A phase 2 study of orally administered live biotherapeutic salmonella-IL2 with FOLFIRINOX for stage IV pancreatic cancer.

Salmonella-IL2 is an attenuated Salmonella Typhimurium strain carrying the human gene for IL-2. When orally administered in preclinical trials, the bacterium colonizes tumors and locally releases IL-2, triggering immunologically-mediated tumor cell killing without untoward side effects. A non-randomized, phase 2 study evaluated the combination of Salmonella-IL2 with standard of care (SOC) chemotherapy where patients received Salmonella-IL2 plus FOLFIRINOX (FFX). Overall survival (OS), progression-free survival (PFS), safety, and biomarker data in each arm were studied. In total, 34 patients (30 in the trial, 4 via EAP) were enrolled: 26 received Salmonella-IL2 with FOLFIRINOX. Those patients who received more than five doses of Salmonella-IL2 with FOLFIRINOX (n = 20) had a mPFS of 15 months while the mOS was 20.3 months. Even though there were no complete responses, the partial response rate and the overall response rate was 70.0%. In addition, 41 serious adverse events were noted and attributed to SOC chemotherapy agents but none to Salmonella-IL2. Addition of Salmonella-IL2 to FOLFIRINOX is associated with increased mPFS and mOS when compared to previously reported outcomes with FOLFIRINOX alone in the literature. A multicenter, randomized, phase 3 trial is warranted. ClinicalTrials.gov identifier: NCT04589234.