Efficacy and safety of ripretinib vs. sunitinib in patients with advanced gastrointestinal stromal tumor previously treated with imatinib: A phase 2, multicenter, randomized, open-label study in China

Aim: A bridging study of INTRIGUE study to assess the efficacy and safety of ripretinib versus sunitinib as second -line treatment in Chinese GIST patients. Methods: This was a phase 2, multicenter, randomized, open-label study in China. GIST patients previously treated with imatinib were randomized (1:1) to receive ripretinib 150 mg once daily (QD) by continuous dosing in 42-day cycles or sunitinib 50 mg QD in 42-day cycles (four weeks on/two weeks off). Primary endpoint was progression-free survival (PFS) by independent radiological review (IRR). Results: Between 6 December 2020 and 15 September 2021, 108 patients were randomized to receive ripretinib (n = 54) or sunitinib (n = 54) (all-patient [AP] intention-to-treat [ITT] population). Seventy patients had pri-mary KIT exon 11 mutations (ripretinib, n = 35; sunitinib, n = 35; Ex11 ITT population). By data cut-off (20 July 2022), in AP ITT population, PFS by IRR was comparable between ripretinib and sunitinib arms (HR 0.99, 95 % CI 0.57, 1.69; nominal p = 0.92; median PFS [mPFS] 10.3 vs 8.3 months). In Ex11 ITT population, PFS by IRR was longer for ripretinib than sunitinib (HR 0.46, 95 % CI 0.23, 0.92; nominal p = 0.03; mPFS not reached in ripretinib arm and 4 & sdot;9 months in sunitinib arm). Fewer patients experienced grade 3/4 treatment-related treatment-emergent adverse events with ripretinib (17%) versus sunitinib (56%). Conclusions: Ripretinib demonstrated similar efficacy and a favorable safety profile versus sunitinib as second -line treatment in Chinese GIST patients. Furthermore, ripretinib provided greater clinically meaningful benefit versus sunitinib in patients with KIT exon 11 mutation.