FDA Approves Ripretinib Tablets for Advanced Gastrointestinal Stromal Tumor

Ripretinib is now indicated for adult patients with advanced gastrointestinal stromal tumor who have received prior treatment with 3 or more kinase inhibitor therapies.

The FDA approved ripretinib (Qinlock) tablets as the first new drug specifically approved as a fourth-line treatment for advanced gastrointestinal stromal tumor (GIST).

Ripretinib is now indicated for adult patients who have received prior treatment with 3 or more kinase inhibitor therapies, including imatinib (Gleevec).

“Despite the progress that has been made over the past 20 years in developing treatments for GIST, including 4 FDA-approved targeted therapies - imatinib in 2002, sunitinib (Sutent) in 2006, regorafenib (Stivarga) in 2013, and avapritinib (Ayvakit) earlier this year - some patients don’t respond to treatment and their tumors continues to progress,” Richard Padzur, 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, said in a press release. “Today’s approval provides a new treatment option for patients who have exhausted all FDA-approved therapies for GIST.”

The approval of ripretinib was based on the results of the international, multi-center, randomized, double-blind, placebo-controlled INVICTUS trial that enrolled 129 patients with advanced GIST who had received prior treatment with other FDA-approved targeted therapies, including imatinib, sunitinib, and regorafenib. 

The trial was designed to compare patients who were randomized to receive either ripretinib or placebo in order to determine whether progression free survival (PFS) was longer in the ripretinib group compared to the placebo group.2

Trial participants received ripretinib or placebo once a day in 28-day cycles until disease progression, or the patient experienced intolerable adverse events (AEs). Notably, patients who were randomized to placebo were given the option of switching to ripretinib after disease progression.

On average, the PFS rate in those receiving ripretinib was 6.3 months compared to 1 month for those in the placebo group. 

The most common AEs observed in patients receiving ripretinib were alopecia, fatigue, nausea, abdominal pain, constipation, myalgia, diarrhea, decreased appetite, palmar-plantar erythrodysesthesia syndrome, and vomiting. 

Additionally, ripretinib has been found to cause serious AEs including skin cancer, hypertension, and cardiac dysfunction manifested as ejection fraction decrease. Given this, the FDA recommends that healthcare providers routinely check for symptoms and signs of these and other risks related to ripretinib. 

“Today’s approval of [ripretinib] establishes a new standard of care for patients who have received three prior therapies," Margaret von Mehren, MD, chief of Sarcoma Oncology and associate director of Clinical Research at Fox Chase Cancer Center, said in a press release.2 "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. In the INVICTUS study, [ripretinib] has demonstrated compelling clinical benefit in progression-free and overall survival. [Ripretinib] is well tolerated and is a crucial new therapy for these patients with a high unmet need.”

Importantly, the FDA indicated that ripretinib may cause harm to a developing fetus or a newborn baby. Healthcare professionals should therefore 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 1 week after the last dose. Patients should also be advised not to breastfeed while taking ripretinib. 

Previously, the FDA granted this application priority review and fast track designation, as well as breakthrough therapy designation. Ripretinib also previously received orphan drug designation. 


1. FDA. FDA Approves First Drug for Fourth-Line Treatment of Advanced Gastrointestinal Stromal Tumors. FDA website. Published May 15, 2020. fda.gov/news-events/press-announcements/fda-approves-first-drug-fourth-line-treatment-advanced-gastrointestinal-stromal-tumors. Accessed May 15, 2020. 

2. FDA Grants Full Approval of Deciphera Pharmaceuticals’ QINLOCK™ (ripretinib) for the Treatment of Fourth-Line Gastrointestinal Stromal Tumor [news release]. Waltham, Massachusetts. Published May 15, 2020. businesswire.com/news/home/20200515005575/en/FDA-Grants-Full-Approval-Deciphera-Pharmaceuticals’-QINLOCK™. Accessed May 15, 2020.