A Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Biologic Effect of VG2025 in Patients With Solid Tumors

Study Overview
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Brief Summary
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VG2025 is a Recombinant Human IL12/15 Dual-Regulated Oncolytic HSV-1 Injection. This Phase I study will be conducted in herpes simplex virus (HSV) -seropositive subjects with advanced malignant solid tumors that are refractory to conventional therapies. This is an open label study to determine the safety and tolerability of VG2025, and recommended dose of VG2025 for Phase II trials.

Detailed Description
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This is a Phase 1, open-label, dose-escalation trial using standard 3+3 dose-escalation design in patients with advanced malignant solid tumors. The trial will be conducted in multiple dosing cohorts, and evaluated for safety to determine the Maximum Tolerated Dose (MTD) and the Recommended Phase 2 Dose (RP2D). Dose limiting toxicity (DLT) evaluation period is for 4 weeks from the start of treatment Day 1 through Day 28.

Official Title
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A Dose Escalation, Open-label Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Biologic Effect of VG2025 in the Treatment of Patients With Advanced Malignant Solid Tumors

Conditions
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Advanced Malignant Solid Tumor

Intervention / Treatment
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* Drug: Recombinant Human IL12/15 Dual-Regulated Oncolytic HSV-1 Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed written informed consent form. Age 18 to 75 years (inclusive), male or female. Subject with advanced malignant solid tumors who have failed standard treatment and for whom there is no effective treatment at this stage. Eligible patients of childbearing potential (male and female) must agree to use a reliable method of contraception during the trial and for at least 90 days after dosing; females of childbearing potential must have a negative blood pregnancy test 7 days before enrollment. Exclusion Criteria: Subjects who have received other unlisted drugs clinical trial treatment 4 weeks before the first dose of the study drug. Subjects who underwent major organ surgery (excluding needle biopsy) or had significant trauma 4 weeks before the first dose of the study drug. In the herpes simplex virus recurrence and infection period, and there are corresponding clinical manifestations, such as oral herpes labialis, herpetic keratitis, herpetic dermatitis, genital herpes and so on. Other active uncontrolled infection. Known alcohol or drug dependence. Subjects with mental disorders or poor compliance. Women who are pregnant or breastfeeding. Subjects in the opinion of the investigator are not suitable for this clinical study due to other serious systemic diseases or other reasons.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 3+3 design<br>This is an open label, single-arm trial using standard 3+3 design, in up to 30 HSV seropositive subjects. This rule-based design proceeds with cohorts of three patients | Drug: Recombinant Human IL12/15 Dual-Regulated Oncolytic HSV-1 Injection<br>* Dose level 1 Dose level 2 Dose level 3 Dose level 4 Dose level 5<br>* Other names: VG2025;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MTD/RP2D | Maximum tolerable dose (MTD) / Recommended dose for phase II (RP2D) | During the 28 day DLT observation period | 
| Adverse Events (AEs) and Serious Adverse Events (SAEs) | Occurence of Adverse Events (AEs) and Serious Adverse Events (SAEs)as assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Level of deoxyribonucleic acid (DNA) | Shedding profile of detectable VG2025 deoxyribonucleic acid (DNA) | 12 months | 
| Interleukin level | Evaluate the interleukin-12 (IL-12) and interleukin-12 (IL-15) levels | 12 months | 
| ORR | Objective response rate (ORR) | Multiple time points before and after administration | 
| DCR | Disease control rate (DCR) | 12 months | 
| PFS | Progression-free survival (PFS) | 12 months | 
| OS | Overall Survival (OS) | 12 months | 
| Antibodies | VG2025 anti-drug antibodies (ADA) and neutralizing antibody (Nab) | 12 months |