Background: Tyrosine kinase inhibitors (TKI) have considerably improved outcome of advanced GIST. First-line imatinib treatment achieves an excellent mOS of 5 years, yet, a mPFS of approximately 2 years with first-line imatinib and 24 weeks with second-line sunitinib calls for treatment alternatives. Nilotinib is a second-generation TKI with at least similar inhibitory activity as imatinib, but reaching 7-10 fold higher intracellular concentrations. A Phase I study has shown that nilotinib monotherapy has clinical activity in GIST. Methods: Patients (pts) failing all available therapeutic options had access to nilotinib on a compassionate use (CU) programm. Nilotinib starting dose was 400 mg bid, with an allowed dose reduction to 400 mg qd for toxicity. 94 pts were approved for nilotinib CU in 10 European countries. We herein present retrospective data of 36 pts from 5 European countries treated in 8 centers. Results: Median age at nilotinib treatment start was 59 years (median; range 24-79 y), and 70% of pts were male. Most pts had metastatic disease of gastric origin at initial diagnosis. KIT exon 11 mutations were most frequent. The median number of surgical resections was 1 (range 0-8). All pts had failed both imatinib and sunitinib before nilotinib, and 8% had also received additional investigational treatments. Nilotinib was well tolerated, as only 14% discontinued nilotinib due to toxicity. Median follow-up is 156 days (range 15-765 d). Nilotinib treatment duration is 60 days (median; range 3-727 d) and one third of pts were treated for longer than 3 months. Partial remission with nilotinib treatment was seen in 6% of pts. Median OS was 211 days (Kaplan-Meier). Conclusions: This is the largest series assessing efficacy of nilotinib for imatinib- and sunitinib-refractory GIST reported yet. Nilotinib displays significant clinical activity in this heavily pretreated group of pts. One third of pts have disease control on nilotinib for longer than three months. These results warrant further investigation of nilotinib in GIST, including its use in first or second-line treatment. Patient and data collection is ongoing, updated results will be presented at ASCO 2008.