CRCPhase 2VVSHIPNCT07381309
Oncolytic Virus (H101) + SBRT + Chemotherapy + Targeted Therapy + Immunotherapy for Unresectable CRLM
A Phase 2 study testing SBRT, PD-1 Antibody and H101 in people with CRC and Liver Metastasis Colon Cancer, run by Jun Huang at 1 site in China.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- CRC, Liver Metastasis Colon Cancer
- What is being tested?
- SBRT, PD-1 Antibody and H101
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 114 participants
- Where
- 1 siteChina
- Study dates
- 1 Jun 2026to 1 Feb 2029
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
- Past or current other active malignancies (except malignancies cured >3 years ago or carcinoma in situ treated curatively).
- Severe ECG abnormalities; active coronary artery disease, severe/unstable angina, newly diagnosed angina, or myocardial infarction within 12 months; New York Heart Association (NYHA) class II or higher congestive heart failure.
- Active infection (with fever >38°C).
- Poorly controlled hypercalcemia, hypertension, or diabetes.
- Severe pulmonary disease (interstitial pneumonia, pulmonary fibrosis, severe emphysema, etc.).
- Psychiatric disorder affecting clinical treatment or history of central nervous system disease.
- Severe complications (intestinal obstruction, renal insufficiency, hepatic insufficiency, cerebrovascular disorders, etc.).
- Persistent toxicity ≥ Grade 2 (CTCAE v5.0) from prior therapy (except anemia, alopecia, skin pigmentation).
- Use of any other investigational drug or participation in another interventional trial within 14 days prior to study treatment.
- Pregnant, breastfeeding, or planning pregnancy during the study; men or women unwilling to use effective contraception.
- Any unstable medical condition that may affect patient safety or compliance, as judged by the investigator to be unsuitable for the trial.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
Sixth Affiliated Hospital, Sun Yat-sen University
Guangzhou, Guangdong
About this study
Official title: Oncolytic Virus (H101) Peritumoral Injection Combined With SBRT, Chemotherapy, Targeted Therapy, and Immunotherapy for Unresectable MSS/pMMR Colorectal Cancer Liver Metastases (CRLM)
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.
Read the 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
- Being tested
- SBRT, PD-1 Antibody, H101, Target Therapy, FOLFIRI
- Keywords
- Stereotactic body radiation therapy, Targeting Therapy, PD-1 Monoclonal Antibody, Oncolytic Virus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SBRTRadiation
Also called stereotactic body radiotherapy
Stereotactic Body Radiotherapy
PD-1 AntibodyDrug
Also called PD-1 Monoclonic Antibody
PD-1 Antibody every 21 days
H101Drug
Also called oncolytic virus
Peritumoral Injection of oncolytic virus (H101)
Target TherapyDrug
Also called Target agents
Targeted agents selected based on genetic testing results
FOLFIRICombination product
Also called irinotecan, leucovorin, and fluorouracil
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.
ChemotherapyCombination product
Also called Fluorouracil-based chemotherapy
Fluorouracil-based chemotherapy regimens, such as FOLFOX, CAPOX, or FOLFIRI.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Target Therapy; Combination Product: FOLFIRI |
What is being measured
The primary outcome is the main question the study is designed to answer.
ORR
Objective Response Rate
Measured: 1 year
Secondary outcomes (6)
1 year PFS
1 year Progression Free Survival
Measured: 1 year
1 year OS
1 year Overall Survival
Measured: 1 year
R0 Resection Rate
R0 Resection Rate
Measured: 1 year
pCR
Pathological Complete Response
Measured: 1 year
DCR
Disease Control Rate
Measured: 1 year
AE rate
Adverse Event rate
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Feb 2026
- Study start1 Jun 2026 (estimated)
- Primary completion1 Feb 2028 (estimated)
- Study completion1 Feb 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CRCStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 114 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Jun Huang
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Jun Huang, Sixth Affiliated Hospital, Sun Yat-sen University
- Investigators
- Jun Huang, Principal investigator, Sun Yat-sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07381309
- Sponsor's protocol ID
- E2025404
- Acronym
- VVSHIP
- Status last verified
- Apr 2026
- First submitted
- 25 Jan 2026
- Last updated
- 28 Apr 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Oncolytic Virus (H101) Peritumoral Injection Combined With SBRT, Chemotherapy, Targeted Therapy, and Immunotherapy for Unresectable MSS/pMMR Colorectal Cancer Liver Metastases (CRLM)
- ClinicalTrials.gov ID
- NCT07381309
- Acronym / sponsor ID
- VVSHIP / E2025404
- Conditions
- CRC, Liver Metastasis Colon Cancer
- Keywords
- Stereotactic body radiation therapy, Targeting Therapy, PD-1 Monoclonal Antibody, Oncolytic Virus
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 114 participants (estimated)
- Lead sponsor
- Jun HuangUniversity, hospital or other
- Study start
- 1 Jun 2026 (estimated)
- Primary completion
- 1 Feb 2028 (estimated)
- Study completion
- 1 Feb 2029 (estimated)
- First posted
- 2 Feb 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| H101 + SBRT + PD-1 Antibody + Targeted Therapy + Chemotherapy | Experimental | Radiation: SBRT, Drug: PD-1 Antibody, Drug: H101, Drug: Target Therapy, Combination Product: ChemotherapyThe 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. |
| Folfiri + Targeted Therapy | Active comparator | Drug: Target Therapy, Combination Product: FOLFIRIPatients 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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.
Key exclusion criteria (26 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SBRTAlso: stereotactic body radiotherapyStereotactic Body Radiotherapy | Radiation | H101 + SBRT + PD-1 Antibody + Targeted Therapy + Chemotherapy |
| PD-1 AntibodyAlso: PD-1 Monoclonic AntibodyPD-1 Antibody every 21 days | Drug | H101 + SBRT + PD-1 Antibody + Targeted Therapy + Chemotherapy |
| H101Also: oncolytic virusPeritumoral Injection of oncolytic virus (H101) | Drug | H101 + SBRT + PD-1 Antibody + Targeted Therapy + Chemotherapy |
| Target TherapyAlso: Target agentsTargeted agents selected based on genetic testing results | Drug | Folfiri + Targeted Therapy, H101 + SBRT + PD-1 Antibody + Targeted Therapy + Chemotherapy |
| FOLFIRIAlso: irinotecan, leucovorin, and fluorouracilFOLFIRI 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 | Folfiri + Targeted Therapy |
| ChemotherapyAlso: Fluorouracil-based chemotherapyFluorouracil-based chemotherapy regimens, such as FOLFOX, CAPOX, or FOLFIRI. | Combination product | H101 + SBRT + PD-1 Antibody + Targeted Therapy + Chemotherapy |
Primary outcome
ORR
Time frame: 1 year
Objective Response Rate
6 secondary outcomes
1 year PFS
Time frame: 1 year
1 year OS
Time frame: 1 year
R0 Resection Rate
Time frame: 1 year
pCR
Time frame: 1 year
DCR
Time frame: 1 year
AE rate
Time frame: 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Apr 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Jun Huang principal investigator
Sun Yat-sen University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing SBRT, PD-1 Antibody and H101 in people with CRC and Liver Metastasis Colon Cancer, run by Jun Huang at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 28 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jun Huang (+86-13926451242, huangj97@mail.sysu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
ORR (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Apr 2026.