Multicenter phase 1 trial of adjuvant personalized mRNA vaccine plus atezolizumab and mFOLFIRINOX for pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is lethal in 88% of patients, yet harbors mutation-derived T cell neoantigens that are suitable for vaccines. A multicenter phase 1 trial in the United States evaluated adjuvant autogene cevumeran, an individualized neoantigen vaccine based on uridine mRNA-lipoplex nanoparticles, in combination with atezolizumab (anti-PD-L1) and mFOLFIRINOX chemotherapy after surgery for PDAC. There were substantial T cell responses in 50% of patients, indicating that the vaccine can induce an improved immune response. At 18-months follow-up the patients with elevated immune responses had longer time to relapse (not reached) compared with patients without elevated immune responses (13.4 months; p=0.003). The authors conclude that the adjuvant regimen of atezolizumab, autogene cevumeran, and mFOLFIRINOX induces substantial T cell activity that may correlate with delayed PDAC recurrence.