Margaret von Mehren, MD
In a late-breaking, oral presentation at the European Society for Medical Oncology (ESMO) 2019 Congress, Margaret von Mehren, MD, presented results from INVICTUS, a pivotal phase III clinical study of ripretinib in patients with advanced gastrointestinal stromal tumor (GIST).1 Ripretinib is an investigational tyrosine kinase inhibitor that was engineered to broadly inhibit KIT- and PDGFRα-mutated kinases. Study findings revealed a statistically significant improvement in progression-free survival with ripretinib vs placebo in patients previously treated with imatinib, sunitinib, and regorafenib for advanced GIST.
“For patients with GIST [in whom currently approved agents have failed], there exists an urgent need for effective and well-tolerated treatment options,” Dr. von Mehren, lead author of the study, said in a statement issued by Deciphera Pharmaceuticals, which owns the commercial rights for the drug product. Dr. von Mehren is with the Department of Medical Oncology, Fox Chase Cancer Center, in Philadelphia.
Pivotal Phase III Study
In the phase III clinical study, 129 patients with advanced GIST were randomly assigned in a 2:1 fashion to receive ripretinib or placebo following previous treatment with at least imatinib, sunitinib, and regorafenib.The study achieved the primary endpoint of improved progression-free survival compared with placebo in the fourth-line or later setting, as determined by blinded independent central radiologic review using modified Response Evaluation Criteria in Solid Tumors version 1.1.
Investigators reported that ripretinib significantly reduced the risk of disease progression or death by 85% compared with placebo and demonstrated a median progression-free survival of 6.3 months compared with 1.0 month in the placebo arm (hazard ratio = 0.15, 95% confidence interval = 0.09–0.25, P < .0001). This benefit in progression-free survival was consistent across all assessed patient subgroups.
Responses and Safety Profile
Eight patients (9.4%) had a confirmed objective response with ripretinib (P = .05) compared with no confirmed responses in the placebo arm, as measured by blinded independent central review, but this was not statistically significant. Treatment-emergent adverse events occurred in 99% of patients on the ripretinib arm compared with 98% on the placebo arm. Grade 3 or 4 adverse events related to treatment occurred in 49% of patients on the ripretinib arm compared with 44% on the placebo arm.
The manufacturer expects to submit a new drug application in 2020 to the U.S. Food and Drug Administration for ripretinib for the treatment of patients with advanced GIST who have received prior treatment with imatinib, sunitinib and regorafenib. ■
Disclosure: Deciphera has an exclusive license agreement with Zai Lab in Shanghai, China, for the development and commercialization of ripretinib in Greater China. The company retains development and commercial rights for ripretinib in the rest of the world. Dr. von Mehren reported advisory, consultancy, research grant, funding (institution), travel/accommodation expenses from Deciphera Pharmacetucials. For further disclosure information and disclosure information from all of the study authors, visit oncologypro.esmo.org.
1. von Mehren M, Serrano C, Bauer S, et al: INVICTUS: A phase III, interventional, double-blind, placebo-controlled study to assess the safety and efficacy of ripretinib as fourth-line therapy in advanced GIST. 2019 ESMO Congress. Abstract LBA87. Presented September 30, 2019.