Deciphera Pharmaceuticals, Inc. announced that the Journal of Clinical Oncologyhas published results from its INTRIGUE Phase 3 study of QINLOCK® (ripretinib) in patients with advanced gastrointestinal stromal tumor (GIST) previously treated with imatinib. Although QINLOCK did not offer a statistically significant improvement in progression-free survival (PFS) compared to sunitinib, QINLOCK showed meaningful clinical activity with fewer Grade 3/4 treatment-emergent adverse events (TEAEs) and improved tolerability. The article, titled “Ripretinib versus sunitinib in patients with advanced gastrointestinal stromal tumor after treatment with imatinib (INTRIGUE): A randomized, open-label, phase III trial” is now available online and will be published in a future print issue of the Journal of Clinical Oncology. INTRIGUE is an international, multi-center study conducted in 122 active sites across 22 countries, where 453 patients with second-line GIST were randomized to receive ripretinib (n=226) or sunitinib (n=227). Key study results include: In patients with a KIT exon 11 primary mutation, ripretinib demonstrated a median PFS (mPFS) of 8.3 months compared to 7.0 months for the sunitinib arm (Hazard Ratio [HR] 0.88, p=0.36). In the intention-to-treat (ITT) population (n=453), ripretinib demonstrated an mPFS of 8.0 months compared to 8.3 months for the sunitinib arm (HR 1.05, nominal p value=0.72). In patients with a KITexon 11 primary mutation, ripretinib demonstrated an objective response rate (ORR) of 23.9% (n=39 of 163) compared to 14.6% (n=24 of 164) for sunitinib (nominal p value=0.03). In the ITT population, ripretinib demonstrated an ORR of 21.7% (n=49 of 226) compared to 17.6% (n=40 of 227) for sunitinib (nominal p value=0.27). Ripretinib was generally well tolerated. Fewer patients in the ripretinib arm experienced Grade 3/4 treatment-emergent adverse events compared to sunitinib (41.3% vs 65.6%). Patients receiving sunitinib were three times more likely to develop Grade 3 hypertension compared to patients receiving ripretinib (26.7% vs. 8.5%) and patients receiving sunitinib were seven times more likely to develop Grade 3 palmar-plantar erythrodysesthesia compared to patients receiving ripretinib (10.0% vs. 1.3%).
Patient reported outcome measures also showed a more favorable tolerability profile for patients receiving ripretinib compared to patients receiving sunitinib. Patients receiving ripretinib experienced less deterioration in their ability to engage in either work or leisure activities during treatment, and fewer patients receiving ripretinib experienced moderate to extremely large impact on their lives due to skin toxicity across treatment cycles compared to patients receiving sunitinib. QINLOCK is approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with advanced GIST who have received prior treatment with three or more kinase inhibitors, including imatinib. The new drug application (NDA) for QINLOCK was based on positive results from the Phase 3 INVICTUS trial in patients with fourth-line and fourth-line plus GIST.