FDA Approves Qinlock (Ripretinib) For Gastrointestinal Stromal Tumors

The FDA recently approved Deciphera Pharmaceuticals’ ripretinib (Qinlock), the first drug for fourth-line treatment of advanced gastrointestinal stromal tumors (GIST). The medication is only indicated for adults who have previously received treatment with 3 or more kinase inhibitor therapies, including imatinib.

Between 4000 to 6000 adults are diagnosed with a GIST in the United States each year. The tumors occur when abnormal cells form in gastrointestinal tract tissues. Although GISTs are most common in the stomach, small intestine, and large intestine, the tumors can originate in any place along the gastrointestinal tract.

Over the past 20 years, the FDA approved targeted therapies imatinib, sunitinib, and regorafenib for GIST. However, some patients do not respond to these treatments and tumors may continue to progress.

Ripretinib is a kinase inhibitor that was granted a Fast Track designation and Priority Review by the FDA. The medication also received Breakthrough Therapy designation, and will become commercially available in the United States next week.

The approval follows positive results from the phase 3 INVICTUS trial of 129 patients with advanced GIST. Participants were randomized to receive either ripretinib or placebo once a day in 28-day cycles. The cycles were repeated until tumor growth (disease progression) was found, or the patient experienced intolerable side effects. If disease progression was found in the placebo group, participants were given the option to receive ripretinib. Researchers compared progression free survival (PFS) in each group.

Ripretinib exhibited “a median PFS of 6.3 months compared to 1.0 month in the placebo arm and significantly reduced the risk of disease progression or death by 85% (hazard ratio of 0.15, P <.0001),” according to a Deciphera Pharmaceuticals statement. In addition, the treatment “demonstrated a median overall survival of 15.1 months compared to 6.6 months in the placebo arm and reduced the risk of death by 64% (hazard ratio of 0.36).”

Common adverse reactions (≥20%) included alopecia, fatigue, vomiting, and a variety of additional gastrointestinal complications. Eight percent of patients in the study stopped using ripretinib due to adverse reactions while dose reductions due to side effects occurred in 7% of patients. Overall, 24% of the study population experienced dosage interruptions due to an adverse reaction.

The treatment can also cause skin cancer, hypertension, and cardiac dysfunction manifested as ejection fraction disease. Ripretinib may also cause harm to a developing fetus or newborn baby.

“GIST is a complex disease and the majority of patients who initially respond to traditional tyrosine kinase inhibitors eventually develop tumor progression due to secondary mutations,” said Margaret von Mehren, MD, chief of sarcoma oncology and associate director for clinical research at Fox Chase Cancer Center.

“In the INVICTUS study, Qinlock has demonstrated compelling clinical benefit in progression-free and overall survival. Qinlock is well tolerated and is a crucial new therapy for these patients with a high unmet need.”