Multicenter randomized phase 2 trial of elraglusib and chemotherapy in metastatic pancreatic ductal adenocarcinoma

Erlaglusib (9-ING-41) is an inhibitor of glycogen synthase kinase-3 beta (GSK-3β). A randomized phase 2 trial at 60 centers in six countries evaluated elraglusib with gemcitabine plus nab-paclitaxel (GnP) in patients with previously untreated metastatic pancreatic ductal adenocarcinoma (mPDAC). Patients were randomized 2:1 to weekly elraglusib plus GnP (n=155) or GnP alone (n=78). Primary endpoints were median overall survival and 1-year survival rate. Median overall survival was 10.1 months with elraglusib plus GnP versus 7.2 months with GnP alone (HR 0.62; p=0.01), with 1-year survival rates of 44.1% versus 22.3%, respectively. The safety profile of elraglusib plus GnP was manageable, with most common grade 3 or higher treatment-emergent adverse events being neutropenia (52.3%, versus 30.8% with GnP alone), anemia (25.2% versus 29.5%) and fatigue (16.8% versus 5.1%). The authors conclude that these findings support clinical activity of elraglusib plus GnP as first-line treatment in mPDAC. A phase 3 trial is being planned.