Phase 1 Lm-LLO-TT Listeria-based tetanus-toxoid cancer vaccine + gemcitabine in PDAC

This Phase 1, open-label, first-in-human dose-escalation study tests intraperitoneal (into the peritoneal cavity) Lm-LLO-TT plus low-dose gemcitabine in adults with previously treated unresectable or metastatic pancreatic ductal adenocarcinoma (PDAC), enrolling up to 18 participants. Loki Therapeutics is sponsoring; the National Cancer Institute is listed as a collaborator. Lm-LLO-TT is a live attenuated Listeria monocytogenes immunotherapy engineered to express tetanus toxoid (and LLO), intended to reactivate tetanus-specific memory T cells and drive broader anti-tumor immune responses; gemcitabine is a nucleoside analog chemotherapy that inhibits DNA synthesis and is used here at low dose as part of the regimen. The protocol includes a screening tetanus booster and placement of an intraperitoneal access port, then a single loading dose of Lm-LLO-TT followed by multiple short cycles of low-dose gemcitabine plus low-dose Lm-LLO-TT over ~17 days, with DLT monitoring to define MTD and a recommended dose for future studies. The angle is route-of-delivery: moving a Listeria-based immunotherapy directly into the peritoneal space, where PDAC commonly spreads, rather than standard IV/systemic delivery. For 2nd+ line metastatic PDAC today, care is sequential systemic regimens (5-FU–based or gemcitabine-based combinations when tolerable), targeted therapy for select biomarkers (e.g., BRCA/PALB2, MSI-H), and clinical trials, with outcomes still poor—this study probes whether localized immune priming plus chemotherapy conditioning can yield signals of activity.