NCT04806464

Brief 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. 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.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
44

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started Mar 2021

Typical duration for phase_1

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 12, 2021

Completed
4 days until next milestone

Study Start

First participant enrolled

March 16, 2021

Completed
3 days until next milestone

First Posted

Study publicly available on registry

March 19, 2021

Completed
1 year until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 21, 2022

Completed
2.8 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2024

Completed
Last Updated

September 19, 2024

Status Verified

September 1, 2024

Enrollment Period

1 year

First QC Date

March 12, 2021

Last Update Submit

September 10, 2024

Conditions

Primary Liver Cancer

Keywords

Liver Cancer

Outcome Measures

Primary Outcomes (6)

  • Part1: MTD/Recommended dose

    MTD (Maximum tolerable dose) /Recommended dose

    7 month

  • Part1: Occurence of DLT

    Occurence of DLT (Dose Limiting Toxicity)

    1month

  • Part1: Numbers of DLT

    Numbers of DLT (Dose Limiting Toxicity)

    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）

    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）

    7 months

  • Part2:ORR

    Evaluate Objective Response Rate by RECIST 1.1

    7 months

Secondary Outcomes (20)

  • Part1:Tmax(h)

    At the end of Cycle 1 (each cycle is 28 days)

  • Part1:Cmax(copies/ugDNA)

    At the end of Cycle 1 (each cycle is 28 days)

  • Part1:ORR

    7 months

  • Part1:DOR

    7 months

  • Part1:PFS

    7 months

  • +15 more secondary outcomes

Study Arms (1)

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

Drug: Recombinant Human IL12/15-PDL1B Oncolytic HSV-1 Injection (Vero Cell))

Interventions

Recombinant Human IL12/15-PDL1B Oncolytic HSV-1 Injection (Vero Cell))DRUG

Intratumoral injection only. The dosing date can be the Day 1 only or Days 1 through 5.

Also known as: VG161
VG161

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may not qualify if:

  • 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.).
  • 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:
  • )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.
  • \. 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.
  • \. 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

The First Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

RECRUITING

Related Publications (1)

  • 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.

    PMID: 40108464DERIVED

MeSH Terms

Conditions

Carcinoma, HepatocellularLiver Neoplasms

Condition Hierarchy (Ancestors)

AdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsDigestive System NeoplasmsNeoplasms by SiteDigestive System DiseasesLiver Diseases

Study Officials

  • Tingbo Liang

    Zhejiang University

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Tingbo Liang, MD.PhD.

CONTACT

0571-87236666liangtingbo@zju.edu.cn

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 12, 2021

First Posted

March 19, 2021

Study Start

March 16, 2021

Primary Completion

March 21, 2022

Study Completion

December 31, 2024

Last Updated

September 19, 2024

Record last verified: 2024-09

Data Sharing

IPD Sharing
Will not share

Locations

CN(1)