On January 3, 2023 Deciphera Pharmaceuticals, Inc. (NASDAQ: DCPH), a biopharmaceutical company focused on discovering, developing, and commercializing important new medicines to improve the lives of people with cancer, reported that 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 (Press release, Deciphera Pharmaceuticals, JAN 3, 2023, View Source [SID1234625730]).

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"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."

"The newly reported clinical results from INTRIGUE demonstrate the remarkable differential benefit of ripretinib in patients with unique molecular subtypes of GIST in the second-line setting, specifically patients with ctDNA demonstrating KIT exon 11 and 17/18 mutations," said Suzanne George, M.D., Associate Division Chief, Sarcoma Center, Dana-Farber Cancer Institute, and the co-lead investigator on the INSIGHT study. "This data is potentially practice changing in second-line GIST and as ctDNA assays are increasingly optimized and utilized in the clinical arena, we must continue clinical drug development which aims to understand the impact of drugs in specific molecular subtypes of GIST with the goal to improve clinical outcomes by giving the right drug to the right patient at the right time."

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.

Summary of INTRIGUE Efficacy Results of ctDNA Analysis for Patients with Mutations in KIT Exon 11 and 17/18 Only

Ripretinib
(n=27)

Sunitinib
(n=25)

Hazard
Ratio/Response
Difference
(95% CI)

Median Progression-Free Survival (1)

14.2 months

1.5 months

0.22 (0.11, 0.44),
nominal p value
<0.0001

Objective Response Rate (1)

44.4%

0%

44.4% (23.0%, 62.7%)
nominal p value =
0.0001

Overall Survival (2)

Not Estimable

17.5 months

0.34 (0.15, 0.76),
nominal p value =
0.0061

Notes: (1) Data cut as of September 1, 2021; (2) Data cut as of September 1, 2022.

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.

Conference Call and Webcast

Deciphera will host a conference call and webcast to discuss this announcement today, January 3, 2023, at 5:00 PM ET. The conference call may be accessed via this link: https://register.vevent.com/register/BI4841f7cb08a04e5ba80127e42e643432. A live webcast of the conference call will be available in the "Events and Presentations" page in the "Investors & News" section of the Company’s website at View Source A replay will be available on the Company’s website approximately two hours after the conference call and will be available for 30 days following the call.

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 (hazard ratio (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%).