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

Phase 1

Recruiting

Interventions: Drug: Recombinant Human IL12/15 Dual-Regulated Oncolytic HSV-1 Injection

Brief Summary: 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: 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.

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
3+3 design	Recombinant Human IL12/15 Dual-Regulated Oncolytic HSV-1 Injection	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

Primary Outcome Measures

Name	Time	Method
MTD/RP2D	During the 28 day DLT observation period	Maximum tolerable dose (MTD) / Recommended dose for phase II (RP2D)
Adverse Events (AEs) and Serious Adverse Events (SAEs)	12 months	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

Secondary Outcome Measures

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

Locations (1): The First Affiliated Hospital，Zhejiang University School of Medicine
🇨🇳
Hangzhou, Zhejiang, China