A Prospective Real-World Observational Study of Intratumoral Oncolytic Virus Injection Combined With Immune Checkpoint Inhibitors for Metastatic Tumors (Colorectal Cancer, Gastric Cancer, and Hepatocellular Carcinoma)

The goal of this single-arm, open-label, prospective clinical trial is to evaluate the safety, feasibility, and preliminary antitumor activity of intratumoral oncolytic virus (H101, recombinant human type 5 adenovirus) combined with immune checkpoint inhibitors (ICIs), and to explore the dynamic remodeling of the tumor immune microenvironment and potential predictive biomarkers, in patients with advanced metastatic colorectal cancer, gastric cancer, or hepatocellular carcinoma who have failed multiple prior lines of therapy. The main questions it aims to answer are: What are the incidence of treatment-related adverse events and serious adverse events, and the completion rate of the combination therapy (safety and feasibility)? What is the objective response rate and local control rate per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) (preliminary antitumor activity)? How does the combination therapy reshape the tumor immune microenvironment in terms of immune cell infiltration, subset proportions, functional status, and signaling pathways, and which differentially expressed genes or immune cell subtypes are associated with clinical response? This is a single-arm study; there is no comparator group. Participants will: Receive intratumoral H101 injection once per cycle (dose stratified by lesion size), followed 5-7 days later by intravenous ICI \[Anti-Programmed Cell Death Protein 1 Antibody (anti-PD-1) with or without Anti-Cytotoxic T-Lymphocyte-Associated Protein 4 Antibody (anti-CTLA-4)\], repeated every 2-3 weeks for a total of 4 cycles. Provide paired tumor biopsy samples and peripheral blood specimens at baseline and after 4 cycles for single-cell RNA sequencing and biomarker analyses. Undergo routine clinical assessments, imaging for tumor response evaluation, and safety monitoring with adverse event grading per Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE v5.0).