FDA approves ripretinib for advanced gastrointestinal stromal tumor

FDA approves ripretinib for advanced gastrointestinal stromal tumor

On May 15, 2020, the Food and Drug Administration approved ripretinib (QINLOCK, Deciphera Pharmaceuticals, LLC.), for adult patients with advanced gastrointestinal stromal tumor (GIST) who have received prior treatment with 3 or more kinase inhibitors, including imatinib.

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 (PFS) based on assessment by blinded independent central review (BICR) 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 (ORR) by BICR and overall survival (OS).

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).

The most common adverse reactions (≥20%) with ripretinib were alopecia, fatigue, nausea, abdominal pain, constipation, myalgia, diarrhea, decreased appetite, palmar-plantar erythrodysesthesia, and vomiting. Other important risks of ripretinib include new primary cutaneous malignancies, hypertension, and cardiac dysfunction.

The recommended ripretinib dose is 150 mg orally once daily with or without food.

View full prescribing information for QINLOCK.

via FDA.gov