Phase I pharmacokinetic (PK) and safety study of intravenous (IV) CI-1033 in patients with advanced solid tumors

3057 Background: CI-1033 is a pan-erbB tyrosine kinase inhibitor. In phase 1 oral (PO) studies, dose limiting toxicities were primarily gastrointestinal (GI), which supported the exploration of IV dosing to achieve higher drug exposures. Methods: Forty-eight patients (pts) with advanced nonhematologic malignancies received IV CI-1033 via 30 min infusions (10–500 mg) on a 3-day weekly (MWF) schedule. PK samples were collected on Days 1 and 8 and evaluated using compartmental analysis (NONMEM ADVAN3). Results: 28M/20F, ECOG PS 0 & 1, median age 54 (42–73), tumors: lung 11, colorectal 10, mesothelioma 9, melanoma 4, unknown primary 2, others 12. Despite a 5 to 10-fold increase in IV Cmax and a 3-fold increase in AUC compared to PO at equivalent doses, treatment-related GI AEs were notably less frequent with this IV regimen than with once weekly dosing of PO CI-1033 (100–1000 mg; n=55; Proc. ASCO 2001,283:72a). The incidences of the most common GI AEs when given IV were Gr 1–2 nausea (15%), vomiting (11%), di...