Intra-Tumoral Immunomodulatory Therapy for Advanced Abdominal Cancers using Lipopolysaccharide: The Regional Immuno-Oncology Trial-1 (RIOT-1) Protocol (NCT05751837)

Background Intra-tumoral immunotherapy has shown potential in treating advanced cancers. Delivery challenges have limited exploration of these modalities in intra-abdominal tumors. In this study, we explore the safety of injecting intra-abdominal tumors with lipopolysaccharide (LPS) from Escherichia coli 0113. This agonist of toll-like receptor 4 (TLR4) holds promise as an agent to enhance the anti-tumor immune response within the tumor microenvironment. Methods This Phase I study will recruit adult patients with peritoneal metastases from gastrointestinal primary malignancies who have at least two suitable intra-abdominal soft tissue tumors for injection. LPS will be administered as a single 1μg dose during diagnostic laparoscopy in patients in whom a subsequent interval laparotomy is planned. A control injection of saline will be injected into a second lesion. Primary outcome is safety, with secondary outcomes being biomarkers of the tumor immune microenvironment in pre- and post-treatment biopsies. Results The primary endpoint is to determine the safety (frequency and nature of adverse events) following intra-tumoral LPS injection. Adverse events will be classified using Common Terminology Criteria for Adverse Events. Secondary endpoints include cellular and molecular biomarkers of immune response. The study will proceed until twelve patients have completed the protocol. Discussion Patients undergoing standard-of-care laparoscopy in preparation for interval cytoreductive surgery may be ideal candidates for intra-tumoral immunotherapy. This study seeks to establish the safety of using E. coli LPS for injection into intra-abdominal tumors and to establish precedent for interval tumor immune microenvironment assessment as a window-of-opportunity concept in the context of abdominal metastatic disease. Trial Registration The trial is registered at Clinical Trials.gov; NCT05751837 (registered February 28th, 2023).