Oncolytic Virus (H101) + SBRT + Chemotherapy + Targeted Therapy + Immunotherapy for Unresectable CRLM (VVSHIP)

Given the complexity and heterogeneity of the tumor microenvironment, the overall efficacy of monotherapy is limited, making combination therapy the prevailing trend in oncology. In recent years, comprehensive cancer treatment strategies have flourished, with targeted therapy, immunotherapy, and gene therapy being key research focuses. Oncolytic adenovirus stands out as one of the most promising directions in gene therapy. Clinical studies have found a synergistic effect between oncolytic adenovirus and PD-1 antibodies, establishing durable anti-tumor immunity. This suggests that the triple combination of an oncolytic virus (OV, e.g., H101), stereotactic body radiotherapy (SBRT), and a PD-1 monoclonal antibody may yield clinical benefits surpassing existing therapies. However, to date, there have been no clinical reports on the combination of H101, SBRT, and a PD-1 inhibitor for treating unresectable liver metastases.

Our institution previously conducted an exploratory treatment on a patient with unresectable colorectal cancer (CRC) liver metastases using a comprehensive regimen of SBRT (40 Gy in 5 fractions, BED=72 Gy) combined with peritumoral H101 injection and a PD-1 inhibitor. Follow-up exceeding one year showed a partial response (PR) on imaging evaluation, with no local progression in the liver metastases and the absence of grade ≥3 radiotherapy-related adverse events. This preliminary result demonstrates the potential efficacy and safety of this combination. Nevertheless, high-quality clinical evidence is still lacking to confirm whether patients with unresectable CRC liver metastases can derive further benefit from the H101+SBRT+PD-1 inhibitor regimen-such as improved objective response rate (ORR) and survival, or even achieving a no evidence of disease (NED) status in liver metastases for some patients-necessitating validation through prospective studies.

Based on the aforementioned background and preliminary exploration, we plan to conduct a multicenter, prospective, single-arm, phase II clinical study. It aims to evaluate the efficacy and safety of the H101 + SBRT + PD-1 inhibitor combination in patients with unresectable CRC liver metastases. This study will investigate whether this triple therapy can improve the ORR, reduce the local recurrence rate, potentially enable some patients to reach NED status, and consequently prolong disease-free survival (DFS). The study plans to enroll 114 participants over a trial period of 3 years, with the goal of providing high-level evidence-based medical support for this innovative combined regimen in treating unresectable CRC liver metastases.