Hepatocellular CarcinomaPhase 2NCT05223816
An Open-Label, Multiple-Center, Phase IIa/IIb Clinical Trial to Evaluate the Efficacy, Safety and Tolerability of VG161 as Monotherapy and in Combination With Nivolumab for Treatment of Patients With Hepatocellular Carcinoma or Intrahepatic Cholangiocarcinoma
A Phase 2 study testing VG161 and Nivolumab Injection [Opdivo] in people with Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma, run by Virogin Biotech Canada Ltd at 3 sites in United States.
Trial summary
Safety Run-in Cohort (cohort 1): 10 patients will be treated with IT injection of VG161 in the cohort 1 at dose level of 1.0x10E8 PFU x 3 days. Monotherapy Cohorts (Cohort 2 and 3) Cohort 2 (HCC) This part is a single-agent, single one-dose level and single-arm design. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatocellular Carcinoma, Intrahepatic Cholangiocarcinoma
- What is being tested?
- VG161 and Nivolumab Injection [Opdivo]
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 97 participants
- Where
- 3 sitesUnited States
- Study dates
- 24 Jan 2024to 31 Dec 2025
- Phase
- Phase 2
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed written informed consent.
- Males or females aged 18 years and older.
- Performance status: Eastern Cooperative Oncology Group (ECOG) 0 or 1.
- For subject in Cohort 2: cytologically confirmed advanced/metastatic or surgically unresectable HCC, with documented disease progression after at least two lines of FDA approved systemic therapy, including immunotherapy or anti-angiogenesis therapy as the first line treatment and at least one regimen of the following agents as the second line: anti-angiogenesis agents, tyrosine kinase inhibitors or immunotherapy.
- For subject in Cohort 3: Histologically or cytologically confirmed advanced/metastatic or surgically unresectable ICC, with documented disease progression after chemotherapy as the first line systemic therapy. For patients with known IDH1 mutation, they must receive the appropriate targeted therapy with a IDH1 inhibitor and for patients with MSI-H tumors, they must receive immunotherapy with PD-1 inhibitors.
- For subjects in Cohort 1 and Cohort 4: should fulfill either inclusion criteria 4) or 5).
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- Liver function: Child-Pugh A-B for cohort 1 and 2.
- At least one measurable lesion per RECIST 1.1
- At least 1 injectable lesion; ≥15 mm in longest diameter and deemed injectable as per Investigator's discretion. Subjects with deep or visceral lesions (such as hepatic or intraperitoneal lymph nodes) that can be safely injected under guided imaging can be considered for intratumoral injection of VG161..
Who cannot join
- Participation in any trial of any other investigational agent within the last 4 weeks prior to dosing. Wash out periods to be reviewed on a case by case basis with Medical Monitor, as required.
- Tumors to be injected lying in mucosal regions or close to an airway, major blood vessel or spinal cord that, in the opinion of the Investigators, could cause occlusion or compression in the case of tumor swelling or erosion into a major vessel in the case of necrosis.
- Subjects with any primary Central Nervous System (CNS) malignancy including glioma and current, active, progressing CNS malignancy, including carcinomatosis meningitis are excluded. Subjects with treated brain metastases are eligible if there is no evidence of progression for at least 4 weeks after CNS-directed treatment, as ascertained by clinical examination and brain imaging (magnetic resonance imaging [MRI] or computed tomography [CT] scan) during the screening period and off steroids (for at least 2 weeks prior to first dose of IP).
- Major surgery within 14 days prior to dosing.
- Intercurrent serious infections within 28 days prior to Screening or treated systematically with antibiotics within 14 days prior to signing ICF.
- Life-threatening illness unrelated to cancer.
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- Active Herpes infection.
- Treatment with antiviral agents within 14 days prior to dosing.
- Uncontrolled congestive heart failure.
- Known to test positive for human immunodeficiency virus (HIV) or syphilis.
- Active infection including hepatitis B (HBV) or hepatitis C (HCV) that currently under anti-virus treatment which can affect study drug treatment as per investigator's decision.
- Use of ganciclovir or acyclovir within 14 days prior to dosing.
- Subjects with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days prior to dosing. Inhaled or topical steroids, and adrenal replacement steroid doses ≤10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
- Subjects who have been on systemic anticoagulants within 14 days prior to dosing and/or with International Normalized Ratio (INR) > 1.5 x the upper limit of the reference range are excluded from this study.
- Subjects with prior radiation therapy to the tumor lesion to be injected are excluded from the study, unless there is evidence of tumor progression in the most recent imaging, following completion of radiotherapy.
Trial locations and contacts
3 sites in 1 country.
Mike Teng contact
United States3 sites, 3 recruiting
- Recruiting
Mayo Clinic Florida
Jacksonville, Florida, 32224
Hani Babiker, MD
- Recruiting
Mayo Clinic
Phoenix, Arizona, 85054
Mitesh Borad
- Recruiting
Mayo Clinic
Rochester, Minnesota, 55905
Lionel Kankeu-Fonkoua
About this study
Safety Run-in Cohort (cohort 1):
10 patients will be treated with IT injection of VG161 in the cohort 1 at dose level of 1.0x10E8 PFU x 3 days.
Read more
Monotherapy Cohorts (Cohort 2 and 3) Cohort 2 (HCC) This part is a single-agent, single one-dose level and single-arm design. Approximately 39 subjects will be enrolled in the study to receive VG161. In the first stage, 21 subjects will be enrolled. If there is only 1 or fewer subjects has been observed with objective response and no more than 12 (<13) subjects have PFS longer than 3 months, the trial will be stopped. Otherwise, this study will continue to enter the second stage, and 18 additional subjects will be added, and the total number of trial subjects will reach 39.
Cohort 3 (ICC) This part is a single-agent, single one-dose level and single-arm design. The trial will be carried out in two periods. In the first period, a total of 20 subjects will be enrolled. If there is only 1 or fewer response case in the 20 subjects, the trial will be stopped to investigate the efficacy of the IP, otherwise, subjects will continue to enter the second period, and 13 additional subjects will be added, and the total number of trial cases will reach 33.
Cohort 4 (ICC and HCC) Combination with Nivolumab Combination cohort and subjects will receive VG161 at the same schedule as the monotherapy cohorts and 240 mg of intravenous Nivolumab on days 8 and 15 of each treatment cycle. The Nivolumab dose can be changed to 480 mg every 4 weeks after cycle one based on investigator's discretion.
- Being tested
- VG161, Nivolumab Injection [Opdivo]
- Medical subject headings
- Carcinoma, Hepatocellular, Cholangiocarcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VG161Drug
Name: VG161 (Recombinant Human IL12/15-PDL1B Oncolytic HSV-1 Injection (Vero Cell)) Concentration/Content: ≥1×107 PFU/mL; 1.0 mL/vial. Actual titer will be recorded on Certificate of Analysis.
Composition: VG161,50 mM Tris-HCl, 150mM NaCl, <5% glycerol Route of Administration: Intratumoral injection or image guided intratumoral injections.
Nivolumab Injection [Opdivo]Drug
immunotherapy treatment
| Study group | Role | What they receive |
|---|---|---|
| Safety Run-in Cohort | Experimental | 10 patients will be treated with IT injection of VG161 in the cohort 1 at dose level of 1.0x10E8 PFU x 3 days. Receives: Drug: VG161 |
| Cohort 2 (HCC) | Experimental | 21 patients will be treated with IT injection of VG161 in the cohort 1 at dose level of 1.0x10E8 PFU x 3 days. Receives: Drug: VG161 |
| Cohort 3 (ICC) | Experimental | 20 patients will be treated with IT injection of VG161 in the cohort 1 at dose level of 1.0x10E8 PFU x 3 days. Receives: Drug: VG161 |
| Cohort 4 (HCC and ICC) | Experimental | Up to 12 patients will be treated with IT injection of VG161 ar dose level of 1.0x10E8 PFU x 3 days. and Nivolumab per approved label. Receives: Drug: VG161; Drug: Nivolumab Injection [Opdivo] |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety in Cohort1
Occurrence and severity of AEs, SAEs (according to NCI CTCAE version 5.0) in Safety Run-in Cohort (cohort 1)
Measured: 12 months
ORR
Objective response rate in HCC Cohort (Cohort 2) and ICC Cohort (Cohort 3)
Measured: 12 months
PFS
Progression-free survival in HCC Cohort (Cohort 2)
Measured: 3 months
Secondary outcomes (14)
Blood concentration of VG161
Quantity of Blood concentration of VG161 in cohort 1
Measured: 12 months
PD-L1 blocking peptide and IL12, IL-15 concentrations
Quantity of PD-L1 blocking peptide and IL12, IL-15 concentrations in cohort 1
Measured: 12 months
serum antibodies in cohort 1
Quantity of serum antibodies in cohort 1
Measured: 12 months
Viral shedding
VG161 DNA tested in cohort 1
Measured: 12 months
Immunogenicity endpoints
serum antibodies (ADA and Nab) at different time points in cohort 1
Measured: 12 months
ORR in cohort 1
objective response rate in Cohort1
Measured: 12 months
PFS
Progression-free survival in all cohorts
Measured: 12 months
OS
Overall survival rate in all cohorts
Measured: 12 months
DOR
Duration of response in all cohorts
Measured: 12 months
Safety in Cohort2 and Cohort3
Occurrence and severity of AEs, SAEs (according to NCI CTCAE version 5.0) in cohort 2 and cohort 3
Measured: 12 months
peripheral blood lymphocyte subsets
Quantity of peripheral blood lymphocyte subsets (CD3+, CD4+, CD8+, CD4+/CD8+ ratio, CD19+, CD16+CD56+ (NK) cells) in cohort 2 and cohort 3
Measured: 12 months
plasma cytokines
Quantity of plasma cytokines (IL-15, IL-6, TNF-a, IFN-γ) in cohort 2 and cohort 3
Measured: 12 months
immune-related indicators
Quantity of immune-related indicators (PD-L1, PD-1, CD69, CD8+Ki67high) in cohort 2 and cohort 3
Measured: 12 months
anti-HSV-1 antibody
Quantity of anti-HSV-1 antibody in cohort 2 and cohort 3
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Feb 2022
- Study start24 Jan 2024
- Primary completion1 Oct 2025 (estimated)
- Study completion31 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular CarcinomaStudies 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
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 97 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Virogin Biotech Canada Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05223816
- Sponsor's protocol ID
- VG161-A201
- Status last verified
- Aug 2024
- First submitted
- 20 Dec 2021
- Last updated
- 9 Aug 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label, Multiple-Center, Phase IIa/IIb Clinical Trial to Evaluate the Efficacy, Safety and Tolerability of VG161 as Monotherapy and in Combination With Nivolumab for Treatment of Patients With Hepatocellular Carcinoma or Intrahepatic Cholangiocarcinoma
- ClinicalTrials.gov ID
- NCT05223816
- Acronym / sponsor ID
- VG161-A201
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 97 participants (estimated)
- Lead sponsor
- Virogin Biotech Canada LtdIndustry (pharma, biotech, devices)
- Study start
- 24 Jan 2024 (actual)
- Primary completion
- 1 Oct 2025 (estimated)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 4 Feb 2022 (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.
Safety Run-in Cohort (cohort 1):
10 patients will be treated with IT injection of VG161 in the cohort 1 at dose level of 1.0x10E8 PFU x 3 days.
Monotherapy Cohorts (Cohort 2 and 3) Cohort 2 (HCC) This part is a single-agent, single one-dose level and single-arm design. Approximately 39 subjects will be enrolled in the study to receive VG161. In the first stage, 21 subjects will be enrolled. If there is only 1 or fewer subjects has been observed with objective response and no more than 12 (<13) subjects have PFS longer than 3 months, the trial will be stopped. Otherwise, this study will continue to enter the second stage, and 18 additional subjects will be added, and the total number of trial subjects will reach 39.
Cohort 3 (ICC) This part is a single-agent, single one-dose level and single-arm design. The trial will be carried out in two periods. In the first period, a total of 20 subjects will be enrolled. If there is only 1 or fewer response case in the 20 subjects, the trial will be stopped to investigate the efficacy of the IP, otherwise, subjects will continue to enter the second period, and 13 additional subjects will be added, and the total number of trial cases will reach 33.
Cohort 4 (ICC and HCC) Combination with Nivolumab Combination cohort and subjects will receive VG161 at the same schedule as the monotherapy cohorts and 240 mg of intravenous Nivolumab on days 8 and 15 of each treatment cycle. The Nivolumab dose can be changed to 480 mg every 4 weeks after cycle one based on investigator's discretion.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Safety Run-in Cohort | Experimental | Drug: VG16110 patients will be treated with IT injection of VG161 in the cohort 1 at dose level of 1.0x10E8 PFU x 3 days. |
| Cohort 2 (HCC) | Experimental | Drug: VG16121 patients will be treated with IT injection of VG161 in the cohort 1 at dose level of 1.0x10E8 PFU x 3 days. |
| Cohort 3 (ICC) | Experimental | Drug: VG16120 patients will be treated with IT injection of VG161 in the cohort 1 at dose level of 1.0x10E8 PFU x 3 days. |
| Cohort 4 (HCC and ICC) | Experimental | Drug: VG161, Drug: Nivolumab Injection [Opdivo]Up to 12 patients will be treated with IT injection of VG161 ar dose level of 1.0x10E8 PFU x 3 days. and Nivolumab per approved label. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Signed written informed consent.
- Males or females aged 18 years and older.
- Performance status: Eastern Cooperative Oncology Group (ECOG) 0 or 1.
- For subject in Cohort 2: cytologically confirmed advanced/metastatic or surgically unresectable HCC, with documented disease progression after at least two lines of FDA approved systemic therapy, including immunotherapy or anti-angiogenesis therapy as the first line treatment and at least one regimen of the following agents as the second line: anti-angiogenesis agents, tyrosine kinase inhibitors or immunotherapy.
- For subject in Cohort 3: Histologically or cytologically confirmed advanced/metastatic or surgically unresectable ICC, with documented disease progression after chemotherapy as the first line systemic therapy. For patients with known IDH1 mutation, they must receive the appropriate targeted therapy with a IDH1 inhibitor and for patients with MSI-H tumors, they must receive immunotherapy with PD-1 inhibitors.
Key exclusion criteria (15 listed)
- Participation in any trial of any other investigational agent within the last 4 weeks prior to dosing. Wash out periods to be reviewed on a case by case basis with Medical Monitor, as required.
- Tumors to be injected lying in mucosal regions or close to an airway, major blood vessel or spinal cord that, in the opinion of the Investigators, could cause occlusion or compression in the case of tumor swelling or erosion into a major vessel in the case of necrosis.
- Subjects with any primary Central Nervous System (CNS) malignancy including glioma and current, active, progressing CNS malignancy, including carcinomatosis meningitis are excluded. Subjects with treated brain metastases are eligible if there is no evidence of progression for at least 4 weeks after CNS-directed treatment, as ascertained by clinical examination and brain imaging (magnetic resonance imaging [MRI] or computed tomography [CT] scan) during the screening period and off steroids (for at least 2 weeks prior to first dose of IP).
- Major surgery within 14 days prior to dosing.
- Intercurrent serious infections within 28 days prior to Screening or treated systematically with antibiotics within 14 days prior to signing ICF.
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 |
|---|---|---|
| VG161Name: VG161 (Recombinant Human IL12/15-PDL1B Oncolytic HSV-1 Injection (Vero Cell)) Concentration/Content: ≥1×107 PFU/mL; 1.0 mL/vial. Actual titer will be recorded on Certificate of Analysis. Composition: VG161,50 mM Tris-HCl, 150mM NaCl, <5% glycerol Route of Administration: Intratumoral injection or image guided intratumoral injections. | Drug | Cohort 2 (HCC), Cohort 3 (ICC), Cohort 4 (HCC and ICC), Safety Run-in Cohort |
| Nivolumab Injection [Opdivo]immunotherapy treatment | Drug | Cohort 4 (HCC and ICC) |
Primary outcome
Safety in Cohort1
Time frame: 12 months
Occurrence and severity of AEs, SAEs (according to NCI CTCAE version 5.0) in Safety Run-in Cohort (cohort 1)
ORR
Time frame: 12 months
Objective response rate in HCC Cohort (Cohort 2) and ICC Cohort (Cohort 3)
PFS
Time frame: 3 months
Progression-free survival in HCC Cohort (Cohort 2)
14 secondary outcomes
Blood concentration of VG161
Time frame: 12 months
PD-L1 blocking peptide and IL12, IL-15 concentrations
Time frame: 12 months
serum antibodies in cohort 1
Time frame: 12 months
Viral shedding
Time frame: 12 months
Immunogenicity endpoints
Time frame: 12 months
ORR in cohort 1
Time frame: 12 months
PFS
Time frame: 12 months
OS
Time frame: 12 months
DOR
Time frame: 12 months
Safety in Cohort2 and Cohort3
Time frame: 12 months
peripheral blood lymphocyte subsets
Time frame: 12 months
plasma cytokines
Time frame: 12 months
immune-related indicators
Time frame: 12 months
anti-HSV-1 antibody
Time frame: 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Aug 2024.
- Virogin Biotech WebsiteLink provided by the sponsor.
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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.
Mike Teng contact
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing VG161 and Nivolumab Injection [Opdivo] in people with Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma, run by Virogin Biotech Canada Ltd at 3 sites in United States.
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 9 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 9 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Naghmeh Esmaeili (7785589840, nesmaeili@virogin.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety in Cohort1 (time frame: 12 months). The study lists 3 primary outcomes in all. 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 9 Aug 2024.