Intrigue: Phase III study of ripretinib versus sunitinib in advanced gastrointestinal stromal tumor after imatinib

Future Oncol. 2020 Jan;16(1):4251-4264. doi: 10.2217/fon-2019-0633. Epub 2019 Nov 22.


Ripretinib (DCC-2618) is a novel, type II tyrosine switch control inhibitor designed to broadly inhibit activating and drug-resistant mutations in KIT and PDGFRA. Ripretinib has emerged as a promising investigational agent for the treatment of gastrointestinal stromal tumor owing to targeted inhibition of secondary resistance mutations that may develop following treatment with prior line(s) of tyrosine kinase inhibitors. Here we describe the rationale and design of intrigue (NCT03673501), a global, randomized (1:1), open-label, Phase III study comparing the safety and efficacy of ripretinib versus sunitinib in patients with advanced gastrointestinal stromal tumor following imatinib. The primary end point is progression-free survival and key secondary objectives include objective response rate and overall survival. Clinical Trial Registration: NCT03673501.

Keywords: DCC-2618; KIT; PDGFRA; Phase III trial; gastrointestinal stromal tumor; receptor tyrosine kinase; ripretinib; sarcoma; targeted therapy; tyrosine kinase inhibitor.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Drug Resistance, Neoplasm / drug effects*
  • Female
  • Follow-Up Studies
  • Gastrointestinal Neoplasms / drug therapy*
  • Gastrointestinal Neoplasms / pathology
  • Gastrointestinal Stromal Tumors / drug therapy*
  • Gastrointestinal Stromal Tumors / pathology
  • Humans
  • Imatinib Mesylate / administration & dosage
  • Male
  • Middle Aged
  • Mutation
  • Naphthyridines / therapeutic use*
  • Prognosis
  • Protein Kinase Inhibitors / therapeutic use*
  • Proto-Oncogene Proteins c-kit / antagonists & inhibitors
  • Proto-Oncogene Proteins c-kit / genetics
  • Receptor, Platelet-Derived Growth Factor alpha / antagonists & inhibitors
  • Receptor, Platelet-Derived Growth Factor alpha / genetics
  • Research Design*
  • Sunitinib / administration & dosage
  • Survival Rate
  • Urea / analogs & derivatives*
  • Urea / therapeutic use
  • Young Adult


  • Naphthyridines
  • Protein Kinase Inhibitors
  • Imatinib Mesylate
  • Urea
  • ripretinib
  • KIT protein, human
  • Proto-Oncogene Proteins c-kit
  • Receptor, Platelet-Derived Growth Factor alpha
  • Sunitinib

Associated data