FDA Denies Approval of Avapritinib in Fourth-Line GIST
May 15, 2020 02:00pm
By Nichole Tucker
"Today’s approval of Qinlock establishes a new standard of care for patients who have received three prior therapies."
The FDA has granted approval to ripretinib (Qinlock) for the treatment of adult patients with advanced gastrointestinal stromal tumor (GIST) who had at least 3 prior lines of therapy with kinase inhibitors, including imatinib (Gleevec), announced Deciphera Pharmaceuticals, Inc, in a press release. The approval is 3 months ahead of the Prescription Drug Fee Act target action date.
The approval was based on data from the phase III INVICTUS trial (NCT03353753), which led to a median progression-free survival was 6.3 months compared with 1.0 month with placebo, meeting the primary end point of the study. Ripretinib induced an 85% reduction in the risk of disease progression or death compared with placebo (HR, 0.15; P <.0001).
"Today’s approval of Qinlock establishes a new standard of care for patients who have received three prior therapies,” states Margaret von Mehren, MD, chief of Sarcoma Oncology and associate director for Clinical Research, Fox Chase Cancer Center. “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, 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.”
The overall response rate (ORR) was 9.4% versus 0% with ripretinib and placebo, respectively (P <.0504), although this was not significant. The median overall survival (OS) was 15.1 months with ripretinib versus 6.6 months with placebo (HR, 0.36, nominal; P=.0004).
The most common adverse events (AEs), which occurred in ≥20% of patients included alopecia, fatigue, nausea, abdominal pain, constipation, myalgia, diarrhea, decreased appetite, palmar-plantar erythrodysesthesia syndrome, and vomiting. AEs that led to treatment discontinuation occurred in 8% of patients, dosage interruptions in 24% of patients, and dose reductions in 7% of patients.
The randomized, double-blind, placebo-controlled, international, multicenter INVICTUS trial evaluated the safety, tolerability, and efficacy of ripretinib in patients with advanced GIST who had previously received imatinib, sunitinib (Sutent), regorafenib (Stivarga), and patients were randomized 2:1 to either the study drug or placebo. Ripretinib was given at a 150 mg dose once daily. Secondary end points included ORR, time to progression, and OS.
Patients were eligible to enroll if they had an ECOG performance status of 0 to 2 and at least 1 measurable lesion. Patients had to have all toxicities resolved related to prior therapy to grade 1 or lower within 1 week of beginning treatment in the study. For those who had prior anticancer therapy, prior treatment with ripretinib, and other treatment that may limit their chances of responding to ripretinib, they were excluded. Patients were excluded from the study if they had clinically significant comorbidities, gastrointestinal abnormalities, and other conditions.
Ripretinib is an investigational KIT and PDGFRα kinase switch control inhibitor. The company plans to make this therapy commercially available in the United States within the next week. They remain committed to supporting patients with GIST and overcoming barriers to treatment access.
"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, in a press release. “I would like to thank the patients, their families and caregivers, and the healthcare professionals who made the Qinlock clinical studies possible. With their contributions and the dedication of the team at Deciphera, we are delivering on our promise to provide important new medicines for the treatment of cancer.”
The NDA for ripretinib was reviewed via the FDA’s Real-Time Oncology Review, which helped the application move more quickly through the system. Prior to the approval, ripretinib was granted Priority Review, Fast Track, Breakthrough Therapy, and an Orphan Drug designations.2
To guide global partners in their potential approvals of ripretinib, the NDA was also reviewed as a part of Project Orbis. Applications for approval are now being considered in Australia and Canada.