Deciphera Pharmaceuticals announced findings of a planned exploratory analysis of data from the INTRIGUE Phase 3 clinical study of QINLOCK using circulating tumor DNA from a subgroup of patients with gastrointestinal stromal tumor previously treated with imatinib who harbor mutations in KIT exon 11 and 17/18 only. "We are extremely pleased by the exploratory analysis showing that QINLOCK, already the standard of care for fourth-line GIST patients, provided substantial clinical benefit to this subgroup of second-line patients compared to sunitinib. We look forward to presenting additional data from the overall ctDNA analysis at a medical meeting later this month," said Matthew L. Sherman, M.D., Chief Medical Officer of Deciphera. "Given the strength of these results, and after consultation with the FDA, we plan to initiate our INSIGHT pivotal Phase 3 study in the second half of 2023. If positive, we believe this trial will transform the standard of care for this subgroup of second-line GIST patients based on their mutational profile." An exploratory objective in the INTRIGUE Phase 3 study in GIST patients previously treated with imatinib 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. Of the 453 patients in the overall intent-to-treat population (ITT), baseline ctDNA was analyzed in 362 patients for whom evaluable samples were available. ctDNA was detected in 280 samples and KIT mutations were detected in 213 patients. Primary mutations in KIT were detected in exon 11 in 157 patients and in exon 9 in 36 patients. Common resistance mutations in KIT were detected in exons 17/18 in 89 patients and in exons 13/14 in 81 patients. In patients with a KIT exon 11 primary mutation, 52 patients had mutations in exon 17/18 only, 41 had mutations in exon 13/14 only, and 22 patients had mutations in both exon 13/14 and exon 17/18. Patients with mutations in KIT exon 11 and exon 17/18 only had substantially improved progression-free survival (PFS), objective response rate (ORR), and overall survival (OS) with QINLOCK versus sunitinib. Efficacy results in patients with detectable ctDNA in KIT exon 11 and in the ITT populations were consistent with the primary analysis of the INTRIGUE study based on tumor data used for randomization. The subgroup safety profiles were consistent with the primary analysis.
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