Publication of Phase III INTRIGUE clinical study result of Qinlock in Journal of Clinical Oncology

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.

“These full Phase III INTRIGUE study results continue to deepen our understanding of Qinlock and its place in the GIST treatment landscape,” said Matthew L. Sherman, M.D., Chief Medical Officer of Deciphera. “Although the INTRIGUE study did not meet its primary endpoint of superiority in PFS compared to sunitinib for patients in the post-imatinib setting, the efficacy of Qinlock was comparable to sunitinib. In addition, Qinlock had a more favorable safety profile than sunitinib with fewer Grade 3/4 adverse events and patients in the Qinlock arm reported less deterioration in role functioning and better outcomes on several other key patient-reported outcome measures of tolerability compared to sunitinib.”.

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: i 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). ii. 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). iii. In patients with a KIT exon 11 primary mutation, ripretinib demonstrated an objective response rate (ORR) of 23.9% (n=39 f 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). iv. 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%). v. 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%). vi. Patient reported outcome measures also showed a more favorable tolerability profile for patients receiving ripretinib compared to patients receiving sunitinib. vii. 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 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 III INVICTUS trial in patients with fourth-line and fourth-line plus GIST.

See-"Ripretinib Versus Sunitinib in Patients With Advanced Gastrointestinal Stromal Tumor After Treatment With Imatinib (INTRIGUE): A Randomized, Open-Label, Phase III Tria": Sebastian Bauer, Robin L. Jones, Jean-Yves Blay, Hans Gelderblom, et al.