WASHINGTON — The FDA approved ripretinib (Qinlock) tablets, the first drug indicated as a fourth-line treatment for patients with advanced gastrointestinal stromal tumors (GIST).
For this approval, the FDA worked with the Australian Therapeutic Goods Administration (TGA) and Health Canada through Project Orbis, as well as granting the drug priority review, fast track, orphan drug, and breakthrough therapy designations, allowing the agency to approve ripretinib 3 months ahead of schedule. The drug, a kinase inhibitor, is indicated for patients who have received at least three prior kinase inhibitor therapies, including imatinib.
“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 continue to progress,” said Richard Pazdur, MD, 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, in a statement. “Today’s approval provides a new treatment option for patients who have exhausted all FDA-approved therapies for GIST.”
This approval was based on results from an international, multi-center, randomized, double-blind, placebo-controlled trial of 129 patients with advanced GIST who had previously undergone treatment with imatinib, sunitinib, and regorafenib. Patients were randomized to either ripretinib or placebo once daily for 28-days, repeated until disease progression or the patient experienced intolerable side effects. After disease progression, placebo patients were given the option of switching to the study drug, the agency explained.
“On average, the [progression-free survival] rate in the [ripretinib] group was 6.3 months, compared to one month for patients in the placebo group,” the FDA wrote.
The agency pointed out several common side effects to the drug — alopecia, fatigue, nausea, abdominal pain, constipation, myalgia, diarrhea, decreased appetite, palmar-plantar erythrodysesthesia syndrome, and vomiting — as well as several more serious adverse effects, including skin cancer, hypertension, cardiac dysfunction manifested as ejection fraction decrease.
“Health care providers should routinely check for symptoms and signs of these and other risks of [ripretinib],” the FDA advised.”
The agency added that the drug “may cause harm to a developing fetus or a newborn baby. Health care professionals should advise pregnant women of this risk and should advise both females of reproductive potential and male patients with female partners of reproductive potential, to use effective contraception during treatment and for one week after the last dose. Patients should be advised not to breastfeed while taking [ripretinib].”
Ripretinib is manufactured by Deciphera Pharmaceuticals, Inc.
John McKenna, Associate Editor, BreakingMED™
Cat ID: 120
Topic ID: 78,120,730,188,120,935,192,725