Deciphera Pharmaceuticals, Inc. announced findings of a planned exploratory analysis of data from the INTRIGUE Phase 3 clinical study of QINLOCK using circulating tumor DNA (ctDNA) from a subgroup of patients with gastrointestinal stromal tumor (GIST) previously treated with imatinib who harbor mutations in KIT exon 11 and 17/18 only. Planned Exploratory Efficacy Analysis using ctDNA in INTRIGUE Study: 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. Based on the results of the ctDNA analysis and discussions with regulators, the Company plans to initiate the INSIGHT pivotal Phase 3 clinical study of QINLOCK versus sunitinib in second-line GIST patients with mutations in KIT exon 11 and 17/18 only.

In the planned study, approximately 54 patients will be randomized 2:1 to either QINLOCK 150 mg once daily or sunitinib 50 mg once daily for four weeks followed by two weeks without sunitinib. The primary endpoint will be PFS as determined by independent radiologic review using modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. The Company expects to initiate the INSIGHT study in the second half of 2023.