Deciphera Pharmaceuticals, Inc. announced the presentation of additional data from the planned exploratory analysis from the INTRIGUE Phase 3 clinical study of QINLOCK® using circulating tumor DNA (ctDNA) from patients with gastrointestinal stromal tumor (GIST) previously treated with imatinib. The presentation titled “Mutational heterogeneity of imatinib resistance and efficacy of ripretinib vs sunitinib in patients with gastrointestinal stromal tumor: ctDNA analysis from INTRIGUE” was presented by Sebastian Bauer, M.D., University Hospital Essen, University Duisburg-Essen and German Cancer Consortium at the American Society of Clinical Oncology (ASCO) Plenary Series Session. Results of ctDNA Analysis: 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 mutational status.

Baseline peripheral whole blood was analyzed by Guardant360, a 74-gene ctDNA next-generation sequencing liquid biopsy assay. Key highlights from the analysis presented include the following: Mutational Subgroups: 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.

In patients with a KIT exon 11 primary mutation: 52 patients had additional mutations in KIT exon 17/18 only. 41 patients had additional mutations in KIT exon 13/14 only. 22 patients had additional mutations in both KIT exon 13/14 and exon 17/18.

Efficacy Results of ctDNA Analysis: Patients with mutations in KIT exon 11 and exon 17/18 only derived substantially improved clinical benefit with QINLOCK versus sunitinib. QINLOCK demonstrated a median PFS (mPFS) of 14.2 months compared to 1.5 months for the sunitinib arm (Hazard Ratio [HR] 0.22, nominal p value <0.0001). QINLOCK demonstrated a confirmed objective response rate (ORR) of 44.4% (n=12 of 27) compared to 0% for sunitinib (nominal p value 0.0001).

OS for the QINLOCK arm has not reached a median, while patients randomized to the sunitinib arm had a median OS (mOS) of 17.5 months (HR 0.34, nominal p value 0.0061). Patients with mutations in KIT exon 11 and 13/14 only derived substantially improved clinical benefit with sunitinib versus QINLOCK. QINLOCK demonstrated a mPFS of 4 months compared to 15 months for the sunitinib arm (HR 3.94, nominal p value 0.0005).

QINLOCK demonstrated a confirmed ORR of 9.5% (n=2 of 21) compared to 15% (n=3 of 20) for sunitinib (nominal p value 0.5922). QINLOCK demonstrated a mOS of 24.5 months, while patients randomized to the sunitinib arm has not reached a median (HR 1.75, nominal p value 0.2085). Safety and Tolerability: QINLOCK was generally well-tolerated and the safety profiles were consistent with the primary analysis of the INTRIGUE study.

For patients with mutations in KIT exon 11 and exon 17/18 only, fewer patients in the QINLOCK arm experienced Grade 3-4 treatment-related adverse events compared to sunitinib (33% vs 50%). Based on the results of the ctDNA analysis and discussions with the U.S. Food and Drug Administration (FDA), 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. About the INSIGHT Study: The planned INSIGHT Phase 3 clinical study is a randomized, global, multicenter, open-label study to evaluate the efficacy and safety of QINLOCK compared to sunitinib in patients with GIST previously treated with imatinib with mutations in KIT exon 11 and 17/18 only (excluding patients with mutations in KIT exons 9, 13, or 14).

In the study, 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 is PFS as determined by independent radiologic review using modified RECIST 1.1 criteria. Secondary endpoints include ORR as determined by independent radiologic review using modified RECIST 1.1 criteria and OS.

About the INTRIGUE Study: The INTRIGUE Phase 3 clinical study is a randomized, global, multicenter, open-label study to evaluate the efficacy and safety of QINLOCK compared to sunitinib in patients with GIST previously treated with imatinib. In the study, 453 patients were randomized 1:1 to either QINLOCK 150 mg once daily or sunitinib 50 mg once daily for four weeks followed by two weeks without sunitinib. As previously reported, the study did not achieve the primary efficacy endpoint of PFS as determined by independent radiologic review using modified RECIST 1.1 criteria.

The statistical analysis plan included a hierarchical testing sequence that included testing patients with a KIT exon 11 primary mutation and then in the all patient intent-to-treat (AP) population. In patients with a KIT exon 11 primary mutation (n=327), QINLOCK demonstrated an mPFS of 8.3 months compared to 7.0 months for the sunitinib arm (HR 0.88, p=0.360). Although not formally tested due to the rules of the hierarchical testing sequence, in the AP population QINLOCK demonstrated a mPFS of 8.0 months compared to 8.3 months for the sunitinib arm (HR 1.05, nominal p=0.715).

QINLOCK was generally well tolerated. Fewer patients in the QINLOCK arm experienced Grade 3-4 treatment-emergent adverse events compared to sunitinib (41.3% vs 65.6%).