Clinical Study of VG161 in Combination With Nivolumab in Subjects With Advanced Pancreatic Cancer

Clinical Trial to Evaluate the Safety, Tolerability and Preliminary Efficacy of VG161 in Combination With Nivolumab in Patients With Advanced Pancreatic Cancer

VG161 is a recombinant human-IL12/15/PDL1B oncolytic HSV-1 Injectable. This is a multicenter, open, single-arm design clinical trial coducted in HSV-seropositive subjects with advanced pancreatic cancer to determine the safety, tolerability and preliminary efficacy of VG161 combined with PD-1 inhibitor (Nivolumab Injection).

Study Overview

• Status: Recruiting
• Conditions: Advanced Pancreatic Cancer
• Intervention / Treatment: Drug: Recombinant Human IL12/15-PDL1B Oncolytic HSV-1 Injection (Vero Cell)) in combination with Nivolumab

Detailed Description

A multicenter, open, single-arm design of clinical trial of VG161 in combined with PD-1 inhibitor (Nivolumab) in the treatment of patients with advanced pancreatic cancer with metastasis. The standard 3 + 3 design was used in the dose-finding study to explore the safety of the combination treatment, determine the recommended safe dose (RP2D) of the combination treatment in the second phase of efficacy study. The first cycle was observed until Day 28, i.e., DLT observation period. In the efficacy investigation trial, Simon two-segment design was used to continue to investigate the preliminary efficacy of the combination at a safe dose.

• Study Type: Interventional
• Enrollment (Anticipated): 51
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Tingbo Liang, Doctor; Phone Number: 13967159109; Email: liangtingbo@zju.edu.cn
• Study Contact Backup: Name: Yinan Shen, Doctor; Phone Number: 13486180288; Email: fysyn@163.com

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • Recruiting
      • the First Affiliated Hospital, School of Medicine, Zhejiang University

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:

• Subjects must give informed consent to this study before the trial and voluntarily sign a written informed consent form
• Age 18 to 75 years (inclusive), male or female
• According to the Guidelines for the Diagnosis and Treatment of Pancreatic Cancer, patients with histologically or cytologically confirmed advanced primary pancreatic ductal adenocarcinoma, acinar cell carcinoma or adenosquamous carcinoma, accompanied by metastasis (TxNxM1), who have failed standard treatment, or have no effective treatment at this stage
• The presence of at least one intratumoral injection lesion with the longest diameter (the longest diameter of lymph nodes) greater than or equal to 1.5 cm that is required by the dose volume of the acceptable current dose group, including superficial lesions or deep lesions that can be injected under B ultrasound/CT guidance (such as liver metastases, etc.)
• Herpes simplex virus type I (HSV-1) antibody test results (HSV-1IgG or HSV-1IgM) are positive
• ECOG performance score 0-1
• The expected survival time is more than 3 months
• Adequate organ function: 1) blood routine (No blood transfusion or colony-stimulating factor treatment Within 14 days): ANC ≥ 1.5 × 10^9/L, PLT ≥ 75 × 10^9/L, Hb ≥ 90 g/L, lymphocyte count ≥ 1.5 × 10^9/L (for lymphocyte count 1.0 × 10^9/L to 1.5 × 10^9/L, the investigator judges whether it is necessary); 2) liver function: TBIL ≤ 1.5 × ULN, ALT ≤ 3 × ULN, AST ≤ 3 × ULN (patients with liver metastases can receive ALT ≤ 5 × ULN, AST ≤ 5 × ULN); 3) Child-Pugh score: A-B; 4) renal function: Cr ≤ 1.5 × ULN, and creatinine clearance ≥ 45ml/min (calculated according to CockftGault formula); 5) coagulation function: activated partial thromboplastin time (APTT) ≤ 1.5 × ULN, international normalized ratio (INR) ≤ 1.5 × ULN
• Eligible patients of childbearing potential (male and female) must agree to use a reliable method of contraception (hormonal or barrier method or abstinence) during the trial and for at least 90 days after medication; female patients of childbearing age must have a negative blood pregnancy test 7 days before inclusion

Exclusion Criteria:

• Received chemotherapy, radiotherapy, biological therapy, endocrine therapy, targeted therapy, immunotherapy (including PD-1/PD-L1 inhibitors) and other anti-tumor drug therapy 4 weeks before the first use of the study drug, oral fluoropyrimidines and small molecule targeted drugs are 2 weeks before the first use of the study drug or within 5 half-lives of the drug (whichever is longer)
• Received other unmarketed clinical trial treatment 4 times before the first use of the study drug
• Major organ surgery (excluding needle biopsy) or significant trauma 4 times before the first use of study drugs; 4. Patients who have received systemic corticosteroids (prednisone > 10 mg/day or equivalent doses of the same class of drugs) or other immunosuppressive agents within 14 days before the first use of study drugs; except for the following conditions: the use of topical, ocular, intra-articular, intranasal and inhaled corticosteroids; short-term use of corticosteroids for prophylaxis (such as prevention of contrast agent allergy)
• Have received vaccination 4 times before the first use of the study drug
• The adverse reactions of previous anti-tumor treatment have not recovered to CTCAE 5.0 grade evaluation ≤ 1 (except alopecia and other toxicities that are judged by the investigator to have no safety risk)
• Patients with central nervous system or spinal cord malignant tumors or metastases, which are not suitable for enrollment as judged by the investigator
• Accompanied by spinal cord compression, which is not suitable for the investigator's judgment
• In the period of herpes simplex virus recurrence and infection, and there are corresponding clinical manifestations, such as oral herpes labialis, herpetic keratitis, herpetic dermatitis, genital herpes and so on. 10.Other active uncontrolled infection
• History of immunodeficiency, including a positive HIV antibody test
• Patients with active hepatitis B or active hepatitis C. (Patients with hepatitis B virus carriers, stable hepatitis B after drug treatment [HBV-DNA negative] and cured hepatitis C [HCV RNA test negative]) were excluded. 13.History of severe cardiovascular disease: 1) arrhythmia requiring clinical intervention; 2) QTc interval > 480 ms; 3) acute coronary syndrome, congestive heart failure, stroke or other grade III and above cardiovascular events within 6 months; 4) New York Heart Association (NYHA) functional classification ≥ II or LVEF < 40%; 5) uncontrolled hypertension (judged by the investigator)
• Patients with active or previous autoimmune diseases that may relapse (such as interstitial pneumonia, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism, including but not limited to these diseases or syndromes); patients with clinically stable autoimmune thyroiditis, autoimmune-mediated hypothyroidism treated with stable doses of thyroid replacement hormone, type I diabetes mellitus treated with stable doses of insulin, vitiligo or recovered childhood asthma/allergy, who do not require any intervention in adulthood
• Had received immunotherapy and experienced an irAE grade ≥ 3
• Known alcohol or drug dependence
• Patients with mental disorders or poor compliance
• Women who are pregnant or breastfeeding
• The subject has other serious systemic diseases or other reasons that make the subject unsuitable for this clinical study in the opinion of the investigator

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: Single Arm; Intratumoral injection of VG161 - 1.5*10^8 on D1 + Nivolumab on D8, D22; Intratumoral injection of VG161 - 1.0*10^8 on D1, D2 + Nivolumab on D8, D22; Intratumoral injection of VG161 - 1.0*10^8 on D1, D2, D3 + Nivolumab on D8, D22	Drug: Recombinant Human IL12/15-PDL1B Oncolytic HSV-1 Injection (Vero Cell)) in combination with Nivolumab; Intratumoral injection of VG161 on day 1 only or day 1 through 3, in combination of Nivolumab intravenous injection only, Once every 2 weeks, 3 mg/kg each time.; Other Names: VG161 + Nivolumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MTD	MTD (Maximum tolerable dose)	1 month
Occurrence and numbers of DLT (phase 1)	Occurence of DLT (Dose Limiting Toxicity) and numbers of DLT	1 month
Occurence and frequence of AE and SAE (phase 1)	Occurence and frequence of Adverse Event (AE) and Serious Adverse Event (SAE) (NCI CTCAE 5.0)	24 month
DCR (phase 2)	Evaluate Disease Control Rate by RECIST 1.1	24 month
RP2D (phase 1)	RP2D (Recommended dose for phase II)	1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DCR (phase 1)	Evaluate Disease Control Rate by RECIST 1.1	24 month
ORR	Evaluate Objective Response Rate by RECIST 1.1	24 month
PFS	Evaluate Progression Free Survival by RECIST 1.1	24 month
PD-1	PD-1 level in peripheral blood T cells	24 month
Single cell sequencing	Single-cell sequencing of tumor biopsy samples	24 month
Occurence and frequence of AE and SAE (phase 2)	Occurence and frequence of Adverse Event (AE) and Serious Adverse Event (SAE) (NCI CTCAE 5.0)	24 month
CD3+	Concentration of CD3+	24 month
CD4+	Concentration of CD4+	24 month
CD8+	Concentration of CD8+	24 month
CD4+/CD8+	Concentration of CD4+/CD8+	24 month
NK	Concentration of NK	24 month
CD19+	Concentration of CD19+	24 month
CD56+	Concentration of CD56+	24 month
IL-6	Cytokine levels of IL-6	24 month
TNF-a	Cytokine levels of TNF-a	24 month
IFN-γ	Cytokine levels of IFN-γ	24 month
CA19-9	Tumor markers of CA19-9	24 month
CA125	Tumor markers of CA125	24 month
CEA	Tumor markers of CEA	24 month

Collaborators and Investigators

• Sponsor: Zhejiang University
• Investigators: Principal Investigator: Tingbo Liang, Doctor, The First Affiliated Hospital Zhengjiang University School of Medicine

Study record dates

Study Major Dates

• Study Start (Anticipated): March 8, 2022
• Primary Completion (Anticipated): March 22, 2025
• Study Completion (Anticipated): December 22, 2025

Study Registration Dates

• First Submitted: November 23, 2021
• First Submitted That Met QC Criteria: December 5, 2021
• First Posted (Actual): December 17, 2021

Study Record Updates

• Last Update Posted (Actual): March 9, 2022
• Last Update Submitted That Met QC Criteria: March 8, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Solid Tumor
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab
• Other Study ID Numbers: VG161-IIS-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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