Long-term follow-up results from INTRIGUE phase III clinical study in second-Line GIST patients at the 2024 American Society of Clinical Oncology Gastrointestinal Cancers symposium- Deciphera Pharmaceuticals, Inc.

The presentation titled “Overall survival and long-term safety with ripretinib vs sunitinib in patients with advanced gastrointestinal stromal tumor previously treated with imatinib: final analyses from INTRIGUE” will be presented by John Zalcberg, M.D., Ph.D., Cancer Research Program, Monash University School of Public Health and Preventive Medicine and Department of Medical Oncology, Alfred Health, Melbourne, Victoria, Australia at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium and will be available on the Company’s website at www.deciphera.com/presentations-publications.

“These long-term clinical results demonstrate that the overall survival rate was similar for both Qinlock and sunitinib, and that treatment with Qinlock continued to show a favorable safety profile compared to treatment with sunitinib,” said Dr. Zalcberg. “In addition, the data show that patient outcomes in the third-line setting are comparable for patients that were treated with either Qinlock or sunitinib in the second line.”

Results of INTRIGUE Study Long-Term Follow-Up : In INTRIGUE, 453 patients in the all-patient intent-to-treat population (AP-ITT) with second-line GIST were randomized 1:1 to receive Qinlock 150 mg once daily (n=226) or sunitinib 50 mg once daily (4 weeks on/2 weeks off) (n=227) of which 444 patients received treatment. In the primary analysis of the AP-ITT population based on a data cut of September 1, 2021, while the primary endpoint was not achieved, Qinlock demonstrated similar efficacy with a median progression-free survival (PFS) of 8.0 months versus 8.3 months for sunitinib (hazard ratio [HR] 1.05, nominal p=0.72). There were fewer patients with Grade 3/4 drug-related treatment emergent adverse events (TEAE) with Qinlock (26.5%) compared with sunitinib (55.2%). Based on the primary results from the INTRIGUE study, Qinlock was included in the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology for GIST (version 1.2023) as a preferred second-line regimen for patients with advanced GIST who are intolerant to sunitinib.

The final analysis includes 18 months of additional follow up after the primary analysis based on a data cut of March 15, 2023. Key highlights from the final results presented include the following:Overall Survival (OS): i. There were 211 OS events (46.6%) in the AP-ITT population with median duration of follow-up in the Qinlock and sunitinib arms of 35.1 months and 34.1 months, respectively. ii. Median OS in the AP-ITT population was similar with Qinlock (35.5 months) versus sunitinib (31.5 months) (HR 0.86; 95% CI, 0.65 to 1.13; nominal p= 0.275).Safety and Tolerability: i. Among the 444 patients treated, 9.0% of patients remained on treatment at the time of data cutoff including 12.6% of 223 patients treated with Qinlock and 5.4% of 221 patients treated with sunitinib. ii.The long-term safety profile of Qinlock was consistent with the primary analysis. a. Fewer patients had Grade 3/4 drug-related TEAEs with . Qinlock (27.4%) versus sunitinib (57.9%). b. Dose interruptions and reductions as well as treatment discontinuations due to TEAEs were lower with Qinlock versus sunitinib. Fewer patients discontinued treatment due to any TEAE for Qinlock (4.9%) versus sunitinib (9.0%). iii. The most common TEAEs in the Qinlock arm were alopecia, fatigue, and myalgia. The most common TEAEs in patients treated with sunitinib were palmar-plantar erythrodysesthesia syndrome, diarrhea, and hypertension.

Exploratory Analysis: Efficacy of Next-Line Therapy : i. Median PFS on the next line of therapy after protocol treatment was similar for Qinlock (7.7 months) versus sunitinib (7.4 months) in the AP-ITT population (HR 1.03; 95% CI, 0.78 to 1.35). ii. Following study treatment discontinuation, the most common third-line therapy was sunitinib for patients in the Qinlock arm (59.7%) and regorafenib for patients in the sunitinib arm (42.7%). iii. Patients in the Qinlock arm who received third-line sunitinib had a median PFS on next line of therapy of 8.5 months compared with 6.3 months for patients in the sunitinib arm who received third-line regorafenib (HR 0.90; 95% CI, 0.66 to 1.24).

In January 2024, Nature Medicine published the results of the exploratory ctDNA analysis from INTRIGUE (previously cited), showing substantial clinical benefit of Qinlock compared to sunitinib in second-line GIST patients with mutations in KIT exon 11 and 17/18 only. Patients with mutations in KIT exon 11 and 17/18 had improved progression-free survival, objective response rate, and overall survival with Qinlock versus sunitinib.

Based on the results of this prespecified exploratory objective in INTRIGUE, the Company is enrolling the INSIGHT pivotal Phase III clinical study of Qinlock in second-line GIST patients with mutations in KIT exon 11 and 17/18 only.

About the INSIGHT Study : The INSIGHT Phase III 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 (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.