FDA has approved ripretinib (Qinlock) Deciphera Pharmaceuticals LLC for adult patients with advanced gastrointestinal stromal tumor who have received prior treatment with three or more kinase inhibitors, including imatinib.
Qinlock is sponsored by Deciphera Pharmaceuticals.
“Despite the progress that has been made over the past 20 years in developing treatments for GIST, including four FDA-approved targeted therapies—imatinib in 2002, sunitinib in 2006, regorafenib in 2013 and avapritinib earlier this year—some patients don’t respond to treatment and their tumors continues to progress,” Richard Pazdur, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, said in a statement.
Efficacy was evaluated in INVICTUS (NCT03353753), an international, multi-center, randomized (2:1), double-blind, placebo-controlled trial in 129 patients with GIST who were previously treated with imatinib, sunitinib, and regorafenib. Patients received ripretinib150 mg or placebo orally once daily until disease progression or unacceptable toxicity. Crossover was permitted at disease progression for patients randomized to receive placebo.
The major efficacy outcome measure was progression-free survival based on assessment by blinded independent central review using modified RECIST 1.1 in which lymph nodes and bone lesions were not target lesions and a progressively growing new tumor nodule within a pre-existing tumor mass must meet specific criteria to be considered unequivocal evidence of progression. Additional efficacy outcome measures included overall response rate by BICR and overall survival.
The trial demonstrated a statistically significant improvement in PFS for patients in the ripretinib arm compared with those in the placebo arm (HR 0.15; 95% CI: 0.09, 0.25; p<0.0001). The median PFS was 6.3 months (95% CI: 4.6, 6.9) for ripretinib compared with 1.0 month (95% CI: 0.9, 1.7) for placebo. The ORR was 9% (95% CI: 4.2, 18) in the ripretinib arm compared with 0% (95% CI: 0, 8) in the placebo arm, though this difference was not statistically significant. The median OS in the ripretinib arm was 15.1 months (95% CI: 12.3, 15.1) compared with 6.6 months (95% CI: 4.1, 11.6) in the placebo arm with a HR of 0.36 (95% CI: 0.21, 0.62), though OS was not evaluated for statistical significance as a result of the sequential testing procedure for the secondary endpoints (i.e., PFS, then ORR, then OS).
