Deciphera publishes results from ctDNA analysis of INTRIGUE study

Deciphera announced that Nature Medicine has published results from a circulating tumor DNA, or ctDNA, analysis of the INTRIGUE Phase 3 study of Qinclock in GIST patients with mutations in KIT exon 11 and 17/18 only previously treated with imatinib. The article, titled “Ripretinib versus sunitinib in gastrointestinal stromal tumor: ctDNA biomarker analysis of the phase 3 INTRIGUE trial” is now available online and will be published in a future print issue of Nature Medicine. INTRIGUE is an international, multi-center study conducted in 122 active sites across 22 countries, where 453 patients in the all patient intent-to-treat population with second-line GIST were randomized to receive ripretinib or sunitinib. In the AP-ITT population, Qinclock demonstrated similar efficacy with a median progression-free survival, or PFS, of 8 months versus 8.3 months for sunitinib. There were fewer patients with Grade 3-4 drug-related treatment emergent adverse events with Qinclock compared with sunitinib. Based on the primary results from the INTRIGUE study, Qinclock was included in the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology as the preferred second-line regimen for patients with advanced GIST who are intolerant to sunitinib. A prespecified exploratory objective in INTRIGUE was to evaluate anti-tumor efficacy of QINLOCK according to baseline KIT primary and secondary mutation status. Baseline peripheral whole blood was analyzed by Guardant360, a 74-gene ctDNA next-generation sequencing liquid biopsy assay in patients for whom evaluable samples were available out of whom 280 patients had detectable ctDNA. In patients with a detectable KIT exon 11 primary mutation, 52 patients also had mutations in KIT exon 17/18 only and 41 had mutations in KIT exon 13/14 only. Patients with mutations in KIT exon 11 and 17/18 only had improved progression-free survival, objective response rate and overall survival with Qinclock versus sunitinib while patients with mutations in KIT exon 11 and 13/14 only had improved PFS, ORR, and OS with sunitinib compared to Qinclock. The subgroup safety profile was consistent with the primary analysis in the AP-ITT population and demonstrated a more favorable safety profile for Qinclock compared with sunitinib with fewer patients experiencing Grade 3-4 drug-related TEAEs.