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).
Patients aged 18-75 years.
Pathologically confirmed solid tumors, including superficial metastatic lesions and intra-abdominal or intrathoracic tumors, that are amenable to intratumoral injection with a longest diameter ≥1.0 cm.
For superficial metastatic lesions that have not received local radiotherapy, ablation, or surgical resection; if such treatments have been performed, at least 4 weeks must have elapsed since completion and the lesion must show documented progression.
Prior systemic therapy must have been completed at least 4 weeks or 5 half-lives ago, and the patient must have recovered from previous treatment-related toxicities.
Peripheral blood lymphocyte count <1.0×10⁹/L；
Target superficial or body cavity tumors located adjacent to major blood vessels or nerves, with a high risk of puncture or injection; or lesions with active infection or ulceration；
Known severe hypersensitivity to Oncorine® (H101) or any of its components；
Active intra-abdominal infection or uncontrolled ascites；
This study is designed to enroll a total of 30 patients, aged 18 to 75 years, with advanced, multiply metastatic colorectal cancer, gastric cancer, and hepatocellular carcinoma who have failed multiple lines of prior systemic therapy (approximately 10-15 cases per cancer type). Subjects will be primarily recruited from the patient population at Foshan Fosun Chancheng Hospital. To be eligible, subjects must meet all inclusion criteria and none of the exclusion criteria.
Cohort
Prospective
Not listed
Preliminary antitumor activity
Radiographic tumor response assessment using RECIST 1.1 criteria
Treatment feasibility
The completion rate of the combination regimen (H101 intratumoral injection plus ICIs), and the proportion of dose adjustments, treatment delays, interruptions, or discontinuations resulting from toxicity or other reasons.
Incidence of Adverse Events
National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
Disease Control Rate
Radiographic tumor response assessment using RECIST 1.1 criteria
Changes in Peripheral Blood Immunological Parameters
Peripheral blood laboratory assays
Tumor Immune Microenvironment (TME) Changes
peripheral blood tests and single-cell sequencing of tumor tissues, among others
Progression-Free Survival
Based on comprehensive clinical and imaging assessment
Click on the lead sponsor to view all of their trials.
Jie Yuan，MD
Lead sponsor
Foshan Fosun Chancheng Hospital
Sponsor institution
