NCT07381309

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

Oncolytic Virus (H101) Peritumoral Injection Combined With SBRT, Chemotherapy, Targeted Therapy, and Immunotherapy for Unresectable MSS/pMMR Colorectal Cancer Liver Metastases (CRLM)

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 114 (estimated)
• Sponsor: Jun Huang · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

This prospective study aims to investigate the efficacy and safety of peritumoral injection of the oncolytic virus H101 in combination with stereotactic body radiotherapy (SBRT), PD-1 monoclonal antibody, chemotherapy, and targeted therapy for the treatment of patients with unresectable, microsatellite stable/mismatch repair proficient (MSS/pMMR) colorectal adenocarcinoma liver metastases. The ultimate goal is to provide high-level evidence-based medical support for this combined modality approach.

Detailed description

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.

Conditions

• CRC
• Liver Metastasis Colon Cancer

Interventions

Type	Name	Description
RADIATION	SBRT	Stereotactic Body Radiotherapy
DRUG	PD-1 Antibody	PD-1 Antibody every 21 days
DRUG	H101	Peritumoral Injection of oncolytic virus (H101)
DRUG	Target Therapy	Targeted agents selected based on genetic testing results
COMBINATION_PRODUCT	FOLFIRI	FOLFIRI is a standard biweekly chemotherapy regimen for metastatic colorectal cancer. It consists of irinotecan, leucovorin, and fluorouracil (5-FU) administered sequentially over a 46-hour infusion period per cycle.
COMBINATION_PRODUCT	Chemotherapy	Fluorouracil-based chemotherapy regimens, such as FOLFOX, CAPOX, or FOLFIRI.

Timeline

• Start date: 2026-02-01
• Primary completion: 2028-02-01
• Completion: 2029-02-01
• First posted: 2026-02-02
• Last updated: 2026-02-02

Locations

1 site across 1 country: China