FDA Grants Priority Review to Ripretinib for Treatment of Advanced GIST

The FDA has granted Priority Review to the New Drug Application for ripretinib as treatment of patients with advanced gastrointestinal stromal tumors (GIST). This potential FDA approval has a Prescription Drug User Fee Act (PDUFA) target action date of August 13, 2020, according to a press release from Deciphera Pharmaceuticals, Inc.¹

“The FDA’s acceptance of our NDA brings us one step closer to our goal of providing patients with advanced GIST a potential new treatment option,” said Steve Hoerter, president, and chief executive officer of Deciphera. “With commercial preparations already underway, we believe we will be well-positioned for a potential US launch in 2020. We look forward to working with the FDA during their review of this application.”

The NDA submission was based on positive results from the phase 3 INVICTUS studyin which ripretinib demonstrated an 85% reduction in the risk of disease progression or death compared with placebo (HR, 0.15,P<.0001). The ripretinib arm demonstrated a median progression-free survival (PFS) of 6.3 months compared with only 1.0 month in the placebo arm, meeting the primary end point of the study.²

The overall response rate (ORR) was 9.4% in the ripretinib arm compared with 0% in the placebo arm (P= .0504), which was not considered to be significant. There was a clinically meaningful improvement in overall survival shown with ripretinib of 15.1 months compared with the 6.6 months observed with placebo (HR, 0.36, nominalP= .0004).

Ripretinib was found to be tolerable in patients with advanced GIST. There were grade 3/4 treatment-emergent adverse events (TEAEs), which occurred in 49% of patients in the ripretinib arm (n = 42) versus 44% of patients in the placebo arm (n = 19). The grade 3/4 TEAEs that occurred in more than 5% of patients who received ripretinib were anemia (9%), abdominal pain (7%), and hypertension (7%). In the placebo arm, anemia occurred in 14% of patients, which accounted for 5% of the TEAEs observed in the group overall.

INVICTUS is a randomized, double-blind, placebo-controlled, international, multicenter study which investigated the safety, tolerability, and efficacy of ripretinib in patients with advanced GIST who were previously treated with imatinib (Gleevec), sunitinib (Sutent), and regorafenib (Stivarga). Patients in the study were randomized 2:1 to receive either ripretinib 150 mg once daily or a matching dose of placebo. The secondary end points of the study were ORR, time to tumor progression, and OS.¹

The study included patients with an ECOG performance status of 0 to 2 and at least 1 measurable lesion, who were able to provide an archival tumor tissue sample and had adequate organ function. These patients must have resolved all toxicities related to prior therapy to grade 1 or lower within 1 week of beginning treatment in the study. Individuals who had prior anticancer therapy, prior treatment with ripretinib, and other treatment that may limit their chances of responding to ripretinib were excluded. The study also excluded patients with clinically significant comorbidities, gastrointestinal abnormalities, and other conditions.

Riperitinib is an investigational KIT and PDGFR&alpha; kinase switch control inhibitor. In addition to ongoing clinical trials in GIST, the agent is undergoing evaluation in patients with systemic mastocytosis and other malignancies.

References

1. Deciphera Pharmaceuticals announces U.S. Food and Drug Administration acceptance of new drug application and priority review for ripretinib in patients with advanced gastrointestinal stromal tumors [news release]. Waltham, Massachusetts: Deciphera Pharmaceuticals, Inc; February 12, 2020. https://bit.ly/2SFFO81. Accessed February 12, 2020.
2. Deciphera Pharmaceuticals announces positive top-line results from INVICTUS pivotal phase 3 clinical study of ripretinib in patients with advanced gastrointestinal stromal tumors [news release]. Waltham, Massachusetts: Deciphera Pharmaceuticals, Inc; August 13, 2020. https://bit.ly/2SlVEpj. February 12, 2020.