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).

Sex

All

Minimum age

18 Years

Maximum age

75 Years

Inclusion Criteria:

* 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.
* Adequate cardiopulmonary, hepatic, and renal function to tolerate Oncorine® (H101) intratumoral injection.
* The patient and their family members are willing to participate in this study and provide written informed consent.

Exclusion Criteria:

* 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；
* Currently receiving systemic glucocorticoids or other potent immunosuppressive agents；
* Planned receipt of other antitumor therapies during the study period (except supportive care)；
* Concurrent other malignancy or a history of prior malignancy；
* Tumors complicated by rupture with hemorrhage, massive gastrointestinal bleeding, intestinal obstruction, or other conditions requiring emergency surgery；
* American Society of Anesthesiologists (ASA) classification ≥ IV and/or Eastern Cooperative Oncology Group (ECOG) performance status score \>2；
* Active autoimmune disease, or history of autoimmune disease requiring systemic therapy; uncontrolled severe infections (e.g., HIV, active hepatitis B with HBV-DNA above the lower limit of detection, active hepatitis C); severe cardiovascular or cerebrovascular disease; history of organ transplantation; active bleeding or high bleeding risk；
* History of severe psychiatric illness；
* Pregnant or breastfeeding women；
* Uncontrolled active infection；
* Other clinical or laboratory conditions that, in the opinion of the nvestigator, render the patient unsuitable for participation in this trial.

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