. DLTs of pleural effusions were seen in 3/9 subjects on the 180 mg cohort, 2 of whom had pre-existing effusions. Patients with pleural effusion have been excluded from future enrollment. The maximum tolerated dose has not been identified. There have been no objective responses on CT. Six patients have had stable disease with continued study treatment for 2–10 months. Conclusions: Dasatinib can be safely administered at doses of 140 and 180 mg QD. Clinical efficacy, pharmacokinetics, and correlative studies of tumor biopsy material and early FDG-PET results will be reported. No significant financial relationships to disclose.