The INSIGHT study: A randomized, Phase III study of ripretinib versus sunitinib for advanced gastrointestinal stromal tumor with KIT exon 11 + 17/18 mutations Journal Article
| Authors: | George, S.; Blay, J. Y.; Chi, P.; Jones, R. L.; Serrano, C.; Somaiah, N.; Gelderblom, H.; Zalcberg, J. R.; Reichmann, W.; Sprott, K.; Cox, P.; Sherman, M. L.; Ruiz-Soto, R.; Heinrich, M. C.; Bauer, S. |
| Article Title: | The INSIGHT study: A randomized, Phase III study of ripretinib versus sunitinib for advanced gastrointestinal stromal tumor with KIT exon 11 + 17/18 mutations |
| Abstract: | Somatic KIT activating mutations drive most gastrointestinal stromal tumors (GISTs). Disease progression eventually develops with first-line imatinib, commonly due to KIT secondary mutations, and different kinase inhibitors have various levels of treatment efficacy dependent on specific acquired resistance mutations. Ripretinib is a broad-spectrum switch-control KIT/PDGFRA tyrosine kinase inhibitor for patients with advanced GIST who received prior treatment with three or more kinase inhibitors, including imatinib. Exploratory baseline circulating tumor DNA analysis from the second-line INTRIGUE trial determined that patients with advanced GIST previously treated with imatinib harboring primary KIT exon 11 mutations and secondary resistance mutations restricted to KIT exons 17/18 had greater clinical benefit with ripretinib versus sunitinib. We describe the rationale and design of INSIGHT (NCT05734105), an ongoing Phase III open-label study of ripretinib versus sunitinib in patients with advanced GIST previously treated with imatinib exclusively harboring KIT exon 11 + 17/18 mutations detected by circulating tumor DNA. Clinical Trial Registration:NCT05734105 (ClinicalTrials.gov). © 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. |
| Keywords: | adult; controlled study; treatment outcome; aged; middle aged; exon; genetics; mutation; exons; clinical trial; sunitinib; antineoplastic agents; antineoplastic agent; gastrointestinal stromal tumor; stem cell factor receptor; gastrointestinal stromal tumors; proto-oncogene proteins c-kit; protein kinase inhibitor; randomized controlled trial; drug resistance; pathology; drug resistance, neoplasm; protein kinase inhibitors; gastrointestinal neoplasms; multicenter study; targeted therapy; phase 3 clinical trial; drug therapy; tyrosine kinase inhibitor; kit mutations; urea; gastrointestinal tumor; naphthyridines; predictive marker; humans; human; male; female; phase iii trial; insight; ripretinib; naphthyridine derivative; ctdna mutational analysis; kit protein, human |
| Journal Title: | Future Oncology |
| Volume: | 20 |
| Issue: | 27 |
| ISSN: | 1479-6694 |
| Publisher: | Future Medicine |
| Date Published: | 2024-01-01 |
| Start Page: | 1973 |
| End Page: | 1982 |
| Language: | English |
| DOI: | 10.1080/14796694.2024.2376521 |
| PUBMED: | 39229786 |
| PROVIDER: | scopus |
| PMCID: | PMC11497949 |
| DOI/URL: | |
| Notes: | Source: Scopus |
