4514 Background: HD IL-2 received FDA approval for mRCC in 1992, producing a 14% major response (CR + PR) rate and durable remissions in phase II trials. The Cytokine Working Group conducted the present trial to identify patients (pts) likely to respond to treatment in order to improve the therapeutic index of HD IL-2. Methods: In this multicenter, prospective study pts with histologically confirmed RCC that was metastatic or unresectable, measurable disease, age ≥ 18 years, ECOG PS 0-1 and adequate organ function received HD IL-2 (600,000 U/kg/dose intravenously every 8 hours on days 1 through 5 and 15 to 19 (maximum 28 doses) every 12 weeks. The primary endpoint of the study was to determine the major response rate (RR) of pts with “favorable” predictive features. All pts were consented to provide archived tumor tissue that would be used for pathology risk classification, carbonic anhydrase IX (CAIX) staining and in creation of a tissue microarray. Results: One hundred twenty eligible pts enrolled betwe...