LBA4510 Background: BAY 43–9006 (BAY), a dual-action Raf kinase and VEGFR inhibitor, inhibits tumor cell proliferation and angiogenesis. In Phase II trials, BAY has demonstrated activity in patients (pts) with metastatic RCC. The primary aim of this Phase III, double-blind trial was to assess overall survival (OS) in pts with confirmed advanced clear-cell RCC randomized to BAY vs best supportive care (BSC). Results of a planned analysis on the secondary endpoint, progression free survival (PFS) will be presented in this report. Methods: Pts (ECOG 0–1) who had received one prior systemic therapy for advanced RCC were stratified into intermediate- (1–2 risk factors) or low-risk (no risk factors) groups, according to the MSKCC prognostic index. Pts were randomized to receive continuous BAY 400 mg bid or matched placebo with BSC. Pts were withdrawn from the study if they met any of the following criteria: AEs requiring study drug termination; progressive disease (unless continued treatment was considered appropriate by the investigator); patient/sponsor request; pt lost to follow-up; or death. The primary efficacy endpoint is OS, for which an overall two-sided alpha of 0.04 will be used. Final analysis of OS will be performed after 540 events, required to detect 33% improvement with 90% power. Provided interim monitoring boundaries are not crossed, 884 pts (442 per treatment arm) will be randomized. PFS will be compared at a two-sided alpha level of 0.01 using a log-rank test stratified by prognostic group and country. Adverse events will be tabulated by NCI CTC version 3.0. Results: To date, 611 out of 884 pts have been randomized and 229 PFS events have occurred. PFS analysis will be performed after 363 progressive events have occurred. The results of the PFS analysis and the safety experience will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bayer Healthcare Antigenics, Bayer, CFSB, Deutsche Bank, Genentech, Medacorp, Pfizer, Roche AstraZeneca, Bayer AG Antigenics, Bayer, Centocor, Genentech, Pfizer, Roche, Wyeth Amgen, Antigenics, Bayer, Celgene, Genentech, Pfizer, Wyeth