Clinical testing of Listeria-TT and Gemcitabine in a Phase I clinical trial with PDAC patients

Abstract public domain (NIH RePORTER)

ABSTRACT The Phase II component of this Fast-Track STTR project will evaluate the safety, tolerability, and preliminary anti-tumor activity of LM-TT in combination with low-dose gemcitabine in patients with unresectable pancreatic ductal adenocarcinoma (PDAC). The investigational therapy utilizes attenuated Listeria monocytogenes engineered to selectively deliver tetanus toxoid recall antigens into the tumor microenvironment, thereby reactivating long-lived memory T cell responses generated through prior childhood vaccination. Preclinical studies demonstrated significant tumor reduction and improved survival in murine PDAC models when LM-TT was combined with gemcitabine. The proposed Phase II clinical activities remain unchanged from the originally submitted Fast- Track application. The objectives of the Phase II project are to establish the safety profile, characterize dose-limiting toxicities, evaluate immune activation and tumor response, and support further clinical development of this novel immunotherapeutic platform in advanced PDAC patients. The Phase II study will be conducted as a first-in-human, open-label dose-escalation clinical trial at Albert Einstein College of Medicine/Montefiore. The trial will include comprehensive safety monitoring, immune response characterization, and exploratory efficacy analyses. IND-enabling manufacturing, toxicology, and regulatory activities initiated during Phase I have been completed, and the IND application was submitted to the FDA on April 30, 2026. Pending FDA review and IRB approval, clinical trial initiation is anticipated during the Phase II project period as of July 1st, 2026. The overall goal of the project remains unchanged: to advance LM-TT+GEM as a novel immunotherapeutic approach for patients with unresectable pancreatic cancer who currently face limited treatment options and poor clinical outcomes.

Public health relevance public domain (NIH RePORTER)

PROJECT NARRATIVE This project involves preparation and execution of a Fast-Track clinical trial with Listeria-tetanus toxoid (TT) and Gemcitabine (GEM) in patients with unresectable PDAC. This includes production of GMP Listeria-TT, tox and safety profiles in mice, IND and IRB approval, and testing of Listeria-TT+GEM in a Phase 1 clinical trial.