A phase I dose-escalation and pharmacokinetic (PK) study of a novel multiple-targeted receptor tyrosine kinase (RTK) inhibitor, XL647, in patients with advanced solid malignancies

3142 Background: XL647 is an orally bioavailable small molecule inhibitor of multiple RTKs involved in tumor cell growth, angiogenesis, and metastasis including EGFR (erbB1), erbB2, VEGFR-2, and EphB4. Methods: Patients (pts) with advanced solid malignancies were enrolled in successive cohorts to receive XL647 orally as a single dose on day 1 with PK sampling, followed by 5 continuous daily doses starting on day 4 with additional PK sampling. Pts then continued to receive dosing for 5 continuous days followed by a break with cycles repeated every 14 days. Imaging was done at baseline, after the first 3 or 4 cycles and then after every 4 cycles. Pts with stable or improving disease were allowed to stay on study. Results: A total of 12 pts (5 non-small cell lung cancer (NSCLC), 3 colon cancer, 2 renal cell carcinoma, 1 chordoma, 1 adrenal cortical carcinoma) have been treated across 4 dose levels to date (3 per cohort): 0.06, 0.12, 0.19 and 0.28 mg/kg. No grade 3/4 toxicities have been recorded to date and ...