10553 Background: A previous analysis of a phase I study demonstrated that nilotinib has promising clinical activity in patients (pts) with GIST who are resistant to prior tyrosine kinase inhibitors (TKIs) including imatinib. The current analysis of a phase 1 study reports on the efficacy and long-term safety of nilotinib alone and in combination with IM. Methods: Pts with imatinib-resistant GIST received nilotinib alone (400 mg orally BID) or escalating doses of nilotinib (200 mg QD, 400 mg QD, or 400 mg BID) in combination with IM (400 mg orally BID), or nilotinib 400 mg BID plus IM 400 mg QD. Results: A total of 53 pts received nilotinib, alone (n = 18, 5 IM-intolerant) or in combination with IM (n = 35). Thirty-nine pts (74%) were resistant, refractory, and/or intolerant to one or more prior therapies. Sixteen pts received combination therapy at the nilotinib 400 mg BID/IM 400 mg QD dose (N 400BID/IM 400QD). Median duration of therapy in this combination arm was 217 days (range, 27–492) versus 186 days (range, 8–718) for nilotinib alone. Grade 3/4 AEs were experienced by 9 (50%) pts in the nilotinib alone arm and 7 (44%) pts in the N 400BID/IM 400QD arm. The most common of these was grade 3 GI disorders, which occurred in 8 (44%) pts in the nilotinib alone arm and 2 (12.5%) pts in the N 400BID/IM 400QD arm. One pt on nilotinib alone experienced dose- limiting hyperbilirubinemia; 3 patients on N 400BID/IM 400QD experienced dose-limiting rash. No patients experienced QTcF > 500 msec. Two pts, one on nilotinib alone and one in the N 400BID/IM 400QD arm, achieved partial response (PR) lasting 197 days and 176 days, respectively. Thirteen pts (72%) and 9 pts (56%) in the nilotinib alone and N 400BID/IM 400QD cohorts, respectively, experienced stable disease (SD). Median progression-free survival was 168 days for nilotinib alone and 203 days for N 400BID/IM 400QD. Median duration of disease control (CR, PR or SD) was 158 days for nilotinib alone and 259 days for the N 400BID/IM 400QD cohort. Conclusions: Nilotinib, alone and in combination with IM, has significant activity in pts with GIST who are resistant to prior TKIs. The efficacy and safety of nilotinib in third- line GIST are being studied in an ongoing phase III trial. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis Amgen, Bayer, GlaxoSmithKline, Infinity, MedImmune, Novartis, Pfizer, PharmaMar, Roche, sanofi-aventis GlaxoSmithKline, MedImmune, Novartis, Pfizer, PharmaMar, Roche, SigmaTau Amgen, Bristol-Myers Squibb, Infinity, Jansen Cilag, Novartis, OSI Oncology, Pfizer, SigmaTau Infinity, Novartis, Pfizer Novartis, PharmaMar