Influence of salmonella-IL2 in combination with FOLFIRINOX on overall and progression-free survival in stage IV metastatic pancreatic cancer.

2571 Background: Salmonella-IL2 is an attenuated Salmonella Typhimurium strain carrying the human gene for IL-2. When orally administered, the bacterium colonizes tumors and locally releases IL-2, triggering immunologically-mediated tumor cell killing without untoward side effects. Salmonella-IL2 was tested in a phase 2 clinical trial in which patients with stage IV metastatic pancreatic cancer were treated with standard of care chemotherapy (SOC) combined with Salmonella-IL2. Methods: A Health Canada and local IRB approved, non-randomized, two-arm human study evaluated the combination of Salmonella-IL2 with standard of care (SOC) chemotherapy; Arm One patients received Salmonella-IL2 plus FOLFIRINOX (FFX). Arm Two patients received Salmonella-IL2 plus Gemcitabine/nab-Paclitaxel (GEM/nabP). Overall survival (OS), progression-free survival (PFS), safety, and biomarker data in each arm were compared to corresponding values for reference patients (SOC Controls) receiving care at the study site in the four years preceding the clinical trial (2016 to 2020). Four patients with stage IV pancreatic cancer were treated via Salspera’s Expanded Access Program (EAP) using the Arm One regimen. Results: In total, 34 patients (30 in the trial, 4 via EAP) were enrolled: 26 received Salmonella-IL2 with FOLFIRINOX (average age 58.7 years, range 32-74, 54% born female) and eight received Salmonella-IL2 with GEM/NabP (average age 68 years, range 56-82, 54% born female). SOC Control patients comprised 37 administered FOLFIRINOX (average age 58 years; range 33-75 years; 46% born female) and 31 given GEM/nabP (average age 65.1 years; range 45-84 years; 42% born female). Patients receiving more than five doses of Salmonella-IL2 with FOLFIRINOX (n = 20) had a mPFS of 15 months vs. 5.8 months in control patients who had received only FOLFIRNOX (p < 0.0001, 95% CI, HR 0.3, Concordance Index 0.64). For those same compared cohorts, the mOS was 20.3 months vs. 11.5 months (p = 0.07, 95% CI. HR 0.59, Concordance Index 0.59). Only eight patients were enrolled in the GEM/NabP Arm thus limiting useful conclusions. Overall, 41 serious adverse events were noted and attributed to SOC chemotherapy agents but none to Salmonella-IL2. Conclusions: Addition of Salmonella-IL2 to FOLFIRINOX for treating stage IV pancreatic cancer is associated with increased mPFS and mOS. A multicenter, randomized, phase III trial is warranted. Clinical trial information: NCT04589234 .