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

NCT07381309 | Not Yet Recruiting Phase 2

• 1 other identifier: E2025404
• Study Type: interventional
• Target: 114
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

CRC; Liver Metastasis Colon Cancer

Keywords

Stereotactic body radiation therapy; Targeting Therapy; PD-1 Monoclonal Antibody; Oncolytic Virus

Outcome Measures

Primary Outcomes (1)

• ORR

  Objective Response Rate

  1 year

Secondary Outcomes (6)

• 1 year PFS

  1 year

• 1 year OS

  1 year

• R0 Resection Rate

  1 year

• pCR

  1 year

• DCR

  1 year

Study Arms (2)

H101 + SBRT + PD-1 Antibody + Targeted Therapy + Chemotherapy

EXPERIMENTAL

The treatment regimen is administered sequentially as follows. Following stereotactic body radiotherapy (SBRT), a peritumoral injection of H101 is administered one week later. Three days after the H101 injection, combination therapy with chemotherapy and the PD-1 monoclonal antibody is initiated. This is followed by four cycles of a combined regimen consisting of peritumoral H101 injection, PD-1 monoclonal antibody, chemotherapy, and targeted therapy, with each cycle administered every 21 days.

Radiation: SBRT; Drug: PD-1 Antibody; Drug: H101; Drug: Target Therapy; Combination Product: Chemotherapy

Folfiri + Targeted Therapy

ACTIVE COMPARATOR

Patients will receive four cycles of the FOLFIRI chemotherapy regimen combined with targeted therapy selected based on genetic testing results, with each cycle administered every 21 days.

Drug: Target Therapy; Combination Product: FOLFIRI

Interventions

SBRT RADIATION

Stereotactic Body Radiotherapy

Also known as: stereotactic body radiotherapy

H101 + SBRT + PD-1 Antibody + Targeted Therapy + Chemotherapy

PD-1 Antibody DRUG

PD-1 Antibody every 21 days

Also known as: PD-1 Monoclonic Antibody

H101 + SBRT + PD-1 Antibody + Targeted Therapy + Chemotherapy

H101 DRUG

Peritumoral Injection of oncolytic virus (H101)

Also known as: oncolytic virus

H101 + SBRT + PD-1 Antibody + Targeted Therapy + Chemotherapy

Target Therapy DRUG

Targeted agents selected based on genetic testing results

Also known as: Target agents

Folfiri + Targeted Therapy; H101 + SBRT + PD-1 Antibody + Targeted Therapy + Chemotherapy

FOLFIRI COMBINATION_PRODUCT

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.

Also known as: irinotecan, leucovorin, and fluorouracil

Folfiri + Targeted Therapy

Chemotherapy COMBINATION_PRODUCT

Fluorouracil-based chemotherapy regimens, such as FOLFOX, CAPOX, or FOLFIRI.

Also known as: Fluorouracil-based chemotherapy

H101 + SBRT + PD-1 Antibody + Targeted Therapy + Chemotherapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The patient or their legal representative understands and signs the informed consent form.
• Patients with pMMR/MSS colorectal adenocarcinoma.
• Aged 18-75 years.
• Patients with histologically or cytologically confirmed colorectal cancer liver metastases. There must be at least one injectable lesion in the liver, which must also meet the criteria for a measurable target lesion according to RECIST version 1.1 (≥10 mm in the longest diameter on spiral CT/MRI scan with a slice thickness of no greater than 5 mm).
• Patients with definitively unresectable metachronous liver metastases; OR patients deemed surgically resectable but who refuse surgery, provided the liver metastases meet the following requirements: ① The number of metastatic lesions must be no more than 5, and the sum of the longest diameters of all metastatic lesions must be ≤100 mm; ② The longest diameter of a single lesion must be ≤100 mm; ③ The longest diameter of the lesion to be injected must be ≥10 mm and ≤80 mm.
• The liver metastases have not received prior radiotherapy, OR the area of the liver near the planned radiotherapy site has not been previously irradiated. At least 700 cc of liver volume must be preserved outside the treatment area.
• Prior treatments such as hepatic resection, systemic chemotherapy, local ablation therapy, or hepatic artery infusion pump chemotherapy are allowed, provided a washout period of 2 weeks is observed. Patients must have recovered from prior anti-tumor therapy-related adverse events to baseline or Grade ≤1 (according to CTCAE version 5.0) (excluding alopecia and Grade 2 anemia).
• Child-Pugh score A or B
• ECOG Performance Status 0-1
• Peripheral blood counts and liver/renal function within the allowable ranges (tested within 15 days before treatment initiation)
• No prior history of other concomitant malignancies. Patients must not be pregnant or breastfeeding and should use effective contraception during the study and for 6 months after the last dose.
• Life expectancy ≥6 months.

You may not qualify if:

• Synchronous colorectal cancer liver metastases.
• Active hepatitis, cirrhosis, or Child-Pugh class C.
• Extralepatic metastases to: central nervous system / bone marrow / brain (UICC 8th edition).
• Liver metastases not measurable.
• Prior history of oncolytic virus therapy (e.g., T-VEC).
• Liver metastases not meeting the requirements for peritumoral injection volume or unsuitable for peritumoral injection.
• History of severe drug allergy (e.g., to oncolytic adenovirus, PD-1 monoclonal antibody, platinum agents, 5-FU, leucovorin, 5-HT3 receptor antagonists, bevacizumab, etc.).
• Antiviral therapy (e.g., acyclovir, ganciclovir, valacyclovir, vidarabine) within 4 weeks prior to the first dose of study treatment.
• Participation in another clinical trial within 4 weeks or ongoing participation.
• History of prior therapy targeting PD-1, PD-L1, PD-L2, CTLA-4, or any other T-cell co-stimulation or checkpoint pathway.
• Severe electrolyte abnormalities.
• Significant portal hypertension: history of upper gastrointestinal bleeding or severe hypersplenism.
• Arterial or deep venous thrombosis within the past 6 months; history or evidence of bleeding tendency within the past 2 months.
• Pregnant or breastfeeding women, or women with a positive pregnancy test before the first dose; or female participants and their partners unwilling to use strict contraception during the study.
• Active autoimmune disease requiring systemic treatment (e.g., immunomodulators, corticosteroids, immunosuppressants) within the past 2 years.

Sponsors & Collaborators

• Jun Huang: lead

Study Sites (1)

Sixth Affiliated Hospital, Sun Yat-sen University

Guangzhou, Guangdong, China

Location

MeSH Terms

Interventions

Radiosurgery; spartalizumab; Oncolytic Virotherapy; IFL protocol; Irinotecan; Leucovorin; Fluorouracil; Drug Therapy

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques; Biological Therapy; Camptothecin; Alkaloids; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Jun Huang

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jun Huang

CONTACT

+86-13926451242; huangj97@mail.sysu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: No mask
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 25, 2026
• First Posted: February 2, 2026
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): February 1, 2029
• Last Updated: April 28, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)