Background: Regorafenib in the standard intermittent dosing schedule (160 mg po per day for 3 weeks followed by 1week rest) was proven effective in the GRID trial in refractory gastrointestinal stromal tumors (GISTs). However, with this dosing schedule, frequent dose reduction was needed and progression of GIST tumors or tumor-related symptoms during the off-treatment period were also noted in some patients (pts).Therefore, we conducted this phase 2 trial to evaluate the efficacy and safety of regorafenib in lower dose continuous dosing schedule (NCT02889328). Methods: Pts with measurable, metastatic or recurrent GIST who failed both imatinib and sunitinib were eligible for this study. Regorafenib 100 mg po per day was administered continuously. The primary endpoint was disease control rate [DCR] (CR + PR + SD) lasting for at least 12 weeks by the RECIST v1.1. Results: From September 2016 to August 2017, a total of 25 pts were enrolled.The median age was 60 years (range, 42-74), and male was dominant (84%). Small bowel was the most common primary site (n = 15, 60%), followed by stomach (n = 7, 28%). The median treatment duration of imatinib and sunitinib was 40.5 months (range, 7.1–100.5) and 8.3 months (range, 0.7–37.5), respectively. Primary mutation was in kit exon 11 (n = 16, 64%) and 9 (n = 5, 20%), with 3 wild type (12%). The best response was PR in 2 (8%), SD in 16 (64%), and PD in 6 (24%) pts. DCR lasting for at least 12 weeks was 64% (16 of 25). With a median followup of 8.6 months (range, 2.3–14.6), the median PFS was 7.3 months (95% CI, 5.9–8.6), and the median OS was not reached with 1-year survival rate of 64.5%. Treatment was well tolerated. Ten pts (40%) experienced grade 3-4 toxicities including hand-foot skin reaction (n = 4, 16%), and elevation of alanine aminotransferase (n = 2, 8%). Only 5 pts (20%) needed dose modification with relative dose intensity of 91.8% for 8 cycles in all pts. Conclusions: With comparable efficacy and better safety profile compared to standard intermittent dosing schedule, regorafenib in this trial with lower dose continuous schedule might be an alternative treatment in GIST pts after failure of imatinib and sunitinib. Clinical trial information: NCT02889328