Deciphera Pharmaceuticals to Present Data from INTRIGUE Phase 3 Study of QINLOCK (ripretinib) and Trial-in-Progress Poster for INSIGHT Pivotal Phase 3 Study of QINLOCK at the 2023 American Society of Clinical Oncology Annual Meeting - Seite 2

Session Time: 1:15 – 4:15 PM CT
Poster Discussion Session: 4:30 – 6:00 PM CT
Key Highlights:

• INTRIGUE is a randomized, open-label, global, multicenter phase 3 study comparing the efficacy and safety of ripretinib vs. sunitinib in patients with GIST who had disease progression on, or were intolerant to, first-line treatment with imatinib
• 453 patients were randomized 1:1 to receive ripretinib 150 mg QD or sunitinib 50 mg QD (4 weeks on/2 weeks off) and were stratified by KIT mutational status and imatinib intolerance
• 51 of 444 treated patients (11.5%; intent-to-treat population (ITT)) remain on treatment; 33/223 (14.8%) on ripretinib and 18/221 (8.1%) on sunitinib
• Overall survival (OS) was measured at the second interim analysis (IA) as of September 1, 2022, with 185 OS events (41%) in the ITT population and 133/327 (41%) in the KIT exon 11 ITT population
• OS was similar with ripretinib vs. sunitinib in the ITT population (median 35.5 months vs. 30.9 months; HR 0.88; 95% CI, 0.66 to 1.18; nominal P = 0.39) and KIT exon 11 ITT population (median 34.0 months vs. 31.5 months; HR 1.05; 95% CI, 0.75 to 1.48; nominal P = 0.77)
• PFS on next line of therapy in the second IA was similar with ripretinib vs. sunitinib in the all patient (AP) ITT population (median 7.7 months vs. 6.5 months; HR 1.01; 95% CI, 0.76 to 1.34) and KIT exon 11 ITT population (median 8.2 months vs. 7.5 months; HR 1.14; 95% CI, 0.81 to 1.59)
• The updated safety profile was consistent with the primary analysis
  • Fewer patients had grade 3/4 treatment-emergent adverse events (TEAEs) with ripretinib vs. sunitinib (95 [42.6%] vs. 149 [67.4%])
  • Dose interruptions, and reductions, and treatment discontinuations due to TEAEs were lower with ripretinib vs. sunitinib
  • The most common TEAEs of any grade in the ripretinib arm were alopecia, fatigue, and myalgia, whereas the most common TEAEs of any grade in patients treated with sunitinib were palmar-plantar erythrodysesthesia syndrome, diarrhea, and hypertension

Abstract Number: 11536
Title: Outcomes in patients with advanced gastrointestinal stromal tumor who did not have baseline ctDNA detected in the INTRIGUE study
Presenter: Jonathan Trent, M.D., Ph.D., Associate Director for Clinical Research, Sylvester Comprehensive Cancer Center, University of Miami Health System
Session Date: Saturday, June 3
Session Time: 1:15 – 4:15 PM CT
Key Highlights:

• An exploratory objective in the INTRIGUE Phase 3 study was to evaluate anti-tumor efficacy of QINLOCK according to baseline KIT primary and secondary mutational status using circulating tumor DNA (ctDNA)
• Data cutoff was September 1, 2021 for all data except OS, which had a data cutoff of September 1, 2022
• Of the 453 patients in the ITT population, baseline ctDNA was analyzed in 362 patients for whom evaluable samples were available
  • Among 82 patients (22.7%) who had no detectable ctDNA (ctDNA-ND), 40 were in the ripretinib arm and 42 in the sunitinib arm
  • Among the 280 patients (77.3%) with ctDNA detected (ctDNA-D), 135 were in the ripretinib arm and 145 in the sunitinib arm
• Clinical efficacy was higher in patients with ctDNA-ND vs. ctDNA-D
  • Objective response rate (ORR) rate was higher in patients with ctDNA-ND (25.6%) vs. ctDNA-D (17.5%)
  • Progression-free survival (PFS) was higher in patients with ctDNA-ND (12.3 months) vs. ctDNA-D (6.8 months), HR 1.81; 95% CI, 1.28 to 2.56; nominal P = 0.0006
• Overall survival (OS) was higher in patients with ctDNA-ND (not estimable) vs. ctDNA-D (28.9 months), HR 4.69; 95% CI, 2.54 to 8.68; nominal P < 0.0001
• In the ctDNA-ND group, ripretinib demonstrated a numerically higher PFS vs. sunitinib (median 16.6 months vs. 11.0 months; HR 0.73; 95% CI, 0.39 to 1.39; nominal P = 0.3362) and in the ctDNA-D group. PFS was comparable between ripretinib and sunitinib (median 6.8 months vs. 6.9 months; HR 1.23; 95% CI, 0.92 to 1.64; nominal P = 0.1583)
• In the ctDNA-ND group, OS was similar with ripretinib vs. sunitinib (not estimable for both ripretinib and sunitinib; HR 0.84; 95% CI, 0.25 to 2.75; nominal P = 0.7674) and in the ctDNA-D group (median 27.7 months vs. 29.5 months; HR 1.05; 95% CI, 0.75 to 1.47; nominal P = 0.7609)
• Patients with ctDNA-ND were younger (median 55.5 years vs. 62.0 years) and had smaller sums of longest diameters of target lesions vs. patients with ctDNA-D
• Safety was similar between ctDNA groups and consistent with the primary analysis
  • Fewer patients had grade 3/4 TEAEs with ripretinib vs. sunitinib in both groups (ctDNA-ND, 14 [35.0%] vs. 29 [69.0%]; ctDNA-D, 56 [41.5%] vs. 94 [65.7%])
  • Dose interruptions, dose reductions, and treatment discontinuations due to TEAEs were lower with ripretinib vs. sunitinib

Abstract Number: TPS11582