4594 Background: Lapatinib is an oral reversible inhibitor of ErbB1 (EGFR) and ErbB2 (HER-2/neu) receptor tyrosine kinases. Methods: The primary endpoint was RECIST response rate. Key eligibility criteria included stage IIIB/IV TCC of the bladder, progression following a first-line platinum regimen, expression of ErbB1 and or ErbB2 (1, 2 or 3+ by IHC) and KPS ≥ 70. Lapatinib (1250 mg, qd) was administered until disease progression or unacceptable toxicity. Tumor and safety assessments were performed every 8 and 4 wks, respectively. Cardiac function was monitored at baseline and every 8 wks. Tumor tissue was analyzed for biomarkers (TUNEL, p53, pAkt, Her3, pHer3, pErk, IGF-1R, Rb, pS6). Results: Fifty-nine pts were enrolled. Investigators reported 2 (3%) PRs and 12 (20%) SD; independent radiologic review (IRR) reported 1 (2%) PR and 18 (31%) SD. Based upon investigator and IRR, six and three pts had durable SD lasting 4 and 6 mos, respectively. At wk 8, 10 pts had some degree of cytoreduction; however, mos...