Primary Liver CancerPhase 1NCT04806464
Clinical Study of VG161 in Subjects with Advanced Primary Liver Cancer
A Phase 1 study testing Recombinant Human IL12/15-PDL1B Oncolytic HSV-1 Injection (Vero Cell)) in people with Primary Liver Cancer, run by CNBG-Virogin Biotech (Shanghai) Ltd. at 1 site in China.
Trial summary
VG161 is a recombinant human-IL12/15/PDL1B oncolytic HSV-1 Injectable. This phase I study will be conducted in HSV-seropositive subjects with advanced primary liver cancer that are refractory to conventional therapies. This is an open label study and it's divided into two parts. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Primary Liver Cancer
- What is being tested?
- Recombinant Human IL12/15-PDL1B Oncolytic HSV-1 Injection (Vero Cell))
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 44 participants
- Where
- 1 siteChina
- Study dates
- 16 Mar 2021to 31 Dec 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
None listed.
Who cannot join
- Subject in prior anti-tumor therapies such as chemotherapy, radiotherapy, biotherapy, endocrinotherapy, targeted therapy, immunotherapy within 4 weeks of study treatment initiation. Oral fluorouracil analogues and small molecule targeted drugs were 2 weeks prior to the first dose of study drug or within 5 half-lives of the drug (whichever was longer).
- Transcatheter arterial chemoembolization(TACE) within 4 weeks of study treatment initiation
- Participation in clinical trials of any other investigational agents within 4 weeks of study treatment initiation.
- Major organ surgery (excluding puncture biopsy) or significant trauma within 4 weeks of study treatment initiation.
- Patients who received systemic treatment with either corticosteroids ( \>10 mg/ daily prednisone or equivalent) or other immunosuppressive medications within 14 days of study treatment initiation.
- Subjects with any ≥Grade 1 toxicity (as per NCI CTC AE Version 5.0) related to prior anti-cancer therapy (except for toxicity that the investigator assessed to be no safety risk, such as alopecia.).
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- Subjects with Central Nervous System (CNS) metastasis or meningeal metastasis .
- Seronegative for Herpes Simplex Virus (HSV) (HSV-1IgG and HSV-1IgM).
- Subjects with the relapse of HSV infection and relevant clinical manifestations, such as lip herpes, herpes keratitis, herpes dermatitis, and genital herpes.
- Subjects with other uncontrolled active infections.
- Known history of immunodeficiency and test positive of human immunodeficiency virus (HIV).
- History of severe cardiovascular disease:
- 1)Ventricular arrhythmias requiring clinical intervention; 2)QTc interval \>480 ms; 3)Acute coronary syndrome, congestive heart failure, stroke or other cardiovascular events of III grade or above within 6 months; 4)The cardiac function grade≥II or left ventricular ejection fraction (LVEF) \<50% per the New York Heart Association (NYA); 5)Uncontrolled hypertension.
- 13. Subjects with active or past autoimmune diseases that are likely to recur (e.g. systemic lupus erythematosus, rheumatoid arthritis, vasculitis, etc.); acceptable for patients with clinically stable autoimmune thyroiditis.
- 14. Previous immunotherapy with an immune-related adverse event (irAE) such as immune-related pneumonia, myocarditis, etc., which, in the judgement of the investigator, may affect the safety of the investigational drug. 15. known to have alcohol or drug dependence. 16. Persons with mental disorders or poor compliance. 17. Pregnant or lactating women. 18. Subjects with any significant unrelated systemic illness that to the investigator's opinion would compromise the subject's eligibility to participate the study.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
The First Affiliated Hospital, Zhejiang University School of Medicine
Hangzhou, Zhejiang
Nan Yi Shen, MD. PhD., fysyn@163.com
Tingbo Liang, MD. PhD.
About this study
Official title: A Dose Ascending, Open Phase I Clinical Study to Evaluate the Safety, Tolerability , Pharmacokinetics Characteristics and Preliminary Effectiveness of VG161 in Subjects with Advanced Primary Liver Cancer
VG161 is a recombinant human-IL12/15/PDL1B oncolytic HSV-1 Injectable. This phase I study will be conducted in HSV-seropositive subjects with advanced primary liver cancer that are refractory to conventional therapies. This is an open label study and it's divided into two parts.
Part 1: This part is ascending dose design to determine the safety and tolerability of VG161 and find recommended dose of VG161.
Part 2: This part is extended dose design to determine the effectiveness of VG161.
Read the detailed description
Part 1: This part will be conducted in 5 dose ascending cohorts, including 2 accelerated titration design dose group and 3 dose escalation groups. Descriptive statistics will be used to summarize data.
Part 2: This part will only include the part 1 recommended dose. Hypothesis test and descriptive statistics will be used to summarize data.
- Conditions
- Primary Liver Cancer
- Being tested
- Recombinant Human IL12/15-PDL1B Oncolytic HSV-1 Injection (Vero Cell))
- Keywords
- Liver Cancer
- Medical subject headings
- Carcinoma, Hepatocellular, Liver Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Recombinant Human IL12/15-PDL1B Oncolytic HSV-1 Injection (Vero Cell))Drug
Also called VG161
Intratumoral injection only. The dosing date can be the Day 1 only or Days 1 through 5.
| Study group | Role | What they receive |
|---|---|---|
| VG161 | Experimental | Part1:
1. 1.0*10^8 PFU on Day 1(1.0×10^8PFU)
2. 1.0*10^8 PFU on Days 1 to 2(2.0×10^8PFU)
3. 1.0*10^8 PFU on Days 1 to 3(3.0×10^8PFU)
4. 1.3*10^8 PFU on Days 1 to 3(4.0×10^8PFU)
5. 1.7*10^8 PFU on Days 1 to 3(5.0×10^8PFU)
Part2:
Depends on the recommended dose in Part1 Receives: Drug: Recombinant Human IL12/15-PDL1B Oncolytic HSV-1 Injection (Vero Cell)) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part1: MTD/Recommended dose
MTD (Maximum tolerable dose) /Recommended dose
Measured: 7 month
Part1: Occurence of DLT
Occurence of DLT (Dose Limiting Toxicity)
Measured: 1month
Part1: Numbers of DLT
Numbers of DLT (Dose Limiting Toxicity)
Measured: 1 month
Part1: Occurence of AE and SAE(NCI CTCAE 5.0)
Occurence of Adverse Event (AE) and Serious Adverse Event (SAE) (NCI CTCAE 5.0)
Measured: 7 months
Part1: Frequency of AE and SAE(NCI CTCAE 5.0)
Frequency of Adverse Event (AE) and Serious Adverse Event (SAE) (NCI CTCAE 5.0)
Measured: 7 months
Part2:ORR
Evaluate Objective Response Rate by RECIST 1.1
Measured: 7 months
Secondary outcomes (20)
Part1:Tmax(h)
Time to peak
Measured: At the end of Cycle 1 (each cycle is 28 days)
Part1:Cmax(copies/ugDNA)
Maximum concentration
Measured: At the end of Cycle 1 (each cycle is 28 days)
Part1:ORR
Evaluate Objective Response Rate by iRECIST
Measured: 7 months
Part1:DOR
Evaluate Disease Control Rate by iRECIST
Measured: 7 months
Part1:PFS
Evaluate medium Progression Free Survival by iRECIST
Measured: 7 months
Part1:OS rate
Evaluate Overall Survival rate
Measured: 17 months
Part 1:CD3+, CD4+, CD8+
Concentration of CD3+, CD4+, CD8+
Measured: 7 months
Part 1:IL15
Concentration of IL15
Measured: 7 months
Part 1:PD-L1, PD-1
Concentration of PD-L1, PD-1
Measured: 7 months
Part 2:PFS
Evaluate medium Progression Free Survival by iRECIST
Measured: 7 months
Part 2:OS rate
Evaluate Overall Survival rate
Measured: 17 months
Part 2: OS
Overall Survival
Measured: 17 months
Part 2:DOR
Evaluate Disease Control Rate by iRECIST
Measured: 7 months
Part 2:Safety indicators:AEs
Incidence of adverse events (NCI CTCAE 5.0)
Measured: 7 months
Part 2:Safety indicators:ECOG
Incidence of abnormal ECOG scores
Measured: 7 months
Part 2:Safety indicators:12-lead electrocardiograms
Incidence of abnormal 12-lead electrocardiograms
Measured: 7 months
Part 2:Safety indicators:laboratory tests results
Incidence of abnormal laboratory tests results
Measured: 7 months
Part 2:CD3+, CD4+, CD8+
Concentration of CD3+, CD4+, CD8+
Measured: 7 months
Part 2:IL15
Concentration of IL15
Measured: 7 months
Part 2:PD-L1, PD-1
Concentration of PD-L1, PD-1
Measured: 7 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2021
- Study start16 Mar 2021
- Primary completion21 Mar 2022
- Study completion31 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Primary Liver CancerStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 44 participants (estimated)
Sponsor and investigators
- Lead sponsor
- CNBG-Virogin Biotech (Shanghai) Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Tingbo Liang, Principal investigator, First Affiliated Hospital of Zhejiang University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04806464
- Sponsor's protocol ID
- VG161-C102
- Status last verified
- Sep 2024
- First submitted
- 12 Mar 2021
- Last updated
- 19 Sep 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Shen Y, Bai X, Zhang Q, Liang X, Jin X, Zhao Z, Song W, Tan Q, Zhao R, Jia W, Gu S, Shi G, Zheng Z, Wei G, Wang Y, Fang T, Li Y, Wang Z, Yang Z, Guo S, Lin D, Wei F, Wang L, Sun X, Qin A, Xie L, Qiu Y, Bao W, Rahimian S, Singh M, Murad Y, Shang J, Chu M, Huang M, Ding J, Chen W, Ye Y, Chen Y, Li X, Liang T. Oncolytic virus VG161 in refractory hepatocellular carcinoma. Nature. 2025 May;641(8062):503-511. doi: 10.1038/s41586-025-08717-5. Epub 2025 Mar 19.
PubMed 40108464
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Dose Ascending, Open Phase I Clinical Study to Evaluate the Safety, Tolerability , Pharmacokinetics Characteristics and Preliminary Effectiveness of VG161 in Subjects with Advanced Primary Liver Cancer
- ClinicalTrials.gov ID
- NCT04806464
- Acronym / sponsor ID
- VG161-C102
- Conditions
- Primary Liver Cancer
- Keywords
- Liver Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 44 participants (estimated)
- Lead sponsor
- CNBG-Virogin Biotech (Shanghai) Ltd.Industry (pharma, biotech, devices)
- Study start
- 16 Mar 2021 (actual)
- Primary completion
- 21 Mar 2022 (actual)
- Study completion
- 31 Dec 2024 (estimated)
- First posted
- 19 Mar 2021 (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.
VG161 is a recombinant human-IL12/15/PDL1B oncolytic HSV-1 Injectable. This phase I study will be conducted in HSV-seropositive subjects with advanced primary liver cancer that are refractory to conventional therapies. This is an open label study and it's divided into two parts.
Part 1: This part is ascending dose design to determine the safety and tolerability of VG161 and find recommended dose of VG161.
Part 2: This part is extended dose design to determine the effectiveness of VG161.
Detailed description
Part 1: This part will be conducted in 5 dose ascending cohorts, including 2 accelerated titration design dose group and 3 dose escalation groups. Descriptive statistics will be used to summarize data.
Part 2: This part will only include the part 1 recommended dose. Hypothesis test and descriptive statistics will be used to summarize data.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| VG161 | Experimental | Drug: Recombinant Human IL12/15-PDL1B Oncolytic HSV-1 Injection (Vero Cell))Part1: 1. 1.0*10^8 PFU on Day 1(1.0×10^8PFU) 2. 1.0*10^8 PFU on Days 1 to 2(2.0×10^8PFU) 3. 1.0*10^8 PFU on Days 1 to 3(3.0×10^8PFU) 4. 1.3*10^8 PFU on Days 1 to 3(4.0×10^8PFU) 5. 1.7*10^8 PFU on Days 1 to 3(5.0×10^8PFU) Part2: Depends on the recommended dose in Part1 |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (15 listed)
- Subject in prior anti-tumor therapies such as chemotherapy, radiotherapy, biotherapy, endocrinotherapy, targeted therapy, immunotherapy within 4 weeks of study treatment initiation. Oral fluorouracil analogues and small molecule targeted drugs were 2 weeks prior to the first dose of study drug or within 5 half-lives of the drug (whichever was longer).
- Transcatheter arterial chemoembolization(TACE) within 4 weeks of study treatment initiation
- Participation in clinical trials of any other investigational agents within 4 weeks of study treatment initiation.
- Major organ surgery (excluding puncture biopsy) or significant trauma within 4 weeks of study treatment initiation.
- Patients who received systemic treatment with either corticosteroids ( \>10 mg/ daily prednisone or equivalent) or other immunosuppressive medications within 14 days of study treatment initiation.
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 |
|---|---|---|
| Recombinant Human IL12/15-PDL1B Oncolytic HSV-1 Injection (Vero Cell))Also: VG161Intratumoral injection only. The dosing date can be the Day 1 only or Days 1 through 5. | Drug | VG161 |
Primary outcome
Part1: MTD/Recommended dose
Time frame: 7 month
MTD (Maximum tolerable dose) /Recommended dose
Part1: Occurence of DLT
Time frame: 1month
Occurence of DLT (Dose Limiting Toxicity)
Part1: Numbers of DLT
Time frame: 1 month
Numbers of DLT (Dose Limiting Toxicity)
Part1: Occurence of AE and SAE(NCI CTCAE 5.0)
Time frame: 7 months
Occurence of Adverse Event (AE) and Serious Adverse Event (SAE) (NCI CTCAE 5.0)
Part1: Frequency of AE and SAE(NCI CTCAE 5.0)
Time frame: 7 months
Frequency of Adverse Event (AE) and Serious Adverse Event (SAE) (NCI CTCAE 5.0)
Part2:ORR
Time frame: 7 months
Evaluate Objective Response Rate by RECIST 1.1
20 secondary outcomes
Part1:Tmax(h)
Time frame: At the end of Cycle 1 (each cycle is 28 days)
Part1:Cmax(copies/ugDNA)
Time frame: At the end of Cycle 1 (each cycle is 28 days)
Part1:ORR
Time frame: 7 months
Part1:DOR
Time frame: 7 months
Part1:PFS
Time frame: 7 months
Part1:OS rate
Time frame: 17 months
Part 1:CD3+, CD4+, CD8+
Time frame: 7 months
Part 1:IL15
Time frame: 7 months
Part 1:PD-L1, PD-1
Time frame: 7 months
Part 2:PFS
Time frame: 7 months
Part 2:OS rate
Time frame: 17 months
Part 2: OS
Time frame: 17 months
Part 2:DOR
Time frame: 7 months
Part 2:Safety indicators:AEs
Time frame: 7 months
Part 2:Safety indicators:ECOG
Time frame: 7 months
Part 2:Safety indicators:12-lead electrocardiograms
Time frame: 7 months
Part 2:Safety indicators:laboratory tests results
Time frame: 7 months
Part 2:CD3+, CD4+, CD8+
Time frame: 7 months
Part 2:IL15
Time frame: 7 months
Part 2:PD-L1, PD-1
Time frame: 7 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
- Derived from this study: PubMed 40108464Shen Y, Bai X, Zhang Q, Liang X, Jin X, Zhao Z, Song W, Tan Q, Zhao R, Jia W, Gu S, Shi G, Zheng Z, Wei G, Wang Y, Fang T, Li Y, Wang Z, Yang Z, Guo S, Lin D, Wei F, Wang L, Sun X, Qin A, Xie L, Qiu Y, Bao W, Rahimian S, Singh M, Murad Y, Shang J, Chu M, Huang M, Ding J, Chen W, Ye Y, Chen Y, Li X, Liang T. Oncolytic virus VG161 in refractory hepatocellular carcinoma. Nature. 2025 May;641(8062):503-511. doi: 10.1038/s41586-025-08717-5. Epub 2025 Mar 19.
- 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. This study is not recruiting at the moment.
Tingbo Liang principal investigator
First Affiliated Hospital of Zhejiang University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Recombinant Human IL12/15-PDL1B Oncolytic HSV-1 Injection (Vero Cell)) in people with Primary Liver Cancer, run by CNBG-Virogin Biotech (Shanghai) Ltd. 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 0 inclusion and 15 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: status not confirmed, as of the sponsor's last update on 19 Sep 2024. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Tingbo Liang, MD.PhD. (0571-87236666, liangtingbo@zju.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part1: MTD/Recommended dose (time frame: 7 month). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04806464, which also lists 1 linked publication.
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 19 Sep 2024.