Data from Pharmawand - Curated by EPG Health - Date added 16 November 2018
Blueprint Medicines Corporation announced updated data for the registration-enabling NAVIGATOR clinical trial of avapritinib, a potent and highly selective KIT and PDGFRalpha inhibitor in development for patients with advanced gastrointestinal tumors (GIST). The data showed that avapritinib was highly active across all lines of therapy for patients with PDGFRalpha D842V-driven GIST and in second-, third- and fourth-line for other GIST patients. In addition, avapritinib was well-tolerated with most adverse events (AEs) reported by investigators as Grade 1 or 2. These results will be presented in an oral presentation at the Connective Tissue Oncology Society 2018 Annual Meeting in Rome, Italy .
The updated data from the ongoing Phase 1 NAVIGATOR trial support Blueprint Medicines' plans to submit a New Drug Application (NDA) in the first half of 2019 to the FDA for the treatment of PDGFRalpha Exon 18 mutant GIST, which primarily includes patients with the D842V mutation, and fourth-line GIST. There are currently no approved or effective therapies in these patient populations. In patients with PDGFRalpha D842V-driven GIST, avapritinib demonstrated an objective response rate (ORR) of 84 percent and a 12-month duration of response (DoR) of 76 percent. In heavily pre-treated patients with fourth-line or later GIST, avapritinib demonstrated an ORR of 20 percent, tumor reductions in 60 percent of patients and a median DoR of 7.3 months. ORR and DoR per central radiographic review will be the primary endpoints for the NDA submission, consistent with regulatory precedent for accelerated approvals based on single-arm oncology studies. In addition, avapritinib demonstrated an ORR of 26 percent in regorafenib-naïve third- and fourth-line GIST and an ORR of 25 percent in second-line GIST. Patients with PDGFRalpha D842V-driven GIST were excluded from both of these populations.