Gastrointestinal stromal tumors (GIST) are the most common sarcoma of the digestive system. The targeted drugs, imatinib, sunitinib, and regorafenib, have been used to treat GIST. However, the mutations of KIT and PDGFRA had been identified as the resistance mechanisms of these targeted drugs. Ripretinib is a novel tyrosine kinase inhibitor that was designed to target KIT and PDGFRα-mutated kinase. In a phase III study (INVICTUS), the anti-tumor efficacy of ripretinib was evaluated in patients with GIST progressed with more than three lines of treatment. The median progression free survival (PFS) was 6.3 months compared with 1.0 month in the placebo arm (HR=0.15, P<0.0001). The median overall survival (OS) was 15.1 months compared with 6.6 months in the placebo arm (HR=0.36, P<0.0004).The results showed that ripretinib improved PFS and OS compared with placebo in heavy-treated GIST. A New Drug Application (NDA) was submitted to FDA based on this phase III trial results.
von Mehren M, et al. 2019 ESMO congress