FDA Approves Deciphera’s Qinlock for the Treatment of Fourth-Line GIST

Rare Daily Staff

The U.S. Food and Drug Administration granted accelerated approval to Deciphera Pharmaceuticals’ Qinlock (ripretinib) tablets as the first new drug specifically approved as a fourth-line treatment for advanced gastrointestinal stromal tumor for adult patients who have received prior treatment with three or more kinase inhibitor therapies.

Gastrointestinal stromal tumor (GIST) is a rare cancer affecting the digestive tract or nearby structures within the abdomen, most often presenting in the stomach or small intestine. GIST is the most common sarcoma of the gastrointestinal tract, with approximately 4,000 to 6,000 new GIST cases each year in the United States and a similar incidence rate in Europe and other countries. Most cases of GIST are driven by a spectrum of mutations. The most common primary mutations are in KIT kinase, representing approximately 80 percent of cases, or in PDGFRα kinase, representing approximately 6 percent of cases. Current therapies are unable to inhibit the full spectrum of primary and secondary mutations, which drives resistance and disease progression. Estimates for 5-year survival range from 48 percent to 90 percent, depending on the stage of the disease at diagnosis.

Qinlock works by blocking a type of enzyme called a kinase, which helps keep the cancer cells from growing. Qinlock targets the broad spectrum of KIT and PDGFRα mutations known to drive GIST.

“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, chief of sarcoma oncology and associate director for clinical research, Fox Chase Cancer Center, Philadelphia.

The FDA approved Qinlock based on the results of an international, multi-center, randomized, double-blind, placebo-controlled clinical trial that enrolled 129 patients with advanced GIST who had received prior treatment with other FDA-approved targeted therapies, imatinib (Gleevec), sunitinib (Sutent), and regorafenib (Stivarga).

The trial compared patients who were randomized to receive Qinlock to patients who were randomized to receive placebo, to determine whether progression free survival (PFS) – the time from initial treatment in the clinical trial to growth of the cancer or death – was longer in the Qinlock group compared to the placebo group. During treatment in the trial, patients received Qinlock or placebo once a day in 28-day cycles, repeated until tumor growth was found (disease progression), or the patient experienced intolerable side effects. After disease progression, patients who were randomized to placebo were given the option of switching to Qinlock.

On average, the PFS rate in patients in the Qinlock group was 6.3 months, compared to one month for patients in the placebo group.

The most common side effects with Qinlock were alopecia (hair loss), fatigue, nausea, abdominal pain, constipation, myalgia (muscle pain), diarrhea, decreased appetite, palmar-plantar erythrodysesthesia syndrome (a skin reaction in the palms and soles) and vomiting. Serious side effects include skin cancer, hypertension (high blood pressure) and cardiac dysfunction manifested as ejection fraction decrease (when the muscle of the left ventricle of the heart is not pumping as well as normal). Qinlock may also cause harm to a developing fetus or a newborn baby.

“The FDA approval of Qinlock is an exciting milestone for people with GIST who have been waiting for a new treatment option designed specifically for their disease,” said Steve Hoerter, President and Chief Executive Officer of Deciphera. 

The FDA approved Qinlock three months ahead of schedule. It had already granted the application Priority Review and Fast Track designation, as well as Breakthrough Therapy designation, which expedites the development and review of drugs that are intended to treat a serious condition when preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapies.

Qinlock also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases. This review used the Real-Time Oncology Review, which streamlined data submission prior to the filing of the entire clinical application, and the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.

Photo: Steven Hoerter, president and CEO of Deciphera Pharmaceuticals