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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Advanced Malignant Solid Tumor
• Intervention / Treatment: Drug: Recombinant Human IL12/15 Dual-Regulated Oncolytic HSV-1 Injection

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.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Yinan Shen; Phone Number: +86-0571-87236666; Email: fysyn@163.com

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • Recruiting
      • The First Affiliated Hospital，Zhejiang University School of Medicine
      • Contact: Tingbo Liang; Phone Number: +86-0571-87236666; Email: liangtingbo@zju.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Signed written informed consent form.
2. Age 18 to 75 years (inclusive), male or female.
3. Subject with advanced malignant solid tumors who have failed standard treatment and for whom there is no effective treatment at this stage.
4. 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:

1. Subjects who have received other unlisted drugs clinical trial treatment 4 weeks before the first dose of the study drug.
2. Subjects who underwent major organ surgery (excluding needle biopsy) or had significant trauma 4 weeks before the first dose of the study drug.
3. 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.
4. Other active uncontrolled infection.
5. Known alcohol or drug dependence.
6. Subjects with mental disorders or poor compliance.
7. Women who are pregnant or breastfeeding.
8. Subjects in the opinion of the investigator are not suitable for this clinical study due to other serious systemic diseases or other reasons.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 3+3 design; 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; Dose level 1; Dose level 2; Dose level 3; Dose level 4; Dose level 5; Other Names: VG2025

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Shanghai Virogin Biotech Co., Ltd.
• Investigators: Principal Investigator: Tingbo Liang, M.D.，PhD, Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): August 23, 2022
• Primary Completion (Anticipated): December 31, 2023
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: July 15, 2022
• First Submitted That Met QC Criteria: July 25, 2022
• First Posted (Actual): July 28, 2022

Study Record Updates

• Last Update Posted (Actual): October 17, 2022
• Last Update Submitted That Met QC Criteria: October 12, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: VG201-C101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No